23,24,25 Flashcards
(116 cards)
1
Q
What is atherosclerosis
A
Degeneration of arterial walls characterised by fibrosis, inflammation and lipid deposition which limits blood circulation and predisposes to thrombosis
2
Q
How does endothelial injury occur?
A
Generation of oxygen free radicals e.g. smoking.
Also haemodynamic injury, chemicals, immune complex, deposition and irradiation
3
Q
How does an atherosclerotic plaque form
A
Hyperlipidaemia
Lipid accumulates in the intimal
Monocytes migrate to the the intimal (due to lipid and endothelial injury)
Monocytes ingest lipids and form foam cells - makes a fatty streak
Monocytes secrete cheekiness to attract neutrophils/macrophages/smooth muscle
Smooth muscle proliferates and makes connective tissue
Atherosclerotic plaque formed consisting of extracellular material, fat and leukocytes of smooth muscle cells
4
Q
What is the structure of an athersclerotic plaque
A
Fibrous Cap
Necrotic core where macrophages due
Fibrosis at the shoulder
5
Q
What is the difference between a macrophage and monocyte
A
It is monocyte in the blood and a macrophage when it enters the tissue
6
Q
What are the 3 consequences of atherosclerosis
A
Occlusion
Haemorrhages - vessel wall weakened can lead to an aneurysm
Erosion - thrombosis forms if cap is eroded
7
Q
What is emobolus
A
A mass of material in the vascular system able to lodge in a vessel a block it
8
Q
What is the most common type of embolus
A
A thrombosis
9
Q
Features of a clot
A
Elastic
Enzymatic process
Takes shape of vessel
Stagnant blood
10
Q
Features of a thrombosis
A
Forms during life
Platelet dependent
Firm
11
Q
What is a thrombosis
A
Solidification of blood constituents formed in the vessel during life
12
Q
Do platelets have a nucleus
A
No - they are just fragments of megakaryocytes
13
Q
What do alpha granules in platelets secrete
A
Fibrinogen, fibrinonectin, PDGF
14
Q
What do dense granules in platelets secrete
A
Chemotactic chemicals
15
Q
What can cause arterial thrombosis
A
Plaque rupture - due to turbulent flow and intimal change
Hyperlipidaemia - change in blood constituents so more likely to clot
Platelets bind and fibrin is produced entrapping RBC’s as chemotactic chemicals are formed
16
Q
What lines of Zahn
A
Show what atherosclerotic plaques look like
17
Q
Describe blood flow around atherosclerotic plaques
A
Laminar flow on the way up
Turbulent flow on the way down - more likely to form clots here
18
Q
Where are clots most likely to form with regards to an athersclerotic plaque
A
On the downside of the atherosclerotic plaque due to the turbulent flow
19
Q
What is likely to cause venous thrombosis
A
Stagnation of blood e.g immobility
Change in constituents e.g. Factor V Leiden
Intimal changes e.g. valves
20
Q
Effect of oestrogen on clotting
A
It is pro-thrombotic
21
Q
What are thrombi in the heart known as
A
Mural thrombi
22
Q
What increases the stickiness of the muscle wall
A
MI and myocarditis
23
Q
Describe the sequelae of a thrombosis
A
Occlusion
Resolution
Incorporation of thrombus into the vessel wall
Recanalisation through the fibrotic thrombosis
Embolization of the thrombus detatches
24
Q
Most common type of emboli
A
Pulmonary emboli
25
How to diagnose a pulmonary emboli
A CTPA
26
Congenital risk factors of thrombtic emboli
Protein S defeciency
| Factor V Leiden
27
Acquired risk factors of thrombotic emboli
Paradoxical emboli e.g. hole in heart
| Immobility, malignancy, smoking, oestrogen, obesity, pregnancy etc
28
What is saddle embolus
Sits where the pulmonary arteries bifurcate
29
Name the different types of emboli
```
Systemic
Infective
Tumour
Air
Amniotic Fluid
Fat
Foreign Body
```
30
Where do systemic emboli form
In the heart - following MI or AF
| Or in arterial circulation
31
Types of systemic emboli
Atheroma - from eroded plaques
| Platelet - often asymptomatic, arise from atherosclerotic plaques and responsible for causing TIA's
32
What causes TIA's
Platelet systemic emboli
33
What are infective emboli
Small emboli that break of from vegetations on infected heart valves
34
What can be the consequence of an infected emboli
Can form a microcytic aneurysm where it lodges
35
Who is infective endocarditis common in
young people with prosthetic heart valves and IV Drug Users
36
What happens in a tumour embolism
Small part of a tumour breaks off - often too small to be symptomatic but major route of tumour dissemination
37
Two types of gas embolism
Air
| Nitrogen
38
How does an air embolism form
Due to obstetric or chest wall procedures
| Only occurs if more than 100ml of air enters
39
How does a nitrogen embolism form
Occurs in divers/tunnel workers
Nitrogen dissolve in the blood under the pressure
When we surface the nitrogen bubble out of the blood
Nitrogen bubbles enter bones, joints lungs affecting all systems neurological/cardiac
40
How does an amniotic fluid embolism occur
High intrauterine pressure during labour forces some amniotic fluid into maternal veins (may contain foreignsbstance)
Emboli lodge in blood causing respiratory distress
41
What histological findings might you get in amniotic fluid embolism
May see shed skin cells in the lung
42
What usually causes a fat embolism
80% occur in patients with significant trauma
E.g. mainly bone fracture or severe burns (fat precipitates out at high temperature)
Fatal in 15%
Sudden onset respiratory distress
43
Why is it hard to detect fat emboli in a post mortem
as we don't specifically stain for fat
44
What is a foreign body emboli
Emboli due to foreign material injected intravenously
E.g. IVDU's
Leads to a granulomatous reaction!
