CVR week 1: Flashcards
valves- name and location?
R atrium to R venticle- tricuspid valve
L atrium to L venrticle- mitral valve
L ventricle to aorta- aortic valve
R ventricle to pulmonary artery- pulmonary valve
describe constituents of plasma?
- plasma 55% of total blood :
- 90% water (solvent)
- 7-8% proteins e.g. albumin (blood volume), globulins (immune function), fibrinogen (blood clotting)
- electrolytes: sodium, potassium, calcium etc.
- nutrients: glucose, fatty acid, amino acid
- gases: oxygen and carbon dioxide)
describe functions of the blood plasma?
- transport nutrients
- carries hormones and other signalling molcules
- maintains blood pressure and volume
- functional proteins e.g. antibodies, complement and clotting factors
- temp and pH
what is normal oncotic pressure value?
30-50g/L
role of plasma in heat regulation?
plasma acts as a heat sink, circulating plasma removes excess heat from ‘hot’ organs and circulates heat to extremities, becomes the fluid for sweat
how does plasma act as a pH regualtor?
proteins act as H+ buffer through binding to amino acid side chain
role of plasma in inflammation and immunity?
- contains and circulates immune cells and proteins produced by these
- contains specialsied proteins that contribute to inflammatory response- complement system
How is complement activated?
3 different ways:
- classical: trigger by antibodies on pathogens
- alternative: activated directly by pathogens or damaged cells
- lectin pathway: initiated by specific sugars on microbe surfaces
Function of complement?
Opsonization/phagocytosis: complex bound to antigen antibody complex or on surface of pathogen activates phagocycotic cells.
Cell Lysis: Directly attacking and rupturing pathogen cell membranes through the formation of the membrane attack complex (MAC)
Inflammation: Complement proteins stimulate inflammation by attracting immune cells to the site of infection or injury
Aid production of antibodies: B cells have complement receptors and bind causing B cell to secrete more antibodies 9amplifies antibody production)
syntheis of plasma proteins- where does it occur?
produced in liver - liver disease levels of these are low leading to swelling, infection and bledding
Coagulation cascade - intrinsic pathway:
activated by damage to endothelial lining, slow and complex:
factor XII is activated by exposed collagen or other damage.
Activated Factor XIIa activates Factor XI
Factor XIa activates Factor IX, which, together with Factor VIIIa, activates Factor X in the common pathway.
Coagulation cascade - extrinsic pathway:
Triggered by external trauma that causes blood to escape from the vessel (e.g., tissue injury),
Faster than the intrinsic pathway
Key steps:
Tissue Factor (TF) is released from damaged tissue
TF combines with Factor VIIa, activating Factor X in the common pathway
Coagulation cascade: common pathway
Activated Factor X (Xa), with Factor Va, converts prothrombin (Factor II) to thrombin (Factor IIa)
Thrombin converts fibrinogen (Factor I) into fibrin, which forms a mesh that strengthens the platelet plug
Thrombin also activates Factor XIII, which cross-links fibrin to form a stable clot
How is the coagulation cascade regulated?
- antithrombin III (Inhibits thrombin and Factors IXa, Xa, XIa, and XIIa)
- Protein C and S (inactivate Va and VIIIa)
- Tissue Factor Pathway inhibitor (TFPI) (blocks tissue factor VIIa complex formation in extrinsic pathway)
Fibrinolysis:
purpose?
how it happens?
- breakdown of fibrin by proteolytic enzymes, example of use is given as a drug during stroke
- plasminogen converted to plasmin (by XIa, XIIa, Kallikrein and Tissue plasminogen activator) which breaks down fibrin
Platelets - what they are? role? lifespan? avg platelet count?
fragments of megakaryocytes found in bone marrow, aid blood clot and wound healing, lifespan of 7-10 days, ranges from 150,000 to 450,000 per microlitre of blood.
platelet function-
Function:
- adhere at site of injory to form plug
- release chmicals to attract more platelest and coagulation factors
- stabalize clot
- relase growth factors to repair tissue
- recruit leucocytes and release pro-inflammatory mediators
platelet activation? physical change that occurs after?
- activated by expose to collagen which they adhere to and release chemical signal to activate more platelts
- undergo shape change to stellate (spiky) to increase SA and form plug to stop bleeding
haemocrit- what is it? percentage of blood volume?
part of blood that’s erythrocytes- 45%
feature of erythrocyte
biconcave shape, lacks nucleus(more haemoglobin), flexible to move through capillaries, 10 micrometers
features of haemoglobin
- each molecule can carry 4 oxygen molecules
- 2 alpha, 2 beta subunits
- porphyrin ring with iron make up heme group (4 in 1 molecule)
what would cause a left shift in oxygen disocation curve? what about right?
