week 6 Flashcards
1
Q
what is atherosclerosis?
A
Degeneration of arterial walls characterised by fibrosis, lipid deposition and inflammation which limits blood circulation and predisposes to thrombosis
2
Q
what are the nonmodifiable risk factors for atherosclerosis?
A
age, FH, gentics and MAle
3
Q
what are the modifiable risk factors for atherosclerosis?
A
smoking, hyperlipideamia (LDL;HDL), diabetes, hypertension
4
Q
what is the actions occur prior to atherosclerosis?
A
chronic injury and repair of the endothelium
5
Q
What causes the first step of endothelial injury and therefore the initiation of atherosclerosis?
A
haemodynamic injury, chemicals, immune complex deposition, irradiation
6
Q
what does injury to the endothelium cause?
A
the endothelium becomes leaky or permeable
7
Q
How does damage to the endothelial lining caues the formation of foam cells in the fatXty streak stage?
A
Due to hyperlipideamia lipid will acumulate in the inner most part of the vessel –> intima
monocytes wil integrate to teh intima due to lipid and endothelium injury (VCAM1) and ingest the lipid to form foam cells
this is fatty streak
8
Q
what does foam cells secrete and what is the action of that?
What do smooth muscle cells secrete and finally what is atherosclerotic plaque made up of?
A
They release chemokines that attract monocytes, macrophages, lymphocytes and smooth muscle cells
Smooth cells proliferate and secrete connective tissue
The mixture of fat, extracellular material, lymphocytes and smooth muscle cells form the ahterosclerotic plaque
9
Q
what is in the necrotic center of atheromatous plaque?
A
foam cells, calcium, cholestrol crystals and cell debris
10
Q
what is the fibrous cap made out of?
A
foam cells, lymphocytes, macrophage, smooth muscle cells, collagen, elastin, proteoglycans and neovascularization
11
Q
what occurs to the smooth muscles during plaque formation?
A
ploriferation and secretion of connective tissues
12
Q
what is the Sequelae of atherosclerosis?
A
Occlusion
Weakening of vessel walls –> aneurysm
Haemorrhage
Erosion –> thrombotic formation
13
Q
what is an embolism?
A
A mass of material in the vascular system able to lodge in a vessel and block it
14
Q
what is thrombosis?
How is it different to a clot pathogensis loand morphology?
A
the solidification/ solid mass of blood content formed in a vessel or heart during the life
Physiologically–> forms differently
Morphology–> looks different
15
Q
what is a clot and what is its is the characterstics?
A
clot is stagnated blood that has amended clotting process either vivo ( the heart) or In vitro (test tube)
stagnant blood, enzymatic process, adopts shape of vessel and elsatic
16
Q
what is the characterstics of thrombis?
A
firm, maintained throughout life, dependent on platelets
17
Q
How are plateletes formed and where are they found? Do they have a nucleus?
A
they are fragment of megakaryocytes in the bone marrow that circulate around the blood stream
They do not have a nucleus
18
Q
how are plateletes activated?
A
They attach to collagen which is exposed due to endothelium damage and become activated
19
Q
what alpha granules do plateletes secrete?
A
fibrinogen, fibronectin, PDGF
20
Q
what dense granules do plateletes secrete?
A
chemotactic chemicals
21
Q
what are the sights where you get thrombusis?
A
heart, arteries, veins
22
Q
Virchow triad says that to get platelett adhesion and subsequent thrombus formation requires changes in:
A
The intimal surface of the vessel
Change in pattern of blood flow
Blood constituents
All three is needed for thrombus formation
23
Q
what three things cause the formation of arterial thrombus?
A
Plaque rupture- turbulent flow and intimal change
Hyperlipidaemia – change in blood constituents
Platelets bind and fibrin is produced entrapping RBC
24
Q
Describe virchow triad for the cause of venous thrombosis
A
Intimal change especially around the valves
Chain in blood constituite:
Inflammatory mediators –> infection and malignancy
Factor v leiden –> common inherited disease
Oestrogen –> high levels of this
Change in blood flow:immobile
25
what drug increase your level of oestrogen and therefore increase risk factor for venous thrombosis?
the pill
26
what are thrombi in the heart usually called and what is the cause?
mural thrombi and occur over areas of endomyocardial injury --> MI and myocarditis
Can also occur due to arrythmias or cardiomyopathy
27
what is cardiomyopathy ?
chronic disease of the heart
28
what is the most common place where pulmonary embolism forms?
