Physiology Flashcards
Fluid balance
Total body volume = 42L (60% total body weight)
Blood volume = 5.6L (plasma + RBC)
Losses via lungs (400ml/day), skin (1L/day), faeces (100ml/day), urine (1.5L/day)
So maintenance fluid requirement 30ml/kg/day
Hormones regulating extracellular fluid volume
ADH directly
ANP (atrial natriuretic peptide) indirectly
Renin-angiotensin system - plasma osmolarity and indirectly blood volume via aldosterone
Minor regulators - glucocorticoids and catecholamines
Osmolarity vs osmolality
Osmolarity = number of osmoles of solution per litre of solution (Osm/L), measure of solute concentration
Osmolality = osmoles of solute per kg of solvent (Osm/kg)
Osmosis
= movement of water from low solute concentration to higher concentration via semi-permeable membrane
Opposed by hydrostatic power
1osmol/L depresses freezing point by 1.86degrees
Plasma osmolarity
= 300mOsm/L
Na+ = 140 (main contributor)
Cl- = 140
K+ = 4
Anion = 4
Glucose = 5
Urea = 5
Starling’s law of capillaries
Relating to fluid movement across the capillary membrane as a result of filtration
Starling’s forces show relationship between hydrostatic and oncotic pressures:
Oncotic - 26mmHg blood, 1mmHg interstitial
Hydrostatic - 35mmHg arterial, 16mmHg venous, 0 interstitial
Net filtration pressure NFP = pressure promoting filtration - pressure promoting reabsorption
so NFP arterial= (35+1) - (26+0) = 10mmHg
NFP venous = (16+1) - (16+0) = -9mmHg
Oedema
Increased fluid in interstitial space
Anasarca is generalised oedema with SC tissue swelling
Due to - increased hydrostatic pressure, reduced plasma oncotic pressure, lymphatic obstruction, sodium retention, inflammation
Acid-base balance and anion gap
Regulated by respiratory, kidneys, blood, bones, liver
Anion gap normally 8-16mEq/L.
= Na - (HCO3 + Cl)
Raised anion gap (more +ve)
- lactic acidosis (methanol, salicylate, paraldehyde)
- ketoacidosis
- hypoalbuminaemia
Reduced anion gap (less +ve)
- bromide
- myeloma
Henderson-Hasselbach equation
HA + H2O <-> A- + H3O+
H2O + CO2 <-> H+ + HCO3-
If H+ generated, reaction shifts to left. So generates CO2, consumes HCO3-.
If HCO3- lost, reaction shifts to right. So generates H+, consumes CO2.
Net gain in H+ is the same as a net loss in HCO3-
pH and compensation
Logarithmic relationship
pH = pK + log10[HCO3-]/[CO2]
Respiratory compensation
- only in metabolic disorders, instantaneous
Metabolic compensation
- via kidneys, slower
- for respiratory disorders or metabolic disorders not originating in kidneys
Normal arterial maternal/fetal blood values
Maternal arterial:
O2 sats >97%
pO2 100mmHg
pCO2 40mmHg/4kPa
Base excess -2 to 2
HCO3- 24mEq/L
pH 7.34-44
Hb 12gm/dL
Fetal
O2 sats venous 75%, arterial 25%
pO2 venous 35mmHg, artery 25mmHg
pCO2 8-10kPa
Base excess venous -1 to 9, artery -2.5 to 10
pH venous 7.17-7.48, arterial 7.05-7.38
Hb 18gm/dL
HCO3-
Alkaline
Manufactured in DCT and collecting duct (PCT is not involved in acid-base balance)
DCT cells produce CO2, which reacts with water to form carbonic acid (H2CO3) with carbonic anhydrase as catalyst
H2CO3 is unstable organic acid, so rapidly dissociates into H+ and HCO3-
CO2 + H2o -> H2CO3 -> H+ + HCO3-
HCO3- enters circulation, in urine is buffered by NH4+ (ammonium - increases during acidosis) and HPO4^2- (hydrogen phosphate)
Long-term acidosis effect on K+
H+ enters cell (as high extracellular concentration)
K+ driven out of cell to maintain electrical neutrality
-> hyperkalaemia
Base excess/deficit
= the amount of acid or alkali required to restore 1L of blood to a normal pH (7.4), at a pCO2 of 5.3kPa, and temp 37
Need serum bicarb concentration and pH values to calculate
Normal range -2 to 2 mEq/L
Negative BE = metabolic acidosis
Positive BE = metabolic alkalosis (excess, excess bicarb)
Acid-base changes in fetus
Cord compression -> respiratory acidosis
Placental insufficiency -> metabolic acidosis
Anaerobic metabolism (when O2 sats <25%) -> increased lactate -> acidosis
Electrolyte changes in pregnancy
Osmolarity decreases by 10mOsm/L (in response to progesterone)
HCO3- decreases in response to decreased CO2
Na+ decreases in response to fall in HCO3- and reset of plasma osmolarity
Calcium functions and distribution
Functions - bone formation, muscle contraction, enzyme co-factor, blood clotting (coag cascade), secondary messenger, stabilisation of membrane potentials
Required intake 1g/day, or 1.5g/day when pregnant
Calcium distribution in body
1kg total body calcium, 99% in skeleton
Extracellular (plasma) calcium is 45% ionised, 55% bound to plasma proteins, phosphate, bicarbonate
- in acidosis, increased ionised calcium
Plasma (extracellular) ionised Ca2+ 12,000x more concentrated than intracellular
Intracellular it is sequestrated out of cytosol and within endoplasmic reticulum and mitochondria, only released in certain circumstances or cell damage
Calcium modulation
Via PTH and PTHrP (parathyroid hormone related peptide), and calcitonin
Absorption from GI tract via
- active uptake - Na+/Ca2+ ATPase
- transcellular transport - calbindin
- endocytosis - Ca2+-calbindin complex via TRPV6 membrane Ca channel
Phosphate functions
Intracellular metabolism (ATP synthesis)
Phosphorylation of enzymes
Forms phospholipids in membranes
Parathyroid hormone
Peptide hormone - 84 amino acids, many isoforms
Acts on G-protein receptors
Half life in minutes, store supplies last 90 mins
Does not cross the placenta
INCREASES Ca
DECREASES phosphate
ANTAGONISES calcitonin
Acts on:
- Bone to increase resorption
- Kidney to increase absorption from DCT, decrease re-absorption from PCT, increase vitD production by increasing 1α-hydroxylase, and promoting calcitriol formation
- Gut to increase calcium and phosphate absorption
Calcitonin
Polypeptide, 32 amino acids
Produced by C cells (parafollicular) in thyroid
Secreted in response to high phosphate and calcium
Decreases circulating calcium by:
- preventing osteoclast action
- decreasing reabsorption of phosphate and calcium in PCT
- decreasing calcium absorption in GI tract
Phosphaturic hormone
Decreases phosphate in blood, increases phosphate in urine
Counteracts the actions of vitD
Predominantly made by osteoblasts
Vitamin D
Pro-hormone
In two forms - ergocalciferol (D2) and cholecalciferol (D3)
Made in skin, placenta, decidua
Calcitriol
= 1,25(OH)2D3
Active form of vitD
Short half life of 0.25days, its intermediate 25(OH)D3 is stored with half life 1.5months
Function
- controls osteoblast and osteoclast differentiation
- increases calcium uptake from GI tract
- increases calcium and phosphate reabsorption from kidneys
(- inhibits calcitonin, opposite effects)
- anti-tumour activity
Deficiencies cause secondary hyperparathyroidism (renal osteodystrophy), rickets, osteomalacia
Synthesis of calcitriol
7-dehydro-cholesterol (from skin) converted with UV light to vit D3 (cholecalciferol)
VitD3 in the liver is converted with 25-hydroxylase to 25(OH)D3
25(OH)D3 in the kidney is converted with 1α-hydroxylase to 1,25(OH2)D3 (calcitriol)
Primary hyperparathyroidism
Causes hypercalcaemia
Cause:
80% benign parathyroid adenoma
15% primary parathyroid hyperplasia
2% parathyroid carcinoma - can be part of autosomal dominant familial endocrinopathies eg MEN1, MEN2A, isolates familial hyperparathyroidism
Secondary hyperparathyroidism
In response to lower calcium
Causes:
- kidney disease
- decreased vitD