Shift to left: (increased affinity)
- decrease temp, decrease 2,3-DPG, decrease H+, CO , feotal haemoglobin, myoglobin(very large shift left), lungs
Shift right (Bohr Shift): (decreased affinity)
- increased temperature, increase 2,3-DPG, increase H+, respiring tissues
What is 2,3-DPG? What does it do? How is it produced?
2,3-diphosphoglycerate:
- produced by erythrocytes during glycolysis by lumbering-rapoport pathway
- reduces affinity of haemoglobin for oxygen, promoting release of oxygen to tissues
- increased by factors associated with increase tissue oxygen demand e.g. hypoxia, anaemia, low pH
How is CO2 transported in the blood?
- CO2 binds to haemoglobin forming carbaminohaemoglobin
- CO2 converted to bicarbonate by enzyme carbonic anyhdrase in RBC
- small amount of CO2 dissolves directly in plasma
Erythropoiesis: where and reguated by what?
occurs in bone marrow, regulated by erythropoietin (produced in kidney by peritubular fibroblasts)
Erythrophagocytosis- where and what by?
at spleen and liver old rbc are removed, surface damage is detencted by macrophages which injest them
Buffer coat- what is it? percentage?
1%, white blood cells (also known as leucocytes)
Neutrophills:
amount? role? lifespan? innate or adaptive?
- most abundant, first responders
- phagocytose
- neutrophil extracellar traps (use DNA to trap pathogens)
- lifespace 5-90 hrs
- part of innate response
B lymphocytes- innate or adaptive? purpose? produced? found where?
Lymphocytes: (2nd most common)
- when activated differnetiate: plasma cell and memory cell
- adaptive immunity
- B cells: produce antibodies (immunoglobulins), produced and mature in bone marrow, migrate to lymph node system, found in germinal centres and follicles of lymph nodes
T Lymphocytes: innate or adaptive? purpose? produced? found where?
- adaptive immunity, (2nd most common WBC)
T cells: mature in thymus gland, migrate to lymphoid organ:
- Helper T cells (CD4 receptors on membrane) - Helper T cells signal cytotoxic T cells, B cells and macrophages.
- Cytotoxic T cells (CD8 receptors on membrane)- Directly kill infected or abnormal cells
- Regulatory T cells- Help suppress inappropriate immune responses
Immunoglobins/antibodies:
some examples?
function?
immunoglobulin:
- exist in different forms such as IgG and IgM
- IgG- delayed prolongued response (day8), secondary response is larger
- IgM- initial antibody produced (day4), secondary response is smaller (role in activating compliment)
- IgE- allergic reaction
- neutralisation- antibodies bind preventing them infecting cells or causing damage
- opsonisation- tag pathogens for phagocytes e.g. macrophage, neutrophill
- complement activation
- agglutination- clump pathogens together
- antibody dependent cellular cytotoxicity- triggered to destory virus and cancer cells
Monocytes
- large
- differnetiate into macrophages and dendritic cells in tissue
- phagocytose
- role in chronic inflammation e.g atherosclerosis and immune surveilance
Eosinophills
-2nd least common
- release toxic granules to kill parasites
- involved in inflammatory response e.g. asthama and allergy
Natural killer cell:
type of lymphocyte
-no activation required
- release toxic granules to kill parasites
- involved in inflammatory response e.g. asthama and allergy
Basophills- how common, cell features, role in body?
least common making up less than 1%, granulocyte, large cell with bilobed nucleus and grainy cytoplasm
release histamine during allegic reaction and inflammation
Antigen presentation: MHC I vs II
APC- antigen presenting cells:
- cells that present antigen to T cells
- include B cells but also tissue cells e.g. macrophages and dendritic cells
- MHC II involved in antigen presenting to T cells, MHC I used to recognise cell as self or non-self
what is cooperative binding?
when 1st oxygen moelcule binds there a shape change that makes it easier for more oxygen molecules to bind
lubering rapoport pathway: what does it produce, enzyme mediated by, how is this pathway affected by pH and oxygen levels
mechanism to produce 2,3-bisphosphoglycerate mediated by enzyme bisphosphoglycerate mutase (activity increased at low pH and low oxygen etc.),
Other chain of pathway procuces ATP as side product
Blood flow through different organs
liver 27%
kidneys 22%
muscle 15%
brain 14%
skin 6%
what vessel has highest blood volume?