DVT in deep part of your legs
29
what is paradoxical embolus
type of arterial thrombosis where there is a blood clot of venous origion that goes through a lateral opening of the heart such as foramen ovale and then into the lungs
30
what are the acquired causes of pulmonary embolism?
immobility, malignancy, previous VTE, heart failure, oestrogens, obesity, pregnancy, renal disease, smokers
31
what are the genetic/hereditary cuases of pulmonary embolism?
thrombotic disorders --> Fv leiden and protein S defieiciency
32
what is the outcome of small pulmonary embolism?
asymptomatic at first ---> multiple later will result in pulmonary hypertension
33
what would mediam pulmonary emboslism cause?
Cause acute respiratory and cardiac failure (V/Q mismatch, RV strain)
34
Where do systemic embolism occur
Within the heart after AF or MI
| Within the arteries as a antheroma
35
what is platelet emboli?
Little emboli
Often asymptomatic
Arise from atherosclerotic plaque
Idea that this may what causes TIA
36
How are atheromas formed and where?
From eroded plaques
| Often in lower limbs
37
how is infective embolism work?
Caused by vegetation of the infected heart valves
| this will cause the bacteria present to cause infection and colonise which can lead to myocarditis aneurysm formation
38
which sub group of people is infective embolism commonly seen in?
intravenous drug uses and people wil prosthetic valves
39
what is the cause of tumor embolism?
Bits may break off as tumours penetrate vessels
Do not usually cause immediate physical problems
Major route of dissemination
40
How can air cause a gas embolism?
Have the vessels opened to air such as obstetric procedure and chest wall injury/surgery
Also need more than 100ml of air for it to have clinical effect
41
What is the consequence of too much nitrogen?
| When do you get it and what is the consequence
Gas emboli
```
Decompression sickness (“the bends”)
Divers, tunnel workers
Nitrogen bubbles enter bones, joints and lungs
Little gas bulbels
Bends --> terrible joint pains
Get neurological symptoms
Cardiac symptoms
```
42
how does amniotic fluid embolism happen?
| What is the consequence
Increased uterine pressure during labour may force AF into maternal uterine veins and or the cervical veins
Lodge in lungs which can cause respiratory distress
Can see shed skin cells histologically --> contains debres and fetal cells that are not good for mother
43
When is fat emoblism seen?
| What is the consequence
Microscopic fat emboli found in 90% patients with significant trauma and fractures bone
Mainly fractures but maybe seen in severe burns
Sudden onset of respiratory distress
Fatal in 10%
44
what is the cause of foreign body embolism?
Particles injected intravenously
Leads to a granulomatous reaction --> macrophage and lymphocyte reaction
Can affect lungs and heart
45
what are the two genetic factors that can lead to athersclorsis
familial hypercholesterolemia
| inherited defected apoprotein A
46
what is the common site of athersclorsis?
```
Bifurication ( site of turbulent flow)
Abdominal aorta -->AAA
Coronary arteries
Carotid vessel
Circle of willis
Femoral and popliteal artery
```
47
what is hypoxia?
What process leads to hypoxia?
Any state of reduced tissue oxygen availability
Generalised - whole body e.g. altitude, anaemia
Regional - specific tissues affected
Ischaemia results in tissue hypoxia
48
what is ischaemia and what causes it?
Pathological reduction in blood flow to tissues
Usually as a result of obstruction to arterial flow
commonly as a result of thrombosis / embolism
Ischaemia results in tissue hypoxia
49
what factors need to occur for cell injury to be reversible?
short duration and limited injury to the cells
50
what factors need to occur for cell injury to be irreversible?
prolonged and sustained injury that leeds to necrosis of the tissue (infarction)
51
how is tissue reperfused after a myocardial infarction?
Percutaneous coronary intervention
52
how is tissue reperfused after a stroke?
Use of thromobolytic drugs that break down the clots
53
how can reperfusion of tissue be dangerous?
| Reperfusion injury
Can produced oxygen free radicals from the inflammatory cells that can further damage the tissue and cause further problems such as inflammatory damage
54
when will reperfusion not having a effect?
if the tissue is infarcted
55
what is infarction?