- decreased serum Ca
Results in renal osteodystrophy by increased Ca absorption from bones, reduced glomerular filtration rate by 50%
Pathological calcification
Abnormal deposition of Ca salts with smaller amounts of other mineral salts, common process
2 forms:
Dystrophic calcification - local deposition in dying tissues or areas of necrosis, despite normal serum levels and normal calcium metabolism
Metastatic calcification - deposition in normal tissues due to hypercalcaemia
Causes of hypercalcaemia
- Hyperparathyroidism
- Renal failure - accumulation of phosphate and reduced absorption of Ca, leading to secondary hyperPTH
- VitD disorders - eg sarcoidosis, VitD excess, Williams’ syndrome
- Destruction of bone - bone tumours, immobilisation, Paget’s disease (accelerated turnover)
- Drug induced - vitA intoxication, thiazide diuretics, lithium, oestrogens
- Endocrinopathies - thyrotoxicosis, phaeochromocytoma
Features of hypercalcaemia
STONES - renal
BONES - osteoporosis, osteomalacia, rickets, osteitis fibrosa
ABDOMINAL GROANS - constipation, vomiting, peptic ulcer, pancreatitis
PSYCHIC MOANS - depression, memory loss, psychoses, coma
Other - proximal muscle weakness, keratitis, conjunctivitis
Treatment of hypercalcaemia
Rehydration
Pamidronate disodium (bisphosphonate drug to inhibit osteoclastic bone resorption)
Calcitonin
Plicamycin
Hypocalcaemia causes
Vit D deficiency
Hypoparathyroidism (surgical/radiation, idiopathic, neonatal, familial, autoimmune (DiGeorge), deposition of metals)
Hypomagnesaemia
Acute pancreatitis
Citrated blood transfusion
Hypocalcaemia features
Perioral tingling
Paraesthesia
Tetany - Trousseau’s, Chvostek’s, carpopdeal spasm
Cardiac arrhythmias
ECG changes - prolonged QT, prolonged ST
Subcapsular cataract
Bone remodelling
Cycle takes 90-200 days
Turnover at bone surfaces - periosteal and endosteal
Peak bone density around age 25
OsteoBlasts BUILD - modulated by PTH, oestrogen, glucocorticoids, thyroid hormone
OsteoClasts CRUNCH - modulated by TNF, IL-1/IL-6, GM-CSF (not PTH receptors)
Biochemical markers of bone turnover
Aluminium phosphate
Type 1 collagen (urine)
Hydroxyproline (urine)
Pyridinolines (urine)
TRAP - tartrate-resistant acid phosphatase
Osteoporosis
Reduced bone mineral density and disruption of bone microarchitecture
More in women (50% in >50)
Causes:
- environmental - smoking, alcohol, malnutrition, immobilisation
- autoimmune - diabetes, coeliac
- drugs - immunosuppressive, steroids, PPIs
- endocrine - hyperthyroid, hyperPTH, hypogonadal, cushing’s, pregnancy, lactation, hyperprolactinaemia
- haematological - lymphoma, myeloma, sickle cells
- metabolic - haemochromotosis
So RFs are BMI <19, family history fractures, untreated premature menopause, chronic medical disorders, immobility
T score interpretation
BMD <1SD = normal
BMD 1-2.5SD = osteopenia
BMD >2.5SD = osteoporosis
Treatment of osteoporosis
1g Calcium
800IU VitD
Bisphosphonate - if >75 no need for DEXA, if 65-75 give if OP confirmed on DEXA, if <65 give if low BMD or high risk factors
HRT or raloxifene
Teriparatide (form of PTH for <65yo)
Strontium
Calcitonin
Calcitriol
Testosterone
Calcium in pregnancy
Hypocalcaemic state (though free ionised levels stable) caused by
- active transplacental transport of Ca to fetus
- increased renal loss of Ca (increased GFR)
- decreased serum albumin
Associated increased calcitriol, increased PTH, increased calcitonin
Fetal calcium
Hypercalcaemic compared to mother (1.4:1)
Ca and phosphate actively transported across placenta
Ossification occurs in 3rd trimester
PTH produced from 12 weeks
Cardiac anatomy
Approx fist sized
3 layers - epicardium (part of pericardium), myocardium and inner endocardium
Tricuspid - between RA and RV
Pulmonary - between RV and pulmonary trunk, semilunar
Mitral valve - between LA and LV, bicuspid
Aortic - between LV and aorta, semilunar
Cardiac cycle
Electrical impulses SAN -> AVN -> Bundle of His -> Purkinje fibres
Phases 0.8s total:
0.4s relaxation
0.1s ventricular filling
0.3s ventricular contraction
P wave - atrial depolarisation
PR - time between atrial depolarisation and ventricular depolarisation, 0.1-0.2s
QRS - ventricular depolarisation, 0.12s
ST - time between ventricular depolarisation and repolarisation
T wave - ventricular repolarisation
1st heart sound - AV valve closure (tricuspid and mitral)
2nd - semilunar valve closure (pulmonary and aortic)
3rd heart sound common in pregnancy and young adults due to rapid ventricular filling
Causes of change to QT interval
Normally 0.3-0.4s
Increased QT - hypokalaemia, hypocalcaemia, quinidine
Decreased QT - hyperkalaemia, hypercalcaemia, digoxin
Pressures in cardiac chambers
RA - 1-7mmHg
LA - 10-15mmHg
RV - 35mmHg systolic, 4mmHg diastolic
LV - 140mmHg systolic, 10mmHg diastolic
Stroke volume
Volume ejected by ventricles during systole
SV (80ml) = end systolic volume (120ml) - end diastolic volume (40ml)
Ejection fraction 0.67, EF = SV/ESV
Cardiac output
CO = SV x HR
Resting 5.5L/min male, 4.5L/min female
Cardiac index = CO/body surface area = 3.2L/min/m^2
Starling’s law
Force of contraction is proportional to fibre length
Fibre length is proportional to stretch of ventricular muscle (dilatation)
Ventricular dilatation is proportional to venous return
Venous return (pre-load) depends on - intrathoracic pressure, total blood volume, gravity, calf muscle action, venous tone
Baroreceptors
For cardiac autonomic control
INHIBITORY
Carotid sinus - at bifurcation of common carotids, innervated by glossopharyngeal
Aortic body - at aortic arch, sensitive to partial pressure of O2/CO2 and pH
Floor of 4th ventricle - sensitive to CSF pressure, Cushing’s reflex means raised CSF pressure leads to raised BP
Chemoreceptors
For cardiac autonomic control
Carotid body - at bifurcation of carotid artery, sensitive to pO2, pCO2 and pH
Central chemoreceptor - sensitive to CO2
Blood vessel walls
Tunica interna
Tunica media - thickest layer in artery, smooth muscle
Tunica externa - thickest layer in vein
Capillaries just single layer of tunica interna
Blood pressure
BP = systemic vascular resistance x CO
Depends on blood volume, viscosity, elasticity of vessel walls, length and diameter of blood vessels, hormones (ADH, ACE, Adrenaline)
SVR depends on neurogenic, metabolic, endocrine
Mean arterial pressure
MAP = diastolic pressure + 1/3x(systolic - diastolic)
Blood flow
Poiseuille’s law - resistance is proportional to length of tube, inversely proportional to radius of tube
Proportional to pressure, radius, 1/viscosity, 1/length
Viscosity increases when haematocrit >45%
Blood components
55% plasma
45% blood cells (from stem cells by haemopoiesis)
- erythrocytes - biconcave discs, 8mm diameter, no nucleus, containing Hb with lifespan 120 days
- leukocytes - 1%, contain nuclei
- thrombocytes - release serotonin causing vasoconstriction, forms platelet plug
Blood groups
Based on presence/absence of inherited antigens on surface of RBCs
ABO
- O - no antigens, a/b antibodies in plasma, only O can donate to
- A - a antigens, b antibodies in plasma, A or O can donate
- B - b antigens, a antibodies in plasma, B or O can donate
- AB - a/b antigens, no antibodies, any can donate
Rhesus
- 80% of caucasians Rh+
Also Kell and Lewis systems
Cardiac output changes in pregnancy
CO rises by 40% from 4.5 to 6L/min. Plateaus at 24-30weeks, then further rise by 2L/min in labour.
