Obstetrics and aging Flashcards
What effects does aging have on the airway? (6)
Airway
* Edentulous - increased difficulty with non invasive ventilatory support fitting
* Upper airway prone to collapse - particularly during sleep due to reduced upper airway tone (pharyngeal tone)
* Diminished airway reflexes
* Increased airway reactivity - bronchospasm risk, requires lesser stimuli
* Mild increase of bronchial size
* Decreased ciliary number and activity - clearance of secretion impaired
What effects does aging have on the thoracic cage and breathing apparatus?4
- Thoracic cage becomes more rigid due to calcification of costal cartilages leading to reduced thoracic wall compliance
◦ —>increased effort at baseline to breathe, reduced vital capacity - Vertebral column height loss and deformity leads to kyphosis —> reduced vital capacity
◦ The combination of both above factors mean vital capacity is reduced by 10% between 20 and 70 due to increased thoracic cage rigidity, kyphosis
◦ Total lung capacity however is unchanged from 20 -70 - Diaphragmatic and intercostal muscle atrophy (reduced mass, reduced strength, reduced fast twitch) increasing their fatigue ability in times of stress
◦ Decreased maximum inspiratory pressure
◦ Decreased FEV1
◦ Decreased maximum minute ventilation
◦ Fatigue and exercise capacity reduced - Increased AP diameter - higher residual volume, higher FRC
What effect does vertebral height loss nad kyphosis in aging have on the respiratiry system?
reduced vital capacity
◦ The combination of both above factors mean vital capacity is reduced by 10% between 20 and 70 due to increased thoracic cage rigidity, kyphosis
◦ Total lung capacity however is unchanged from 20 -70
Respiratory muscle weakness with age comprises which 4 changes
reduced mass, reduced strength, reduced fast twitch) increasing their fatigue ability in times of stress
What is the effect of the respiratory muscle weakness seen with aging?
◦ Decreased maximum inspiratory pressure
◦ Decreased FEV1
◦ Decreased maximum minute ventilation
◦ Fatigue and exercise capacity reduced
How does the thoracic cage change with age?
More rigid - reduced compliance, increased effort at baseline to breathe with reduced vital capacity
Increased AP diametre with increased residual volume and FRC
What 3 primary changes occur at the level of the lung parenchyma with age?
Decreased airflow - decreased FEV1 and peak flow rates
Increased respiratory membrane thickness - decline in DLCO
Degeneration of elastic fibres
What is the maximum voluntary ventilation in an average person?
What does this drop to with aging? Why?
100L/min (12-15x what is required for basal metabolism)
This drops to 30-40L due to lost elasticity of lung fibres, increased expiratory work, respiratory muscle weakness and stiffness of the thoracic cage.
What change in respiratory volume soccur with age? 3
‣ Increased ratio of residual volume to TLC –> increased dead space ventilation
‣ Increased ratio of functional residual capacity to TLC - as FRC occurs where inward elastic forces match outward spring and as reduced lung recoil occurs this balance occurs at higher volumes, the anterior posterior diamtre of the lung increases as a consequence of higher resting lung volume flattening the diaphragms putting them at a mechanical disadvantage and increasing the energy expended in inspiration
‣ FRC increasing by 1-3% per decade, and residual volume increases by 5-10% per decade
What happens to FRC with age?
‣ Increased ratio of functional residual capacity to TLC - as FRC occurs where inward elastic forces match outward spring and as reduced lung recoil occurs this balance occurs at higher volumes, the anterior posterior diamtre of the lung increases as a consequence of higher resting lung volume flattening the diaphragms putting them at a mechanical disadvantage and increasing the energy expended in inspiration
‣ FRC increasing by 1-3% per decade, and residual volume increases by 5-10% per decade
What happens to residual volume with aging?
‣ Increased ratio of residual volume to TLC –> increased dead space ventilation
Closing capacity and the effect of age? Why? Magnitude of effect?
‣ increases as small airways collapse at larger lung volumes due to reduced radial traction of terminal bronchioles due to reduction in alveolar septa
‣ As the closing volume increases greater proportion of tidal volume will occur at volumes below closing volume resulting in worsened V/Q mismatch and hypoxia
‣ CC exceeds FRC after age 45 when supine, standing by 65
How does compliance change with age?
‣ Lung compliance improved which partially offsets the reduced thoracic cage compliance however overall it remains lower leading to reduced gradient of the pressure volume curve
‣ Reduced elastic recoil
‣ Decreased diaphragmatic excursion
What happens to the alveolar arterial oxygen gradient with age? Why 3? By how much does resting arterial oxygen tension change?
- Increases with age due to V/Q mismatch associated with increased closing capacity but also due to
◦ Reduced alveolar surface area - reduced alveolar diffusion capacity
◦ Increased alveolar capillary membrane thickness —>reduced diffusion capacity - This leads resting arterial oxygen tension to reduce with age
◦ PaO2 = 100- (0.33 x age) mmHg - Hypoxic pulmonary vasoconstriction is less active with age further exacerbating V/Q mismatch
How do the sensors in the respiratory system get affected by age?
- Blunting of medullary response to hypercapnoea (40% reduction) and hypoxia (50% reduction)
- Increased perception of dyspnoea
What is morbid obesity?
BMI >35
Give the main domains morbid obesity affects haemodynamically?
Central
- Blood volume
- Cardiac output
- Oxygen consumption
- Coronary
- Right heart
Peripheral - SVR
How does obesity affect blood volume?
◦ Total and circulating blood volume increases
◦ Reduced per kg volume (45mL/kg vs 70mL/kg)
◦ Plasma renin is higher —> RAAS activation —> predisposes to hypertension
How does obesity affect BP
◦ Total and circulating blood volume increases
◦ Reduced per kg volume (45mL/kg vs 70mL/kg)
◦ Plasma renin is higher —> RAAS activation —> predisposes to hypertension
How does obesity affect HR
the same as is for ideal body weight
How does obesity affect stroke volume?
◦ Stroke volume increased in proportion to excess in body weight
‣ Increased blood volume —> increased preload
‣ Reduced systemic vascular resistance —> reduced afterload
* In metabolic syndrome and systemic hypertension that often accompanies obesity this may not be the case however increased stroke volume will be maintained by LVH and increased LV work
What effect does obesity have on cardiac output?
◦ Despite increased cardiac output with increasing fat mass the perfusion per unit of adipose tissue decreases with increasing total body adipose - adipose tissue is less vascularised
WHat is normal adipose tissue blood flow
2-3ml/100g/min at rest - can increase 10x, can fall to 1.5ml/100g/min in extreme obesity
Pathophysiological cardiovascular changes associated with obesity
Hypertension - systemic and pulmonary
LVH
Dyslipidaemia
CAD
Increased heart failure
Increased PVD and veinous diease
Increased VTE
Increased CV events
Oxygen consumption vs obesity?
◦ Arterovenous oxygen oxygen difference increased in moderate to severe obesity despite high cardiac output
◦ Increased myocardial work
Coronary effects of obesity?
◦ Increased incidence of IHD due to systemic hypertension, dyslipidaemia and diabetes which may compromise oxygen supply and subsequent ischaemia reduces stroke volume
How is the right heart affected by obesity?
◦ Dependent on LV pathology, sleep apnoea and obesity hypoventilation
◦ Pulmonary capillary wedge pressure and LVEDP range from high normal to elevated
‣ Marked increase in LV filling pressure (LVEDP) even with modest exercise
‣ Likely reflects LV hypertrophy and loading conditions that predispose to hypertrophy —> causing impaired ent of LV diastolic filling
◦ With persistent hypoxaemia, pulmonary hypertension occurs as result fo chronic pulmonary vasoconstriction eventually cause RVH and increased RV work which may progress to RH failure
Peripheral vascular resistance in obesity is affected how?
