Physiology Flashcards
What is stroke volume
Volume of blood ejected by each ventricle during each heart beat
Equation of stroke volume
SV = End diastolic volume - end systolic volume
What is end diastolic volume
The volume of blood in each ventricle after diastole, before ventricular systole
What is end systolic volume
Volume of blood left in each ventricle after ventricular systole
What is cardiac output
Volume of blood pumped out of ventricles per minute
Equation for cardiac output
CO = SV x HR
What is Frank Starling’s law
the more blood is filled in each ventricle at the end of diastole, the more blood will be ejected during systole
What is preload
Diastolic stretch of myocardial fibres
What is afterload
The resistance that the heart needs to pump against to pump blood through
How does Frank Starling’s mechanism partially compensate for increase in afterload
Increase in afterload causes not all stroke volume pumped out
so increase in EDV for next cardiac cycle
increase in EDV then causes increase in stroke volume
How is venous return related to EDV, preload and SV
Increase in venous return stimulates diastolic stretch (increase in preload)
This increases EDV hence increases SV
What is positive chronotropic effect
Increase in heart rate
What is positive inotropic effect
Increase in force of contraction and contractility
What is positive dromotropic effect
Increase conduction velocity through AV node
What is positive lusitropic effect
Decrease in duration of systole
Cause of positive lusitropic effect
Increase in rate of Ca2+ reuptake into the SR
Causes of positive chronotropic effect
Increase in slope of phase 4 (pacemaker potential)
Decrease in threshold
How does slope of pacemaker potential increase
Increase in INa and ICa,L - more Na+ and Ca2+ moving in so depolarises and reaches threshold quicker
How does positive inotropic effect occur
L type Ca2+ channels open with more probability
Increase in sensitization of contractile proteins to Ca2+
PKA phosphorylates phospholamban which activates SERCA so Ca2+ reuptake into SR is quicker (quicker relaxation -> ready to contract sooner)
Effect of sympathetic stimulation on the heart
\+ chronotropic \+ inotropic \+ lusitropic \+ dromotropic increase in automaticity increase in activity of Na+/K+ ATPase
What type of cells do sympathetic nerves supply in the heart
Nodal cells
Myocardial cells
What type of cells do parasympathetic nerves supply in the heart
Nodal cells
Atrial myocardial cells (not ventricles)
Mechanism of parasympathetic stimulation
- ACh binds to muscarinic receptors (M2) on nodal cells
- This activates Gi complex and causes it to dissociate into alpha and beta+gamma subunits
- alpha subunit inhibits adenylyl cyclase -> reduce cGMP -> reduce cellular responses
- beta+gamma subunit opens GIRKs
What are GIRKs
G protein coupled inward rectifier K+ channels
Effects of parasympathetic stimulation on heart
Negative chronotropic effect
Negative dromotropic effect
Negative inotropic effect (only in atria)
Describe the phases of nodal action potential
Phase 4 (pacemaker potential) - Na+ influx through HCN and Ca2+ influx through voltage gated Ca2+ channels. This causes slow depolarisation of the membrane, reaching threshold (-40mV)
Phase 0 - L type Ca2+ open, causing fast depolarisation
Phase 3 - repolarisation; K+ channels open, L type Ca2+ channels close
HCN channels will open once membrane potential is lower than -50mV
What are HCN channels
Allows Na+ influx during phase 4 of nodal action potential
List the ion channels involved in each phase of nodal action potential
Phase 4 - HCN and voltage gated Ca2+ channels
Phase 0 - L type Ca2+ channels
Phase 3 - K+ channels
Definition of automaticity
Heart being able to beat rhythmically without any external stimuli due to regular, spontaenous generation of electrical activities
How do electrical excitation spread from SA node to AV node
Mostly cell to cell conduction
some internodal routes
How do electrical excitation spread from AV node to ventricles
Bundle of His -> Purkynje fibres -> cell to cell conduction throughout ventricular myocytes
What is cell to cell conduction
Electrical excitation spreads between adjacent cells via gap junctions
What are gap junctions
Low resistance electrical communication pathways
What are desmosomes
Intercellular cell junctions that provides adhesion between cardiac cells
Why does AV node have slower conduction
So atrial systole occurs before ventricular systole
What is vagal tone
Continuous vagal influence on heart rate under normal conditions to produce normal heart rate
Normal heart rate range
60 - 100bpm
Type of beta adrenoceptors in nodal and myocardial cells
beta 1
Type of muscarinic receptor in nodal cells