HR rises by 20%
SV rises by 30%
Peripheral vascular resistance decreases by 5%
BP decreases by 10%
Vasodilation due to progesterone
ECG changes in pregnancy
LV hypertrophy and dilatation
Apex shifted anteriorly and to left
LAD 15 degrees
Inverted T waves lead 3
Q wave in lead 3 and aVF
Non-specific ST changes
Haematological changes in pregnancy
Plasma volume rises by 50%, from 2600 to 3800ml, plateaus at 32weeks
Total volume of RBCs rises by 18% - so haemodilution, physiological anaemia with HCT decrease
Leukocytes increase, clotting factors increase
Endothelial changes in pregnancy
Vasodilatation due to increased nitric oxide, decreased asymmetrical dimethylarginine, increased PGI2 (prostacyclin)
Pro-coagulant state
Pharynx
130mm length total
Nasopharynx - contains eustachian tube opening and pharyngeal tonsils (adenoids)
Oropharynx - separated from oral cavity by uvula and pillars of fauces (anterior fold palatoglossal arch, posterior fold palatopharyngeal arch), contains palatine tonsils
Laryngopharynx
Larynx
aka voice box
4 cartilages:
- epiglottis
- thyroid cartilage
- cricoid cartilage
- arytenoid cartilage
Trachea and bronchi
Trachea
120mm length
16-20 incomplete cartilage rings
Bronchi
Bifurcation at carina - right bronchus more acute for 3 lobes
Incomplete cartilage rings
Muscles of ventilation
Diaphragm
Intercostals (11 pairs)
Accessory muscles (sternocleidomastoid, platysma, scalene)
Supplied by phrenic nerve from C3-5
Pulmonary vascular resistance
PVR depends on:
- lung volume - when small, PVR high. Initial increase then PVR falls, but further increase then PVR rises exponentially.
- pulmonary vascular tone via NO action
- hypoxia, leads to pulmonary vasoconstriction
- pulmonary artery and venous pressure
Respiration
Physiological respiration
- ventilation - movement of air in and out of lungs as a result of pressure difference
- pulmonary gas exchange
- gas transport
- peripheral gas exchange
Cellular respiration (to obtain energy)
- metabolic process, O2 + glucose -> CO2 + H2o + ATP
Ventilation
Inspiration - active (based on Boyle’s law)
Expiration - passive
Affected by airway compliance and resistance
Minute ventilation = tidal volume x RR, = the total volume of gas entering lung per minute
Alveolar ventilation = (TV - dead space volume) x RR, = 4.2L/min, the volume of gas that reaches the alveoli
Dead space ventilation = the volume of gas per min that remains in airways, not involved in gas exchange
Control of ventilation
Nervous control - resp centre in brainstem
Chemical control - medulla oblongata centrally, aortic and carotid bodies peripherally
Bezold-Jarisch reflex - causes hypopnoea and bradycardia, due to increase in parasympathetic activity, caused by veratrum alkaloids, nicotine and antihistamines
J-receptors (proprioceptors) - in lung innervated by vagus nerve, stimulation causes increase in breathing
Intrapleural pressure
Prevents tendency of lung to collapse due to elastic recoil
Resting IP = -5cmH2O
Falls during inspiration, becomes positive during forced expiration (can get up to +30)
Gaseous exchange
Fick’s law describes diffusion - resp surfaces must have large surface area, thin permeable surface, moist exchange surface
Affected by:
- temperature (high temp - increased velocity - increased pressure)
- composition
- diffusion gradient
Lung compliance changes
= 200mL/cmH2O, = change in lung volume per unit change in pressure
Laplace’s law - transpulmonary pressure is proportional to wall tension, and inversely proportional to radius.
