CV Flashcards
What is a Haematocrit
The volume of blood cells in blood, it is also referred to as the packed cell volume, so the normal haematocrit is 0.45
Give a composition of blood with a percentage of its components
Fluid plasma - 55%
Cells - 45% (erythrocytes 44%, white blood cells and platelets 1%)
What causes the red bloods to become bi-concave discs
The loss of the cell nucleus causes the red blood cells to become bi-concave discs
In human, how many red blood cells are there
4 to 6 million erythrocytes per ml of blood
Give the diameter of a red blood cell
7 to 7.5 micrometers (um)
What is a reticulocytes and how much of the circulating red blood cell population does it make up
Reticulocytes are immature red blood cells and make up less than 1% of circulating red blood cells, they usually might have visible ribosomes still in them
Categorise the white blood cells into two groups, describing each type
Granulocytes
Neutrophil (ploymorphonuclear leukocytes) 40 - 75% = most numerous, phagocytotic and multilobar (number of lobes increases with age), can survive in hostile environments like low oxygen, contains myeloperoxidase because they use respiratory burst
Eosinophil (acidophilic leukocytes) about 5% = bi-lobar or tri-lobar with dark pink granules (losenge-shaped with crystalline cores- Charcot-leyden crystals), highest in the morning and numbers change, can phagocytose and associated with parasites, neutralise action of histamine, has receptors for IgE
Basophils (basophilic leukocytes) about 0.5% = contain large blue granules, similar role to mast cells, secretes histamine and vasoactive substances that increase blood flow to the local area, very rare, involved in anaphalactic shock
Agranulocytes
Lymphocytes (T and B) 20-50% = it is not possible to differentiate between T and B lymphocytes by just using a stain but immunohistochemistry can differentiate them
Monocytes 1-5% = kidney shaped (reniform) nucleus, differentiate into tissue macrophages
Give the 3 types of granules within a neutrophil and what they do
Type 1 - lysosomes involved in digestion of phagocytosed material e.g myeloperoxidase and acid hydrolases, most numerous (not unique to neutrophils)
Type 2- secretions from neutrophil involved in inflammatory response (unique to neutrophils)
Type 3 - contains enzymes (gelatinases and adhension molecules) which when secreted by the cell facilitate the insertion of proteins into the membrane of cell surface, this allows the neutrophils to squeeze between cells
What do the four types of platelet granules contain and what are their functions
Alpha granules = contain clotting factors
Delta granules = contains serotonin which is absorbed into them after discharge of clotting factors
Peroxisomes = contains catalase, an enzyme used to eliminate oxygen radicals
What is plasma
Plasma is blood without all the cells, it includes
Water
Salt and minerals
Plasma proteins (albumins, globulins, fibrinogen)
Hormones, signal molecules and other clotting factors
Makes up about 55% of blood
What is serum
Serum is plasma without clotting factors
Where are blood cells produced and destroyed
They are produced in the liver (in a foetus) and in the bone marrow (in adults)
They are destroyed in the liver and the spleen
Give the role of spectrin in red blood cells
Spectrin is an important protein in the endoskeleton of red blood cells
Give the different types of B and T lymphocytes and what they do
B cells - produce antibodies
T Helper (TH) cells - help B cells and activate macrophages
T Cytotoxic (TC) cells - kill previously marked target cells
T Suppressor (TS) cell - suppress TH cells and hence suppress the immune response
Natural Killer (NK) cells - mainly kill virus infected cells
Give the different cells that monocytes differentiate into
Tissue macrophages - everywhere Antigen presenting cells - everywhere Kupffer cells - liver Osteoclasts - bone Alveolar macrophages - lung
What is the progenitor cell for platelets
Megakaryocyte
What is hematopoiesis and where are all blood cells derived from
Hematopoiesis is the formation of the blood cells
All blood cells are derived from a pluripotent (multipotential) hematopoietic stem cell ( a hemacytoblast)
The haemacytoblast gives rise to common myeloid progenitor cells and he common lymphoid progenitor cells
Cardiac and voluntary (skeletal) muscle appear similar in many respects but (a) how do they differ structurally? (b) how do they differ physiologically? Try to think of 3 differences in each category
Structually
- interclated discs in cardiac muscle only
- single nucleus in cardiac muscle instead of syntitium of skeletal muscle
- central nucleus
Physiologically
- cardiac muscles are myogenic so dont need nerves
- secrete atrial natiuretic peptide hormone (NPH)
What does atrial natriuretic peptide do?