- Systemic vascular resistance lower in normotensive
◦ Capillary bed in fat are parallel arrangement with systemic circulation —> reduced resistance
◦ ADipose tissue is surrounded by extensive capillary network with high permeability and low hydrostatic pressure
◦ Resting blood flow can increase markedly 10x
◦ Interstitial portion contains large quantity of fluid
◦ This increases when someone becomes hypertensive
What are the domains you use when describing the effect of something on respriatory function
Airway
Chest wall - bone, muscle
Airway resistance and compliance
Lung parenchyma
Lung volumes
Closing capacity
Gas exchange
Feedback and control of ventilation
Describe the airway changes in morbid obesity
◦ Decreased pharyngeal diameter - uvula descent, posterior wall collapse, tonsils pushed inwards
◦ Increased tendency to collapse during sleep and sedation
Structural properties of the chest wall and lung volumes in morbid obesity
◦ Decreased chest wall compliance
◦ Decreased FRC (mainly due to decreased ERV)
◦ Decreased lung compliance due to decreased lung volume (FRC) - slips down the volume-compliance curve
◦ Slightly decreased total lung capacity (TLC) - due to reduced FRC, as ERV has decreased (inspiratory capacity and reserve volume remain the same)
Airway resistance in morbid obesity?
◦ Increased airway resistance due to decreased lung volumes
◦ Specific airway conductance remains the same i.e. indexed to lung volumes essentially the same
Function of respiratory muscles in morbid obesity
◦ Increased total respiratory muscle mass
◦ Increased respiratory effort and increased oxygen use by respiratory muscles
‣ 150% of normal values for work of breathing at rest
Gas exchange in morbid obesity
◦ Lower PaO2 chronically (in some studies)
◦ Increased V/Q mismatch due to decreased FRC
Control of ventilation in morbid obesity
◦ Obesity hypoventilation syndrome:
◦ Resting increased PaCO2 even when awake - decreased reactivity induced
◦ Decreased reactivity of respiratory control reflexes
Demands on the respiratory system in morbid obestiy
◦ Increased body mass = increased total body oxygen demand and increased ventilatory requirements for the clearance of the excess CO2
‣ The demand increase is less than would be expected for actual body weight, but greater than lean body weight/ideal body weight
What changes to HR are seen in pregnancy?
- HR may increase as early as 4 weeks after conception, 17% increase by the end of the first trimester and up to 25% above baseline at the middle of the 3rd trimester after which no further rise occurs
◦ Reflects reflex increase due to reduced BP
How does the HR change over the course of the pregnancy
- HR may increase as early as 4 weeks after conception, 17% increase by the end of the first trimester and up to 25% above baseline at the middle of the 3rd trimester after which no further rise occurs
◦ Reflects reflex increase due to reduced BP
Stroke volume changes in pregnancy
- Increases by 20-30% predominantly in the first trimester due to increased preload and sustains
Total peripheral vascular resistance in pregnancy
- Total peripheral vascular resistance decreases by 30% by the 12th week, 35% by the 10th week and remains at 30% below non pregnant values
How is the pVR different throughout pregnancy
- Total peripheral vascular resistance decreases by 30% by the 12th week, 35% by the 10th week and remains at 30% below non pregnant values
Why is PVR idfferent during pregnancy?
- Total peripheral vascular resistance decreases by 30% by the 12th week, 35% by the 10th week and remains at 30% below non pregnant values
- Due to vasodilation in kidney, gut, heart, breasts, skin —> by (cerebral not altered)
◦ Progesterone
◦ PG
◦ Down regulation of alpha receptors - Placental flow acts as an AV shunt and flow is passive, non autoregulated and pressure dependent and this reduces TPR
What is the mediator for vasodilation in pregnancy? 3
- Due to vasodilation in kidney, gut, heart, breasts, skin —> by (cerebral not altered)
◦ Progesterone
◦ PG
◦ Down regulation of alpha receptors - Placental flow acts as an AV shunt and flow is passive, non autoregulated and pressure dependent and this reduces TPR
Which organ systems are responsible for a drop in PVR in pregnancy
- Due to vasodilation in kidney, gut, heart, breasts, skin —> by (cerebral not altered)
◦ Progesterone
◦ PG
◦ Down regulation of alpha receptors - Placental flow acts as an AV shunt and flow is passive, non autoregulated and pressure dependent and this reduces TPR
How does blood pressure change in pregnacy?
- Systolic and diastolic pressures decrease by about 10% reaching their lowest at 20 weeks
◦ Diastolic fall often more than systolic
Cardiac output changes in pregnancy
- Increases progressively to 40-45% above non pregnant values at the 12th to the 28th week
◦ 50% above normal peak during 32nd-36th week then decreasingly slightly to 47%
How does cardiac output change throughout pregnancy?
- Increases progressively to 40-45% above non pregnant values at the 12th to the 28th week
◦ 50% above normal peak during 32nd-36th week then decreasingly slightly to 47%
When is the peak in cardiac output during pregnancy
- Increases progressively to 40-45% above non pregnant values at the 12th to the 28th week
◦ 50% above normal peak during 32nd-36th week then decreasingly slightly to 47%
Why does cardiac output increase during pregnancy?
- Large proportion is directed to uteroplacental circulation
◦ Increased BF to this region 10 fold to about 750ml/min at term
◦ Renal blood flow increases by 80% in first trimester but decreases towards term
◦ Increased blood flow to breasts, GIT and skin
How is the increased cardiac output facilitated during oregnancy
- Produced by
◦ Increased venous return due to venodilation
◦ Increased intravuulasr volume caused by oestrogen
What is uteroplacental flow at term?
- Large proportion is directed to uteroplacental circulation
◦ Increased BF to this region 10 fold to about 750ml/min at term
◦ Renal blood flow increases by 80% in first trimester but decreases towards term
◦ Increased blood flow to breasts, GIT and skin
What blood flows other than placental increase during pregnancy? 4
- Large proportion is directed to uteroplacental circulation
◦ Increased BF to this region 10 fold to about 750ml/min at term
◦ Renal blood flow increases by 80% in first trimester but decreases towards term
◦ Increased blood flow to breasts, GIT and skin
What is supine hypotension in pregnancy? What % of women does it affect? Other name ofr it?
- 15% of women near term experience compression of the IVC by the gravid uterus reducing venous return - can occur as early as 20 weeks
What are the symptoms of aortocaval compression
- 15% of women near term experience compression of the IVC by the gravid uterus reducing venous return - can occur as early as 20 weeks◦ Symptoms
‣ Nausea, pallor, hypotension, cardiovascular collapse whensupine resolving in lateral position
Why does aortocaval compression occur in pregnancy
◦ Physiology
‣ Uterine perfusion is diminished because of increased uterine venous pressure + reduced cardiac output + potentially by direct compression of the aorta may also occur
‣ Placental perfusion is not autoregulated
What regulatory responses try to prevent changes in cardiac output with aortocaval compression?
◦ Most patients able to compensate by
‣ Sympathetic outflow increases - increased SVR and HR
‣ SOme blood bypasses the compressed IVC returning from the lower limbs tot he heart through collateral pathways
* Blood returns via paravertebral, epidural veins and the azygous veins
◦ Prevented by positioning on left side
How can you prevent aortocaval compression?
◦ Most patients able to compensate by
‣ Sympathetic outflow increases - increased SVR and HR
‣ SOme blood bypasses the compressed IVC returning from the lower limbs tot he heart through collateral pathways
* Blood returns via paravertebral, epidural veins and the azygous veins
◦ Prevented by positioning on left side
How does blood volume change towards term in pregnancy?
- Extracellular fluid volume increases by about 3L at term - 1-1.5L intravascular increase in volume (35-40%)
What % does blood volume increase i pregnancy?
- Extracellular fluid volume increases by about 3L at term - 1-1.5L intravascular increase in volume (35-40%)
When in the pregnancy does the blood volume start changing?