45
What is hypoxia
state of reduced oxygen availability
general = anemia/altitude
can be tissue specific
46
what is ischaemia
pathological reduction on blood flow, can cause hypoxia
47
Problems with therapeutic reperfusion
Can get reperfusion injury
48
What is reperfusion in jury
the generation of oxygen free radicals produced during hypoxia and released in repercussion
Activates inflammatory cascade causing widespread damage
49
What is infarction
Ischaemic necrosis due to the occlusion of arterial supply
50
Causes of infatction
```
Thrombus/emoblus
Vasopasms
Atheroma spasm
Steal - at the branching of the vessels if one is narrowed blood goes down the path of least resistance
Venous occlusion
Extrinsic compression
Volvulus
Vasculitis
Hyperviscosity
```
51
Morphology of infarction
Red (hemorrhagic) - occurs if there is dual blood supply/venous infarction e.g. pulmonary embolus
White (anaemia) occurs with single blood supply
52
4 factors affecting the degree of ischaemic damage
Blood supply
Oxygen demands of tissue
Rate of occlusion
Blood oxygen content
53
What areas have dual blood supply
liver, lungs, hands
54
what areas have single blood supply
Kidney, testis, spleen
Watershed regions between anastamosis e.g. the splenic flexure
Portal vasculature e.g. part of exocrine pancreas
55
How does rate of occlusion affect ischaemic damage
If slow can generate collateral circulation
| E.g. coronary arteries have small anastomosis between main branches through which blood can be redirected
56
Which tissue is most vulnerable to hypoxia
Brain - uses 20% of bodies oxygen
Neutrons die within 3 to 4 minutes
Cardiac myocytes can live for 20 to 30 minutes
57
Why does congestive heart failure make ischaemic damage more likely
Poor cardiac output and pulmonary ventilation
| Decreases the oxygen content in the blood
58
What do we give to treat angina
GTN
59
What is TIA
Stroke reduced within 24 hours
60
When would we suspect ischaemic bowel disease
Pain after eating due to increased blood demand
61
What are the 2 types of cerebrovascular disaese
Ischaemic stoke
| Haemorrhagic stroke
62
What is a hemorrhagic stroke
Intracerebral haemorrhage secondary due to hypertension
Get ruptured aneurysm e.g. berry aneurysm
common in patients with tissue disroders
63
What type of incident is common in people with connective tissue disorders
Intracerebral haemorrhage
64
What is gangrene
The infarction of entire portion of a limb or organ
65
When do you get gas gangrene
Necrosis with superimposed infection of a gas producing organism e.g. clostridium perfringens
66
What is shock
Significant reduction of systemic perfusion (HYPOTENSION) causing reduced oxygen delivery to the tissue
67
Cellular effects of shock
Membrane ion pump dysfunciton
Cellular swelling
Leakage of intracellular proteins into extracellular space
Anaerobic respiration - makes lactic acid - inappropriate pH regulation
68
Systemic effects of shock
Alteration in pH (Acidic)
Endothelial dysfunction - vascular leakage
Stimulation of inflammatory and anti-inflammatory cascades
End organ damage
69
Cardiac output =
Stroke volume x heart rate
70
What affects stroke volume
Skeletal pump
Respiratory pump
Blood volume
71
Mean arterial prssure =
cardiac output x total peripheral resistance
72
What affects total peripheral resistance
arterial radius
73
Name the 3 main types of shock
Hypovolaemic
Cardiogenic
Distributive
74
What happens in hypovolaemi stroke
Due to intravascular fluid loss
| Decreased cardiac output - increased SVR (vasconstriction)
75
Causes of hypovolaemic stroke
Haemorrhagic - e.g. trauma, GI leed, fractures etc
| Non-haemorrhagic - DnV, burns, third spacing
76
What is third spacing
Loss of fluid into body cavities - occurs commonly post op and in intestinal obstruction
Can cause hypovolaemic shock
77
What is cardiogenic shock
Cardiac pump failure
| Decreased cardiac output and increased systemic vascular resistacnce
78
4 types of cardiogenic shock
Myopathy
Arrythmias
Mechanical
Extra-cardiac
79
What is myopathy cardiogenic shock
Occurs after MI, RV Infarction =, cardiomyopathies etc
| Stunned myocardium
80
What is arrhythmia cardiogenic shock
Occurs with atrial and ventricular fibrillations, tachycardias and arrhythmias etc
81
What is mechanical cardiogenic shock
Problems with valves, septal defects etc
82
What is extra-cardiac cariogenic shock
Anything that impairs cardiac filling or ejection of blood from heart
E.g. massive PE, tension pneumothorax, restrictive pericarditis, cardiac tamponade
83
What is distributive shock
Decreased SVR due to severe vasodilation. Increase cardiac output by increasing heart rate
84