Atrial natriuretic peptide hormone is secreted by the atrium, it is released when cells are excessively stretched
It inhibits renin secretion
It increases the excretion of sodium, water and potassium in the kidneys
Which are smaller myocytes in the atrium or the ventricle
Myocytes in the atrium are smaller because of less resistance and workload
What are contained in the electron dense granules and alpha granules of platelets
Electron dense granules
- ADP
- Serotinin
- Calcium ions
Alpha granules
- platelets derived growth factor (PDGF)
- heparin antagonist factor (PF4)
- Von willebrand factor (vWF)
- Fibrinogen
Where are the sino atrial node and atrioventricular node located
The sino atrial node is located on the medial side of the superior vena cava at its junction with the right atrium
The atrioventricular node is located at the base of the inter-atrial septum, anterior to the opening of the cardiac sinus
Where are the purkinje fibres found and give some characteristics they have
They are found under the endocardium in the interventricular septum
They have large vacuoles an large stores of glycogen so stain magenta with a PAS stain
There is a delay between the contraction of the atria and the ventricles. What physical features cause this delay?
Rings of fibrous tissue between the atrium and ventricle prevent direct passage of an electrical signal so signal has to go through only the AV node which delays the signal slightly
Describe the structure of valves and change in the structure can lead to damage
The valves are made from thick collagen fibres and covered by a layer of endothelial cells
Damage to the valves can cause excessive collagen scarring leading to stenosis or regurgitation (incompetence)
What do the chordea tendinae do
The chordea tendinae anchor the valves to the papillary muscles
- allowing the contraction of the papillary muscles to open the valves
- preventing everting of the valves during ventricle contraction
Give conditions that can damage the heart valves
Calcification due to advanced age (mainly affects aortic valve)
Rheumatic fever (mainly affects aortic and mitral valve)
Staphylococcus aureus infection causing infective endocarditis
Rupture of papillary muscles making the valves incompetent
Describe the layers in the valve and what type of connective tissue they contain
Aortic side
- a layer of endothelial cells
- fibrosa (dense fibrous connective tissue)
- spongiosa (loose fibrous connective tissue) - contains interstitial cells, smooth muscle cells, fibroblasts and myofibroblasts
- ventricularis (collage and elastin)
- a layer of endothelial cells
What is endomysium
The loose fibrous connective tissue between the cadiac myocardium cells
Describe the 4 layers of the heart histology
The heart is inside the pericardial sac
Pericardium
- the lining of the pericardiac sac is the parietal pericardium
- the lining of the heart is the visceral pericardium
- outermost layer of the heart
Epicardium
- adipose tissue containing nerves and coronary vessels
Myocardium
- thickest layer and contains myocytes
- striated, interclated discs, branched and central nuclei
Endocardium
- innermost layer of the heart
- a layer of endothelial cells on a basement membrane with loose fibrous connective tissue
How does a defective valve lead to heart failure
A defective valve can either be incompetent allowing blood regurgitation back into the preceding heart chamber or be stenosed increase afterload
These both mean the heart cannot meet the metabolic needs of the body so hypertrophies
The heart still cannot sufficiently circulate the blood which leads to heart failure
Describe how the interatrial septum is formed and what the fossa ovalis signifies
In foetal development, the lungs are not fully funtional
- the increased resistance means that there is great pressure in the right side of the heart than left so blood moves down the concentration gradient
- at the 4th week, the septum primus (thin tissue) starts to develop between the two atria
- perforations called formen secondum develop in the septum primus before it totally separates the atria
- the septum secondum (thicker tissue) develops to the right of the septum primus
- another perforation called the foramen ovale develops in the side of the septum secondum
- the septum primus starts to disintegrate but still covers the foramen ovale
- the septum primus is now called the valve of the foramen ovale because when blood is travelling from the right atrium to the left it pushes the valve to the side
At first, when the baby takes it’s first breath, the lung fill up with air decreasing the pressure on the right side of the heart so the left side is higher
The high pressure in the left side of the heart pushes the valve of the foramen ovale against the septum secondum and they fuse within the first 3 months of a child’s life