Ischaemic necrosis caused by occlusion of the arterial supply or venous drainage
56
what is infarct?
An area of infarction in tissues
57
what is the most common cause of infarction and where does it usually occur?
thrombosis and embolism most common cuase in the arteries
58
what does spasm do to artery wall?
make them narrow
59
Other than embolism and thrombus what are other caues of infarction?
Spasm
Antheroma expansion from the tunica intima
Steal
Compression
Vasculitis --> inflammation of the artery walls
Hyperviscosity
Volvus
Rupture of supply such as Abdominal aorta aneurysm
60
what is the cause of compression on arteries?
the growth of a tumor underneath the blood vessel and therefore narrows the blood vessel
61
what is the name of the condition where there is twisting of blood vessel causing infarction?
volvulus
62
Infarction can be classified by morphology.
| What are the 2 colours the groups are based on?
anemic --> white infarction
| haemorrhagic --> red infarction
63
what is red infacrtion?
Organ that has Dual blood supply / venous infarction
64
what occurs in white infarction?
Single blood supply hence totally cut-off in organs with one blood supply e.g. the heart
65
what shape is most infarction and usually where is the point of obstruction?
Wedge shaped and the obstruction is usually at the upstream point.
Therefore all of the down stream is infarcted
66
what is the usual histological characterstic of a infarct tissue?
Coagulative necrosis
67
what is the histological characterstic of infarction in the brain?
Colliquative necrosis
68
if some one dies of a heart attack (instant) why won't there be any histological characterstic straight away?
this is because it takes at least a few hours for the tissue to show signs of damage --> not enough time for inflammatory response
69
what factors infuence the degree of ischeamic damage?
Nature of the blood supply
Rate of occlusion
Tissue vulnerability to hypoxia
Blood oxygen content
70
in terms of nature of blood supply what is key in the degree of ischaemic damage?
whether or not the organ has a dual blood supply or not. If they do then they have another route for blood supply and therefore damage is not as bad
71
Give examples of organs with dual blood supply
Lungs (pulmonary and bronchial arteries)
Liver (hepatic artery and portal vein)
Hand (radial and ulnar artery)
72
Give examples of organs with singal blood supply?
Kidneys, spleen, testis and heart and are prone to infarction
73
What is the advantage of slow developing occlusion?
Give example in terms of coronary arteries?
Less likely for infarction to occur
Allows the development of alternative (collateral) perfusion pathway
In coronary arteries of the heart there are small anastomosis between the main branches.
This allows the flow of blood through these channels if there is a slow occlusion and can even divert and get around large occlusions.
74
how quickly does irreversible cell damage occur to neurones in the brain?
within 3 to 4 minutes
75
What is the weight of the brain and what does it require in terms of cardiac output and the percentage of oxygen consumption required?
1-2 of our body weight but requires 15% of cardiac output and 20% of body oxygen consumption
76
how long does it take for irreversible cell damage of cardiac myocytes of the heart?
20 to 30 minutes
77
what is a stable angina?
occurs after a certain distance and after taking a GTN spray it is relieved. Constant
78
what is unstable angina?
patients develop chest pain after shorter and shorter distances or more frequently or when they are even sat a rest --> there atherosclerotic plaque is enlarging and therefore it is getting worse
79
what is a TIA?
short lived --> blockage is overcome--> only last 24 hours -->blood flow restored
80
what is difference beteen TIA and Stroke?
In stroke the blockage last for over 24 hours and therefore damage is perminant
81
What occurs in 90% of cases in ischeamic heart disease?
Caused by Impaired coronary artery flow due to complications of athersclorotic diease
82
what are the two types of stroke?
ischeamic caused by thrombosis secondary to atherscolorsis or embolism from mural thrombus (heart)
haemorrahagic --> bleeding
83
what is the cause of haemorrahagic stroke?
Intracerebral haemorrhage cause by hypertension
Berry aneurysm (Ruptured aneurysm in the circle of Willis) --> subarachanoid
Tearing of small veins in the brain --> subdural
Trauma to middle meningeal artery --> Extradural haemorrahge
84
how is haemorrahagic stroke treated?
controlling of blood pressure and coiling by blocking the aneurysm
85
what is the cause of ischaemic bowel disease?
| How is it presented?
