Physiology notes part1

GIT Physiology
STRUCTURE OF THE GASTRO-INTESTINAL TRACT
_ MUCOSA – made up of the epithelium, lamina propria (which contains lymph
nodes) and the muscularis mucosa, a thin layer of smooth muscle which throws the mucosa into folds and ridges
_ SUBMUCOSA – Loose connective tissue. Contains glands
_ MUSCULARIS EXTERNA – inner circular and outer longitudinal smooth muscle
_ MEISSNER’S plexus is located in the sub-mucosa – important role in the
regulation of secretion; MYENTERIC (Auerbach’s ) plexus is located between the
circular and longitudinal muscle layers – controls motility
AUTONOMIC CONTROL OF THE GI TRACT
_ PARASYMPATHETIC – Vagus nerve or sacral parasympathetic (S2,3&4) which supplies the distal colon
_ Post-ganglionic fibres originate in the Meissner’s or myenteric plexuses. Pre- and post-ganglionic neurons have acetylcholine as the neurotransmitter. Stimulation causes increased motility and secretion
_ SYMPATHETIC – pre-ganglionic fibres originate from the spinal cord (T8 – L2)
and pass through the sympathetic chain to the celiac and other mesenteric ganglia.
Acetylcholine is the neurotransmitter
_ Post-ganglionic fibres originate in the celiac and other mesenteric ganglia –
noradrenaline is the neurotransmitter. Cause decreased motility and decreased
secretion though contraction of the muscularis mucosa is stimulated

SWALLOWING
_ Oral phase – under voluntary control
_ Pharyngeal phase – involuntary – the vocal cords are strongly approximated and the epiglottis covers the opening into the larynx, preventing the passage of food into the trachea
_ Oesophageal phase – involuntary, peristalsis conveys food into the stomach
_ Under control of the swallowing centre in the medulla
_ Afferent impulses travel in the trigerminal and glossopharyngeal nerves. Motor
impulses from the swallowing centre travel in the 5th, 9th, 10th and 12th cranial
nerves
SALIVA
_ Produced by the parotid, submandibular, sublingual and several small buccal
salivary glands
_ Contains serous secretion with salivary amylase which begins carbohydrate
digestion and mucus for lubrication
_ Secretions from the buccal glands do not contain any amylase. The parotid gland only has serous secretion
_ Higher potassium and bicarbonate than plasma but lower sodium and potassium.
Hypotonic compared to plasma
Secretion is stimulated by the parasympathetic nervous system, impulses from
higher centres and from the stomach
FUNCTIONS OF THE STOMACH
_ Storage of food; mixture with gastric secretions and controlled release into the
small intestine for digestion
_ Motility and gastric emptying is stimulated by the presence of food in the stomach
_ Gastrin released from the antral mucosa stimulates gastric emptying – enhances the activity of the pyloric pump and relaxes the pylorus
_ The presence of chyme in the duodenum, especially acidic chyme triggers the
entero-gastric reflex inhibiting gastric emptying. Secretin, cholecystokinin and gastric inhibitory peptide are secreted by the duodenum and jejunum and inhibit gastric emptying
_ Gastric emptying is decreased in pregnancy due to the inhibitory effects of
progesterone on smooth muscle activity. Gastric emptying is especially decreased in labour
GASTRIC SECRETION
Gastric glands contain different cell types: Mucus cells, Oxyntic (parietal cells),
Peptic (Chief) cells and G-cells
_ The Oxyntic glandular region occupies most of the mucosa except the lesser
curve. The glands of the pyloric region secrete mainly mucus (essential for protection of the mucosa) and gastrin
_ Oxyntic cells secrete hydrochloric acid and intrinsic factor. The pH of the oxyntic cell secretion is ~0.8
_ Peptic (Chief) cells secrete pepsinogen
_ G-cells secrete gastrin while the mucus neck cells of the gastric glands secrete
mucus
PEPSIN
_ Proteolytic enzyme secreted by the peptic or chief cells of the gastric glands as the pro-enzyme pepsinogen which is converted to pepsin by hydrochloric acid
_ pH for optimal activity is <3.0
INTRINSIC FACTOR
_ Glycoprotein secreted by the oxyntic cells of the gastric glands
_ Essential for the absorption of vitamin B12 by the terminal ileum
CONTROL OF GASTRIC SECRETION
THREE PHASES
_ Cephalic – before food reaches the stomach – vagal control
_ Gastric – stimulated by the presence of food in the stomach, stretch, gastrin,
histamine
_ Intestinal phase – presence of food in the small intestine – initially stimulatory due to gastrin secretion by the duodenum but overall inhibitory effect
_ Secretion is stimulated by:
1) Vagal stimulation / acetylcholine
2) Gastrin
3) Histamine
4) Presence of food in the stomach
_ Secretion is inhibited by
1) Stomach pH < 2.0
2) Secretin
3) Cholecystokinin
4) Gastric inhibitory peptide
5) Somatostatin
6) Vasoactive intestinal peptide
7) Sympathetic stimulation