The foramen ovale is called the fossa ovalis
The fossa ovalis in an adult heart signifies where the valve of the foramen ovale permanently covered the foramen ovale
Describe the division of the atrioventricular canal to form two precursors to the atrioventricular valves
While the interatrial septum is forming, the atrioventricular canal starts to divide
The primordial atrium and primordial ventricle fuse (two endocardial tubes fuse) to become one heart tube, the heart begins to fold and starts beating (day 22)
Endocardial cushions (masses of tissue on either side of the atrioventricular canal) start to pinch the middle of it, dividing it into two
The percursors for the atrioventricular valves are now formed
Describe the development of the aorta, pulmonary trunk and the interventricular septum
At this point, blood flowed from the right and left atrium through the atrioventricular canals into the primordial ventricle and through the truncus arteriosus
By the end of the 4th week, a muscular septum starts to grow superiorly from the base of the ventricle
It stops before the atrioventricular canals which still have the gap created by the endocardial cushions between them
By the end of the 5th week, two ridges (called conotruncal ridges or tuncoconcal swellings) start to grow from the truncus arteriosus
The conotruncal ridges grow superiorly and form a spiral which becomes the articopulmonary septum, it divides the truncus arteriosus into the aorta and pulmonary trunk
The articopulmonary septum also grows inferiorly and fuse with the endocardial cushion (that form the interventricular foramen) and the muscular ventricular septum (this finishes by the end of week 8)
Blood now flows from the right atrium to the right ventricle and into the pulmonary trunk, and from the left atrium to the left ventricle and into the aorta
Describe the development of the aortic arch vessels and when it occurs
Occurs from week 4 (day 27) to week 7
Arch 1 = regresses into the maxillary artery
Arch 2 = regresses into the stapedial artery
Arch 3 = forms the left and right common/internal/external carotid arteries
Arch 4 = right forms part of the right subclavian artery, left forms part of the aortic arch
Arch 5 = no arch 5
Arch 6 = right forms part of the right pulmonary artery, left forms the ductus arteriosus
7th segmental arteries = right forms part of the right subclavian artery, left forms the left subclavian artery
Dorsal aorta = right forms part of the right subclavian artery, left forms the descending thoracic aorta
What are the hormones that drive embryonic vessel development (vasculogenesis)
Angiogenic growth factors and repulsive signals
Angiogenic growth factors
- vascular endothelial growth factor
- angiopoietin 1 and 2
Repulsive signals
- plexin/ semaphorin signalling
- ephrin/eph interactions
Between when does vascularization of the yolk sac, chorionic villus and stalk occur?
Day 17-21
When does vasculogenesis begin and where does it begin from
Day 18
From the lateral mesoderm
What is the difference between haemopoiesis, erythropoiesis, myelopoiesis and thrombopoiesis
Haemopoiesis = production of blood cells Erythropoiesis = production of red blood cells Myelopoiesis = production of white blood cells Thrombopoiesis = production of platelets
Give the hormones involved in erythropoiesis, myelopoiesis and thrombopoiesis
Erythropoiesis = erythropoietin (EPO) Myelopoiesis = Granulocyte-macrophage colony-stimulating factor (GM-CSF) Thrombopoiesis = thrombopoietin (TPO)
Give methods used to separate the different types of haemoglobin and explain them
High Performance Liquid Chromatography (HPLC)
-separates the Hb on basis of electrical charge
Hb Electrophoresis
- separates HB on basis of size
- acid and alkaline conditions
What is anaemia
Give some signs and symptoms
A deficiency of Hb
<130g/L in adults males
<110g/L in adult females
Signs
Palor
Tachycardia
Signs relating to underlying cause
Symptoms
Tiredness/lethargy/malaise
Shortness of breath on exertion/ reduced exercise tolerance
Angina & claudication (in older individuals)
Give the causes of anaemia
Results from production failure and increased removal
Production failure
- hypoplastic anaemia (not enough red blood cells produced)
- dyshaemopoietic anaemia (ineffective red blood cells produced)
Increased loss
- blood loss (acute or prolonged)
- haemolytic anaemia (breaking of red blood cell)
What can causes hypoplastic anaemia
Renal failure
Endocrine issues
PRCA
Aplastic anaemia (when body stops producing new blood cells, can affect all blood cell types)- can be inherited, acquired (idiopathic, drugs and chemical or viral)
What is dyhaemopoietic anaemia
Multiple mechanisms e.g caused by chronic disease
Defective Hb synthesis e.g in the globin e.g thalassaemia, in the haem e.g iron deficiency
