Cardiovascular Flashcards
Describe red blood cells
Aka erythrocytes
Lifespan 120 days and are removed in the spleen, liver bone marrow and through blood loss.
Structure of haemoglobin
4 globin chains, each has a harem group which can reversibly bind with oxygen
2 beta and 2 alpha chains in most adult haemoglobin.
Thalassemia is the mutation or absence of the a or b chains.
What are leukocytes?
Two main types: lymphocytes (adaptive immune response) and granulocytes (innate immune response).
Types of granulocytes:
* Neutrophil - most abundant wbc, phagocytise and release chemokines and cytokines to induce inflammation.
* monocytes - mature into macrophages or dendritic cells, both antigen presenting.
* basophils: mature into mast cells. Will express surface IgE and release histamine. Role in allergies and immunity.
* eosinophils -role in fighting infection and has regulatory functions.
Lymphocytes comprise b and T cells:
* B cells are made and matured in bone marrow. 20% proportion and has antibody like B cell receptor. Creates antibodies.
* T cells made in bone marrow mature in thymus. 80% of cells and T cell receptors on surface. Has various functions.
What comprises blood plasma?
It is the fluid component of blood, makes up ~55% of blood vol.
Contains water, salts, glucose and proteins.
Proteins in plasma:
* Albumin is produced in the liver. Determines oncotic pressure. Keeps intravascular fluid and within that space.
* carrier proteins.
* coagulation proteins.
* immunoglobulins, produced by activated b lymphocytes. Key role in immunity and vaccination.
What is the coagulation cascade?
It is the process which aids in blood clotting by stabilising the platelet plug (though not to be confused with).
Coagulation ultimately converts soluble fibrinogen into fibrin which forms a stable fibrin clot.
More knowledge is required (future lecture)
What are the 4 blood types?
A and B are dominant. O is recessive.
So 4 types are A, B, AB, O.
A blood type contributes to the antigens on red blood cells and the antibodies present in plasma. These can be used to identify blood types.
How are blood types identified?
If the thing it present, they will agglutinate and won’t pass through the gel.
D shows rhesus - if top, Rh+.
What is the rhesus blood group system?
A series of C,D or E antigens on the surface of red blood cells.
If the protein is present, you are rhesus positive. If it is not present, you are rhesus negative.
We only really consider rhesus D. RHD codes for RhD
What is rhesus disease (HDFN)?
Haemolytic disease of the foetus and newborn. Only happens if the mother is RhD- and the mother if RhD+.
Small amount of the baby’s red blood cells leak over the placenta. The mother makes rhesus D antibodies but this doesn’t harm the current baby.
On the second pregnancy, the rhesus d antibodies kill the foetus by killing the foetal red blood cells (haemolysis).
What is cross-matching blood?
Checking whether donor and recipient blood is compatible by mixing them.
Either exact match (A+ and A+) or compatible matches (O- for A+).
This is done by a DAT.
What tests are performed on blood before transfusion?
What are the different forms in which transfusion is given?
- Red cells: to treat anaemia. Check B12 and iron levels before transfusion. Also to treat hypovolaemia (low volume of blood).
- Plasma: male donors only.i
- Platelets: 4 donations. Only used in severe thrombocytopenia or when there is thrombocytopenia and bleeding. ABO type still important due to white cell presence.
What is the common way bacterial contamination happens in transfusion?
More often with platelets but still rare.
Happens soon after transfusion.
Causes fevers, hypotension and shock.
Unit may show cloudiness if infected.
What is DAT?
Direct anti-globulin test.
Used to detect antibodies, inc ones that are already on rbc. If red cells clump, blood is not viable.
Indirect coombs test - red cells of donor and plasma of recipient to see if there is a reaction. If there is no agglutination, shouldn’t cause an issue in transfusion.
What are the typical settings of an ECG?
Note: positive indicates current is moving towards the sensor.
Negative indicates current is moving away from senior.
Show the p wave
P wave: depolarisation of the SAN, NOT contraction of atria.
Ventricles relax and mitral valves open. Atrial contraction happens after the P wave. The ventricle dilates as blood is pumped into it to maintain lower pressure than the atrium.
Show the PQ interval
show the QRS complex
QRS Complex: depolarisation of the ventricle. Blood fills the LV and mitral valve closes as LV gets full. Isovolumic contraction occurs, creating a pressure of 120mmHG.
This contraction opens the aortic valve and blood flows into the aorta and the end of isovolumic contraction, as volume has changed. Ejection.
Show the T wave
Repolarisation of the ventricles. they are still contracting, but ejection begins to decrease and there is a fall in pressure.
ATP hydrolysis breaks the bond of Ca++ TnC and muscle reax. This is all known as isovolumic relaxation. Pressure continues to decrease and reaches 0mmHg.
Summarise the ECG
How lazy are you?
Lazy enough to say I can’t be bothered to put the electrode stuff onto flashcards. Use a revision guide or somebody else’s flashcards. Or you do it, lazy bugger. I won’t, I’ve been working all evening.
What is atrial fibrillation?
What is atrial flutter?
Atrial flutter
Organised atrial activity ~300/min
Ventricular capture at ratio to atrial rate (usually 2:1 so 150 bpm)
Usually regular
Can be irregular if ratio varies
What are bundle branch blocks?
What does it mean if the ST segment is raised?
