Cardiovascular (summary Sheets) Flashcards
What are the two phases of blood?
- Cellular component
- Fluid component
What does the cellular component of the blood consist of?
Red cells (99%), white cells and platelets
What does the fluid component of the blood consist of?
Plasma
What is an estimate of the volume of blood in the body?
5 litres
What is a haematocrit?
The volume of red blood cells i.e. haemoglobin in the blood
What is a normal haemocrit level?
0.45
What is haemopoiesis?
The process of production of blood cells and platelets which continues throughout life
Where does adult haemopoiesis occur?
Bone marrow
Where does embryonic/early life haemopoiesis occur?
Sites other than the bone marrow
What are the most primitive cells in the blood?
Stem cells
What do stem cells do in the bone marrow?
Proliferate and differentiate into mature cells
What is an erythrocytes lifespan?
120 days
What is a platelets lifespan?
7-10 days
What is a white blood cell lifespan?
6 hours
Name two cells of the blood which are anucleate
Erythrocytes and platelets
Where are the precursor cells of erythrocytes located?
Bone marrow
In which bones is the bone marrow stored, which contains the precursor to erythrocytes in adults?
Axial skeleton - skull, ribs, spine, pelvis and long bones
In which bones is the bone marrow stored, which contains the precursor to erythrocytes in children?
All bones
In which bones is the bone marrow stored, which contains the precursor to erythrocytes in utero?
Yolk sac, then liver and spleen
What abnormality of the blood could be a sign of leukaemia?
If precursor cells are found in the blood - they shouldn’t be in the blood of someone healthy
What is the function of hormonal growth factors?
Stimulate precursor stem cells to proliferate and differentiate
What is the hormonal growth factor for erythrocytes and where is it made?
Erythropoietin - made in the kidney
What is the hormonal growth factor of white cells?
G-CSF (granulocyte colony stimulating factor)
What is the hormonal growth factors for platelets?
TPO
Give 2 times when the oxygen dissociation curve shifts right
- Decrease in pH
- Increase in temperature
Give two times when the oxygen dissociation curve shifts left
- Increase in pH
- Decrease in temperature
Why do simple cells have a short life span?
They have no nucleus or mitochondria, therefore can’t repair themselves
What is the name of a young red blood cell?
Reticulocyte
What does a reticulocyte consist of?
A membrane (to enclose haemoglobin), enzymes of glycolysis and haemoglobin
What is the primary function of haemoglobin?
Carries oxygen from lungs to tissues, where it transfers oxygen to myoglobin in muscles
How does binding occur in haemoglobin?
Oxygen binds to Fe2+ in haem reversibly
What is the structure of haemoglobin?
- 2 alpha and 2 beta chains & 4 haem groups
- quaternary structure due to more than 2 tertiary structures
Which antibodies do those with type A blood have? Is this blood type dominant?
- Anti-B antibodies in the blood
- A antigen in co-dominant
Which antibodies do those with type B blood have? Is this blood type dominant?
- Anti-A antibodies in the blood
- B antigen is codominant
Which antibodies do those with type AB blood have?
- Neither anti-A nor anti-B antibodies in the blood
- Has A & B antigens on surface of red blood cells
Which antibodies do those with type O blood have? Is this blood type dominant?
- Has both anti-A and anti-B antibodies in the blood
- O antigen is recessive
What are the anti-A and anti-B antibodies known as?
Anti-erythrocyte (natural) antibodies
In a wrong transfusion, what causes issues?
The destruction of transfused cells
In terms of the D antigen, what does it mean if someone is rhesus positive?
The D antigen is present
In terms of the D antigen, what does it mean if someone is rhesus negative?
The D antigen isn’t present
What is anaemia?
Reduction in haemoglobin in the blood
What is a normal level of haemoglobin?
12.5-15.5 g/dL
What happens when levels of haemoglobin are lower than they should be?
Anaemia
What happens when levels of haemoglobin are higher than they should be?
Polycthaemia
Give 3 symptoms of anaemia
- Tiredness
- Lethargy
- Shortness of breath on exertion
Give 3 signs of anaemia
- Pink hands
- Sore tongue
- Cracking at corners of the mouth
What are the different classifications of anaemia?
