PPoP Flashcards
What are the fractions of blood?
Plasma - 50%
Haematocrit - 40-45%
White blood cells & platelets - 1-5%
What are the sites of haematopoesis?
In foetus:
spleen, bone marrow, liver, yolk sac, lymph nodes
In adults:
bone marrow and lymph nodes
What are the features of red blood cells?
Biconcave
no nucleus, golgi body or mitochondria
120 day life span
What are the precursors of RBCs?
Normoblast in bone marrow
nucleus removed and moves to blood = reticulocyte
reticulocyte matures and loses organelles
What are some features of platelets?
produced in bone marrow from megakaryocytes discoid anuclear 8-12 day life span increase surface area when activated
What are some features of megakaryocytes?
giant cells
large irregular nucleus
What are some features of neutrophils
most common, make up 60% of leukocytes
polymorphonuclear
rapidly respond to chemotactic substances
first cell type recruited to inflammation sites
What are some features of eosinophils
rare pholymorphonucleus involved in parasite healing can live several days cytotoxic secretory substances
What are some features of monocytes?
mononuclear
highly phagocytic and motile
mature into macrophages
What is the process leading to platelet plug formation?
Damage to blood vessel -> platelets exposed to collagen, vWF and thrombin -> platelets adhere and activate -> release mediators -> vasoconstriction and aggregation of platelets -> soft platelet plug formation
What are the 3 stages of clotting?
initiation, amplification and propagation
What activates initiation of clotting
Tissue factor expressed on cells
What activates amplification and propagation of clotting?
Thrombin (FIIa) on activated platelets
What cofactors are required for initation clotting?
calcium ions and phospholipid
What are the features of a plaque
fibrous cap and lipid rich core
What are the features of an arterial plaque?
white
platelets are the major component
treated with anti-platelet drugs
caused by MI and stroke
What are the features of a venous plaque?
red
fibrin and RBCs are major component
treated with anti-coagulants
caused by trauma and surgery
What are the 3 components of Virchow’s triad?
blood flow
endothelial injury
hypercoagulability of blood
What are the 3 types of anti-platelet drugs?
Aspirin - COX inhibition -> no TXA2 production
P2Y12 antagonists -> receptor on platelet for aggregation
GPIs -> compete with fibrinogen and vWF
What is the main anticoagulant drug?
Heparin
- inhibits factors in clotting pathway
- for prevention and rapid treatment
What are the pros and cons of unfractioned heparin
Pros:
cheap, effective, short half life
Cons:
variable bioavailability, risk of HIT and haemorrhage
What are the pros and cons of low molecular weight heparin (LMWH)?
Pros:
- increased bioavailability and half life
- less risk of HIT
Cons:
- expensive
- risk of haemorrhage
What is heparin induced thrombocytopenia (HIT)?
When heparin binds to PF4 and an antibody is produced
2nd exposure of heparin leads to immune-mediated platelet activation
What is pharmacodynamics?
The actions of a drug on the body
What is pharmacokinetics?
The actions of an organism on a drug
Includes absorption, distribution, metabolism and excretion
What are the 3 types of names a drug is given?
Proprietary (brand), common and chemical names
What is Emax?
the maximum effect of a drug (max heigh of log dose-response graph)
What is LogEC50?
The concentration of a drug that gives 50% of the maximum response
- value on x axis at 50% of y axis
What is KD?
The molar concentration of a drug needed to occupy 50% of receptors at equilibrium
measures affinity of a drug - high KD = low affinity
What do agonists need to be effective?
affinity and efficacy
What is the difference between full and partial agonists?
full agonists have high efficacy, partial agonists have low efficacy
What are the properties of reversible antagonists?
affinity but no efficacy
surmountable (effects can be overcome)
shifts dose-response graph to the right
What is pA2?
affinity of an agonist (extent of shift in curve)
-log[antagonist] that requires 2x[agonist] to get the same response
`What is a key properties of irreversible antagonists?
The effects are not summountable
What type of kinetics are most drugs?
first order kinetics
how do you calculate the half life of drugs?
Ln(A0) / K
A0 = initial concentration K = elimination rate constant
How do you calculate the volume of distribution?
Dose A/AO
What limits clearance of drugs?
organ blood flow
How do you calculate clearance?
Cl = K x Vd
or
Cl = dose/AUC
How do you calculate hepatic clearance?
liver blood flow (Q) x extraction ration (Eh)
How do you calculate bioavailability (F) ?
For IV = 100%
For oral administraton = AUC (oral)/ AUC (IV)
What is the funny current?
mixed Na+ and K+ current in pacemaker cells
causes unstable resting membrane potential
triggers contraction
Which ion channels are involved in pacemaker cell contraction?