◦ Rises in the first trimester - primarily a rise in plasma volume causing rise in total blood volume - red cell volume actually falls in first 6 weeks
What happens to colloid osmotic pressur ein pregnancy
falls 15%
How does blood volume change during pregnancy?
How does red cell mass change? What effect does this have?
◦ The ongoing rise in plasma volume (slower rate of rise) and red cell volume
‣ Blood volume 40% greater
* Red cell volume/mass 20% greater - due to EPO
* Peak plasma volume 50% greater - due to oestrogen increased stimulation of RAAS system
‣ Fall in haematocrit to 33% - physiological anaemiaof pregnancy falling from 150 —> 120 at term
◦ Plasma volume increased due to sodium and water retention by oesotgen stimulation of renin angiotensin system; EPO causes rise in red cell
Why is there water retention in pregnancy?
◦ The ongoing rise in plasma volume (slower rate of rise) and red cell volume
‣ Blood volume 40% greater
* Red cell volume/mass 20% greater - due to EPO
* Peak plasma volume 50% greater - due to oestrogen increased stimulation of RAAS system
‣ Fall in haematocrit to 33% - physiological anaemiaof pregnancy falling from 150 —> 120 at term
◦ Plasma volume increased due to sodium and water retention by oesotgen stimulation of renin angiotensin system; EPO causes rise in red cell
CVP in pregnancy
the same
PCWP in pregnancy
The same or very slighty decrease due to reduction in PVR
How does cardiac output compare in the 2nd and 3rd trimester
the same
Peaks at the end of 2nd trimester or start of 3rd then decreases very slightly
When is the HR the highest in pregnancy
Mid third trimester
How does contractility change in pregnancy
Unchanged
What happens to BV during lavour
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
What happens to cardiac output during labour
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
Why is the CO increased during labour
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
Is an epidural beneficial or not to strain on the heart in labour?
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
Blood loss average for vaginal vs C section
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
BP changes with contractions?
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
Immediately after delivery cardiac output changes how?
terine contraction squeezes 300ml from the uterus into central circulation —> cardiac output increasing by 15% during latent stage of labour, 30% during active phase, and 45% during expulsive phase
◦ Catecholamine secretion aids the increase by 25-50% and epidurals reduce this and canlesson the impact of labour on the heart
◦ Blood loss is 300mL for vaginal delivery and 500mL for C section typically but protected from this by autotransfusion of 500mL during uterine involution
◦ BP increases by 10-20mmHg with contractions
* Immediately after delivery cardiac output is 60-80% above pre labour values —> autotransfusion and increased venous return with uterine involution
◦ This is a period of danger for cardiac failure
* Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction
* It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
How long does it take for cardiac status post birth to return to normal?
- It takes 2 weeks for cardiac output and arterial BP to return o non pregnant values
Respiratory changes of pregnancy begin when? When are they most significant?
Changes begin as early as 4 weeks gestation but most significant in 2nd and 3rd trimester
Anatomically what 3 major things change in pregnancy?
- Thoracic
◦ Diaphragm displaced upwards 4cm by gravid uterus but contraction not markedly restricted
◦ Anterior posterior and transverse diameters of thoracic cage increase by 2-3cm - lower ribs flare out, subcostal angle increases from 58 —> 103 degrees at term
◦ Circumference of thoracic cage increased by 5-7cm
◦ Changes due to relaxin secreted by corpus luteum relaxing ligamentous atttachements of the ribs - Airway
◦ Vocal cords swollen or oedematous - capillary engorgement
◦ large airways dilated decreasing airway resistance by 35%
◦ Oropharyngeal mucosa capillary engorgement and oedema - Timing
◦ Begin early in pregnancy but major changes from 20th week onwards
How does the thoracic cage change in pregnancy
- Thoracic
◦ Diaphragm displaced upwards 4cm by gravid uterus but contraction not markedly restricted
◦ Anterior posterior and transverse diameters of thoracic cage increase by 2-3cm - lower ribs flare out, subcostal angle increases from 58 —> 103 degrees at term
◦ Circumference of thoracic cage increased by 5-7cm
◦ Changes due to relaxin secreted by corpus luteum relaxing ligamentous atttachements of the ribs
How is the thoracic cage change in pregnancy facilitated?
- Thoracic
◦ Diaphragm displaced upwards 4cm by gravid uterus but contraction not markedly restricted
◦ Anterior posterior and transverse diameters of thoracic cage increase by 2-3cm - lower ribs flare out, subcostal angle increases from 58 —> 103 degrees at term
◦ Circumference of thoracic cage increased by 5-7cm
◦ Changes due to relaxin secreted by corpus luteum relaxing ligamentous atttachements of the ribs
Anteiror-posterior and transverse diamtres of thoracic cage in pregnancy change by how much
- Thoracic◦ Anterior posterior and transverse diameters of thoracic cage increase by 2-3cm - lower ribs flare out, subcostal angle increases from 58 —> 103 degrees at term
Diaphragm effect of pregnancy
- Thoracic
◦ Diaphragm displaced upwards 4cm by gravid uterus but contraction not markedly restricted
Circumference of the thoracic cage changes by what in pregnancy?
- Thoracic
◦ Circumference of thoracic cage increased by 5-7cm
Airway changes in pregnancy 3
- Airway
◦ Vocal cords swollen or oedematous - capillary engorgement
◦ large airways dilated decreasing airway resistance by 35%
◦ Oropharyngeal mucosa capillary engorgement and oedema
How does respiratory volume change in pregnancy?
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Expiratory reserve and residual voluem changes in pregnancy?
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
FRC at term in pregnancy
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Why is FRC smaller at term in pregnancy
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Tidal volumes in pregnancy do waht
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Inspiratory capacity in pregnancy
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Expiratory capacity in pregnancy
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
TLC in pregnancy
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Vital capacity in pregnancy
- Expiratory reserve volume and residual volume - gradually decrease as pregnancy progresses
◦ FRC - At term 20% less seated and 30% less supine (primarily reduction in residual volume)
◦ Due to progressive elevation fo diaphragm by the gravid uterus and increase in pulmonary blood volume - Tidal volume
◦ Increases in first trimester
◦ 28% - 40% above non pregnant values at term - Inspiratory capacity - 10% increase at term
- Expiratory capacity - decreases by 20% at term
- TLC - decreases by 5%
- Vital capacity unchanged
- No change when sitting in airway closure, closing capacity or flow volume curves
Closing capacity in pregnancy
Unchanged sitting, lying down worse
Draw a pregnant vs non pregnant lung volume graph
TLC 4200mls for a non pregnant person, what is it during rpegnancy
4100mls
TV in pregnancy on average
600mls increased by 30-40%
ERV in pregnancy vs baseline
ERV 700ml at baseline
ERV 550mls in pregnancy 20% decreased
RV in pregnancy vs not
1000ml in non pregnant
800ml in prnancy
How does FRC compare in pregnancy to non pregnant
Non pregnant 1700mls
- ERV 700ml, RV 1000ml
Pregnant
- ERV 550mls, RV 800mls
Therefore FRC 1350mls (20% reduction)
How does minute ventilation change at term
50% increase
The increase in minute ventilation seen at term is due to?
40% increased TV
10% increase in RR
RR changes in pregnancy
Increased by 10% at term
When do most of the pregnancy related chnages in ventilation occur
2nd trimester
How is compliance affcected by pregnancy? Which component of compliance is affected?
- Compliance - lung compliance unchanged, chest wall compliance decreases by 20% with elevation of the diaphragm therefore total respiratory compliance decreases as well
Dead space in pregnancy affecte dhow?
- Dead space - anatomical dead space increases by 45% due to larger conducting airways with airway dilation (progesterone induced smooth muscle relaxation), but dead space to TV ratio remains unchanged
Dead space to TV ratio in pregnancy
- Dead space - anatomical dead space increases by 45% due to larger conducting airways with airway dilation (progesterone induced smooth muscle relaxation), but dead space to TV ratio remains unchanged
Maximal hyperventilation of pregnancy occurs when?
