Pathology Flashcards
1
Q
Some uses for PCR?
A
Diagnosis of neoplasms
Identification of micro-organisms
2
Q
Steps in PCR?
A
94-96ºC - The strands are separated, this is called denaturing.
50-60ºC - The oligonucleotide primers attach to the separated strand (annealing)
72ºC - The taq DNA polymerase binds and extends the strand from the primer (amplification).
3
Q
How long does PCR typically take?
A
A couple of hours
4
Q
What is the drawback to the extreme sensitivity of PCR?
A
contamination.
5
Q
What is grade in cancer?
A
How closely the neoplasm resembles normal tissue.
6
Q
What grade represents a better prognosis in cancer?
A
Well differentiated cancer (resembles normal tissue)
7
Q
What is stage in cancer?
A
The anatomical spread of the cancer.
8
Q
What is TNM?
A
A staging system for cancer.
9
Q
What is an atheroma ?
A
The patchy accumulation of fat with the arteries.
10
Q
What is a fatty streak?
A
The deposition of fat within the tunica intima this is digested by macrophages.
11
Q
How does a fatty streak become a plaque?
A
- Some of the foam cells die and release fat into the extracellular space.
- Prompts a chronic inflammatory response.
- More macrophages and T-cells are recruited.
- Smooth muscle cells in the media multiply and migrate into the intima, they become fibroblast like and start secreting collagen and other matrix compounds.
12
Q
What is in the core of a plaque?
A
Necrotic lipid tissue.
13
Q
What is superficial to the core of the plaque?
A
The fibrous cap containing smooth muscle cells and collagen (facing the lumen)
The chronic inflammation with macrophages, T-lymphocytes and smooth muscle cells.
14
Q
What are the vascular effects in inflammation?
A
- Relaxation of pre-capillary sphincters to produce hyperaemia (increased blood flow)
- Increased capillary permeability.
15
Q
What are the actions of circulating cells in inflammation?
A
- Adhesion of leucocytes
- emigration
- chemotaxis
16
Q
What is diapedesis of red cells in inflammation?
A
Escape of red cells through the damaged endothelium.
17
Q
Degranulation of mast cells can release what pre-synthesised mediators?
A
Histamine
Serotonin
Heparin
Proteases
18
Q
Degranulation of mast cells can release what newly synthesised mediators?
A
Prostaglandins
Platelet activating factor
Cytokines
Eosinophil chemotactic factor
19
Q
What are the roles of macrophages in inflammation?
A
- Phagocytosis
- Release of antimicrobial factors such as proteases
- Release of cytokines
- Presentation of antigens to activate other cells
20
Q
How can we distinguish between neoplastic and reactive proliferations?
A
Reactive proliferations are polyclonal, neoplastic proliferations are monoclonal.
PCR can be used to distinguish between the two.
21
Q
What are Natural killer cells, what is their role?
What receptors do they have?
A
Leucocytes that that can destroy virally infected and neoplastic cells with requiring previous sensitisation.
They have Ig Fc receptors
22
Q
What is the role of fibroblasts? (2)
A
ECM secretion in healing
Cytokine secretion
23
Q
What are the four cascade systems of plasma proteins?
A
- Coagulation
- Complement
- Fibrinolytic
- Kinin
24
Q
Explain briefly the complement cascade?
A
The Classical stimulation is Ab-Agor manna-binding lectin.
The alternative is endotoxin,
This causes C3b to cause opsonisation, C3a/C5a to cause chemotaxis and degranulation of mast cells and the membrane attack complex
25
Brief description of the kinin system?
Activated factor XII can activate bradykinin which can:
- Activates plasmin
- Pain
- Vascular dilation and permeability
26
What are the three alternative routes of action that can happen following tissue injury?
If there is a population of cells that can regenerate and there is minimal damage to the matrix then healing by resolution can occur.
If the cells cannot regenerate and/or there is extensive tissue damage then granulation tissue and scarring occurs
If there is continued tissue damage then chronic inflammation can occur.
27
What are the tow conditions that cause COPD?
Chronic bronchitis and Emphysema
28
What is chronic bronchitis and what is it's clinical definition?