PANCREATIC JUICE
_ Proteolytic enzymes: trypsin, chymotripsin, carboxypeptidase, ribonuclease and deoxyribonuclease. Secreted as pro-enzymes. Trypsinogen is activated by
enterokinase (enteropeptidase) secreted by the intestinal mucosa and also by
trypsin. Chymotrypsinogen is activated by trypsin
_ Pancreatic amylase – hydrolyses starch and glycogen to disaccharides and
trisaccharides
_ Pancreatic lipase, cholesterol esterase and phospholipase – fat digestion
_ Also contains bicarbonate which neutralises acid chyme and trypsin inhibitor which prevents the premature activation of trypsinogen in the pancreatic ducts
_ Duodenal enzymes function optimally at a neutral or slightly alkaline pH
CONTROL OF PANCREATIC SECRETION
_ Secretion occurs during the cephalic and gastric phases of gastric secretion –
under vagal control. Results in secretion into the acini with little secretion flowing into the intestine
_ Secretin – secreted as an inactive peptide by the mucosa of the small intestine
then activated. Stimulates pancreatic secretion of copious amounts of bicarbonate by the ducts with very little enzyme secretion by the acini
_ Cholecystokinin – peptide secreted by the mucosa of the small intestine.
Stimulates secretion of digestive enzymes by the acini
_ Gastrin – secreted during gastric secretion. Stimulates enzyme secretion


BILE AND CONTROL OF GALL BLADDER SECRETION
_ Secreted by hepatocytes into bile canaliculi and conveyed through bile ducts either directly into the gut or into the gall bladder
_ Concentrated by the gall bladder
_ Contains bile salts, bilirubin, cholesterol, fatty acids, lecithin, water and electrolytes
_ Contraction of the gall bladder is stimulated by cholecystokinin and this induces
reflex relaxation of the sphincter of Oddi
_ Pregnancy is associated with an increased risk of both cholesterol and pigment
stones in the gall bladder
BILE SALTS
_ Synthesised from cholesterol
_ Converted to cholic or chenodeoxycholic acid and then conjugated with taurine or glycine to form glyco – or tauro- conjugates
_ Have an emulsifying effect on fat in the intestine – decrease surface tension
_ Play an important role in fat absorption, forming micelles which are highly soluble.
Important in the absorption of fat soluble vitamins A,D,E&K
_ 94% of bile salts entering the gut are actively absorbed in the terminal ileum and re-circulated.
SMALL INTESTINAL SECRETION
_ Brunner’s glands – located in the proximal duodenum. Secrete mucus which
protects the duodenum from acidic chyme. Mucus secretion is inhibited by
sympathetic stimulation
_ The entire small intestine contains crypts of Leiberkuhn which produce ~1.8l of
secretion per day + mucus
_ Contain digestive enzymes – peptidases; sucrase, maltase, isomaltase & lactase; lipase