8-10 weeks
Why does hyperventilation occur in pregnancy
Progesterone stimulation
◦ THis is not for oxygenation - arterial PAO2 is minimally changed, only very slightly increased and arterial oxygen content is almost at maximum anyway. The cardiac output increase is the most important factor in oxygen flux
How is oxygenation affected by hyperventilation of pregnancy
◦ THis is not for oxygenation - arterial PAO2 is minimally changed, only very slightly increased and arterial oxygen content is almost at maximum anyway. The cardiac output increase is the most important factor in oxygen flux
What is the purpose of Respiratory alkalosis of pregnancy? How is this accomplished?
◦ Progesterone stimulates the respiratory centres and shifts the ventilation-carbon dioxide response curve to the left so CO2 tension is reduced to about 26-32mmHg at end of first trimester —>this facilitates transfer of carbon dioxide out fo the foetus
Draw a spirogram for a pregnant vs non pregnant adult
Draw a spirogram labelet with volume and % change for pregnant term vs non pregannt
What is the average CO2 at term in pregnancy?
26-30mmHg
Respiratory alkalosis of pregnancy compensated for by?
◦ Respiratory alkalosis of pregnancy is compensated by renal excretion of bicarbonate decreasing to 18-21 and a base deficit of -2 to -3
‣ Reduced bicarbonate means the mother has reduced buffer capacity
‣ A normal pH keeps the maternal oxygen dissociation curve in a normal position despite low maternal PCO2 as most of PCO2 effect is due to pH and an increased maternal 2-3 DPG counteracts any CO2 effect
Why is a normal pH in the mother important for the foetus?
◦ Notably foetus cannot correct pH disturbances so maternal acidosis will cause foetal acidosis therefore ventilation is important to maintain at normal pregnant values —> likewise maternal alkalosis should be avoided to prevent oxyhaemoglobin dissociation curve shifts that will reduce O2 transfer to the foetus
How is oxygen consumption affected in prengnacy
Increased 20%
Why is respiratory reserve reduced in pregnancy (4)
Increased oxygen consumption 20%
Reduced FRC
Already significantly increased cardiac output, however haematocrit has dropped so the gain in oxygen delivered is ~10% for a 20% higher demand
Increased dead space and already increased TV and RR with reduced mechanical advantage
How does labour affect ventilation
- Minute ventilation - 70% above normal (pain)
- The uterine contractions increase oxygen consumption by 60%
- Transient hypoventilation post birth with hypocapnoea induced hypoventilation and hypoxaemia
- After delivery FRC and RV return to normal within 48 hours and tidal volume by 5 days
- Respiratory systems sensitivity to carbon dioxide changes rapidly after delivery
3 functions of the placenta
endocrine
Immunological barrier
Interface for gas and nutrient exchange
What is exchanged across a placenta 5
◦ Gas exchange - oxygen and carbon dioxide
◦ Glucose, amino acids, lipids
◦ Removal of waste - urea, bilirubin
◦ Water and electrolytes
◦ Drugs
What determines gas exchnage across placental membrane?
Ficks laws of simple diffusion
Distance ofr diffusion minimised to foetal endothelial cell layer, 2 chorionic cell alyers
What lies between circulations as barriers to diffusion in a placental membrane
◦ Distance for diffusion minimised to foetal endothelial cell layer, 2 chorionic cell layers only between blood flows
How do water and electrolytes get transported between foetus and mother
Simple diffusion, bulk flow and solvent drag
Lipids - fatty acids, steriods, fat, fat soluble vitamins are transported how between foetus and mother
Simple diffusion
What substanes simply diffuse across the foetomaternal placental membrane
Gases
Fats - fatty acids, fat soluble vitamins
Water
Electrolytes
Drug
How does glucose move from mother to foetus?
facilitated diffusion - and therefore still concentration gradient dependent. The only substance at the placenta transferred by this mechanism
◦ Maternal glucose levels are critical for foetus’ who have no significant insulin or glucagon synthesis
How does a foetus regulate BSL
facilitated diffusion - and therefore still concentration gradient dependent. The only substance at the placenta transferred by this mechanism
◦ Maternal glucose levels are critical for foetus’ who have no significant insulin or glucagon synthesis
How are amino acids transported from mother to foetus
ACTIVE cotransported with sodium
How are calcium, iron transported across foetomaternal membrane
Active co transport with sodium
What is endocytosed or pinocytosed across the foetomaternal cell mebrane
IgG, lipoproteins, globulins, phospholipids
Endocrine functions of the palcenta
- Oestrogen, progesterone, beta human chorionic gonadotrophin (LH like) and human placental lactogen are synthesised
- Other hormones
◦ Placental corticotropin
◦ Human chorionic somatostatin
◦ Human chorionic thyrotropin
◦ Epidermal growth factor
◦ Somatomedin - Pseudocholinesterase, alpha line phosphatase, monoamine oxidase and catechol-O-methyl transferase are all present also
What does the placenta synthesize apart from hormones? 4
Glycogen
Cholesterol
Fatty acids
Enzymes
Why is the foetomaternal cell barrier not immunogenic
- Tolerance barrier between maternal and foetal circulations and cells - Trophoblast cells which go on to implant and form the placenta lose many of their major histocompatability complexes (class 1 and 2) making them less immunogenicity and cover themselves in mucoprotein to avoid maternal immune response activation
◦ Prevents antigen presentation to lymphocytes or recognition by activated cytotoxic T lymphocytes
Aside from being a barrier what other important immunological functions does the foetomaternal membrane provide?
- Immunological barrier preventing maternal immune activation against the foetus as well as bacteria and virus transmission through chorionic cell layer
◦ but it does selectively allow passage of maternal IgG antibodies to provide passive immunity to the foetus
‣ Syncytiotrophoblast possesses receptors for the Fc fragment of IgG, and bound IgG is endocytosed and released by exocytosis
‣ In Rh isoimmunisation maternal antibodies against foetal red cells cross the membrane causing foetal haemolysis
What immunologically non favourable factors do cross the foetomaternal cell membrane
◦ Some bacteria and pathogens can pass
‣ Autoimmune antibodies are also able to cross e.g. thyrotoxicosis, myasthenia gravis, idiopathic thrombocytopenia
‣ Listeria
‣ Rubella, parvovirus, hepatitis, HIV
How is maternal immunity impacted by pregnancy
reduced
Progesterone and alpha fetoprotein maternally immunosuppressive
What is baseline placenta blood flow?
600ml/min
Where does placental blood flow come from
uterine and overian arteries –> arcuate and radial arteries (80% to plcenta)
Placental blood flow autoregulation comprises of
Minmial
Maximally vasodilated at baseline
Have alpha adrenergic receptors whcih can decrease
Maternal placenta flow dependent on? 3
◦ Maternal arterial blood pressure - as there is an absence of auto regulation within the system maternal arterial blood pressure has a direct effect on placental blood flow
◦ Intrauterine pressure e.g. during contractions reduced placental blood supply - this effectively reduces the pressure gradient between arterial and venous ends of the system therefore reduced pressure differential reduces flow
◦ Alpha agonism - sympathetic stimulation or extrinsic noradrenaline cause vasoconstriction and reduced blood flow
How does placental oxygen and carbon dioxide transfer compare to the lung
less efficient
What is the major determinant of O2 and CO2 difference between maternal and foetal circulations
Flow - 2x maternal blood flow compared to foetal blood flow in umbilical vessels
Maternal blood flow increses 20x over the pregnancy
Uterine blood flow
500-750ml/min
85% to palcenta
600ml/min
Foetal blood flow - cardiac output? Umbilical vessel flow?