M2
Describe the phases of action potential in myocardial cells
Phase 4
- voltage gated Na+ and L type Ca2+ channels are closed
- NCXR transports 3Na+ in for 1 Ca2+ out
- K+ channels are open, allowing K+ efflux
Phase 0
- nodal action potential reaches the myocyte to trigger this
- fast depolarisation
- K+ channels close
- voltage gated Na+ channels open
Phase 1
- early repolarisation
- Na+ channels close
- L type Ca2+ channels begin to open
- transient K+ channels open
Phase 2
- plateau phase
- efflux of K+ via rectifier channel = influx of Ca2+
Phase 3
- repolarisation
- L type Ca2+ channel close while K+ remains open
Phases that represent the refractory period of action potential of myocardial cells
phase 1 to 3
Na+ channels cannot open during this period
Why do myocardial cells have long refractory period
to prevent tetanic contractions
When do myocardial cells contract
Phase 1 to 2
When L type Ca2+ channels are open, it causes CICR from SR
Why do myocardial cells stop contraction in phase 3
1) L type Ca2+ channels close so no CICR
2) Ca2+ actively transported back into SR
3) Ca2+ actively transported out of the cell via NCXR using 3Na+ gradient
= no intracellular Ca2+
How does Ca2+ cause smooth muscle constriction
- Ca2+ binds to CaM to form Ca2+ - CaM
- Ca2+ - CaM activates myosin LCK
- myosin LCK phosphorylates myosin LC into myosin LC + phosphate
- myosin LC + phosphate causes muscle contraction
Equation for ejection fraction
Stroke volume / end diastolic volume
How do non polar lipids travel in blood
In lipoproteins
Examples of non polar lipids
Cholesterol
Triacylglyceride
Esters
Examples of lipoproteins
Chylomicron
VLDL
HDL
LDL
What does the outer layer of lipoproteins contain
Cholesterol
Apoprotein
Phospholipids
Function of apoprotein
Signaling molecules recognized by the liver receptors, allow lipoproteins to bind
What apoproteins do HDL have
apoA-I and apoA-II
What apoproteins does VLDL have
apoB-100
apoB-48 is the aporpotein of
chylomicron
What is the feature of chylomicron
Highest proportion of TAGs
What does the core of apoproteins contain
cholesteryl ester
triacylglycerols
What is the feature of VLDL
Highest proportion of cholesterol
What are lipids used for
Energy source
Membrane biogenesis
Precursors for hormones and signaling molecules
Where are chylomicrons and VLDL metabolised
Muscle cells and adipocytes
Where are chylomicrons made
Enterocytes
Where are VLDL made
hepatocytes
Formation of TAGs and cholesteryl ester
1) pancreatic lipase hydrolyses TAG into monoglycerides and fatty acids
2) Monoglycerides and fatty acids diffuse into enterocytes by simple diffusion
3) cholesterol from diet enters enterocytes via NPC1L-1
4) Monoglycerides and fatty acids are resynthesized to TAG in SER
5) cholesterol is esterified into cholesteryl ester with a free fatty acid
Where is cholesterol obtained
Diet
Formed by liver using HMG-CoA reductase
Where does the formation of chylomicrons occur
RER
Formation of chylomicron
1) apoB-48 is moved into RER by MTP
2) TAG and phospholipid added to apoB-48 to form primordial chylomicron
3) more TAG added by MTP
4) cholesteryl ester also added, chylomicron formed
How are chylomicrons released
1) chylomicron move from RER to golgi apparatus
2) apoA-I is added to chylomicron
3) chylomicron is then released into lymphatic system by exocytosis
How does the content of lymphatic system drain into systemic circulation
By thoracic duct draining into subclavian vein
Metabolism of chylomicrons and VLDL
1) ApoC-II from HDL is added to VLDL and chylomicrons
2) VLDL and chylomicrons bind to lipoprotein lipase
3) lipoprotein lipase hydrolyzes the TAGs in core
4) TAGs depleted, forming chylomicron and VLDL remnants
Feature of chylomicron and VLDL remnants
They are enriched with cholesteryl ester due to depletion of TAG
Formation of LDL
1) apoC-II is transferred back to HDL in exchange for apoE
2) remnants are transported back to liver to be further metabolised by hepatic lipase
3) all chylomicron and 50% of VLDL are cleared
4) the remaining 50% of VLDL lose more TAG and more enriched with cholesteryl ester
5) eventually, VLDL loses apoE and forms LDL
Where are remnants of chylomicron and VLDL metabolised
Liver
Where does LDL clearance occur
liver
How are LDL cleared
1) LDL binds to LDL receptors on cells hence moved in by endocytosis
2) forms lysosome
3) LDL receptors are recycled back onto surface
4) cholesteryl ester in LDL hydrolysed in lysosome
5) cholesterol is released
Effects of release of cholesterol
Inhibits HMG CoA reductase = stops synthesis of cholesterol
Downregulates LDL receptors
Uses of cholesterol
To form bile
Stored as cholesteryl ester
What is the normal stroke volume
50-100ml
