Physiology 22 Flashcards
Pregnancy
How does cardiac output change throughout pregnancy and delivery?
Increases due to Increased heart rate (+25% by term) and stroke volume (+30% by term)
CO increases by 40% at the end of the first trimester and plateaus at +50% by the end of the second trimester until delivery
During labour, CO further increases by 45% and during the 3rd stage rises to 80% above 3rd trimester levels (partly due to uteroplacental transfusion), this can result in increased CO immediately post-delivery
How does SVR change during pregnancy?
Decreases to 60% of non-pregnant SVR due to:
- Development of a low-resistance vascular bed (intervillious space)
- Vasodilatory effect of progesterone, oestrogens and prostacyclin
How does blood pressure change during pregnancy?
Falls to trough in mid-pregnancy, returning to normal by term
SBP reaches trough of -8%
DBP reaches trough of -25%
(thus MAP reduced to trough ~-20%)
In the supine position, 70% of mothers have a drop in BP of >10%. 8% have a drop of 30-50% (supine hypotension syndrome)
How does blood flow change during pregnancy?
Uterine flow:
-Increases to 12% of CO (700ml/min)
Renal flow:
-Increases
Skin flow:
-Increases
Hepatic and cerebral flow is unchanged
What factors affect aortocaval compression?
- Position
- Gestation
- BP
- Presence of sympathetic block
IVC compression starts from 13 weeks gestation and is maximal at 36-38 weeks. May decline after this due to descent of foetal head.
How is CVP affected by pregnancy / labour?
CVP is normal in pregnancy (except during IVC compression)
During contractions, CVP may increase by 5cmH2O
During delivery, CVP may increase by 50cmH2O
IV ergometrine can increase CVP by around 8mcH2O, lasting around an hour
How does pregnancy affect the blood volume?
- Plasma volume increased by +50% at term, continuing to increase in the first 24h after delivery, then falling to normal by day 6 postpartum
- Plasma expansion occurs due to oestrogen and progesterone stimulating the RAAS
- RBC volume falls in the first 8 weeks, then returns to normal by 16 weeks and rises to +30% by term, due to increased EPO production from week 12
- [Hb] and haematocrit is reduced by around 15% by term
- Total blood volume is increased by 10% (end of 1st trim), 30% (end of 2nd trim) and 45% by term
How does pregnancy affect WCC?
Increased to around 9-11 x10^9
Further increased during labour to ~15x10^9
Primarily polymorphonuclear cell proliferation
How does pregnancy affect coagulation?
Increases in:
Platelet turnover:
- thrombocytopaenia in up to 1% of women
- Increased platelet factor
- Increased β thromboglobulin
Clotting:
- Increase in all coagulation factors except:
- XI, XIII - decreased
- II, V - unchanged
- AT-III reduced
Fibrinolysis:
-Increased fibrinogen degradation products and plasminogen
PT, APTT and bleeding time fall slightly
How does pregnancy affect plasma proteins?
Reduced:
- Albumin
- α acid glycoprotein
- Pseudocholinesterase (-25%)
Increased:
- Globulin
- Fibrinogen
Overall conc. drops by 65-70g/L leading to:
- Decreased colloid osmotic pressure
- Altered drug binding
- Increased ESR (decreased blood viscosity)
Outline anatomical changes in the respiratory system during pregnancy
Mediated by increased progesterone
- Upper airway capillary engorgement -> tissue oedema
- Flaring of ribcage increases thoracic circumference by 5-7cm, reducing chest wall movement
- Bronchial SM relaxation maintains lung compliance by reducing airway resistance. FEV1, FVC and flow-volume loops are unchanged.
- Enlarging uterus displaced diaphragm upward later in pregnancy
Volumes/capacities:
- TV ↑ by 45% at term
- RR ↑ by 10%, plateauing at 20 weeks
- Thus MV ↑ by 50% and AMV ↑ by 70% at term
- FRC ↓ by 20-30% at term due to decreases in both ERV and RV
- Closing capacity encroaches on FRC, leading to potential V/Q mismatch and hypoxia
How are ABG values affected by pregnancy?
- PaCO2 reduced to 3.7-4.2 kPa by increased AMV
- Compensation by reduction in plasma HCO3- to 19-21 mmol/L
- Incomplete compensation results in increase in blood pH of ~0.04 units
- PaO2 is higher in erect pregnant women due to lower PaCO2 levels
- PaO2 reduces approaching term due to increased O2 consumption not fully compensated for by increased CO and DO2
What is the effect of pregnancy on the HbO2 dissociation curve?
pCO2 decreased -> left pressure
Increased 2,3-DPG -> right pressure
Net movement of HbODC to right
P50 non-pregnant: 3.5 kPa
P50 pregnant: 4.0 kPa
How is PVR affected by pregnancy?
Reduced by around 1/3 at term, increasing pulmonary blood flow and volume.
No effect on RV/PA/PC pressures in health
How does pregnancy affect a woman’s risk of aspiration of stomach contents?