Ca2+ influx -> K+ loss -> If triggers next contraction
What ion channels are involved in cardiac cell contraction?
Fast Na+ influx -> Ca2+ entry through L-type channels -> K+ lost
What are the 7 stages of the cardiac cycle?
- atrial systole
- isovolumetric ventricular systole
- ventricular ejection
- reduced ventricular contraction
- isovolumetric ventricular relaxation
- rapid ventricular filling
- reduced ventricular filling
What 3 factor regulate cardiac pumping?
preload
afterload
autonomic nervous system (SNS increases, PNS decreases)
What is preload?
End diastolic pressure
stretch in ventricles prior to contraction
What is afterload?
The resistance the heart needs to overcome to eject blood into the systemic circulation
Why does pulmonary circulation have low resistance?
the arteries are short and wide
allows low pulmonary artery pressure generated by the RV
What is pulse pressure?
systolic-diastolic
How do you calculate mean arterial pressure?
MAP = diastolic + (systolic - diastolic)/3
how is change in pressure calculated?
CO x TPR
What are some features of the venous system?
Low resistance
skeletal muscle pump
respiratory pump
What factors can change CVP?
blood volume
venous constriction
posture/orthostasis
How do you calculate stroke work from a pressure-volume loop?
area inside the loop
How do you calculate stroke volume from a pressure-volume loop?
End-diastolic volume - end-systolic volume
max vol on graph - min volume on graph
What are the features of the jugular venous pressure wave?
biphasic
low pressure
affected by bulging, stenosis and regurgitation of tricuspid valve
What are the components of the jugular venous wave?
a wave = atrial contraction c wave = carotid pulse x descent = atrial relaxation v wave = atrial filling y descent = passive atrial emptying
What are the features of the peripheral arterial pressure wave?
Monophasic
influenced by reflected waves, compliance, resonance, interference and damping
How is CVP measured?
From the internal jugular vein pulse
- needs to be at 45 degrees to see pulse and avoid collapse
- measures height of pulse above the manubriosternal angle
Why is the internal rather than external jugular vein used to measure CVP?
closer to RA
valveless
visible
external is superficial and prone to kinks
How does the shape of the JVP wave change in tricuspid stenosis?
A wave is enhanced
V wave is diminished
How does the shape of the JVP wave change in tricuspid regurgitation
A wave is diminished
V wave is enhanced
What are the features of the arterial pressure pulse wave?
- big pulse followed by a reflected wave
- elastic in arteries maintains pressure
- shape is affected by aging, hypertnesion, drugs etc
What are the primary heart sounds?
s1 = AV valve closure s2 = semilunar valve closure
What are the additional heart sounds?
s3 = av valve opening s4 = atrial systole
What is gallop rhythm and when is it heard?
When additional heart sounds are heard
occurs when end-diastolic pressure is raised
What are murmurs?
Sounds heard due to turbulence of blood
occur in valve stenosis or regurgitation
What kind of murmur is heard in mitral stenosis?
diastolic
what kind of murmur is heard in aortic incompetence?
early diastolic murmur
what kind of murmur is heard in aortic stenosis?
systolic murmur
what kind of murmur is heard in mitral incompetence?
pan systolic lush
When is jugular venous pressure considered pathological?
if it is more than 3cm above the manubriosternal angle
Why is jugular venous pressure important?
indicates right atrium pressure
can indicate cardiac or pulmonary disease
e.g. congestive heart failure or pulmonary embolism
What determines preload?
central venous pressure (CVP)
- vasconstriction (e.g. excercise) increases
- blood loss decreases
What factors influence afterload?
TPR and aortic stiffness
what are the 4 factors that directly influence Cardiac output?
- afterload
- preload
- contractility
- heart rate
What is Starling’s law?
Stroke volume increases with volume due to stretch
Why is cardiac muscle more sensitive to starling’s law than skeletal?
It becomes more sensitive to calcium with stretch
- steeper graph
What are the consequences of starling’s law?
- stroke volume of LV and RV are matched
- CVP (and therefore preload) determines CO
- CO is maintained in increased afterload or decreased contractility
What happens to the frank-starling curve in heart failure?
becomes lower
- decreased bp -> less water and salt excretion -> increased blood volume
- activation of SNS and RAAS increase HR = compensated heart failure
What is the effect of afterload on `CO
No real effect, as it causes a reduction in stroke volume, but this is overcome by secondary effects:
- increased blood in heart = increased SV (frank-starling)
- ANREP effect
- depression of CO by barroceptor reflex
What is the main regulator of contractility?
intracellular calcium concentration
What is the effect of the ANS on the funny current?