Surfactant secreted by type 2 pneumocytes, composed of dipalmitylphosphatidylcholine and cholesterol, to reduce wall tension and thus compliance
Elastance = 1/compliance (elastic recoil of lung)
Increased in
- obstructive lung disease (asthma, COPD, CF)
- expiration
- old age
Decreased in
- restrictive lung disease (interstitial lung disease, scoliosis, neuromuscular disorders)
Airway resistance
Poiseuille’s law
- resistance proportional to length of tube
- inversely proportional to radius of tube
Diameter of airways influenced by respiratory secretions, lung volumes, smooth muscles of respiratory tree
Lung volumes
Vital capacity - inspiratory reserve + tidal volume + expiratory reserve
Residual volume - volume that remains in lungs following maximal expiration
Inspiratory reserve volume - volume that can be inspired above the tidal volume
Total lung volume = VC +RV
Inspiratory capacity = TV + IRV
Functional residual capacity = volume left in the lung at the end of quiet respiration (RV +ERV)
- increased in obstructive lung disease, CPAP
- decreased in restrictive lung disease, pregnancy, anaesthesia
Spirometry
FVC = total amount of air that can be forcibly exhaled after inspiration
FEV1 = forced expiratory volume in 1s
FEV1/FVC = 75-80%
Peak expiratory flow rate around 600ml/breath
OBSTRUCTIVE PATTERN
- total lung volume increase
- FRC increase
- RV increase
- PEFR decrease
- reduced FEV1/FVC
RESTRICTIVE PATTERN
- all lung volumes reduced
- FEV1/FVC increased or normal
Dead space in respiration
Volume of inspired air that is not involved in gas exchange
3 types:
- anatomical - approx = body weight in lbs
- alveolar - ventilated but not perfused
- physiological (= anatomical + alveolar, 2-3mL/kg)
Respiratory changes in pregnancy
Due to progesterone:
Tidal volume increase by 30-40%, so resp minute volume increases, so oxygen consumption rises, pO2 up to 14kPa, pCO2 down to 30mmHg
Exp reserve decreases
Total lung volume decreases but vital capacity unchanged
Anatomically - bronchiole relaxation, decreased airway resistance
Mechanically - increased O2 demand, more diaphragmatic than thoracic breathing
Maternal and fetal oxygen transport
Cyanosis when deoxyhaemoglobin >5g/dL
Decrease in O2 sats by 1% causes increase in ventilation by 600ml/min
Haematocrit of venous blood is 3% higher than that of arterial blood
Carbon monoxide 240 times more affinity for haemoglobin than oxygen
Oxygen dissociation curve
Sigmoid shape, with plateau at pO2>60mmHg
P50 = the pO2 in blood where Hb is 50% saturated, 26.6mmHg
LEFT SHIFT - higher affinity for O2, decreased unloading, decrease in P50
- carbon monoxide
- fetal Hb
- decreased 2,3-DPG
RIGHT SHIFT - decreased affinity for O2, increased unloading, increase in P50, so higher pressures are required to maintain sats
- hyperthermia
- acidosis
- hypercapnia
Bohr effect
In the presence of CO2, the O2 affinity for dissociation of respiratory pigment decreases
So oxyhaemoglobin dissociation curve to the right when the pH is low, even with a relatively high PO2
+ Haldane effect - deoxygenation of blood increases its ability to carry CO2
CO2 transport
3 forms:
Solution - 10% - CO2 is 24x more water soluble than O2
Carbamino compounds - 30%
Hydration - 60% - CO2 + H2O -> H2CO3 -> H+ + HCO3- in RBCs
(RBCs have carbonic anhydrase, plasma does not)
In Cl- shift, HCO3- leaves RBCs and moves into plasma, Cl- moves into RBCs to maintain electrical neutrality
2,3-DPG changes
Product of glycolysis
Increases in
- exercise
- high altitude
- elevated androgens
- elevated thyroxine
- elevated growth hormone
SO CAUSES RIGHT SHIFT
Decreases in
- acidosis
SO LEANS TO LEFT SHIFT
Teeth and salivary glands
Deciduous milk teeth - 20, from 6 months
Permanent teeth - 32, from 6 years
Salivary glands
- parotid - duct opens at 2nd upper molar
- submandibular - ducts open on either side of tongue frenulum
- sublingual - ducts on floor of mouth
1.5L saliva produced per day
Contains amylase
Layers of digestive tract and gastric secretions
Mucosa
Submucosa - has blood vessels, nerves, lymph, and submucosal plexus. Responsible for secretions.
Muscular layer - has mesenteric plexus
Serosa - continuation of peritoneum
Gastric secretions - 3L produced per day
- HCl (pH 1.5-3.5)
- pepsinogen
- intrinsic factor (for B12 absorption)
3 phases of digestion
Cephalic - saliva containing amylase, 1.5L/day
Gastric - gastrin secreted, continues until stomach emptied and pH 1.5
- takes 2-6 hours, protein stays the longest
Intestinal
- gastric inhibitory peptide (GIP) inhibits gastric motility and secretion
- secretin inhibits gastric secretion
- cholecystokinin (CCK) inhibits gastric emptying
- emptying takes 3-5 hours, making chyme (digested food)
Small intestine
pH 7.5
Microvilli brush border
3L intestinal secretions per day
Peristalsis and segmentation to move food
Ileum is only site of absorption of B12 and bile salts, critical in fluid and Na conservation. Motility 3x slower than jejunum. So in resection, loss of bile salts, reduced water and salt absorption, diarrhoea, increased transit time, short gut syndrome, renal calculi.
Jejunum contents are isotonic
Large intestine
Mucus secreting, no enzymes
Commensal bacteria produce some vitBs, vitK
90% efficiency of salt and water absorption
Transit time 24-150hours
Flatus = hydrogen, methane, CO2
Bile
1L produced per day
Alkaline
Contains bile salts, bile pigments, cholesterol
Bile salts = bile acids (cholic acid and chenodeoxycholic acid) conjugated to glycine or taurine for absorption of fat and fat-soluble vitamins
Bilirubin
Is a bile salt!
Product of Hb breakdown
Lipophilic
Converted to stercobilin (excreted in faeces) and urobilinogen (excreted in urine)
Physiological jaundice common at day 3-7 of life, due to immature liver enzymes and haemolysis of fetal RBCs
- can cause kernicterus (deposition of bilirubin in basal ganglia)
Pancreatic juices
1.5L produced per day
Alkaline
Contains:
- water
- sodium chloride
- sodium bicarbonate
- enzymes (trypsinogen, chymotrypsinogen, proelastase, amylase, lipase)
Recommended nutrition intake
2200kcal/day non-pregnant
2400kcal/day pregnant
2800kcal/day lactating
400g carb
100g fat
Protein - 1.5g/kg body weight/day non-pregnant, 2g when pregnant
6g salt
400microgram folic acid
2.8mg/day iron non-pregnant, or 6mg/day pregnant
Iron deficiency anaemia
When iron <12micromol/L
TIBC saturation <15%
Microcytic
Microchromic
Total body iron = 40mg/kg body weight
Recommended vitamin intake (in microgram/day)
ADEK are fat soluble
A - retinol - 800
B1 - thiamine - 1000
B2 - riboflavin - 1500
B3 - niacin - 15000
B6 - pyridoxine - 2000
B12 - cobalamin - 2
C - ascorbic acid - 30000
D - calciferol - 10
E - tocopherol - 10000
Recommended mineral intake (in micrograms/day)
Ca - 800
Iron - 12
Na - 3000
Cl - 3500
K - 1000
Iodide - 0.1
Zinc - 150
Mg - 300
Vitamin A
Retinol, active form is retinoic acid
Deficiency - keratomalacia, night blindness
Toxicity - hypervitaminosis A
Vitamin B1
Thiamine
Deficiency - beribero, Wernicke-Korsakoff syndrome
No known toxicity
Vitamin B2
Riboflavin
Deficiency - Ariboflavinosis
No known toxicity
Vitamin B3
Niacin
Deficiency - pellagra
Toxicity - liver damage
Vitamin B5
Pantothenic acid
Deficiency - paraesthesia
No known toxicity
Vitamin B6
Pyridoxine
Deficiency - microcytic anaemia, peripheral neuropathy
Toxicity - impaired proprioception
Vitamin B7
Biotin
Deficiency - dermatitis, enteritis
No known toxicity
Vitamin B9
Folic acid