Chronic bronchitis is persistent inflammation of the bronchi. Definied clinically as a persistent cough for at least 3 consecutive months in 2 years.
29
What causes Chronic bronchitis?
Caused by irritants that damage the respiratory mucosa, most commonly Tobacco smoke.
30
What can cause narrowing of the brochi in chronic bronchitis? (3)
Increased mucus in the lumen (due to hypertrophy of mucus glands)
Inflammatory oedema of the wall.
Hypertrophic smooth muscle layer.
31
When chronic damage to the bronchial epithelium results in metaplasia of that epithelium what is the resultant type of epithelia?
Stratified squamous.
32
What symptoms is the nickname Blue Bloater used to describe in patients and what is this usually the result of?
Blue - due to cyanosis
Bloater - overweight due to exercise intolerance
Usually the cause of chronic bronchitis.
33
What is an infective exacerbation of chronic bronchitis?
Infection due to the fact the the excess mucus in bronchitis has increased the chances of this occurring.
34
What do clinicians mean when they refer to a chest infection?
infective exacerbation of chronic bronchitis or pneumonia.
35
What exactly is emphysema?
The abnormal enlargement of the airspaces distant to the terminal bronchioles due to destruction of the alveolar walls and the respiratory bronchiole walls.
36
What is the pathogenesis of emphysema?
Protease/anti-protease imbalance.
The tobacco smoke causes neutrophils and macrophages to release large amounts of proteases
The tobacco smoke free-radicals inactivates anti-proteases so that more proteases are present.
The proteases go onto destroy lung tissue.
37
What is alpha-1-antitrypsin deficiency?
Inherited deficiency in alpha-1-antitrypsin, so that even air-pollution can lad to early onset emphysema.
38
What are the clinical features of emphysema?
The 'pink puffer' image. Patients typically use accessory muscles and a lot of effort to breathe and therefore are not cyanotic, they may also breathe through pursed lips.
Can be Barrel chested and have a low BMI.
39
What is bullous emphysema and what complication can arise from it?
When bullae (air filled sacs) are produced just below the visceral pleura in emphysema
If a Bulla ruptures this can cause pneumothorax.
40
What is the type of pathogen associated with acute bronchitis?
Viruses e.g. in laryngotracheobronchitis
41
In type 2 respiratory failure what causes increased inspiration hpoxia or hypercapnia?
Hypoxia (it is usually hypercapnia)
42
Effects of lung cancer?
Ectopic hormone production
Cachexia
43
What is a haemothorax?
Blood in the pleural cavity.
44
What is the characteristically coloured sputum in pneumonia?
Rusty coloured and green speckled.
45
What does pyrexial mean?
Fever.
46
What exactly is pneumonia?
Inflammation of the parenchyma by a virus or bacteria.
47
Two main anatomical types of pneumonia?
Lobar or bronchopneumonia.
48
What are the five physiological means by which hypoxaemia occurs?
```
Hypoventilation
Shunt
Inspired PO2 (Altitude)
V/Q mismatch (ventilation/perfusion)
Diffusion block
```
49
What is hypoxaemia?
Low oxygen in blood.
50
What are the two main blood supply systems to the lungs? what does each supply?
Bronchial circulation - arises from systemic circulation to supply smooth muscle, nerves and interstitial tissue
Pulmonary circulation - arises from the pulmonary arteries and the right side of the heart, supplies capillary networks of the alveoli.
51
Difference in pulmonary and systemic circulation?
Low pressure, low resistance.
52
What is a pulmonary embolus?
Obstruction of the pulmonary arterial system by a factor that was previously in the venous system.
53
What clinical signs would a large pulmonary embolus produce?
Sudden onset of chest pain
Breathlessness
Collapse
Low BP
54
Why might you not perform thrombolysis?
Coma
Recent Haemorrhage
Severe hypertension
55
Activating factors for platelets and their function?
Activating factors: Thrombin, Exposed collagen
Function: Secretion of pro-thrombotic substances, Aggregation to form a plug of platelets stuck together.
56
Activating factors for the coagulation cascade and it's function?
Activating factors: Abnormal surfaces, tissue thromboplastin.
Function: Production of thrombin, production of fibrin
57
What substances do endothelial cells produce which inhibit blood clotting?