300ml/min
Foetal cardiac output 1l/min (25-55% to plcenta)
Maternal oxygen levels in placenta
50mmHg
Foetal oxygen tension in arterial limb
20mmHg
mean gradient for diffusion of oxygen at foetomaternal membrane
30mmHg
Carbon dioxide pressure in foetal umbilical artery
50
Carbon dioxide pressure in intervillous space
37mmHg
Explain the double Bohr effect in placenta gas transfer
- Foetal blood releases carbon dioxide as carbon dioxide moves down its concentration gradient - shift of the oxyhaemoglobin dissociation curve to the left —> increasing oxygen affinity (Bohr effect)
- Maternal blood at the same time is exposed to higher concentrations of carbon dioxide —> shifting dissociation curve to the right —> enhancing oxygen release (double Bohr effect)
- Accounts for 2-8% of the transfer of oxygen transplacentally as the oxygen dissociation curves move apart
What % of oxygen transfer does the double bohr effect accoutn for
- Foetal blood releases carbon dioxide as carbon dioxide moves down its concentration gradient - shift of the oxyhaemoglobin dissociation curve to the left —> increasing oxygen affinity (Bohr effect)
- Maternal blood at the same time is exposed to higher concentrations of carbon dioxide —> shifting dissociation curve to the right —> enhancing oxygen release (double Bohr effect)
- Accounts for 2-8% of the transfer of oxygen transplacentally as the oxygen dissociation curves move apart
What are the main factors determining placental gas transfer
Partial pressure difference
Blood supply
DOuble Bohr effect
double haldene effect
Anatomical diffusion distance
Haemoglobin properties
Foetal Hb conc
180g/L
Foetal Hb vs HbA is different in that?
- Foetal haemoglobin itself also has a greater affinity for oxygen than adult haemoglobin so at the partial pressures seen in the placenta it can carrying 20-50% more oxygen than maternal blood
◦ The placenta actively produces 2, 3 DPG (diphsophoglycerate) which binds avidly to Beta globin chains of Hb A causing a rightward shift and oxygen offloading, but cannot bind to the gamma globin chains fo HbF therefore offloading maternal oxygen by shifting it to the right.
◦ P50 of foetal haemoglobin is 18-20mmHg (adults is 26.6) - and foetal Hb has a saturation of 80% at PaO2 of 30mmHg
How different is the affinity for Hb in Foetal Hb
- Foetal haemoglobin itself also has a greater affinity for oxygen than adult haemoglobin so at the partial pressures seen in the placenta it can carrying 20-50% more oxygen than maternal blood
◦ The placenta actively produces 2, 3 DPG (diphsophoglycerate) which binds avidly to Beta globin chains of Hb A causing a rightward shift and oxygen offloading, but cannot bind to the gamma globin chains fo HbF therefore offloading maternal oxygen by shifting it to the right.
◦ P50 of foetal haemoglobin is 18-20mmHg (adults is 26.6) - and foetal Hb has a saturation of 80% at PaO2 of 30mmHg
How does 2,3 DPG play into foetal gas transfer?
- Foetal haemoglobin itself also has a greater affinity for oxygen than adult haemoglobin so at the partial pressures seen in the placenta it can carrying 20-50% more oxygen than maternal blood
◦ The placenta actively produces 2, 3 DPG (diphsophoglycerate) which binds avidly to Beta globin chains of Hb A causing a rightward shift and oxygen offloading, but cannot bind to the gamma globin chains fo HbF therefore offloading maternal oxygen by shifting it to the right.
◦ P50 of foetal haemoglobin is 18-20mmHg (adults is 26.6) - and foetal Hb has a saturation of 80% at PaO2 of 30mmHg
p50 of foetal Hb
18-20
adult p50
26.6
Foetal Hb saturation at 30mmmHg
80%
Explaion the double haldane effect
he increased ability of de-oxygenated haemoglobin to carry CO2
* Carbon dioxide transfer from foetus to mother enhanced by this process
◦ As maternal blood releases oxygen its carrying capacity for carbon dioxide increases without any increase in CO2 tension
◦ As foetal blood takes up oxygen this facilitates the release of CO2 from HbF
* Accounts for 46% of the transfer of carbon dioxide from foetus to mother
How important is the double haldane effect in foetal CO2 gas transfer
he increased ability of de-oxygenated haemoglobin to carry CO2
* Carbon dioxide transfer from foetus to mother enhanced by this process
◦ As maternal blood releases oxygen its carrying capacity for carbon dioxide increases without any increase in CO2 tension
◦ As foetal blood takes up oxygen this facilitates the release of CO2 from HbF
* Accounts for 46% of the transfer of carbon dioxide from foetus to mothe
How is the placenta surface are and diffusion distance optimised for gas transfer
- Villi - vascular projections of foetal tissue maximising surface area of exchange 16 metres squared - however this is still 1/3 to 1/4 of the surface area of the lung 50 - 60 metres squared
- Distance however is 7x further in the placental villi at 3.5 micrometers rather than 0.5 micrometers - however diffusion distance minimised by maternal blood contacting foetal chorion
- Permeability of the gas barrier is lower than in the lung
3 primry differences anatomically in foetal circulation?
umbilical vessels
Vascular shunts - ductus arteriosis and ductus venosis
PFO
PaO2 of oxygenated blood returning in umbilical vessels
30mmHg
Sats 80%
Where do the umbilical veins joint
left branch of the hepatic portal vein
Where does umbilical vein blood go
60% bypasses the liver through the ductus venosis between portal and IVC circulations
40% mixed with blood from GIT and perfuses the lliver
Blood in foetal RA comprises what % of its supply from where
70% IVC
20% SVC
10% coronary sinus and lungs
What % of RA blood goes through the PFO? What characteristics does this blood have? Why does it get funnelled here?
◦ 60% from the RA into the LA through the foramen ovale by crista terminalis/eustachian valve a muscle ridge in the RA (this is primarily the IVC highly oxygenated blood that directs IVC blood freshly oxygenated from the ductus venosis through the foramen ovale
What % of blood from the RA goes into the RV? What saturation does this have?
◦ 40% remainder of IVC blood + deoxygenated (O2 sats 40%) flowing from head and neck (SVC), remaining IVC blood and coronary sinus and passes into the RV then PA (mixed venous salts 55%).
Lungs receive what % of RV output
10%
What facilitates the shunt between PA and Aorta? Where does it joint the aorta? What % of RV output goes here? What % of total venous return goes here?
‣ Ductus arterioles a wide muscle arterial channel between the PA and the aorta (descending) and the shunted blood PaO2 19-20 Sats 60% perfused the lower half of the body and returns to the placenta
* Resistance of placenta low, resistance of remaining lower limbs high
* Thus the least oxygenated blood goes to the placenta to be oxygenated and return
40% of RA return goes to RV –> 90% of this gets shunted. 36% through ductus arteriosus
What saturations do you find in the ductus arteriosis
‣ Ductus arterioles a wide muscle arterial channel between the PA and the aorta (descending) and the shunted blood PaO2 19-20 Sats 60% perfused the lower half of the body and returns to the placenta
* Resistance of placenta low, resistance of remaining lower limbs high
* Thus the least oxygenated blood goes to the placenta to be oxygenated and return
LA blood PaO2 of?
25-28mmHg and sats of 65%
LV ejection supplies what
- LA blood PaO2 25-28, Sats 65% flows into the LV and ejected into the aorta supplying the coronaries and the brain with the most oxygenated blood (high afterload from upper body and cerebral circulation)
RV and LV work in parallel or series in foetus?
Parallel
Equal size and wall thickness
Cardiac output in foetus and newborn a function of?
HR
5 major changes with birth
Loss of umbilical circulation - increased PVR
Closure of ductus venosis
Closure of ductus arteriosus
Functional closure of PFO
Increase in pulmonary circulation
The major description of the change of transitional circulation is?
A circulation in parallel to a circulation in series
What effect does losing the placenta from ciruclation have?