Types of distributibe shock
Septic
Anaphylactic
Neurogenic
Toxic shock
85
What is septic distributive shock
Sever overwhelming systemic infections
Increase cytokine mediators causing vasodilation
Procoagulation - causes DIC
86
What is anaphylactic distributive shock
Allergen causes IgE cross linking - mast cell degranulation - vasodilation
Contraction of bronchioles causing respiratory distress
Laryngeal oedema
Circulatory collapse - death
87
When does laryngeal oedema occur
In anaphylactic shock
88
What is neurogenic shock
Occurs in spinal injury/anaesthetic
Loss of sympathetic tone
vasodilation
89
What is toxic shock syndrome
S. aureus and S. pyogenes produce exotoxins
Exotoxins do not require processing by APC
Non-specific binding of MHCII to T cells receptors
Upton 20% of all T cells activated - widespread release of cytokine - decreases of SVR
90
What type of shock can tampons cause
Toxic shock syndrome (part of distributive shock)
91
How can shock types combine
One type can lead to the next e.g.
Septic shock - primary causing inflammatory and anti-inflammatory cascades - increaes vascular permeability
Hypovolaemic opponent - decreased oral intake and insensible losses through VnD
Cardiogenic shock - sepsis-related myocardium dysfunction
92
Mortality of septic shock
35-60% die within 1 hour
93
Cardiogenic shock mortality
60-90%
94
When do most inborn errors of metabolism present
In childrhood
95
What are most inborn errors of metabolism defects in
Defects in enzymes
96
What can occur if blockages occur in pathways in inborn errors of metabolism
Can get accumulation of one substance
| This substance may then be converted into compounds not usually seen - potentially toxic
97
Role of cofactors in inborn errors of metabolism
Need to determine it is an enzyme defect not a cofactor deficiency
Problems making co factors cause the same effects as a defecient enzyme
If we replace the cofactor we can maximise what residual enzyme activity might be remaining
98
Mechanisms of disease in inborn errors of metabolism
Accumulation of toxins
Enzyme defeciency
Defecienct production of essential metabolite/structural component
99
When does ammonia accumulate
Defects in the urea cycle
100
What does the urea cycle aim to do
Remove ammonia produced from the breakdown of amino acids
101
What are the symptoms of ammonia accumulation
Lethargy, vomiting, tachypnoea, convulsions, coma, death
102
When does a childhood with defects in the urea cycle become recognised
Usually normal at birth as using the mothers metabolism
| Usually presents over the next few days/weeks
103
When do porphyrins accumulate
Problems in harm synthesis
| can only have mild problems as severe problems are incompatble with life
104
What are the 2 types of problems in porphyrias
```
Acute attacks - only in times of stress
Photosensitivity porphyria (thought of as werewolfs)
```
105
What happens in acute porphyria attacks
```
Severe abdominal pain
Chest/back pain
Vomiting, constipation, diarrhoea
Red/brown urine
Insomnia/anxiety
Hypertension
Seizures/metnal changes
Breathing problems/muscle problem
```
106
What happens in photosensitive porphyria attacks
```
Sensitivity to sun/artifical light
Itching
Sudden painful erythema and oedema
Fragile skin
Increased hair growth
Red/brown urine
```
107
When can enzyme defeciency present
Present due to defects in fatty acid oxidation e.g. could be hypotonic
Often well until the patient becomes ill
108
Describe a type of deficient production of essential metabolties
Healthy female phenotype but the abnormal breast development and absent pubic hair - genetic male
Occurs due to defect in androgen receptor
Presentation of primary amenorrhoea, infertility and ambiguous genitalia
Usually needs surgical resection of residual gonads
109
How to diagnose Inborn errors of metabolism
Pre-symptomatic screening
| Investigating symptomatic individuals e.g. basic urine screens for amino acids etc.
110
Problems of homocytinuria
```
Mental retardation
Marfinoud habitus
Ectopia lentis
Osteoporosis
Thromboembolism
```
111
What is the presence of hyperhomocystinanaemia
5%
112
Complication of mild hyperhomocystinaemia
Higher risk of stroke, peripheral vascular disease and coronary artery disease
113
What do classic organic acidaemias often defects in
Branched chain amino acid catabolism
114
What are the 3 inborn errors commonly picked up
Leucine, isoleucine, valine
115
What do we test for in the first trimester for Down's syndrome
PAPA, hCG, nuchal translucency
116
What do we test for in the second trimester for Downs Syndrome
Maternal serum AFP, hCG, inhibin and estriol
| Also test free foetal DNA