- Iron deficiency
- Folate deficiency
- Haemolysis
- Bone marrow failure
- Of chronic disorder
What is the principle behind iron deficiency anaemia?
- Iron needed for haemoglobin production
- Reduced production of red blood cells
What is a red cell size also a measure of?
Mean cell volume
What is a normal MCV level?
82-96 fl
What are the two conditions for iron deficiency anaemia?
- Low haemoglobin
- Lower than normal MCV
Give the two main causes of iron deficiency anaemia
- Bleeding
- Dietary
What is Macrocytic anaemia?
When erythrocytes are larger than normal
What causes Macrocytic anaemia?
A folate/B12 deficiency
What is the pathology behind Macrocytic anaemia?
Less B12/folate —> RBCs can’t be made by bone marrow —> less are released —> anaemia
Name a cause of B12 deficiency in the stomach
- Intrinsic factor is required for B12 absorption
- Damaged stomach —> less parietal cells —> less intrinsic factor —> less B12 —> anaemia
What is pernicious anaemia?
Causes antibodies to be made against parietal cells, so less intrinsic factors
Give 3 causes of folate deficiency
- Malabsoprtion
- Dietary e.g. not enough fruit/veg
- Increase in need e.g. haemolysis/increased cell division
What is haemolysis?
Normal/increased cell production but decreased life span
Give 3 causes of congenital haemolysis
- Membrane issues
- Enzyme issues
- Haemoglobin issues
Give 3 causes of acquired haemolysis
- Autoimmune
- Mechanical
- Pregnancy
What is rhesus disease of pregnancy?
- Mum RhD negative and 1st baby RhD positive
- RhD positive seen as foreign to mother —> antibodies made. Doesn’t affect this baby.
- Mother sensitised to RhD positive blood
- 2nd baby RhD positive —> antibodies work ASAP, giving newborn anaemia/jaundice
Where do WBCs mature?
Bone marrow
What is the pathway to form a WBC?
Stem cells —> immature precursor cells —> WBCs
How is the rate of production of WBCs controlled?
By the hormone G-CSF
What is the most numerous WBC?
Neutrophils
What are the two function of neutrophils?
- Phagocytose and kill bacteria
- Release chemotaxins (initiates more WBC to come) and cytokines (inflammatory response)
What results with a lack of neutrophils?
Recurrent bacterial infections
What are the two types of lymphocytes?
B and T cells
What is the function of lymphocytes?
- Vital to immunity
- Some generate antibodies against specific foreign antigens
- Immunological memory
Where are B lymphocytes produced?
Bone marrow
Where are B lymphocytes stored?
Secondary lymphoid organs
How do B lymphocytes work?
- Differentiate into plasma cells
- Produce immunoglobulins when stimulated by exposure to foreign antigen
Where are T lymphocytes made and where do they mature?
- Made in bone marrow
- Mature in thymus
What are the two types of T cells?
- Antibody generation/cell mediated immunity
- Cytotoxic cells
Name 4 white cell conditions
- Acute leukaemia
- Acute myeloblastic leukaemia
- Acute lymphocytic leukaemia
- High grade lymphoma
What do platelets determine?
Bleeding time —> PT (prothrombin time)
What are platelets?
Small cytoplasmic anucleate cells that block up holes in blood vessels
Where are platelets derived from?
Made in bone marrow from megakaryotes?
Give two features of platelets
- Spherical
- Enucleate
What occurs when there is a reduced number of platelets?
Thrombocytopenia —> increased bleeding (main risk cerebral) and spontaneous bleeding
What occurs when there is a increased number of platelets?
Thrombocytosis —> can lead to arterial/venous thrombosis —> increased risk of heart attack/stroke
Name 5 different types of protein in the blood
- Coagulation proteins (enzymes)
- Plasma proteins
- Albumin
- Carrier proteins
- Immunoglobulins
Where are coagulation proteins formed?
Liver
What is the key coagulation protein and why?