Defective DNA synthesis e.g folic acid, B12 deficiency
What causes haemolytic anaemia
Intrinsic red blood cell abnormalities
Acquired e.g PNH
Hereditary e.g membrane disorders like Hereditary Spherocytosis enzyme disorders, Pyruvate Kinase deficiency
Extrinsic abnormalities Antibody mediated e.g AIHA Mechanical trauma e.g DIC Infections e.g Malaria Chemicals e.g lead poisoning Sequestration e.g hypersplenism
What is the most common cause of anaemia
Iron deficiency is the most common cause of anaemia
What are the causes of iron deficiency and does it lead to
Causes: Chronic bleeding Poor diet Malabsorption Hookworm
Leads to:
Anaemia
Reduced mean corpuscular Hb (MCH)- amount of Hb in cell
Reduced mean corpuscular volume (MCV) - size of cell
What does reduced mean corpuscular volume mean and what causes it
Reduced mean corpuscular volume (MCV) is the reduced size of the cell
It is caused by iron deficiency
Give some examples of platelet disorders, their causes and effects
Bernard- Soulier Syndrome
Cause - deficiency of GP1b receptor
Effect - so no platelet adhesion
Glanzmanns thrombasthemia
Cause - deficiency of GP2b/GP3a receptors
Effects - no platelet cross-linking or aggregation
Hermansky-Pudlak syndrome
Cause- deficiency of electro dense granules
Effect - no platelet activation or aggregation
What produces erythropoietin
Erythropoietin is produced by the juxtaglomerular cells of the kidney
How would acute blood loss affect anaemia and blood volume
No real effect on anaemia if stopped quickly because same amount of plasma is lost as red blood cells
It is just blood volume that is lost
Give common cell markers of T cells
CD4+ = for the T helper cells - which supress and regulate the immune response CD8+ = for the cytotoxic cells - target and damage infected cells for death
Give a cell marker for B-lymphocyte cell
CD20 - hummoral immunity
What is thalassemia
Thalassemia is when the gene to produce globin chains are absent so ineffective red blood cells produced which leads to anaemia
Alpha thalassemia is a lack of alpha globin chains are more rare because alpha chains are needed for the feotus to survive
Beta thalassemia is a lack of beta globin chains so is more common as usually the feotus would survive to adulthood but then would get anaemia
Which globin chains are present in fetal and adult haemoglobin
Foetus = 2 alpha chains, 2 gamma chains Adults = 2 alpha chains, 2 beta chains
Give the effects of reduced platelet number
- Thrombocytopenia
- > 10 to <140x109/L - increased bleeding
- <10 x 109/L - spontaneous bleeding
Give the effects of increased platelet number
- Thrombocytosis
- Arterial thrombosis
- Venous thrombosis
Give the different types of platelet bleeding
Muco-cutaneous (into skin) = displayed as epitaxis, mennorhagia, prolonged bleeding from cuts, easy bruising and bleeding after haemostatic challenge (surgery, childbirth, tooth extraction and trauma)
Haemophilia (into joints and muscle) = hameophilia type A (1 in 100,000 so common) is caused by a deficiency in factor 8 and is treated with recombinant factor 8, haemophilia type B (1 in 500,000) is caused by a deficiency in factor 9, treated with recombinant factor 9
Give the causes of platelet bleeding
Genetic - haemophilia (x-linked disease)
Liver disease - creates clotting factors and albumin
Vitamin K deficiency - vitamin K is needed to make factors 10, 9, 7 and 2 so without it no clotting and more bleeding
DIC (disseminated intravascular coagulation
Drugs - warfarin and heparin affect coagulation cascade, aspirin and clopidogrel affect platelet function, steroids thin the tissue which causes easy bruising and bleeding
Give the frequency of different blood types in the population
O = 45% A = 40% B = 12% AB = 3%
What are the blood type antigens made from
Carbohydrates
When do anti-bodies to blood type start occuring
At 6 months
How can blood types be determined
With cells and serum
How can rhesus status be determined
With two different reactants
What is the trigger for transfusion in a fit and healthy woman with some blood loss
8g/dl
What is William Harvey famous for
William Harvey 1578 - 1657
Describing the circulation of blood
Describing the heart as a pump and circulation as a closed system
Publishig the De Motu Cordis in 1628
What is Richard Lower famous for
First transfusion in a dog
What is Jean Baptiste Dervy famous for
Transfused 12oz of blood from a sheep into a boy
Resulting deaths from his later transfusions resulted in the transfusion ban of 1670
What is James Blundell famous for
1829
First obstetric transfusion, it was done is a lady who suffered postpartum haemorrage
4 oz was transfused from her husband
What is Karl Landsteiner famous for
1868 - 1948
Discovered the 3 blood groups (A, B and O)
Identified the Rhesus Factor
He won the 1930 Nobel Prize
Give the different types of antibodies
Think IggMEAD