Cardiovascular Physiology
CARDIAC MUSCLE
_ Striated muscle
_ Contains both actin and myosin with overlapping fibrils similar to skeletal muscle
_ Mononucleated cells – connected to other cells in series at intercalated discs. The electrical resistance at the intercalated discs is 1/400 that through the rest of the cell membrane. Action potential therefore is readily transmitted across intercalated discs.
The muscle mass forms a functional syncytium.
_ Have T-tubules similar to skeletal muscle and sarcoplasmic reticulum. However,require extracellular calcium influx for effective contraction
_ The atrial muscle mass is separated from the ventricular muscle mass by fibrous rings around the heart valves. Action potential is transmitted from atria to ventricles through a specialised conducting system
_ All-or-nothing principle – action potential spreads through the entire atrial or ventricular syncytium
CARDIAC ACTION POTENTIAL
_ Resting membrane potential ~-85 to -95mv
_ Initial depolarisation caused by increased sodium permeability through fast voltage gated sodium channels
_ When a notch is present, it is due to a decrease in sodium permeability and anincrease in potassium permeability (K moves out of the cell)
_ The plateau is due to the balance between K permeability (outwards) and calcium influx through the slow L-type calcium channels
_ Repolarisation is caused by increased potassium efflux and a decrease in calcium influx
_ There is an absolute and a relative refractory period. The refractory period for atrial muscle is shorter than for ventricular muscle
CARDIAC CYCLE
_ Systole – ventricular contraction; Diastole – ventricular relaxation
_ Atrial contraction occurs during Diastole
_ P wave – atrial depolarisation
_ QRS complex – ventricular depolarisation
_ T wave – ventricular repolarisation – occurs just before the end of ventricular contraction
_ Atrial pressure a wave – atrial contraction
_ Atrial pressure c wave – ventricular contraction
_ Atrial pressure v wave – venous return while A-V valve is closed
_ Aortic pressure wave – notch is caused by closure of the aortic valve
_ First heart sound – closure of the A-V valves; second heart sound – closure of the aortic and pulmonary valves
_ End diastolic volume – volume of blood in ventricle at the end of ventricular filling
_ End systolic volume – volume of blood in ventricle at the end of ventricular
contraction
_ Stroke volume – end diastolic volume minus end systolic volume
_ Ejection fraction – percentage of end-diastolic volume that is ejected per
contraction - ~ 60%
_ Cardiac output is stroke volume multiplied by heart rate. Increases in pregnancy
_ Blood flows continuously into the atria and most of this flows directly into theventricles without atrial contraction. Atrial contraction adds a further 20-30% to ventricular filling
_ Ventricular pressure must rise above 80mmHg to open the aortic valves. The period of ventricular contraction before the aortic valves open is the period of isometric / isovolaemic contraction
_ Over 70% of ventricular output is ejected during the first third of the period of ejection which is called the period of rapid ejection
THE NORMAL ELECTROCARDIOGRAM
_ P wave – atrial depolarisation
_ QRS complex – ventricular depolarisation. The Q wave is frequently absent
_ T-wave – ventricular repolarisation
_ PQ (PR) interval - ~0.16s
_ QT interval – beginning of Q wave to end of T wave – duration of ventricularcontraction – 0.35s
_ Heart rate can be determined from the interval between successive QRS complexes – 0.83s, giving a heart rate of 60/0.83 or 72/ minute
CONDUCTING SYSTEM OF THE HEART
_ SINOATRIAL NODE – natural pacemaker
_ Resting membrane potential is less negative (-55 to -60mv) than ordinary cardiac muscle (-85 to -95mv). As a result, the fast voltage gated sodium channels are inactivated
_ The SA node is leaky to sodium and this causes a gradual rise in membrane potential until it reaches the threshold at which point an action potential is generated
_ Depolarisation is caused by activation of slow calcium-sodium channels
_ Repolarisation is caused by increased potassium permeability and inactivation of slow calcium-sodium channels
_ The SA node has a spontaneous rhythmic rate of 70-80 per minute
_ Impulses spread from the SA node to the left atrium through the anterior inter-atrial band
_ Impulses spread from the SA to the AV node through anterior, middle and posterior internodal pathways
_ There is a delay in the cardiac impulse at the AV junction and the AV node – this ensures that the atria contract before the ventricles. The AV node has a longer refractory period than ordinary cardiac muscle and an intrinsic rhythmic rate of 40-60 per minute
_ The Purkinje fibres transmit impulses to the ventricular myocardium. The intrinsic rhythmic rate of Purkinje fibres is 15-40 per minute
_ Parasympathetic (Vagal) stimulation decreases the rate of the rhythm of the SA node and the excitability of the AV node and AV junctional fibres
_ Sympathetic stimulation increases the rate of the rhythm of the SA node, the excitability of the AV node and AV junctional fibres and the strength of myocardial contraction