- Low resistance placenta is excluded causing an increase in systemic vascular resistance and LV EDP and a fall in right atrial pressure due to reduced IVC flow
◦ Umbilical arteries vasoconstriction immediately due to mechanical stimulation and exposure to cold air
◦ Delaying the clamping of the umbilical arteries for 40-60 seconds allows additional venous return from the placenta to the foetus
How is the first breath triggered? What advantage does vaginal birth have?
- Birth canal compresses some fluid out of lung —> Stimulation + peripheral and central chemoreceptor stimulation post birth from asphyxia and birth itself —> first breath
Lung expansion does what to pulmonary ciruclation
The lungs expand reducing pulmonary vascular resistance and right ventricular end diastolic pressure falls
◦ The pulmonary vascular resistance continues to fall as hypoxic pulmonary vasoconstriction is released with rising alveolar oxygen levels, decreased CO2 levels and increasing pH
◦ PA pressures usually decrease to adult levels by 2 weeks of life - most of the change in 3 days
What happens to LA pressure post birth
- Left atrial pressure rises - increased blood flow through lungs and increased LVEDP
◦ Foramen ovale closes when left atrial pressure > right atrialpressure and permanent closure by fusion of septum secondum with edges fo foramen ovale taking 4-6 weeks
Ductus artiosis constricts due to? 3
How long until physiological closed? How long until permanent closure
- Ductus arteriosis constricts in response to inceased PAO2 after the first breath and to decreasing PGE1 and PGE2 within 10-15 hours is physiologically closed and takes 2-3 weeks to permanent close by thrombosis and fibrosis
When does the ductus venosis close?
1-3 hours
How is oral absorption of drugs affected in pregnancy
2
Absorption
* GI motility —> delayed gastric emptying particularly with the onset of labour reducing oral absorption
* Nausea and vomiting —> impaired oral absorption due to lack of absorption of lost compounds
* Absorption from sites other than GIT
◦ Skin - increased skin blood flow and muscle blood flow increases SC and IM injection absorption rate
◦ Lungs - increased minute volume and reduced FRC increased onset of volatile anaesthetics; although the increased cardiac output may cause a slower onset
◦ Epidural - engorged epidural veins during labour increasing absorption systemically and metabolism
How is non oral absorption affected in pregnancy 3
Absorption
* GI motility —> delayed gastric emptying particularly with the onset of labour reducing oral absorption
* Nausea and vomiting —> impaired oral absorption due to lack of absorption of lost compounds
* Absorption from sites other than GIT
◦ Skin - increased skin blood flow and muscle blood flow increases SC and IM injection absorption rate
◦ Lungs - increased minute volume and reduced FRC increased onset of volatile anaesthetics; although the increased cardiac output may cause a slower onset
◦ Epidural - engorged epidural veins during labour increasing absorption systemically and metabolism
How is distirbution 2 and protein binding 2 affected in pregnancy? What effect does foetal drug distirbution have
- Increased cardiac output increasing rate of distribution to effector sites
- Increased volume of distribution
◦ Increased fat mass increasing Vd for lipophilic drugs
◦ Increased total body water and plasma volume increases both intravascular and general extra vascular body fluid and therefore water soluble drugs volume of distribution
◦ This increased in Vd will prolong half life and also contribute to more delayed maintenance dosing with drugs with lower protein binding ratios due to increased Vd - Reduced plasma albumin and alpha 1 acid glycoprotein reduces plasma binding of drugs which will reduce total drug but not free drug levels
- Respiratory alkalosis leading to different ionisation
- Foetal involvement in drug distribution depends on the drug nature
◦ Placental transference of drug depends on - free drug concentration gradient (degree of protein binding), lipophilicity as the placental membrane is selectively permeable to polar compounds but freely permeable if lipid soluble, placental blood flow will determine free drug concentration delivery over time
◦ Ionic trapping can occur in the foetus for basic drugs which increase their dissociation in the acidic foetal blood creatinine a persistent concentration gradient as well as inability for drug to diffuse out
What does placental transference of drug depend on?
◦ Placental transference of drug depends on - free drug concentration gradient (degree of protein binding), lipophilicity as the placental membrane is selectively permeable to polar compounds but freely permeable if lipid soluble, placental blood flow will determine free drug concentration delivery over time
Metabolism of drugs in pregnnacy 5
- Increased hepatic flow increasing clearance of drugs with high intrinsic clearance
- Foetal metabolism may play some role in drug metabolism
- Progesterone is an enzyme inducer which will increase metabolism and inactivation of certain drugs while potentially contribution to increased activation of drugs such as clopidogrel to their active metabolites contributing to increased action
- Oestrogen competes for rocuronium metabolism leading to prolongation —> ketamine nightmares
- Reduced plasma cholinesterase activity rarely clinically important - succinylcholine
How is excretion affected by pregnant
- Increased clearance fo drugs with renal clearance due to increased GFR and renal plasma flow
Pharmacodynamics of pregnancy 3
- Reduced MAC - increased sensitivity to volatile anaesthetics
- Increased sensitivity to local anaesthetics
- Foetal effects
Describe changes in Vd in pregnancy (do not include protein binding or foetus)
- Increased volume of distribution
◦ Increased fat mass increasing Vd for lipophilic drugs
◦ Increased total body water and plasma volume increases both intravascular and general extra vascular body fluid and therefore water soluble drugs volume of distribution
◦ This increased in Vd will prolong half life and also contribute to more delayed maintenance dosing with drugs with lower protein binding ratios due to increased Vd
How does cardiac output affect drug distribution in pregnacy
Rate of distribution increased
3 drugs which increase uterine tone
Oxytocin anaolgues
Ergometrin
Carboprost
How does oxytocin analogues increase uterine tone
Gs GPCR –> increased phospholipase C –> increased IP3 –> increased intracellular Ca through ligand gated and L type calcium channels –> calmodulin regulation and increased myosin activation leading to contraction
Side effects of oxytocin (4)
headache,
hypotension, water retention, arrhythmias + tachycardia
anaphylaxis,
foetal distress,
How does ergometrine act
- Egrot alkaloid with an unknown mechanism of action stimulating uterine contraction - likely via alpha and 5HT2 receptors on uterine and vascular smooth muscle
Ergometrine side effects
Headache
Hypertension - coronary and peripheral vasoconstriction, risk of pulmonary oedema and reflex bradycardia
Carboprost MOA
Prostoglandins act via Gs GPCR to activate protein lipase C and increase IP3 leading to increased calcium channel opening in SR and membrane causing activation of myosin
Carboprost is a synthetic anaologue of?
PGF2alpha
Side effects of carboprost
Nausea, vomiting
Cardiovascular collapse
Bronchospasm
Drugs which reduce uterine tone
Beta 2 agonists
NSAIDs
CaB
Mg
How does magnesium effect uterine tone?
Magneisum blocks ligand gated Ca channels and L type calcium channels leading to reduced activation of myosin
How do calcium channel blockers affect uterine tone
block L type calcium channels in uterine muscle reducing contraction
How do beta 2 agonists affect uterine tone
Beta 2 –> cAMP rise –> increased phospholipase A –> increased phosphorulation of myosin light chain kinase –> reduced activation
How does nitric oxide affect uterine contraction
Nitric oxide stimulates soluble guanylyl cyclase –> cGMP –> protein kinase G –> myosin light chain kinase inhibiting myosin action
What effect does calmodulin have on smooth musce contration
PROMOTES it
Side effects of NSAIDs in pregnancy
◦ Premature PDA closure
◦ Necrotising enterocolitis
◦ Oliguria
◦ Intracranial haemorrhage
◦ Bronchopulmonary dysplasia
How would NSAIDs act as tocolytics
- Decrease formation of PGE2 and PGF 2 alpha due to COX enzyme inhibition for metabolism of arachadonic acid —>reduced stimulation of uterine muscle secondary to above prostaglandins
What intrinsic drug characteristics/factors (note dose/pharmcokinetics) affect the transfer of placental drug transfer 4
- Molecular weight
◦ Lipid soluble small molecular weights ideal - <500 daltons easily transferred, but >1000 daltons impermeable
◦ Water soluble >100 daltons impermeable - Lipid solubility - increases diffusion
- Free drug concentration gradient - the more drug protein bound in maternal circulation the less is available for free diffusion, the ratio of concentration gradient between maternal and foetal circulations will determine the transfer of drugs - increased concentration difference increases transfer
- PKa - drugs that remain in their non-ionic form will be more lipophilic and more readily able to diffuse, but ionised drugs are less able to transfer
What maternal factors affect transfer of drug to foetus? 3
- Maternal protein bidning - increased protein binding = reduced transfer
- Maternal plasma pH - this is relative to foetal pH as usually maternal pH is higher, the more acidic maternal pH is this will affect the drugs ionised state which if there is reduced ionisation will increase transfer to the foetus, but reduce ion trapping.