Deficiency - macrocytic anaemia
No known toxicity
Vitamin B12
Cobalamin
Deficiency - megaloblastic anaemia
No known toxicity
Vitamin C
Ascorbic acid
Deficiency - scurvy
Toxicity - vitC megadosage
Vitamin D
Calciferol
Deficiency - rickets, osteomalacia
Toxicity - hypervitaminosis vit D
Vitamin E
Tocopherol
Deficiency - haemolytic anaemia in newborns
Toxicity - haemorrhage/anti-coagulant
Vitamin K
Phylloquinone
Deficiency - bleeding diathesis (hypocoag)
No known toxicity
Formation of urine
- Glomerular filtration
- Selective tubular reabsorption
- Tubular secretion (H+ and K+)
GLOMERULUS - mass of capillaries in Bowman’s capsule, containing afferent and smaller efferent arterioles
PCT - reabsorbs water passively and solutes actively, 80% filtrate reabsorbed here, inc glucose when in physiological range. Renal threshold reduced in pregnancy
LOOP OF HENLE - to concentrate urine, solute reabsorption at ascending loop (impermeable to water), water reabsorption at descending loop
DCT - influenced by ADH and aldosterone, only 5% filtrates reach here, mostly for water absorption
Juxtaglomerular apparatus
Ascending loop of Henle - macula densa - measures Na concentration
Afferent arteriole - juxtaglomerular cells - modified endothelial cells are pressure sensitive
Synthetic functions of kidney
Glucose
EPO
Vitamin D: 25(OH)D3 is converted with 1α-hydroxylase to 1,25(OH2)D3 (calcitriol)
Structure of ureters and bladder
3 layers of ureter: outer fibrous, middle muscular, inner transitional epithelium
Bladder is 4 layers (mucosa, inner longitudinal, circular, outer longitudinal muscles) is stimulated at 300ml volume, capacity 500ml
Nerve supply via Lee-Frankenhauser plexus
Micturition
Under voluntary control - mediated by pontine reticular formation in cerebellum
Bladder contractility from sacral spinal reflex
Urethral function by pudendal nerve
STORAGE - as bladder fills, bladder wall receptor -> pelvic splanchnic nerve -> sacral root S2-4 -> lateral spinothalamic tract -> higher centres
INITIATION - relaxation of pelvic floor and suppression of descending inhibitory impulses via parasympathetic system (M2 and M3 muscarinic receptors in bladder)
VOIDING - when the rising intravesical and falling urethral pressures equalise
(descending inhibitory reflexes via sympathetic NS - alpha receptors in bladder neck and urethra to increase outlet resistance, beta receptors on detrusor muscle to cause relaxation)
Normal urodynamic values
Residual <50ml
1st sensation 200ml
Voiding volume 400ml
Capacity 600ml
Flow rate >15ml/s
Pressures:
- negligible rise in detrusor pressure on filling (<15cmH2O)
- maximum voiding detrusor pressure <50cmH2O
- intraurethral at rest (contracted sphincter) 50-100
- no systolic detrusor pressure during filling
Urinary system changes during pregnancy
Increased uterus size -> nocturia, frequency
Lower renal threshold -> glycosuria
Renal hypertrophy -> increased renal size (no hyperplasia)
Mild renal pelvis and ureteric dilatation due to progesterone and obstruction from uterus
Increased renal blood flow
Increased GFR
Decreased filtration fraction
Urine output increases for 7 days post partum
Renal metabolic changes in pregnancy
Decreased HCO3- (decreased CO2)
Decreased Na
Decreased osmolarity (progesterone)
Decreased urea
Decreased creatinine (frmo 73 to 47)
Folliculogenesis
Growth and development of follicle, in two main phases:
Pre-antral - independent of FSH
Antral (Graafian) - dependent on FSH
Lasts 375 days - 13 menstrual cycles
Based on 2-cell 2-gonadotrophin hypothesis for oestrogen production
- in response to LH, thecal tissues produce androgens, which are then converted to oestrogen in granulosa cells via FSH-induced aromatisation
- FSH for early folliculogenesis
- LH for final stages of follicle maturation and growth of dominant follicles
Primordial -> primary -> secondary -> graafian -> dominant
Theca cells
Secrete androgens and progesterone
Do NOT secrete testosterone as lack 17beta-HSD
Only have LH receptors
Granulosa cells
Secrete oestrogen and progesterone
(androgens converted to oestrogen via FSH)
P450 aromatase
Have LH and FSH receptors
Primordial follicles
Primary oocyte surrounded by a single layer of granulosa cells and basal lamina
Formed at 6 months gestation (5-7million), down to 2million by birth, 300-500,000 by puberty
Primary follicle
When granulosa cells in the primordial follicle change from flat to cuboidal -> zona pellucida forms around the ovum
FSH receptors develop
Independent of gonadotrophin stimulation
Secondary follicle
When primary follicle attains second layer of granulosa cells, by recruited theca cells (theca interna and externa)
With capillary network between theca layers
At day 5 of cycle
Follicle mitotic activity high
Graafian follicle
aka tertiary/antral follicle
Marked by formation of fluid-filled cavity between granulosa cells
Corona radiata = granulosa cells immediately surrounding the ovum
Dependent on FSH
Grows to >1cm
Secretes oestrogen
Pre-antral follicle
Secondary follicle in late stage of development
Contains:
Oocyte
Zona pellucida
9 layers of granulosa cells
Basal lamina
Theca interna
Capillary network
Theca externa
Preovulatory follicle
Graafian follicle in late stages of development
5-7 preovulatory follicles enter menstrual cycle and compete to become the dominant follicle
Follicles with low FSH receptors will stop developing and undergo atresia, leaving one dominant follicle to undergo ovulation
Oogenesis
Process to form mature ova, from primordial germ cell -> oogonium -> primary oocyte -> secondary oocyte -> ovum:
Oocytogenesis
Ootidogenesis
Maturation
Primordial germ cells -> oocyte
Primordial germ cells migrate from yolk sac to ovaries, mature to oogonia
Oogonia are diploid (46 chromosomes) then divide by mitosis to form primary oocyte at 3rd month gestation
Primary -> secondary oocyte
Primary oocyte is diploid 46 chromosomes, then undergoes meiosis 1 at 5th month gestation, arrests at prophase 1 and is not completed until ovulation (dictyate = resting phase)
At ovulation, completes meiosis 1 -> secondary oocyte and 1st polar body
Secondary oocyte is haploid 23 chromosomes
- primitive ovum, surrounded by secondary follicle
- enters meiosis 2, arrests at metaphase 2 and then is not completed until fertilisation occurs
At fertilisation, completes meiosis 2 -> ovum and 2nd polar body
Menstrual cycle
= proliferation and shedding of functional layer of endometrium
Menstruation day 1-5 - due to withdrawal of progesterone, usual loss 50-150ml
- oestrogen + progesterone low, so GnRH increase -> FSH increase -> stimulates secondary follicle to secrete oestrogen
Proliferation day 6-15 = follicular phase, influenced by oestrogen from Graafian follicle (oestrogen inhibits release of FSH and stimulates LH, so ovulation)
Secretion day 16-28 = luteal phase, influenced by corpus luteum secreting progesterone, which decreases LH levels
Hormone levels in menstrual cycle
FSH - low at beginning, rises in response to GnRH, then inhibited by oestrogen for ovulation, low by the end
LH - rises through follicular phase (GnRH), mid-cycle surge (oestrogen) then rapid decline (progesterone)
Oestradiol rises up to mid-cycle, falls, then peaks in luteal phase
Progesterone starts low then has one peak in luteal phase
Ovulation
When ovarian follicle ruptures and releases ovum
Defines transition from follicular to luteal phase
18 hours after peak LH