CONTROL OF CARDIAC OUTPUT
_ INTRINSIC REGULATION – FRANK-STARLING LAW: The greater the heart is filled during diastole, the greater will be the quantity of blood pumped into the aorta – due to response of myocardium to stretch. Venous return is the most important regulator of cardiac output
_ Variation in systolic arterial pressure over 120-170mmHg does not significantly alter cardiac output
_ Stretch of right atrium results in increased heart rate and increased cardiac output
_ EXTRINSIC REGULATION – sympathetic stimulation increases while parasympathetic stimulation decreases cardiac output – effect on both heart rate and contractility
_ Cardiac output in males is ~5.6L/min and ~5L/min in females. Cardiac output increases with increasing body surface area and the cardiac index is the cardiac output per square meter of body surface area = 3L/min /sq meter. Cardiac index increases with age to a peak at the age of ~10 years then falls with increasing age
_ Cardiac output is decreased with a fall in blood volume, acute venous dilatation, venous obstruction (compression of inferior vena cava by pregnant uterus).
VENOUS RETURN
_ Gravity causes venous pooling and reduces venous return
_ The activity of lower limb muscles and the presence of venous valves creates a pump mechanism moving blood into the right atrium
_ Venous return is increased during inspiration (negative pressure in chest) and decreased during expiration
RESISTANCE TO BLOOD FLOW
_ Calculated from Poiseuille’s law
_ Proportional to the length of the vessel and the viscosity of blood
_ Inversely proportional to the fourth power of the radius of the vessel
_ Greater if vessels are arranged in series – total resistance = sum of resistance of individual vessels. In an arrangement in parallel: 1/total resistance = 1/R1 + 1/R2 + 1/R3…
MEAN ARTERIAL PRESSURE
_ Average arterial pressure over a cardiac cycle
_ Calculated from diastolic pressure + 1/3(Pulse pressure)
_ Pulse pressure = systolic minus diastolic pressure
_ Arterial pressure = cardiac output X total peripheral resistance
SHORT TERM BLOOD PRESSURE REGULATION
_ Baroreceptor reflex
_ Chemoreceptor reflex
_ Response of the vasomotor centres to ischaemia
_ Peripheral vasoconstriction – stress-relaxation properties of arterioles and activation of the sympathetic nervous system
The above mechanisms are activated within seconds
_ Capillary fluid shifts
_ Activation of the renin-angiotensin pathway
_ Vasopressin vasoconstrictor mechanism
The above mechanisms are activated within minutes
Fluid retention by the kidneys is activated over several hours – days.
BARORECEPTORS
_ Located in the walls of all major arteries, but mainly in the carotid and aortic sinuses. Reflex is initiated by stretch receptors
_ Not stimulated at pressures below 60mmHg. Respond most effectively to changes in arterial pressure around normal and are maximally stimulated at pressures 180mmHg
_ Impulses are transmitted to the tractus solitarius of the medulla oblongata and cause activation of vagal centres and inhibition of vasoconstrictor centres. Net result is peripheral vasodilatation and decreased heart rate and myocardial contractility
_ Not important in the long-term regulation of blood pressure as they adapt over 1-2 days to whatever pressure they are exposed to
_ The pulmonary circulation has low pressure barareceptors which are necessary for the full expression of blood pressure regulation
CHEMORECEPTORS
_ Located in the carotid body at the bifurcation of the common carotid artery, and the aortic bodies adjacent to the aorta
_ Have a rich arterial supply and are sensitive to the O2 and CO2 tensions as well as pH
_ Reflexes cause vasoconstriction
_ More important in the regulation of respiration
_ There are other chemosensitive centres in the Medulla which respond mainly to CO2 and pH. This response can cause extensive vasoconstriction and rise in blood pressure. Prolonged severe hypoxia has a depressant effect on response.
LOCAL CONTROL OF BLOOD FLOW
_ Bradykinin – formed from alpha2-globulins and causes vasodilatation and increased capillary permeability
_ Histamine – released from mast cells during tissue damage, cause vasodilatation and increased capillary permeability
_ Prostaglandins – can cause vasoconstriction or vasodilatation
_ Serotonin – released from chromaffin tissue in the gut and can cause either vasodilatation or vasoconstriction
_ Hypoxia, increased CO2 and decreased pH cause vasodilatation
_ Calcium stimulates while magnesium and potassium inhibit smooth muscle
_ Increased Na causes vasodilatation through the effect of increased osmolarity

RESTING POTENTIAL
_ Most important factor in setting the resting potential is the Na / K pump
_ The diffusion of potassium (out) and sodium (into) the cell also affects resting
potential. Membranes are more permeable to potassium than sodium therefore
potassium diffusion contributes more
_ The presence of impermeant anions such as chloride within the cell
_ The resting membrane potential of large skeletal muscle fibres and nerves is -
90mv
ACTION POTENTIAL
_ Rapid changes in membrane potential
_ Resting cell is POLARISED, with a resting membrane potential of ~-90mv
_ DEPOLARISATION – due to increased sodium permeability and activation of
voltage gated sodium channels. The membrane potential must rise above a
threshold for stimulation for an action potential to be generated. The membrane
potential, however, does not necessarily have to become positive. Once generated, the action potential spreads throughout the membrane (all or nothing principle) maintaining the same shape and size
_ RE-POLARISATION is due to increased potassium permeability and activation of voltage gated potassium channels in addition to inactivation of the voltage gated sodium channels
_ The action potential of cardiac muscle shows a plateau due to activation of slow voltage gated calcium-sodium channels
_ The speed of conduction of action potentials is proportional to the fibre diameter in myelinated fibres and proportional to the square root of fibre diameter in unmyelinated fibres
_ In myelinated fibres, conduction of action potential is SALTATORY – jumping from one node of Ranvier to the next – myelination dramatically increases the conduction velocity of an axon
_ Following an action potential, there is an absolute refractory period during which another action potential cannot be generated (voltage gated sodium channels cannot open) and a relative refractory period during which a stronger stimulus is required