Thrombin, as it makes the platelet plug
Which coagulation factors require vitamin K for correct synthesis?
2, 7, 9, 10
What is the function of coagulation proteins and how do they work?
- To make a blood clot
- Circulate in inactive form
- Converts soluble fibrinogen into insoluble fibrin polymer
What occurs when there is overactivity of coagulation proteins?
Thrombosis
What occurs when there is underactivity of coagulation proteins?
Bleeding
Are plasma proteins soluble and where are they found?
They are soluble and are found in plasma
What is the most numerous protein in the plasma?
Albumin
Where is albumin produced?
Liver
Give 2 functions of albumin
- Maintains oncotic pressure
- Carries FA, steroids and thyroid hormones
What happens where there is a lack of albumin?
Oedema
What do carrier proteins carry?
Nutrients and hormones
Give the 4 types of immunoglobulins
IgG, IgM, IgA, IgE
What are immunoglobulins?
Antibodies produced by plasma cells (differentiated plasma cells)
What is the most important immunoglobulin?
IgG
Which immunoglobulin do all of them start as?
IgM
When are immunoglobins produced?
In response to non-self antigens
What is haemostasis and what does it involve?
When the blood flow stops. This involves coagulation and contraction of damaged blood vessels
Name 3 factors which contributes to blood remaining fluid
- Proteins of the coagulation cascade and platelets circulate inactively
- Protein and platelets are only activated by tissue factor (on all cells except endothelial). Endothelial punctured —> blood contact with tissue factor and clotting begins
- Correct balance is vital
What is the coagulation cascade?
Series of proteolytic enzymes that become activated in a cascade to generate thrombin which cleaves fibrinogen into fibrin —> blood clot
Is the coagulation cascade all or nothing?
No, so it can be graduated depending on the severity
Which cell is responsible for primary haemostasis?
Platelets
What are the functions of platelets in bleeding?
- Adhere to damaged endothelium
- Aggregate to form platelet plug that blocks hole in vessel
What is the pathology of haemophilia A?
- X-linked
- Bleeding into muscles and joints
- Deficiency in clotting factor 8
What is the pathology of haemophilia B?
- X-linked
- Bleeding into muscles and joints
- Deficiency in clotting factor 9
- Less common compared to A as smaller gene
What is the pathology of Von Willebrand’s disease?
- Autosomal dominant inheritance
- Lack of VWF
- Muco-cutaneous bleeding (bleeding in skin and mucous membranes)
What is VWF used for?
- Required for platelets to bind to damaged blood vessels
- Lack —> platelet dysfunction so muco-cutaneous bleeding
Give 5 examples of acquired bleeding disorders
- Anti-platelet/anti-coagulation medication
- Liver disease
- Vitamin K deficiency
- Drugs
- Disseminated intravascular coagulation
How can liver disease cause an acquired bleeding disorder?
- Liver is site of synthesis of coagulation factors and fibrinogen
- Prolonged prothrombin time
How can a vitamin K deficiency cause an acquired bleeding disorder?
- Needed for formation of coagulation factors 2, 7, 9, 10
- A fat soluble vitamin
What causes vitamin K deficiency and especially in what condition?
Malabsorption - especially in obstructive jaundice
How does vitamin K deficiency present and what’s the link to coagulation factors?
- Prolonged PTT
- Coagulation factors are still produced but don’t work
How does aspirin work?
Affects platelet function
How do heparin and warfarin work?
- Inhibits vitamin K
- Affects coagulation cascade
What 2 affects can steroids have cardiovascularly?
- Makes tissues thin
- Causes bleeding/bruising
What is disseminated intravascular coagulation (DIC)?
- Breakdown of haemostasis
- Simultaneous bleeding and microvascular bleeding
Give 3 causes of DIC
- Sepsis
- Pregnancy
- Malignancy
What happens when the coagulation cascade is activated inside blood vessels?
- Thrombin is produced
- Fibrinogen is converted to fibrin
- Platelet plugs are formed
What is the pathway when a small vessel is damaged?
- Constricts (due to endothelin-1)
- Temporarily slows flow of blood to affected area
- This presses opposed endothelial surfaces of the vessel together
What are the interdependent processes of stopping bleeding?