Ruptured follicle becomes corpus luteum - produces oestrogen and progesterone, has LH receptors
- Mittelschmerz (mid-cycle pain)
- fluid in POD
Corpus luteum in fertilisation / not
FERTILISATION
corpus luteum degenerates only when placenta takes over function (between 3-6 months)
NO FERTILISATION
corpus luteum decays after 14 days to become corpus albicans (mass of fibrous scar tissue) and start menstruation
Menarche
Age 10-16, average 12.8 Western 12.3 African
Does NOT signal that ovulation has occurred - usually around 3 years post menarche
In response to
- sufficient body mass (48kg with 17% fat)
- activation of GnRH pulse generator
- ovarian oestrogen-induced growth of uterus
- fluctuating oestrogen levels
Primary amenorrhoea
Failure of menarche to occur
- 3 years after thelarche (breast development)
- by age 16 in presence of normal secondary sexual characteristis
- by age 14 in absence of other secondary sexual characteristics
Menopause
45-55years, average in UK 51
- age reduced by smoking, hysterectomy (even with ovarian conservation, by around 4 years), uterine artery embolisation
- process takes 6months - 3years
Biochemically
- fall in oestradiol (predominant oestrogen will be oestrone)
- decreased levels inhibin
- rise in LH and FSH
Premature menopause
If before age 40
1% of women, higher incidence in identical twins (5%)
Symptoms of menopause
Vasomotor - hot flushes, migraine
Urogenital - vaginal atrophy, urinary urgency/frequency
Skeletal - osteopenia, osteoporosis
Psychological - mood disturbance, memory loss, insomnia
Sexual - decreased libido, dyspareunia
Spermatogenesis
= spermatogonium -> primary spermatocyte -> secondary spermatocyte -> spermatid -> spermatozoa
Produced in seminiferous tubule, when mature move into lumen
70-80 days to produce, new cycle every 16 days
Under influence of FSH
Spermatocytogenesis, and spermatidogenesis
Spermatogonium undergoes mitosis to produce primary spermatocyte (diploid 46 chromosomes)
Then undergoes meiosis 1 to produce seoncdary spermatocyte (haploid 23)
Then undergoes meiosis 2 to produce 4 spermatids
Spermiogenesis
Maturation of spermatids under the influence of testosterone
Structural changes:
- axoneme forms
- golgi apparatus becomes acrosome (head)
- body contains mitochondria
- centriole of cell becomes tail of sperm
- DNA becomes highly condensed
- excessive cytoplasm removed
Spermiation = release of mature spermatozoa from sertoli cells into lumen of seminiferous tubule
Hormonal control in spermatogenesis
GnRH - released at age 10, to produce FSH and LH
FSH - acts on seminiferous tubules (sertoli cells) to stimulate spermatogenesis
LH - acts on leydig cells to stimulate testosterone production
Testosterone - inhibits GnRH and LH
Inhibin - produced by sertoli cells in response to increased sperm, to inhibit FSH
Semen
Secretions from - seminal vesicles, prostate, bulbourethral (Cowper’s) glands, hyaluronidase (to aid passage through cervical mucus)
Seminal fluid composed of carnithine, inositol, glycerophosphocholine, phosphatase, fructose, citric acid
Semen analysis
> 15million spermatozoa per ml
39million sperm per ejaculate
Vitality >55%
Leukocyte <1million/ml
300million sperm produced per day
pH 7.2-7.6
Survive for 3-4 days
Total motility >38%
Normal morphology >3%
Spermatozoa journey
Semen coagulates in vagina
Cervical passage - glycoprotein molecules arrange in parallel lines, sperm form reservoir in cervical crypt
Capacitation - sperm surface glycoprotein removed in uterus via uterine fluid, initiates whiplash movement of sperm tail
Acrosome reaction - allows sperm to penetrate the zona pellucida
Bone formation
Made of collagen, phosphate and water
Influenced by growth hormone, thyroid, PTH, oestrogen, testosterone
Ossification is membranous, eg top of skull/clavicle, or direct (endochondral), eg long bones, vertebrae, pelvis
Primary centre in diaphysis, secondary centre in epiphysis
Types of bone tissue
Compact/cortical
- hard and dense
- composed of sheets (lamellae)
- arranged in concentric cylinders (Haversian systems), at the centre is Haversian canal
- osteocytes lie in lacunae within lamellae and canaliculi radiate from here
Cancellous
- interior of bones
- irregular honeycomb of thin plates (trabeculae)
- contains red bone marrow
Types of bone
Long - shaft is compact, epiphysis is cancellous
Short - mainly cancellous, cortex is compact
Flat - two parallel plates of compact bone surrounding a layer of cancellous bone
Irregular
Sesamoid - forms in areas of pressure, in tendons
Bone healing
Haematoma forms
Macrophages phagocytose the haematoma
Osteoblast lay down callus (new bone)
Osteoclast reshape bone and form central medullary canal
Types of muscle
Skeletal (voluntary/striated)
- type 1 - slow twitch fibre, red, high levels myoglobin, aerobic
- type 2 - fast twitch fibre, white, large reserve of glycogen, anaerobic
Smooth (involuntary/visceral) - spindle shaped cells connected by gap junctions
Cardiac - branched fibres connected via intercalated disc
Organisation: actin + myosin, in sarcomeres, in myofibrils, in fascicles, in muscle
Myofibrils
Contain actin (thin filament) and myosin (thick filament)
Enclosed in endomysium (single muscle cell), then perimysium (covers bundle), then epimysium (whole muscle)
Muscle contraction
Skeletal:
Action potential -> Ca release from sarcoplasmic reticulum into cytosol -> Ca bind to troponin on actin -> displacement of tropomyosin and exposure of myosin-binding site on actin -> actin and myosin cross link -> myosin slides on actin
Smooth muscle:
Associated with calmodulin
Contraction following phosphorylation of myosin
Muscle fuels
Phosphocreatine
Glycogen
Blood glucose
Fatty acids
MSK changes in pregnancy
Muscle relaxation - via progesterone, suppression of mRNA production for oxytocin, oxytocin receptor and prostaglandin F receptor, increase in cAMP, decreased number of gap junctions
- takes up to 3mo postpartum for muscle tone to normalise
Relaxation of sacroiliac joints
Separation of pubic symphysis - normal joint space up to 9mm, if >10mm then significant separation
Cells of the nervous system
Neurones - cell body, dendrites, axon, presynaptic terminal
Glial cells - non-neuronal, non-excitable
- to provide support and nutrients to neurones, and form myelin
- 4 types of glial cell in CNS - astrocytes, oligodendrocytes (make myelin in CNS), microglia, ependyma (membrane lining cavities)
- 3 types of glial cell in the PNS - schwann (make myelin in PNS), satellite, enteric glial
Nerve fibres
= axon of nerve cell, organised into fascicle bundles, nerves are grouped fascicles
A fibres
- largest diameter, shortest refractory period, myelinated, 12-130m/s, for touch/pressure/joint position/temperature, motor innervation to skeletal muscles
B fibres
- myelinated, 15m/s, found in autonomic NS
C fibres
- unmyelinated, smallest diameter, longest refractory period, 2m/s, for pain, and viscreal motor fibres to heart and smooth muscle
Coverings of nerve fibres
Endoneurium covers individual groups of axons
Perineurium covers groups of fascicles
Epineurium covers the nerve
Axonal degradation pathway
Degeneration of synaptic terminal distal to lesion (Wallerian degeneration) -> myelin degeneration -> debris clean-up by microglia, macrophages and schwann cells -> chromatolysis (neuronal cell body change) -> transneuronal degeneration
Action potentials
Plasma membranes
- have membrane potential (electrical voltage difference across membrane), resting MP -70mV (inside of cell negative)