IgG IgM IgE IgA IgD
IgG, IgE IgD are the classic Y shape
IgM is a big wheel shape molecule (5 Ys in a circle)
What class of antibodies react with antigens A and B, and at what temperature do they react optimally
IgM and at cold temperatures (4 degrees)
What class of antibodies react to most immune responses and what temperature do they work optimally at
IgG and at warm temperatures (37 degrees)
Which are the only antibodies that can pass through the placenta wall from mother to fetus
IgG
Give 5 important Rhesus antigens and which chromosome codes for them
C, c, D, E, e
Chromosome 1 codes for the rhesus genes
What is the clinical significance of Rhesus D
Rh D is inherited the child gets one gene (haplotype) from their mother and one from their father
The clinical importance is in Rhesus D negative mother
This is because the father might be rhesus positive and since its dominant, the child becomes rhesus positive
The mother might then recognised the Rd + in the child as foreign and create antibodies to attack the blood cells of the child
This usually does not affect the first pregnancy but the usually the second as the mother has built up a lot of antibodies to quickly attack the second child
This is treated by sensitisation which is when artificial antibodies are given to the mother tricking her immune system to believe she has already produced antibodies and does not need anymore- the sensitisation is done multiple times throughout the pregnancy, Anti- D antibodies are given to the mother
What is sensitisation in terms of Rh D treatment
It is when artificial antibodies (Anti- D antibodies) are given to the mother tricking her immune system to believe she has already produced antibodies and does not need anymore- the sensitisation is done multiple times throughout the pregnancy, Anti- D antibodies are given to the mother
Give the requirements for blood donor selection
Between 17-70 years old
Weight is above 50kg
Hb is above 134g/L in males and 120g/L in females
Pregnant or lactating women are excluded
Donation interval is every 12 weeks (4 months) so can only give 3 donations a year
12 months post risk taking behaviour: peircings, tatoos, paid sex
2 months post live vaccinations
Asked about recent holidays
What would you find on a packed cell transfusion bag
Packed red cells
ABO/Rh group Collection date Product code Expiry date Special testing
At what temperature are platelets stored and why could it be an issue
Platelets are stored at body temperature and this could be an issue because bacteria can thrive at that temperature
At what temperature is fresh frozen plasma stored and what does it contain
Fresh frozen plasma is frozen within 6 hours of arrival and contains coagulation proteins and inhibitors
Stored at below -30 degrees
What is Cryoprecipitate
Rich in fribrinogen
Used in cases like DIC
Give some transcriptions factors involved in embryonic cardiac development and their effects
Overexpression of Nkx2 increases heart size
Inhibiting GATA4 causes cardiac bifida - failure of fusion of endocardial tubes
Preventing Fog-1 prevents cardiac looping
Cascade of (lefty, Pitx2 and Fog-1) transduce cardiac looping
Give the 3 main steps of embryonic cardiac development
Formation of the heart tube
Cardiac looping
Cardiac septation = endocardial cushion formation creating two atrioventricular canals, development of the outflow tract and ventricular septal formation
What percentage of blood is usually in the veins
64%
What percentage of blood usually lies in arteries
7% in the large arteries
8% in the small arteries and arterioles
What percentage of blood is usually in the heart
7%
How is blood flow regulated in the capillaries
Precapillary sphincter
What are the vasa vasorum and where do they lie
Blood vessels that supply the arteries with blood and they lie in the adventitia
Give the modifiable and non-modifiable risk factors for cardiovascular disease also include the psychosocial risk factors
Modifiable risk factors: Obesity High cholesterol Physical inactivity Smoking Stress Diet high in saturated fats and trans fat
Non-modifiable risk factors:
Family history
Diabetes
Psychosocial risk factors: Low socio-economic status Social isolation Work-related stress Depression Panic attacks
Give examples of common causes of failure in management of chronic conditions
- different conditions treated independently (co-morbidities)
- failures in communication between specialists and GP
- difficulty in managing frequent changes in presentation and severity of symptoms
- polypharmacy
Define Evidence based medicine
Evidence based medicine is the conscientious, explicit and judicious use of the best evidence to make decisions on the care of an individual. It integrates the individual clinical expertise, best available clinical evidence with patient values, preferences and beliefs.