Formation of a platelet plug and blood coagulation
When does permanent closure of a vessel occur by construction and contact stickiness?
In the very small vessels of the microcirculation
Briefly describe the formation of a platelet plug
- Injury to vessel disrupts endothelium so exposes collagen fibres
- Platelets adhere to collagen via VWF (using glycoprotein 1b receptor)
- This binding to the collagen triggers the platelets to release the contents of their secretory vesicles by exocytosis
- One of these contents are platelet dense granules. ADP is released from these granules which acts on P2Y1 and P2Y12 causing platelets amplification
- These actions result in the platelet changing shape from smooth discoid to spiky, which increases SA of platelet (activation)
- Activation causes an increase in expression in GPIIB/IIIa receptors on platelets which binds to fibrinogen, enabling new platelets to adhere (aggregation)
- Adhesion rapidly induces thromboxane, which is released into ECF to stimulate further aggregation
What does thromboxane A2 do?
Causes vasoconstriction and platelet activation
What enhances the effectiveness of a platelet plug?
Contraction - platelets contain a high conc. of actin and myosin, which results in compression and strengthening of the platelet plug
What happens to the smooth muscle in the damaged vessel during platelet activation, aggregation and plug formation?
It is simultaneously being stimulated to contract - decreasing blood flow to the area and pressure within the damaged vessel (caused by thromboxane A2)
Why does vasoconstriction to the area of a ruptured vessel occur?
As a result of platelet activation - due to thromboxane A2 release
Why doesn’t the platelet plug expand away from the damaged endothelium?
- The undamaged endothelium either side synthesises and releases prostacyclin which inhibits platelet aggregation
- Also releases nitric oxide which vasodilates, but is an inhibitor of platelet adhesion, activation and aggregation
Is the formation of a platelet plug quick?
Yes - very quick
What is the primary mechanism used to seal breaks in vessel walls?
Platelet plug
What is blood coagulation?
The transformation of blood into a solid gel (clot/thrombus) which consists mainly of fibrin
Where does blood clotting usually occur?
Locally around a platelet plug - dominant haemostat defence
What is the function of a blood clot?
To support & reinforce the platelet plug and to solidify blood that remains in the wound channel
What are the two divisions of the coagulation cascade?
- Extrinsic (as a cellular element outside to blood is needed)
- Intrinsic (everything needed is in the blood)
Briefly describe the intrinsic pathway of the coagulation cascade
- Factor 12a is activated when it comes into contact with exposed collagen fibres underlying damaged epithelium
- Eventually get to factor 10a –> converts prothrombin into thrombin
- Thrombin is the enzyme which converts fibrinogen to fibrin
- Fibrin can be used to secure the blood clot and build it up
Briefly describe the extrinsic pathway of the coagulation cascade
- Begins with tissue factor
- Blood is exposed to sub endothelial cells when vessel damage disrupts the endothelial lining
- Tissue factor binds to factor 7, which initiates the formation of more factors
- Eventually get to factor 10a —> converts prothrombin to thrombin
What are the indirect roles that the liver plays in clotting?
- The site of production for many plasma clotting fibres
- Produces bile salts which are needed for the absorption of vitamin K. It is required to produce prothrombin
What is fibrinolytic system?
A fibrin clot is not designed to last forever, it is a temporary fix until permanent repair of the vessel occurs
How are blood clots broke down?
- Plasminogen is converted by plasminogen activators into plasmin
- Plasmin goes on to break fibrin down, and so the entire clot
Where is cardiac muscle found?
Only in the heart
What does cardiac muscle do in relation to other muscles?
Combines properties of both skeletal and smooth muscle
What gives cardiac muscle a striated appearance?
The regularly repeating sarcomeres composed of myosin-containing thick filaments interdigitating with thin filaments that contain actin
What are present in an actin thin filament?
Troponin and tropomyosin
What are intercalated discs (cardio)?
- Adjacent cells which are joined end to end at structure
- There are desmosomes which hold the cells together and to which the myofibrils are attached
- There are also gap junctions