- Placental blood flow - increased placental blood flow will increase the concentration gradient due to increase delivery of maternal high concentrations and increased turnover to low concentration foetal blood increasing concentration difference and transfer
What foetal and placental factors regulate foetal dose exposure 4
Placental metabolism
* Protein binding - increased protein binding will increase drug transfer
* Foetal plasma pH - acidic with respect to the mother and therefore may ionise certain substances post transfer and prevent passive diffusion and equilibration causing ion trapping
* Metabolism of some drugs
What pharmacokinetic factors will influence placental drug transfer
Administration site - bioavialability and peak levels vs duration of exposure
Single dose, repeated dose, infusion
Maternal protein binding
5 neonatal airway differences to adult
◦ Narrow nasal passages and nasal breathing is preferred
◦ Smaller mandible
◦ Large tongue relative to airway
◦ Larger tonsils and adenoids relative to airway
◦ Superior laryngeal position - steeper intubation angle
‣ Glottis C3-4 instead of 5-6 in adults + anterior angulation
◦ Epiglottis stuff, U shaped and angled back 45 degrees
◦ Circled narroewest part of the neonatal upper airway
4 lower airway differences between a neonate and adult
◦ Soft narrow and short trachea
◦ Peripheral airways very narrow diamtre contributing to increased resistance in neonatal airways compared to adults 50% of total vs 20% of total
◦ Less bronchial muscle in neonates i.e. bronchospasm uncommon when young
◦ Chest wall is highly compliant, ribs are horizontal and therefore bucket handle and pump handle mechanics to do not occur and neonates are diaphragm breathers
‣ Horizontal insertion of diaphragm impairs mechanical efficiency
‣ Low proportion of high oxidative capacity fibres makes it susceptible to fatigue
‣ Abdominal distension splints the diaphragm causing respiratory distress
narrowest part of the airway in neonate? Why does this matter?
cricoid
Cannot expand as complete cartilagenous ring
Subglottic oedema can therefore cause severe distress
1mm ring of oedema will decrease cross sectional area by 60%
How is the chest wall different in neonates to adults
◦ Chest wall is highly compliant, ribs are horizontal and therefore bucket handle and pump handle mechanics to do not occur and neonates are diaphragm breathers
‣ Horizontal insertion of diaphragm impairs mechanical efficiency
‣ Low proportion of high oxidative capacity fibres makes it susceptible to fatigue
‣ Abdominal distension splints the diaphragm causing respiratory distress
Why is the diaphragm critical for function in neonates
◦ Soft narrow and short trachea
◦ Peripheral airways very narrow diamtre contributing to increased resistance in neonatal airways compared to adults 50% of total vs 20% of total
◦ Less bronchial muscle in neonates i.e. bronchospasm uncommon when young
◦ Chest wall is highly compliant, ribs are horizontal and therefore bucket handle and pump handle mechanics to do not occur and neonates are diaphragm breathers
‣ Horizontal insertion of diaphragm impairs mechanical efficiency
‣ Low proportion of high oxidative capacity fibres makes it susceptible to fatigue
‣ Abdominal distension splints the diaphragm causing respiratory distress
Why are the ribs less effective for breahting in neonates
◦ Soft narrow and short trachea
◦ Peripheral airways very narrow diamtre contributing to increased resistance in neonatal airways compared to adults 50% of total vs 20% of total
◦ Less bronchial muscle in neonates i.e. bronchospasm uncommon when young
◦ Chest wall is highly compliant, ribs are horizontal and therefore bucket handle and pump handle mechanics to do not occur and neonates are diaphragm breathers
‣ Horizontal insertion of diaphragm impairs mechanical efficiency
‣ Low proportion of high oxidative capacity fibres makes it susceptible to fatigue
‣ Abdominal distension splints the diaphragm causing respiratory distress
Why is bronchospasm not a phenomenon in neonates
◦ Soft narrow and short trachea
◦ Peripheral airways very narrow diamtre contributing to increased resistance in neonatal airways compared to adults 50% of total vs 20% of total
◦ Less bronchial muscle in neonates i.e. bronchospasm uncommon when young
◦ Chest wall is highly compliant, ribs are horizontal and therefore bucket handle and pump handle mechanics to do not occur and neonates are diaphragm breathers
‣ Horizontal insertion of diaphragm impairs mechanical efficiency
‣ Low proportion of high oxidative capacity fibres makes it susceptible to fatigue
‣ Abdominal distension splints the diaphragm causing respiratory distress
Lung volumes of a noenate
FRC the same 30Ml/kg
VT same proportion to weight 6-8ml/kg
ERV reduced
Anatomical dead space increased 30%
Closing capacity increased
Closing capacity in neonates vs adults
◦ Closing capacity increased -FRC is less than closing capacity causing gas trapping during normal tidal ventilation causing increased venous admixture and Aa gradient increased
How is alveolar ventilation compared to adult in neonates
2x for body weight
Minute ventilation in neonates vs adults
increased and increased RR
Compliance in neonates vs adults
◦ Lung compliance is decreased due to less surfactant
◦ Chest wall compliance is increased due to cartilaginous ribs
◦ Increased at birth due to smaller bronchi and smaller lung volumes - resistance is inversely proportional to the 4th power of the radius therefore significantly increased in smaller airway diameters
Gas exchange in neonates 3
◦ Increase shunt 10-25% cardiac output due to PDA
◦ Foetal haemoglobin has a L shift of oxyhaemoglobin dissociation curve —> post natal shift to the right but remains leftward fo adults
◦ High Hb - high oxygen carrying capacity
Respiratory control in neonates 3
◦ Immature respiratory centre, rhythmogenesis and reflex response
‣ Periodic respiratory pauses 6-10 seconds especially during sleep, cyclic oscillating respiratory rate
◦ Decreased response to hypercapnoea
◦ Paradoxical response to hypoxia
Oxygen consumption in neonates compared to adults?
2-3x increase
◦ Increased total oxygen consumption 6-10ml/kg/min as opposed to 3mL/kg/min in adults
‣ Due to high metabolic rate
‣ Delivery of this oxygen is aided by high alveolar ventilation, high cardiac output, distribution of high percentage of this cardiac output to metabolically active tissues
What is the work of breathing in neonates compared to adults?