Acute heart attack/ myocardial infarction.
How is the resting potential set up?
Inside of cell is negative with respect to outside.
K+ ions diffuse down conc gradient out of the cell.
Excess anions inside cell generates negative potential inside the cell.
Na pumped out of cells.
K pumped into cells
Ca pumped out.
All are against conc gradient so require ATP.
Draw the graph of cardiac myocyte action potential.
- Na/K ATPase pump Na out, K in. Slow leak through Na/K channels (mainly K, some Na).
- Cell is activated, voltage gated Na channels open, and a large number of Na+ ions enter the cell. Cell is depolarised to +20mV from -90mV.
- K+ outflow and inflow of Na+ stops, so there is a small repolarisation.
- Ca channels open, Ca enters the cell, maintaining the depolarised state of the cell. Entry of Ca2+ into the cell causes contraction of the myocyte. Much slower repolarisation than skeletal muscle cells.
- K+ channels are opened again, allowing K+ out of the cell again.
- Na/K ATPase returns to initial voltage.
How is calcium concentration increased inside the myocytes?
Calcium influx from voltage gated Ca channels.
Sarcoplasmic reticulum releases Ca2+ (Ryanodine receptors facilitate transport of more Ca2+ into the cytoplasm when increased Ca2+ is detected in the cell).
What is TPR?
The arterioles are the principal site of resistance to vascular flow- therefore TPR (total peripheral resistance) = total arteriolar resistance.
This is determined by local, neural and hormonal factors.
Has a major role in determining arterial pressure.
When the vascular smooth muscle in the arterioles contracts, radius reduces, increased resistance, decreased flow.
Vice versa for when the VSM relaxes.
What is the pressure in veins?
10mmHg
But has up to 70% of blood volume/
Afterload vs preload.
Systolic pressure vs diastolic pressure
Cardiac vs skeletal muscle
Compare conduction speeds
Describe the ultrastructure of the sarcomere
The sarcomere is the basic contractile unit of muscle tissue. It is composed of 2 main protein filaments, actin and myosin.
Myosin:
* 2 large heavy chains and 4 smaller chains
* 2 globular heads on myosin end which would join the actin
* Globular heads present 40 degrees from each other to maximise chance of connecting with the actin.
* ATPase in the head of myosin molecule.
Actin:
* Globular protein, double stranded by polymerising with other actin molecules to form a helical structure,
* Actin has a myosin binding site which is partially covered by tropomyosin and is help in place by troponin (clamp).
* Tropomyosin is a wire like substance that occupies the longitudinal grooves between the 2 actin strands.
Troponin has 3 subunits:
* TnI - inhibitory: inhibits actin and myosin interaction
* TnT: tropomyosin binding. Troponin binding to tropomyosin.
* TnC - Calcium binding - high affinity calcium binding sites which signal contraction and drives TnI from the myosin binding sitem allowing interaction between actin and myosin again.
TnI is linked to Tnc - when TnC acts, TnI moves away from the groove.
TnC Ca++ bond is so strong that TnI must use energy from ATP hydrolysis to block the groove again.
Draw the graph of the cardiac cycle.
Physiological vs cardiological systole and diastole
Why do platelets become activated?
Collagen in exposed when a tear appears in the endothelial wall. Platelet collagen receptors bind to exposed collagen.
GP1b receptors on the platelets adhere to Von Willebrand factor, which is on the collagen.
GPIIIb/IIIa receptors also bind to von Willebrand factor which is attached to collagen.
GPVI also binds to collagen directly. This leads to platelets synthesis and release of thromboxin A2, which binds to the surface receptor (TPa) of that or other platelets, to activate them. This is known as an amplification pathway.
All of these activate platelets.
How does aspirin operate?
Low dose aspirin inhibits COX1, so less thromboxane A2 so less platelet activation.
High dose aspirin acts on both COX1 and COX2 in endothelial cells. This means reduction in aggregation mediated by platelets and inhibition of prostacyclin mediated inhibition, which means more aggregation.
How are platelets activated by thromboxane A2?
Thromboxane A2 binds to TPa receptors, which increases platelet aggregation and stimulates vasovonstriction.
Arachidonic acid can be converted into different products depending on the COX enzyme and depending on the cell type.
In platelets, arachidonic acid is converted by COX-1 into prostaglandin H2, which is then converted into Thromboxane A2 (when COX-1 is present alone). This leads to vasoconstriction and platelet aggregation.
In endothelial cells, when COX-1 and COX-2 are present, Arachidonic acid is converted into prostaglandin H2, which is then converted into Prostacyclin, which inhibits platelet aggregation and vasoconstriction.
How does the thrombin positive feedback loop happen?
As thrombin binds to PAR1, intracellular stores release Ca++, which result in the inhibition of translocase and activation of the scramblase enzyme (also causes release of dense granules and platelet activation).
Aminohpospholipids on the inner platelet membrane are held in place by translocase. Scramblase and aminophospholipid inhibition of translocase causes expression of aminophospholipids on the outer membrane.
When aminophospholipids are on the outer surface, prothrombinase can be assembled, an enzyme which converts prothrombin into thrombin.
What is the fibrinolytic system?
tPA is released by the endothelium. This converts plasminogen into plasmin. Plasmin breaks down fibrin.
This is regulated by:
PAI-1 inhibits tPA.
Antiplasmin inhibits plasmin.