- due to unequal distribution of ions
- calculated by Goldman equation
- impermeable to ions, good insulator, but has ion pumps and ion channels (leak or gated, which can depend on voltage, chemicals, pressure, light)
Potential
Graded - due to chemical/mechanical/light-gated ion channels
OR
Action - all-or-none
- lasts 1ms
- continuous in non-myelinated, but saltatory in myelinated jumping between nodes of Ranvier
- depolarisation (Na inflow, less negative), rapid opening of voltage-gated Na channels
- repolarisation (K outflow, more negative), slow opening of voltage-gated K channels and closure of Na channels
- then hyperpolarisation after repolarisation phase, due to open voltage-gated K channels
Refractory period
Time when an excitable cell cannot generate another action potential
Absolute (irrespective of stimulus) or relative (only with large stimulus)
Neurotransmitters
Acetylcholine
Amino acids - excitatory (glutamate and aspartate), or inhibitory (GABA and glycine)
Catecholamines - noradrenaline, adrenaline, dopamine, serotonin
Neuropeptides - endorphins, enkephalins, substance P, CCK, gastrin
Gases - nitric oxide, carbon monoxide
Transmission at synapses
RELEASE
Nerve impulse -> depolarisation of synaptic membrane -> voltage-dependent Ca channels open -> higher intracellular Ca triggers exocytosis of synaptic vesicles into synaptic cleft -> transmitter binds to neurotransmitter receptor on postsynaptic membrane
REMOVAL
via diffusion, enzymatic degradation, reuptake into cells
Impulse conduction and synaptic transmission is influenced by
pH
- alkalosis increases excitability of neurones, acidosis depresses
Neurotransmitter agonists/antagonists
Receptor site antagonists
Anticholinesterase agents eg neurostigmine, physostigmine
Fuel for brain
Cerebral blood flow is 15% of CO, 750ml/min
MAP must be >70mmHg for adequate cerebral perfusion
Brain is 2% body weight and consumes 20% oxygen at rest
Fuelled by - glucose, liver glycogen (after glycogenolysis), muscle protein (after gluconeogenesis), and ketone bodies
CANNOT use fatty acids
Reflexes
Involuntary response to stimuli - somatic or autonomic
Reflex arc: receptor -> sensory neurone -> control centre (brain/spinal cord) -> motor neurone -> effector
- can be MONOSYNAPTIC (always ipsilateral eg stretch/tendon reflexes) or POLYSYNAPTIC (eg flexor or crossed extensor reflex)
Reflex receptors
- for stretch, =muscle spindles, causes contraction so change muscle length
- for tendon, = Golgi tendon organ, causes relaxation so monitors change in muscle tension to prevent overload
Autonomic nervous system fibres
All preganglionic fibres are cholinergic
Postganglionic
- parasympathetic are cholinergic
- sympathetic are adrenergic (except sweat glands which are cholinergic)
- absent in adrenal gland as chromaffin cells of medulla are essentially postganglionic cells
Sympathetic NS
FIGHT OR FLIGHT
- preganglionic nerve fibres from T1 to L2
- sympathetic ganglia - paravertebral (sympathetic trunk, paired either side of spinal cord with 22 ganglia each) and prevertebral (coeliac, SupMes and IM ganglions)
- postganglionic nerve fibres
Parasympathetic NS
REST AND DIGEST
- preganglionic nerve fibres from cranial nerves (oculomotor, facial, glossopharyngeal, vagus) and vertebral levels S2-S4
- parasympathetic ganglia in wall of visceral organs
- postganglionic nerve fibres
Lymphatic system
Flow always towards heart, via at least one lymph node before a duct
Maintained by valves, pressure from muscular contraction/pulsating arteries, suction (negative pressure from heart contraction)
Composition similar to plasma
Tissue in lymph nodes (several afferent but only one efferent vessel, contains lymphocytes and macrophages), spleen, thymus
Functions - immune, collect excess fluid, transport fatty acids
Epidermis
- stratified squamous epithelium
- 4 cell types - keratinocytes, melanocytes, langerhans cells (type of immune cell produced by bone marrow), merkel cells (involved in touch)
- 4 layers - stratum corneum (superficial), stratum lucidum, stratum granulosum, stratum spinosum
Dermis
- contains hair follicles, blood vessels, glands (SEBACEOUS in hair follicles and ECCRINE/merocrine sweat glands produce watery secretions all over body, APOCRINE sweat glands produce viscous secretions associated with sexual excitement in axilla, pubic area, areola), nerves
- papillae in dermis give rise to ridges eg fingerprints
Skin changes in pregnancy
Striae gravidarum - due to increased cortisol
Chloasma - due to increased melanocyte-stimulating hormone production
Increased skin pigmentation
Linea nigra (darkened linea alba)
Increased activity of sebaceous and sweat glands - due to increased thyroid hormone
Sight
Three layers to eye - sclera, choroids, retina
Retina has rods (mainly at peripheries) and cones (sensitive to bright light and colour, make up the macula densa)
Hearing
Ear in temporal bone
Three parts:
- outer ear
- middle ear - eustachian tube and tympanic cavity (malleus, incus, stapes)
- inner ear - has oval window and round window openings to middle ear, stapes attaches to oval. Consists of labyrinth (bony and membranous, filled with perilymph between layers and endolymph within membranous labyrinth) and semicircular canals)
Taste
3 zones on tongue:
Front - sweet and salt
Lateral - sour
Rear - bitter
Innervation by facial, vagus, and glossopharyngeal nerves
Olfaction
Smell detected by olfactory sensory neurones in roof of nasal cavity, olfactory epithelium
Sensitivity depends on proportion of olf to resp epithelium in nasal cavity
Odor molecules travel:
superior nasal concha -> olfactory receptor cells -> cribriform plate -> mitral cells in olfactory bulb -> olfactory nerve -> brain
Touch
Consists of touch and pressure
Mechanoreceptors in humans
- Meissner’s corpuscles - encapsulated unmyelinated nerve endings, sensitive to light touch (NOT pain), in papillae of skin and genital region
- Pacinian corpuscles - sensitive to pressure and vibrations, deep in skin
- Merkel’s disc - pressure and sustained touch
- Ruffini corpuscles - skin stretch
Pain
= unpleasant sensory or emotional experience associated with actual or potential tissue damage
SOMATOGENIC
Nociceptive
- superficial - localised pain from skin/superficial tissues
- deep - somatic (poorly localised, dull/aching, initiated by nociceptors in ligaments, tendons, muscles, bones, fascia, blood vessels) and visceral
Neuropathic
PSYCHOGENIC
Amniotic fluid volumes by gestation
10 weeks - 30ml
12 weeks - 50ml
16 weeks - 190ml
35 weeks - 900ml
>35 weeks volume decreases
Formation and clearance of amniotic fluid
In 1st trimester - made and cleared by placenta, can transport across fetal skin (until it keratinises around 22-25weeks)
In 2nd trimester
- urine - first at 8-11 weeks, increased function/volume through pregnancy (700-900ml/day at term) but full development of renal system not until several months post delivery
- swallowing - first at 12 weeks, 250ml/day
- lung secretions - 200-400ml/day
- placenta
Amniotic fluid composition
Osmolality = 275mOsm/L
Fluid exchange 500ml/day
Composition
- urine
- cells - epithelial, glial, non-embryonic stem cells
- hormones - progesterone, cortisol, oestrogen, prolactin, rennin
- antibacterial - zinc, lysozyme, peroxidase, interferon-α
- albumin, lecithin, sphingomyelin, bilirubin (decreases in 3rdT)
- α-fetoprotein - less than in fetal blood, peaks at 10-12 weeks