Usually caused by thrombosis or embolism in the superior or inferior mesenteric arteries
Severe abdominal pain
86
what is gangrene?
Infarction of entire portion of limb (or organ)
87
what is gas gangrene?
Superimposed infection with gas producing organism e.g. clostridium perfringens
88
what is shock?
A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased oxygen delivery to the tissues.
89
what balance in the body is affected by shock?
What affect does this have on oxygen levels of the cells and the biochemical arrangement?
Critical imbalance between oxygen delivery and oxygen consumption.
Impariment of tissue perfusion and ultimately prolonged oxygen deprivation leads to cellular hypoxia and dearanagement of biochemical properties firstly at cellular level and then systemic level
90
what is the cellular effect of shock?
Membrane ion pump dysfunction
Intracellular swelling
Leakage of intracellular contents into the extracellular space
Inadequate regulation of intracellular pH
Anerobic respiration --> lactic acid
91
what is the systematic effects of shock?
Alterations in the serum pH (acidaemia)
Endothelial dysfunction vascular leakage
Stimulation of inflammatory and anti-inflammatory cascades
End-organ damage (ischaemia)
92
what is the sequential result of shock?
Cell death
End-organ damage
Multi-organ failure
Death
93
Is shock reversible or irreversible?
it is initially reversible but becomes quickly irreversible
94
what are the three types of shock?
HYPOVOLAEMIC
CARDIOGENIC
DISTRIBUTIVE
95
what is hypovolaemic shock?
Intra-vascular fluid loss (blood, plasma etc)
96
what happens in hypovolaemic shock?
↓ venous return to heart AKA “pre-load”
↓ stroke volume --> ↓ cardiac output
Mean arterial pressure drops
97
what is the bodies response to hypovolaemic shock?
Systemic vascular resistance (vasoconstriction). Causes increase in heart rate and increased meaning that blood does not go to the non vital organs and only blood going to vital organs.
Get cool and clammy hands.
Tachycardia and oliguria will occur --> Kidney reduced perfusion and capillary refill time will increase
98
what are the haemorrahge causes of hypovolaemic shock?
Trauma, gastrointestinal bleeding (Internally) , ruptured haematoma
Ruptured aortic, abdominal, or left ventricular free wall aneurysm
99
what are the non haemorrahge fluid loss?
diarrohea, vomiting, burns, heat stroke
100
what is third spacing that also can cause hypovoleamic shock?
when you lose your blood volume into your body cavity
101
what occurs in cardiogenic shock?
cardiac pump failure --> reduction in cardiac output
102
what are the 4 categories of cardiogenic shock?
Myopathic (heart muscle failure)
Arrythmia-related (abnormal electrical activity)
Mechanical --> problem with the valves
Extra-cardiac (obstruction to blood outflow)
103
Causes of myopathic cardiogenic shock
Myocardial infarction
Right ventricular infarction,
Dilated cardiomyopathies
Stunned myocardium” following prolonged ischemia or cardiopulmonary bypass.
104
Causes of Arrythmia-related cardiogenic shock
Atrial and ventricular arrhythmias
Atrial fibrillation / flutter ↓CO by impairment of co-ordinated atrial filling of the ventricles.
Ventricular tachycardia, bradyarrhythmias, and complete heart block ↓ CO, while ventricular fibrillation abolishes CO.
105
causes of Mechanical cardiogenic shock?
Valvular defects (e.g. prolapse), ventricular septal defects
Atrial myxomas, ruptured ventricular free wall aneurysm. Valvular
Septum and the walls affected
106
cause of extra cardiac cardiogenic scock?
Anything that impairs cardiac filling or ejection of blood from heart
Massive pulmonary embolism, tension pneumothorax,
Severe constrictive pericarditis, pericardial tamponade etc.
107
What occurs in distributive shock and how is it compensated?
reduction in systemic vascular resistance due to severe vasodilation
compensate by ↑ CO--> Flushed / bounding heart
108
what are the different types of distributive shock?
SEPTIC SHOCK
ANAPHYLACTIC SHOCK
NEUROGENIC SHOCK
TOXIC SHOCK SYNDROME
109
What is the cause of septic shock and in who'm does it occur in?