small vein and venules have pooling of blood which can sit and act as a reserve, capacitance vessels, - skeletal muscle/respiratory pump aids return
- SNS (sympathetic nervous system) mediated vasoconstriction maintains VR/VP
arterioles
- principal state of resistance to vascular flow (control flow of blood)
- Total peripheral resistance- TPR = total arteriolar resistance
- detremined by local neural and hormonal factors
- distribute blood flow
- vascular smooth muscle controls width of radius
- VSM never completely relaxed = myogenic tone
capillaries
- large area so slow flow allowing time for nutrient/waste exchange
- flow is determined by arteriolar resistance as well as number of open pre-capillary sphincters
lymphatics:
- specific ducts to return interstitiasl fluid to CV e.g. thoracic duct, left subclavian vein
- uni-directional flow
how to calculate cardiac output?
stroke volume times heart rate
how to calculate blood pressure
cardiac output times total peripheral resistance
how to claculate mean arterial pressure?
diastolic pressure + 1/3 pulse pressure
how to calculate pulse pressure?
systolic - diastolic pressure
What is the FrankStarling mechanism?
automatic response controlling how strong heart contracts each beat
As preload (end-diastolic pressure) of sarcomeres increases, stroke volume increases.
If preload goes to high (sarcomeres are streched too far) cannot contract properly therefore decreasing stroke volume.
blood volume is an important factor of blood pressure. Things that affect blood volume:
albumin- oncotic pressure, sodium and water, renin-angiotensin-aldosterone system (RAAS), ADH/argenine vasopressin, Adrenal and kindeys
how to take blood pressure?
- blood pressure measured using sphymomanometer
- use brachial artery (convenient and roughly level of heart)
- systolic- fist tapping noise, diastolic pressure- when noise stops
Ability to regulate blood flow- Myogenic auto-regulation? which organs have bettwr control than others?
arterioles stretch and vascular smooth muscles contract (myogenic tone) in response with goal of maintaining blood flow
ability varies around the body:
renal/cerebral/coronary have tight controll
skeletal muscle/splanchnic (abdominal) have moderate controll
cutaneous have little controll
What is intrinsic controll vs extrinsic controll?
intrinsic control is the ability of an organ or tissue to regulate itself, while extrinsic control is the use of external mechanisms to regulate an organ or tissue
ability to regulate blood flow- balance of intrinsic and extrinsic controlls for different organs: brain and heart, skin and skeletal muscle ?
brain and heart- rely on instrinsic controll to maintain blood flow
skin- important in general vasoconstrictor response and also in repsonse to temp (extrinsic)
skeletal muscle- dual effect:
at rest vasoconstrictor (extrinsic) tone is dominant, when excercise intrinsic predominates
ability to regulate blood flow- local humoral factors: examples of vasodilators and vasoconstrictors
Vasocontriction:
- endothelian-1
-internal blood pressure (myogenic contraction)
Vasodilators:
-hypoxia
-adenosine
-bradykinin
-NO (L-Arg is converted into NO by No sythetase)
- K+, CO2, H+
- prostacyclin
- Tissue breakdown product
ability to regulate blood flow- Hormonal factors:
- vasoconstrictors: angiotensin II, ADH, Adrenaline (skin)
- vasodilators: adrenaline (muscle), atrial natriuretic peptide
arterial barorecptors vs cardiopulmonary baroreceptors? location, level of pressure detected,
Cardiopulmonary baroreceptors
Located within the atria, ventricles, and pulmonary vasculature and these low-pressure receptors detect changes in blood volume. They also help regulate the secretion of hormones that affect blood pressure and volume.
Arterial baroreceptors
Located in large arteries like the aorta and carotid, these high-pressure receptors respond to changes in blood pressure and cardiac cycle. They control the sympathetic drive to the heart and blood vessels.
How do baroreceptors regulate blood flow?
If blood pressure is too high the baroreceptors detect this and it’s tranmitted to the brain. There is a decrease in sympathetic pathway firing and an increase in parasympaphetic pathway firing (by vagus nerve). Increased parasympatheic firing and decreased sympathetic firing to pacemaker cells at SAN causes a decrease in heart rate. Decrease in sympathetic firing as well as decraesed angiotensin II causes vasodilation of vessels. Increased sympahetic nervous firing acts on kidneys: decreaes in renin production, causing decraese in angiotensisn II, causing decreaes in aldosterone leading to decreased Na retention and increased urine output.
Therefore reduced total peripheral resistance and decrease in blood pressure.
What affect does continued high blood pressure have on baroreceptors?
Over a period of days or weeks they will reset to a new value. In people with essential hypertension the baroreceptors behave as if the elevated blood pressure is normal and aim to maintain this high blood pressure.