- NO fibrinogen
Fetal membranes
AMNION
- amniotic cavity formed by day 7
- 5 layers - cuboidal epithelium, basement membrane, compact layer, fibroblast layer, spongy layer
- no blood vessels, lymphatics or nerves
CHORION
- 4 layers - cellular, basement membrane, reticular layer, trophoblast
Fetal lung development
Pseudoglandular period - 5-17 weeks
Canalicular period - 16-25 weeks
- primitive alveoli
- low diffusing capacity (huge separation from resp tissue and capillaries)
Terminal sac period - 24w-term
- potential for gas exchange improves
- surfactant synthesis by type2 pneumocytes
Alveolar period - late fetal life - age 8
- alveolar-like structures present at 32w, then final growth
Surfactant
To increase lung compliance
From 24 weeks, by type 2 pneumocytes
Triggered by increase in cortisol (at 32weeks), thyroid hormone, thyrotrophin-releasing hormone, prolactin
Predominant phospholipid is dipalmitoyl phosphatidylcholine DPPC
Lung maturity confirmed by amniotic fluid levels of lecithin:sphingomyelin ratio 2:1
First breath following delivery
10-60ml
For lung inflation to occur - first inspiratory effort needs transpulmonary pressure 60cmH2O, second inspiratory effort needs 40cmH2O
Triggered by hypercapnia and hypoxia in partial occlusion of umbilical cord
Promoted by tactile stimulation and reduced skin temp
Respiratory distress syndrome
10-15% prem babies
Due to surfactant deficiency
More in males, caesareans, perinatal asphyxia, maternal diabetes, 2nd twin
Fetal circulation
Only 10% CO enters lungs
- umbical vein - ductus venosus - IVC -> right atrium
- RA to foramen ovale - left atrium - left ventricle -> ascending aorta
OR - RA to RV - pulmonary artery - ductus arteriosus -> descending aorta - aorta -> umbilical artery
4 shunts in fetal maternal circulation
- Placenta
- Ductus venosus (bypass liver)
- Foramen ovale (between RA and LA)
- Ductus arteriosus (aorta to pulmonary artery, patency mediated by prostaglandins)
Cardiopulmonary adjustments at birth
- Vasoconstriction of umbilical arteries
- Autotransfusion - blood from fetal side of placenta enters baby as umbilical veins (placenta-baby) do not constrict
- Opening of pulmonary circulation due to decreased pulmonary vascular resistance (expansion of lungs and pulmonary vasodilation)
- Closure of foramen ovale due to increased LA pressure, decreased RA pressure
- Closure of ductus venosus within 3hrs
- Closure of ductus arteriosus within few hours - rapid rise in pO2 causes smooth muscle contraction and fall in prostaglandin levels, then permanent closure at 1week old
Hypoxia effects on newborn
Pulmonary vascular resistance remains high
- so ductus arteriosus remains patent
- so right-to-left shunt persists
Fetal erythropoiesis location
Begins at 3weeks - in placenta and yolk sac
By 4 weeks - endothelium of blood vessels and liver
By end of 1stT - bone marrow and spleen
Early fetal erythrocytes are nucleated. 5% reticulocyte count at term (1% in adults). Life span depends on gestation, but 80 days at term.
Placenta structure
Weight 600g at term, 25cm diameter, 3cm thick
Surface area 14m^2 at term
Blood flow 1.5L/min
Consumes 1/3rd of oxygen supplied
Villi (syncitiotrophoblast (multinucleated, no mitotic activity, hormone synthesis), cytotrophoblast (uninucleated), mesenchyme) arranged as lobules, each receiving spiral artery
40-60 lobules
Development of placenta
Trophoblasts differentiate from day12
Extravillous trophoblast invasion and conversion of spiral arterioles:
Wave 1 - 8-10 weeks
- intestitial cells migrate to inner 1/3rd of myometrium and form giant cells
- endovascular migration down spiral arteries
Wave 2 - 16-18weeks
Leads to loss of smooth muscle of spiral arterioles, dilatation, and loss of vasoreactivity, low-pressure and high capacity vessels
Placental blood circulation
Umbilical artery - 50mmHg (deoxygenated blood from fetus to placenta)
Umbilical vein - 20mmHg (oxygenated blood to fetus)
Maternal spiral artery - 70mmHg
Intervillous space - 10mmHg
Placental barrier:
Syncitiotrophoblasts outer - contacts maternal blood
Cytotrophoblasts
Extra-embryonic mesoblast - contains Hofbauer cells (macrophages involved in restructuring stroma to ensure plasticity during villi development)
Fetal capillaries
Functions of placenta
Maternal-fetal transport
- passive diffusion of urea, free fatty acids, respiratory gases
- facilitated transport of glucose
- active transport of amino acids
- receptor-mediated endocytosis of IgG (from 35 weeks)
Hormone synthesis - hCG(chorionic gonadotrophin), hPL (placental lactogen), placental growth hormone between 10-20 weeks, progesterone
Barrier to pathogens
Immunological interface
How does the placenta make oestrogen?
It does NOT synethesize de novo
- placenta works with fetal adrenals to synthesize DHEA (dihydroepiandosterone)
- fetal liver converts DHEA -> oestriol (can measure this for fetal wellbeing)
- placenta then converts DHEA to oestradiol and oestrone
Length of twin pregnancy?
3 weeks shorter than singleton
Fetal adrenal glands
Fetal zone (80-90% of cortex volume) disappears soon after birth
Role in maturation via cortisol production - of lungs, liver, thyroid, GI tract
Role in development - hypothalamic function, pituitary-thyroid axis, hepatic enzymes
Role in sequential change of placental structure
Promote thymic involution
Meconium
Consists of amniotic fluid, mucus, desquamated GI mucosa cells, fatty acids, bile salts
Usually passed within 48hrs of delivery
1/10 present intrapartum - due to post-dates or fetal distress
1/1000 aspirate -> mechanical lung obstruction, displacement of surfactant, pneumonitis, decreased efficiency of gas exchange. Can lead to pneumothorax or persistent pulmonary hypertension of the newborn
Neonatal skin
Sterile in utero
Milia - enlarged sebaceous glands on nose and cheek
Protected by
- vernix caseosa - fatty film that develops over the skin from 20weeks
- lanugo - fine covering of hair from 20weeks until 36weeks (usually shed)
Fetal weight at 16, 20, 24, 36, 40 weeks
16w - 150g
20w - 330g
24w - 670g
28w - 1200g
32w - 1950g
36w - 2810g
40w - 3620g
(so doubles roughly every 4w 16-28w. Then gains slow to 6-700g per 4w)
Cardiovascular changes in pregnancy
Increased plasma volume by 40-50% (2600-3800ml) up until 32w
Increased red cell mass by 18% (1400ml-1650ml)
Increased CO by 40%
HR rise by 20%
BP decrease by 10%
Pulmonary changes in pregnancy
RR unchanged
Tidal volume rises by 30-40%
Exp reserve decreases
Total lung volume decreases
Vital capacity unchanged
O2 consumption rises by 20%
- 20ml/min to fetus, 6ml/min for raised CO, 6ml/min for increased renal work, 18ml/min to increased maternal metabolic rate
GI changes in pregnancy
Sphincter tone decreases
GI emptying time increases
(GI reflux, constipation)
Liver changes in pregnancy
ALP increases by 3x (placental production)
CCK release decreases
Gallbladder contractility decreases (more cholestasis, gallstones)
Renal changes in pregnancy
Increased renal flow 25-50%
GFR increases
Serum urea and creatinine falls
Glycosuria
Urinary acid excretion rate rises
Metabolic changes in pregnancy
Lower bicarb
Lower Na
Lower osmolarity
Increased iron demand and absorption
Increased volume of distribution
Increased drug excretion
Haematological changes in pregnancy
Increased EPO and hPL
Physiological anaemia and thrombocytopenia
Increased WBC
Hypercoaguable - increase in all coagulant factors, increased fibrinogen