5 steps of evidence based practice
Asking focused questions Finding the evidence Critical appraisal Making a decision Evaluating performance
What is the purpose of critical appraisal
To assess the
- validity
- reliability
- applicability
Give some tools for critical appraisal
Critical appraisal skills programme (CASP)
NICE guidelines manual checklists
Cochrane Handbook for systematic reviews for interventions
What is the disability paradox
This is when expectations shift to adjust to their current condition
Their challenged health status leads to a re-evaluation of what is important for life quality
Their lower expectations translate to higher satisfaction
What is intermediate care
This is care that happens after primary care and self care but before (or instead of) large acute hospital care
Examples:
Pre-admissions assessment units, early and supported discharge schemes, community hospitals, domiciliary stroke units or rehabilitation unit
Give examples of intermediate care
Examples:
Pre-admissions assessment units, early and supported discharge schemes, community hospitals, domiciliary stroke units or rehabilitation unit
What is the range for normal serum osmolality
275-295mOsm/Kg
What is the urine osmolality range
50-1400mOsm/Kg (50 being dilute and 1400 being concentration)
What is diabetes Insipidus (differentiate between cranial and nephrogenic)
This is when the body does not respond to ADH
Cranial is when there is an issue with the hypothalamus and the pituitary gland
Nephrogenic is when the kidney itself does not respond to ADH
What is coronary artery disease (CAD)
A disease process that is characterised by the build of atherosclerotic plaque in the coronary arteries
Define Obesity
Accumulation of excess body fat defined by a body mass index greater than 30kg/m (meter square)
What is angiogram
An agiogram (also known as cardiac catheterisation) is a type of xray which uses contrast dye to show an image of the coronary arteries
It shows any narrowing or blockages in the coronary vessels
A catheter is inserted into an artery in the arm or groin and passed up into the heart, the dye (called contrast) will show up on the xray
Blood tests used to asses heart conditions
Cardiac enzyme test (troponin) - help to diagnose a heart attack
Full blood count (FBC) - shows if there is an infection or anaemia due to different cells in the blood
Thyroid function test - shows if an overactive or under active thyroid is present
Lipid profile - measures cholesterol level and other fats in the blood
Liver test - liver enzymes
Clotting screen - to see how quickly the blood clots
BNP (B-type natriuretic peptides) - if elevated can be a sign of heart failure
U and Es test - urea and electrolytes (sodium, potassium, magnesium and calcium) show heart and kidney health
Describe the journey of the right phrenic nerve
The right phrenic nerve arises from nerve C3, 4 and 5 passes through the neck, anterior to the hilum and passes through the diaphragm with the inferior vena cava - supplies sensation and motor innervation to the diaphragm
Some intercostal nerves also supply the periphery of the diaphragm
Where would the vagus nerve be found in the thorax (include the relation to the phenic)
The vagus nerve passes with the common carotid in the neck into the thorax
The right vagus nerve would be found superior and posterior to the hilum of the lung, between the azygous vein and the superior vena cava
The vagus nerve is always posterior to the phrenic nerve