Increased, due to:
- Reduced barrier pressure (altered stomach position and displacement of lower oesophagus from abdomen into thorax, reducing LOS pressure
- Relaxant effect of progesterone
- Gastric pressure elevation in 3rd trimester (supine and standing) and even further in lithotomy (+5.6 cmH2O)/Trendelenburg (+8.8cmH2O) position
- LOS pressure returns to normal by 48h post-delivery
- Delayed gastric emptying during labour (esp. if opioids given), returning to normal 48h post-delivery in absence of opioids
How common is heartburn in pregnancy?
up to 80% of women may complain of dyspepsia, which may commence earlier than 20 weeks gestation
What is the effect of pregnancy on the epidural space?
Aortocaval compression engorges epidural veins -> reduced volume of epidural space
This increases spread of solutions injected epidurally
Pressure in the epidural space is slightly positive in the pregnant patient. During contractions is can rise to 8cmH2O and during expulsion can rise to 60cmH2O
What is the effect of pregnancy on the subarachnoid space?
Aortocaval compression -> increased CSF pressure
At term CSF pressure is 28cmH2O. Contractions and expulsion may increase this to 70cmH2O
The constituents of CSF do not change
What effect does pregnancy have on the sympathetic ANS?
Increases throughout pregnancy, mainly acting to limit lower limb venous capacitance and counteracting IVC compression
Sympathetic block can result in marked decrease in blood pressure for pregnant women.
How are doses of local anaesthetic for spinal/epidural anaesthesia affected by pregnancy?
- Reduced epidural/subarachnoid volumes
- Increased nerve fibre sensitivity to LAs
- Hypocapnia leads to reduced buffering of LAs so they last longer as free bases
How does pregnancy affect MAC?
Reduced by 40%, possibly due to increased progesterone levels
What happens to β-endorphin levels during pregnancy?
Increased throughout pregnancy, labour and delivery
What is the effect of pregnancy on the thyroid?
- Increased size and vascularity
- Increased iodine uptake and possible goitre development
- Increased TBG levels but free T3/T4 remains constant or fall
What is the effect of pregnancy on adrenal function?
- Increased corticosteroid production (plasma levels increased up to 5x)
- t/12 of cortisol doubled due to decreased clearance
What is the effect of pregnancy on pituitary function?
What are the possible consequences?
- Increases in function and weight but vascularity does not change significantly
- Thus anterior pituitary becomes vulnerable to changes in blood pressure
- Peripartum hypovolaemia can result in postpartum hypopituitarism (Sheehan’s syndrome)
What is the effect of pregnancy on pancreatic function?
- Enlargement of islets of Langerhans and number of β cells, leading to increased insulin production
- Number of insulin receptors increases
- Increased insulin resistance due to hormones of pregnancy
- This results in larger than normal rises in glycaemia following a meal and facilitating placental glucose transfer
What is the effect of pregnancy on the kidneys?
- Renal blood flow increases by 50%
- GFR increases to around 150ml/min
- Urea and creatinine concentrations decline
- Reduction in tubular reabsorption leads to loss of glycos- and proteinuria
- RAAS activation, conservation of K+ and reduced serum osmolality
- Progesterone causes SM relaxation and urinary stasis -> increased risk of UTIs
- Increased VD for drugs
What is the effect of pregnancy on the liver?
- 3x increase in ALP (placental production)
- Increase in gallstone formation due to progesterone-mediated reduction in production of and response to CCK
- Some peripheral stigmata of liver disease may occur, but this is usually not of any consequence.
What is the effect of pregnancy on the MSK system?
- Ligamentous relaxation due to placental relaxin
- Widening of pubic symphysis and increased joint mobility
- Increased lumbar lordosis -> back pain
What is the effect of pregnancy on the skin?
Hyperpigmentation of the face, neck and linea nigra may occur due to increased melanocyte-stimulating hormone (MSH)
How does pregnancy affect body weight?
Increases by 10-12kg due to:
- Increased ECF + fat
- Foetus
- Placenta
- Amniotic fluid
- Uterine enlargement
- Breast enlargement
What is the effect of pregnancy on the breast tissue?
Enlargement due to human placental lactogen (HPL) secretion
Outline the structure of the placenta
- Contains maternal and foetal tissues
- Consists of projections of foetal tissues (villi) into maternal vascular spaces (intervillous spaces)
- Maternal blood flows into the intervillous spaces from spiral arteries and drain into uterine veins
- Foetal blood flows into the the villi via two umbilical arteries and return to the foetus via a single umbilical vein
How does the placenta develop?
Foetal part develops from chorion, consisting of an inner mesoderm and an outer trophoblast layer.
Maternal part develops from the decidua of the endometrium
Trophoblast invades the decidua forming the vascular interface.
Trophoblast comprises two layers - inner cytotrophoblast and outer syncytiotrophoblast.
The cytotrophoblast extends into the syncytiotrophoblast to form the villi, along with extensions of the mesoderm and the syncytiotrophoblast accommodates the intervillous spaces
Foetal and maternal blood are separated by the two layers of the trophoblast
Trophoblasts grow adjacent to spiral arteries and reduce vasoconstrictor activity. This develops from 10-16 weeks
What are possible abnormalities of placentation?