How do high pressure arterial baroreceptors controll blood flow vs low pressure cardiopulnonary basoreceptors
arterial:
Stretching of the baroreceptors as a result of increased blood pressure causes an increase in the activity of the vagal nerve by projection to the nucleus ambiguus. It also causes inhibition of the sympathetic outflow and ultimately leads to decreased heart rate and blood pressure.
cardiopulmonary:
The low pressure baroreceptors are involved with the regulation of blood volume.The low pressure baroreceptors have both circulatory and renal effects, they produce changes in hormone secretion which have profound effects on the retention of salt and water and also influence intake of salt and water. The renal effects allow the receptors to change the mean pressure in the system in the long term.
effect of chemoreceptors on blood pressure:
- increase in pCO2 causes vasocontriction, increase in peripheral resistance, increase blood pressure
- low pCO2 decrease medullary tonic activity and decrease bp
- act similarly with pH
Describe the electrical activation of the cardiac myocytes. Inculde the phase, what molecules move, whether its polarisation or depolarisation?
Phase 0, initial depolarisation: voltage-gated Na channels open, large influx of Na+ into cell
Phase 1, small repolarisation: shutting of voltage gated Na+ channels, transient outward current of K+ ions leaving the cell
Phase 2, Maintain depolarisation/plateu: voltage gated calcium channels open causing calcium to enter the cell and maintain depolarised state, countered by continued transient K+ loss
Phase 3, repolarisation: calcium channels close, delayed outward K+ channel open causing repolarisaton back to resting potential
Phase 4, maintaining resting potential: Na/K ATPase moves 3 Na+ out cell, 2 K+ into cell. Na leak channels passively move very small na+ into cell (1:100). K+ leak channels allow large amounts of K+ to diffuse out the cell (down conc gradient)
where in heart in action potential initiated? how does this action potential travel to and across cardiac myocytes?
action potential triggerd by pacemaker cell in SAN, action potential passes to other cells by movemnt of molcules through gap junctions between cardiac myocytes
Describe the electrical activation of the pacemaker cells. Inculde the phase, what molecules move, whether its polarisation or depolarisation?
Phase 0, depolarisation: When membrane potential reaches -40 mV, voltage gated Ca channels open causing an influx of calcium
Phase 1+2: not present i pacemaker cells
Phase 3, Repolarisation: At peak depolarisation voltage gated K channels open causing efflux of K, Ca channels shut
Phase 4: Slow influx of Na through HCN channels until -40mV. Current created is called pacemaker/funny current.
(Do not have a resting potential)
refractory period - what is it? ABSOLUTE VS RELATIVE?
when channels are closed and inactive- 0.25 seconds long
- absolute- cannot
- relative- can but very difficult, some Na channels still inactive and K channels still open, only strong stimuli can cause action potential here
Normal ECG calibration?
25 mm/s and 10 mm/1mV
What do P waves represent?
atrial depolarisation/contraction
What does PR interval represent? how long should this take?
time taken for electrical activity to move from atria to ventricles (AVN delay), should be between 120-200 ms
What does QRS complex represent? How long should this take?
depolarisation/ contraction of ventricles, should be less than 120ms
What does ST segemnt show?
isoelectric line between depolarisation and repolarisation of ventricles
what does T wave show?
ventricular repolarisation
What does QT interval represent?
time taken for ventricles to depolarise and repolarise
isolectric point?
no net current flow in any direction
- movement in negative direction is net current flow away from lead
- movent in positive direction is net movement toward the lead
How should an ECG be set up?
10 electrodes (12 leads)
-1 electrode on each limb (4)
-6 chest leads- V1-V6 on chest
-right leg electrode is used as neutral lead
-Right arm (augmented vector right)
- left arm (augmented vector left)
- left leg (augmented ector foot)
Creates a triangle
difference between bipolar and unipolar leads?
bipolar- measure differnce in voltage between 2 electrodes
unipolar- measure difference between elctrode to reference (calculated from many electrodes)
Leads I and II - rule of thumb
if QRS are ‘leaving each other’ then theres left axis deviation
if QRS are ‘reaching towards each other’ then thats right axis deviation
lead I uses RA as negative and LA as positive
lead II uses RA as negatve and LL as positve
lead III uses LA as negative and LL as positive
which are the inferior leads? what area do they prepresent?
Leads II, III and AVF, right coronary artery
which are the lateral leads? what area do they prepresent?
Leads I, AVL and V5, V6- left circumflex artery
which are the anterior leads? what area do they prepresent?
V2, V3 and V4- LAD
which are the septal leads? what area do they prepresent?
V1 and V2- interventricular septum