SNS increases If to increase heart rate
PNS decreases current
What are the features of a cardiac action potential?
long duration long refractory period short relative refractory period RMP is very permeable to K+ AP duration changes with HR
How are SAN cells adapted for pacemaker activity?
lots of membrane and little cytoplasm
What are the 2 theories for the unstable RMP in cardiac pacemaker cells?
- membrane clock (funny current)
- calcium clock (cyclic release of Ca2+ from intracellular stores)
What allows fast ventricular conduction?
interdigitated junctions (fast along fibre, slower across fibre as less connexons)
What direction is the cardiac dipole in?
depolarisation spreads from base (top right) to apex (bottom left) of the heart
What are the 2 electrodes in ecg called?
Recording and reference
What are the 3 standard limb leads?
limb lead I - LA-RA
limb lead II - LF-RA
limb lead III - LF-LA
Which limb lead gives the standard ECG?
limb lead II
What do the different stages of the ECG indicate?
p = atrial depolarisation q = septum depolarisation r = depolarisation of ventricles towards apex s = depolarisation of ventricles towards atria t = ventricle repolarisation
What happens during the P-Q interval, and name a pathology this affects?
atrial conduction & AV delay
AV block
What happens during the QRS interval, and name a pathology this affects?
ventricular conduction
bundle branch block
What happens during the S-T interval, and name a pathology this affects?
ventricle depolarisation
myocardial infarction
What happens during the Q-T interval, and name a pathology this affects?
action potential duration
long QT syndrome
What is excitation-contraction coupling?
- in contraction of cardiac cells
- action potential opens L-type calcium channels in membrane -> rise in Ca2+
- Ca2+ bind RyR receptors on sarcoplasmic reticulum to induce more calcium release
How does relaxation occur in cardiac myocytes?
SERCA takes Ca2+ up into SR
Na+/Ca2+ exchanger on membrane removes Ca from cell
What do chronotropic agents affect?
heart rate
what do inotropic agents affect?
strength of contraction
what do lusitropic agents affect?
rate of relaxation
what are some chronotropic agents?
Positive = SNS e.g. adrenaline and noradrenaline Negative = PNS e.g. Ach
what is vascular tone?
balance between constriction and dilation
what are some constricting factors?
noradrenaline (main), angiotensin II, adrenaline
what is the myogenic response?
increased pressure causes vasoconstriction
What factors cause dilation?
NO and EDH released from endothelial cells
How does oxidative stress affect endothelial function of blood vessels?
superoxide binds NO, preventing it from mediating dilation
What are the 2 main types of vasodilation?
No-mediated and hyperpolarisation
what is autoregulation of blood vessels?
constant maintenance of blood flow to important vascular beds over a wide range of pressures
What is the main mediator of autoregulation?
myogenic resposne
What is the effect of tissue metabolites on vasculature?
cause vasodilation
what is metabolic hyperaemia?
increased metabolism in excercise, get build up of metabolites causing vasodilation
increases blood flow
what is reactive hyperaemia
cutting off local blood flow e.g. in isometric exercise
metabolites accumulate to cause vasodilation
what types of endothelium are in capillaries?
continuous
fenestrated (kidneys, joints, intestinal mucosa)
sinusoidal (liver, bone marrow, spleen)
What are the pressure gradients driving fluid movement in capillaries?
hydrostatic pressure and osmotic pressure
What are the units between valves in lymphatics called?
lymphangion
what is the baroreceptor reflex
rapidly limits changes to blood pressure
where are the baroreceptors?
carotid sinus and aortic arch
what regulates long term control of blood pressure?
blood volume
- mainly determine salt intake
what is pressure natriuresis?
when high blood pressure increases perfusion to kidneys, so there is increased Na+ excretion
What stimulates the RAAS system?
decreased blood volume, Na+ conc or blood pressure
What is the neurogenic model of BP control?
that the SNS can contribute to long term control of BP as well as the kidneys
Permeability of which ion determines the resting membrane potential in the heart?
potassium
does a positive charge moving into a cell generate an inward or outward current?
inward
does a negative charge moving into a cell generate an inward or outward current?
outward
why is the ventricular action potential long?
to prevent tetany and arrhythmias
What formula is used to calucate a corrected QT interval and normalise the AP duration?
Bazett or Fredericia’s formula
What is the bradycardic agent that blocks the funny current?
Ivabradine
What are the common forms of connexons in the heart?
connexin 43
connexin 45
connexin 40
What does anisotropic mean?
a substance that has different properties when measured in different directions
- e.g. in heart fibre orientation
list the major E-C coupling proteins phosphorylated by PKA?
L-type Ca channels RyRs PLB PLB Myofilament proteins (troponin I and myosin binding protein C).