Increased work of breathing, ideal effiicency is 30-50 breaths per minute and additionally diaphragm more suceptable to fatigue in infants
Describe how an ABG is different in a pregnant woman
Respiratory alkalosis
* Due to tidal volume increase by 35%
* Anatomical dead space increases but VT unchanged
* CO2 increased by increased basal metabolic rate ate
* Enhances foetal excretion fo CO2
Metabolic compensation
* Increased renal excretion fo HCO3
* Inhibition of secretion of hydrogen ions and ammonium
* Base deficit reflects the renal loss of HCO3
Slightly high PaO2 - despite a 20% increase in oxygen consumption
* Enhanced transfer to foetus
Dead space neonate vs adult
3ml/kg vs 2.2ml/kg
Neonate has more dead space
Tidal volume neonate vs adult
7ml/kg
Alveolar ventilation in mls/kg/min adult vs neonate
120-140ml/kg/min in neonate
50-70ml/kg/min adult
I:E ratio in adults vs kids
kids 1:1
Adults 1:1.5
FRC in mls/kg adult vs neonate
30ml/kg for both
What functional breathing effects does upper airway differences between neonates adn adults have
Nasal passages are narrow in obligate nasal breathing increasing airway resistance
Tongue is large
Nasal obstruction can cause respiratory disttess
How is the traceh and main bronchi different in kids
◦ Soft narrow and short trachea
Right main bronchis more in line with trachea increasing risk of RM intubation
How is the piglottis different in children
Stiff
U shaped
Angle back 45 degrees
How is the larynx different in kids
Superior laryngeal position - steeper intubation angle
‣ Glottis C3-4 instead of 5-6 in adults + anterior angulation
Why is it more efficient for children to braethe fast instead of deeper?
Short time constant of the lung and reduced mechanisms for increased force mean fast = less effort
end expiratory intrapleural pressure in neonates?
0 instead of negative as in adults
Less chest wall rigidity opposing lung collapse
What si normal periodic respiratory pattern
6-10 seconds pauses 6x per hour
Apnoea is
20 second or more pausea with bradycardia
Change in weight in pregnancy
Increased BV 1.2 - 1.5kg, ECF total increases by 3L
Increased fat stores 3kg
Increased uterine and breast tissue
Endocrine changes in pregnancy
HCG trophoblastic cell 8-9 days after fertilisation maintains corpus luteal oestrogen and PG until placenta takes over
Placenta HCG peak 10-12 weeks then declines
HPL - human placental lactogen peaks near term, rising throughout pregnance mobilising FFA and antagonising insulin
Oesotrogens
- Uterus growth and enlargement
- Breast - ductal structure growth
Progesterone
- Storage of nutrientsin endometrial cells
- reduce SM contraction
- Breast development
- Natriuretic (opposed by RAAS and aldosterone increases)
Increased prolactin, ACTH and reduction in GH
Increased thyroid hormone and globulin so free conc unchanged.
Ca decreases due to foetal (PTH increases)
BMR in pregnancy
Why
Increases by 20% above non pregnant levels at 36 weeks, then falls just towards term
Increased O2 demand by 20%
- Placenta/foetus
- Hypertrophy of tissues
- Increased respiratory work and HR
How does glucose control change during pregnancy
Insulin secretion increases until 32 weeks, then decreeases as glucose utilisation increases in the foetus
Reduction in insulin sensitivty
Fat - FFA conc decreases with increased fat storage early, then the reverse in second half of pregnnacy
Red cell mass changes in pregnancy
increases 20%
Wite cell count in pregnancy
Increased neutrophils and monocytes
Pregnancy vs coagulation
Increased coagulability and platelet turnover
Increased factor 7, 8, 9 and 10 and increased plt consumption even through platelet count is reduced 5%
Fibrinogen doubles 2.5 –> 5g/L
Plasminogen raised by as is plasminogen activator inhibitors
Antithrombin levels decrease
Increased fibrinolysis
GI changes in pregnancy
Progesterone relaxes smooth muscle ausing reduced lower oesophageal sphincter tone, increased reflux and aspiration risk
Gastric motility reduced, delayed gastric emptying
Increased secretions due to increased gastrin levels and increased gastric acid proudctions
Reduced gall bladder contraction in later pregnancy
Liver blood flow unaltered
Renal changes in pregnancy
Some obstruction of urinary outflow leading to dilation of renal pelvis, calyces and ureters
HFR and effective plasma flow increases by 50% during rist trimester due to increased caridac output so Cr and Urea fall
Tubular function unaltered
Glycosuria more likely
SOme proteinuria not uncommon - increased renal veinous pressure
Draw a graph outlining the effect of the double Haldane effect
Draw a graph representing the double Bohr effect
Define elderly
WHO 60-74
old =
WHo 75 - 90
What changes occur to the nervous system with age?
Neuronal tissue loss - brain weight 6-7% loss between 20 –> 80
Reduction in grey matter as a % of brain matter by 10% (from 45% of total to 35% of total) between 20 -80
Reduced neurotransmitters - ACh and dopamine, depression
Short term memory function
Sleep altered - reduced REM sleep
Autonomic regulation impaired, loss of myelin in peripheral nerves with reduction in axons and synapses
How does resting HR change with age?
It doesn’t
How does HR change with aging
Resting HR does not
Maximum HR decreases from 200bpm to 160bpm
Intrinsic HR without autonomic influence is decreased. Loss of apcemaker tissue so increased susceptability to SVT and ventricular ectopic beats
How does the heart structurally change with age?
Increased connective tissue , replacing elastin with collagen. Amyloid between cells
Myocardiac wall thickness may increased with increase in myocyte size due to LV output impedence –> reduced compliance
Calcification of heart valves can distort and either promote outflow tract obstruciton or leak
Cardiac output vs age>
reduced by about 1% per year after the age of 30 - this to an extent may be wrong, with instead it being similar until at least 80
Exercise performance drops
This may be reduced preconditioning however
max stroke volume vs age
reduces
What are the elderly reliant on for increased cardiac output>
Frank starling
How does afterload change with age?
Increased due to stiffening of arterial vascualture and MAP and SBP increased, DBP mau increased if increased PVR
How does BP change with age
Increased SBP
Increased MAP
Both due to increased stiffening of vasculature
DBP drops deu to rapid run off from stiff arteries
Pulmonary artery ssytolic pressure in elderly vs young
Increased slightly from 20 –> 26 in healthy elderly patients
mild rise in diastolic pulmonary artery pressure also
PVR rises from 70 –> 120 dynes x sec/cm^5
How is blood and fluid affected by age?
Reduced intracellular water
Total water is also reduced by reduction in BV by 20-30% by age 75, reduced plasma albumin
How does hepatic function change with age
Reduced hepatic blood flow
Enzymes should still work just as well
What effect does exercise in adiposity have?
Marked increase in LV filling pressure (EDP)
Why does hypertension sometimes occur in adipose patients
Increased renin activation
Respiratory effects of adiposity
Anatomical
- ADipoituy in upper airway
- Increased difficult intubation
- OSA
Volumes
- FRC and ERV and TLC decreased
- FRC declining exponentially with increasing BMI
(mass loading, diaphragm splinting)
- FRC falls below closing capacity
Gas exchange
- Due to closing capacity changes and small airway closure –> V/Q mismatch and arterial hypoxaemia
- Incrreased shunt fraction
Resistance and compliance
- Decreased compliance lung and respiratory wall –> 30% decrease in thoracic compliance
- Increased resisatnce
Increased O2 consumption and CO2 production
Work of breathing increased 30%
How is airway resistance in children compared to adults
Increased at birth due to smaller bronchi
How does FRC compare between chidlren and adults
SImilar per body weight
VT for children vs adults
Similar per body weight
Minute ventilation for children vs adults
Children much higher
Closing capacity in children vs adults
Increased
Expiratory reserve volume in children vs adults
Decreased
Lung compliance in newborns vs adults
Decreased, less surfactant
Chest wall compliance in children vs adults
Increased, increasing mechanical work
Gas exchange in neonates vs adults
Noenates
- Higher Hb and haematocirt therefore higher oxygen carrying capacity
- 70-80% HbF with a higher affinity
- Oxygen is less available - left shift of the oxyhaemoglobin dissociation curve by lack of response to 2,3 DPG, and foetal Hb
- Increased shunt - 10-25% PDA for the first 24-72 hours especially; but also increased closing capacity causing gas trapping and fluid filled alveoli
Offset by increased cardiac output, increased Hb and increased O2 affinity