Normally the placenta does not penetrate far into the decidua, however this may occur in the following pathologies:
Placenta accreta:
-Chorionic tissue reaches uterine muscle, with loss of normal cleavage plane
Placenta increta:
-Chorionic tissue penetrates uterine muscle
Placenta percreta:
-Placenta invades uterine serosa or surrounding organs
What happens if the trophoblast fails to adequately invade the decidua?
- Can lead to increased vascular resistance in the placental bed
- This can cause IUGR and is found in pre-eclampsia
Outline the vascular system of the placenta
- Low pressure system
- Intervillous space pressure ~10mmHg
- 200 spiral arteries feed placenta
- Placental blood flow at term is 500-800ml/min
What is the size of a normal placenta at term?
500g
20cm diameter, 3cm thick
How is Uteroplacental blood flow calculated?
What factors affect uterine perfusion?
UBF = Uterine arteriovenous gradient / uterine vascular resistance
Thus any changes to the above parameters will affect blood flow
What are the mechanisms by which substances can be exchanged in the placenta?
- Diffusion (O2, CO2)
- Active transport (some ions)
- Secondary active transport (aas)
- Facilitated transport (glucose)
- Pinocytosis (proteins)
- Bulk transport (sodium, water)
- Breaks in placental membrane (eg. Rh sensitisation)
How is the immune system modified in the placenta?
- Not well understood
- Maternal reduction in cell-mediated immunity during pregnancy
- IgG is transported across the placenta
- Placenta forms a barrier to transmission of some but not all infections
How much of the oxygen delivered to the intervillous space is used by the placenta?
30%
What is the double Bohr effect and why is it relevant to placental physiology?
Foetal offloading of CO2 increases O2 affinity of HbF and at the same time increasing CO2 content of the maternal blood encourages O2 offloading, maximising exchange
In what forms is CO2 present in the placenta?
Dissolved (8%)
HCO3- (62%)
Carbamino Hb (30%)
What factors govern the transfer of drugs across the placenta?
Fick principle for non-ionised lipophilic drugs:
Rate of diffusion (Q/T) = (diffusion constant x SA for transfer x conc. gradient) / thickness of membrane
pH will alter ionisation and thus speed of diffusion
Rate of transfer is inversely proportional to molecular weight. Polar molecules become limited above 50-100 Da. Non-polar >600 Da
Protein binding affects free drug available for transfer
Which opioids cross the placenta?
Pethidine (max foetal uptake 2-3h after IM injection) Morphine Fentanyl Alfentanil Remifentanil
All freely cross
Which LAs cross the placenta?
All cross by diffusion given low MW and are poorly ionised at physiological pH
Highly protein bound LAs eg. bupivacaine/etodicaine have reduced transfer compared to lidocaine and mepivacaine which are less protein bound
Do volatile agents cross the placenta?
Yes, rapidly
Do induction agents cross the placenta?
Thiopentone, propofol and ketamine readily cross
Do muscle relaxants cross the placenta?
No, they are fully ionised
Do benzodiazepines cross the placenta?
Yes, readily
What hormones are secreted by the placenta?
hCG Progesterone hPL Oestrogens Hypothalamic releasing factors Hypothalamic inhibitory factors TSH Prostaglandins
Outline the important features of the foetal circulation
- Blood enters the foetus from the umbilical vein (sO2 80%) and enters the IVC via the ductus venosus, causing the majority of blood to bypass the liver
- Blood enters the right atrium (sO2 65%) and relatively more oxygenated IVC blood is favoured to shunt through the foramen ovale into the left atrium -> LV
- LV blood is ejected into the aorta (sO2 62%) and preferentially perfuses the heart and brain
- Desaturated blood enters the right atrium via the SVC and preferentially flows into the RV
- RV blood is pumped into the pulmonary artery (sO2 60%) but only 10% enters the pulmonary circulation due to very high SVR. The remaining 90% flows to the descending aorta (sO2 55%) via the ductus arteriosus.
- The two umbilical arteries branch off the foetal iliac arteries to return blood to the placenta
What is the function of Wharton’s jelly?
Wharton’s jelly coats the umbilical vessels and contracts on exposure to reduced temperature (ie. following delivery), reducing umbilical blood flow naturally
What changes occur in the transitional neonatal circulation?
- Umbilical vein flow ceases -> reduced ductus venosus flow +/- clotting off.
- Lungs fill with air, drastically reducing PVR
- Right heart pressures decrease -> functional closure of foramen ovale
- Constriction of ductus arteriosus (and umbilical arteries) starting in the first few hours due to increased O2 content and reduced placental prostaglandin circulation. This is usually complete by 24h postpartum
- Closure of ductus venosus over the first few days of life
Why is reduction of PVR so important in the neonate?
Persistent pulmonary hypertension of the newborn (PPHN) can occur if physiological changes have not occured properly or if the neonate is exposed to hypoxia, hypothermia, acidosis or hypovolaemia.
This causes reversion back to the foetal circulatory pattern and can lead to death