What is the outcome of septic shock
Severe or over-whelming infection caused by gram positive bacteria, gram negative bacteria or fungi
In Immunocompromised, elderly, very young
Outcome is increase in cytokines and mediators causing vasodilation
Can cause pro-coagulation (DIC) leading to ischaemia
110
what is anaphlaytic shock?
Severe type I hypersensitivity reaction
111
what are the two types sensitized individuals of anaphlaytic shock?
Hospital e.g. drugs (penicillin etc)
Community e.g. peanuts, shellfish, or insect toxins
Small dose of the allergen --> IgE cross linking
112
what occurs in anaphylatic shock?
Massive mast cell degranulation --> Vasodilation --> widespread
Contraction of bronchioles / respiratory distress
Laryngeal oedema
Circulatory collapse --> shock / death
113
what is neurogenic shock?
Spinal injury / anesthetic accidents
| Loss of sympathetic vascular tone
114
what is the cause of toxic shock syndrome?
S. aureus / S. pyogenes produce exotoxins --> “superantigens”
115
How do S.aureus and S.pyogenes cause toxic shock syndrome?
The antigens produced do not need processing by APC
So they non-specific bind class 2 MHC to T cell receptors
Can have up to 20% of T cell activated
Get a huge amount of cytokine release and cause reduction in SVR
116
what is the outcome of toxic shock syndrome?
Is it the same as septic shock
Widespread release of massive amounts of cytokines ↓SVR
Not the same as septic shock
117
Different type of shock can co-exist, give an example of how distributive, hypovolaemic and cardiogenic components can all play a role in a patient with septic shock?
Primary distributive shock - inflammatory and anti-inflammatory cascades lead to increased vascular permeability/vasodilation
Hypovolaemic component - decreased oral intake, insensible losses, vomiting, diarrhoea
Cardiogenic component - sepsis-related myocardial dysfunctio
118
what is the mortality of cardiogenic shock?
60 – 90% mortality
119
what is the mortality of septic shock?
35 – 60% die within one month of the onset
120
how does S.aureus cause toxic shock?
release an exotoxin called toxic shock syndrome toxin-1. This toxin alters the function of mononuclear phagocytes, thus impairing the clearance of other potentially toxic endotoxins.
121
What part of the blood vessel does atherosclerosis form?
Tunica intima of the blood vessel
122
What are common sites of athersoclerosis?
Bifurication of blood vessel --> turbulent flow
Circle of willis
Carotid arteries
Coronary artery --> occlusion will lead to MI but reduction in blood flow will lead to angina
Femoral and popliteal artery
Abdominal aorta
123
What is the line of zahn?
It is a characteristic feature of thrombus especially when formed in the heart or aorta.
Can see microscopically alternative line of platelets mixed with fibrin which look light and then dark line of RBC.
124
What can lead on from thrombosis?
Occlusion of vessel
Resolution or drugs to treat it
Recanalisation--> formation of new blood vessels
Incorporation of the thrombus into the vessel wall
Emoblism
125
What is a emoblis and is it always dangerous?
It is a mass of material in the vascular system where it lodges into a vessel and blocks it
Might not be that important if it blocks vessel going to a tissue/organ with multiple blood supplies
Serious when it only has one blood supply
126
What are the different states of embolism?
May be endo or exogenous
Solid, liquid or gas
127
What is the pulmonary emboli common cause of?
Hospital morbiditiy and mortality
128
What is vegetation and where does it commonly grow?
Commonly grows on valves and is abnormal growth that is made up of fibrin and platelets
129
How does venous occlusion cause infarction and how common is it?
Occlusion causes vein to be blocked and a back log of blood
| Not as common
130
Why is oxygen blood content importent in terms of infarction?
If you have reduce blood concentration due to anemia more chance of having a infarct?
131
How can a congestive cardiac failure (heart failure) caue infacrtion?
You have reduce cardiac output and poor pulmonary perfusion so therefore a small blood occlusion can lead to a infarction when normally it would not.
132
What is the clinical manifestation of infarction in the intestines?
Ischeamic bowel
133
What is the clinical manifestation of infarction in the extreimities?
Peripheral vascular disease
| Gangrene