NO and prostacyclin which inhibit platelets
Thrombomodulin: inhibits the clotting factor pathway
58
What factors that inhibit the coagulation cascade are in the normal circulation?
Antithrombin III
Protein C
59
What spinal levels supplies the sympathetic innervation of the heart?
T1-T5
60
Three components of Virchow's triad?
Damage to vessel wall
Alterations in flow of blood
Alterations in coagulability of blood
61
Two examples of alterations in the flow of blood?
Turbulence, stagnation.
62
What can cause hypercoagulabilty of blood?
Increased viscosity
| Thrombosis/thrombolysis
63
What are the three possible outcomes following a thrombosis?
Complete resolution with disappearance of thrombus
Organisation by granulation tissue to produce a scar, could cause stenosis or complete occlusion
Fragments of the thrombus break off into the circulation (embolism)
64
Possible origins of embolisms?
Gas, e.g. nitrogen in divers, or air in trauma
Fat e.g. after extensive trauma or burns
65
Possible consequences of emboli?
Systemic emboli may cause infarction if they block an end artery
Pulmonary emboli - breathlessness or no symptoms ranging to death.
66
Following endothelial injury, what factors promote coagulation?
Platelets adhere to ECM via Von Willibrand factor
Activated platelets release ADP and thromboxane
Fibrin polymerisation eventually forms platelet plug
67
What are the three major macroscopic types of atherosclerotic lesion?
Fatty streak
Fibrolipid plaque
Complicated lesion
68
Features of Stable and Unstable plaques?
Stable - Concentric, fibrous and smooth muscle rich.
Unstable - Lipid and macrophage rich prominent inflammation and endothelial damage.
69
Process following the formation of a fatty streak?
Lipid accumulates in the intima
Foam cells die releasing lipid into the extracellular space
This promotes a chronic inflammatory response, T-cell and macrophages accumulate.
Smooth muscle in the media proliferate into the intima and become fibroblast-like and start secreting collagen and other matrix components
70
What is the should of the atheroma and what is important about it?
The sides (before it touches the endothelium)
Important because this is where chronic inflammation normally occurs, this is where haemorrhage is most likely to occur
71
What are the two types of atheromatous aneurysms?
Fusiform - equally expanded on either side of the artery
saccular - forming a specific sac
72
What is the part of the vessel/artery that gives it strength?
The media
73
What is a cerebral (berry) aneurysm, what are they commonly caused by?
Aneurysms in cerebral arteries, caused by congenital weaknesses in artery walls.
74
What is the most common cause of aortic aneurysms?
Atheroma
75
How can you treat an aortic aneurysm surgically?
By-pass graft.
76
What's a cardiac aneurysm?
When there is an out-pounching of the actual heart
77
What is aortic dissection?
A tear in the tunica intima meaning blood forces it's way along the media.
78
What is the most common cause of aortic aneurysms?
Atheroma
79
How can you treat an aortic aneurysm surgically?
By-pass graft.
80
What's a cardiac aneurysm?
When there is an out-pounching of the actual heart
81
Treatment for aortic dissection?
Reduction in blood pressure, and surgery if possible.
82
What is a cardiac tamponade?
When blood accumulates in the pericardial sac, stops the heart from beating effectively.
83
What type of murmur would mitral stenosis produce and when would you hear this?
Diastolic murmur, heard after the second heart sound.
84
Clinical features of aortic dissection?
Sudden severe chest and back pain moving inferiorly.
85
Treatment for aortic dissection?
Reduction in blood pressure, and surgery if possible.
86
Normal clinical features of valvular disease?
Heart murmurs.
87
What type of murmur would aortic regurgitation produce?
Diastolic murmur
88
What type of murmur would aortic stenosis produce and when would you hear this?
Systolic murmur, heard after the first heart sound.
89
What is rheumatic fever?
An autoimmune condition where antibodies to group A streptococci cross react with antigens in the heart.
90
Common bacteria that cause endocarditis?
Strep. viridans
| Staph. aureus
91
Clinical features of Infective endocarditis?
Fever, malaise, weight loss
| New or changing murmur
92
Possible causes of valve disease?
Congenital heart disease, rheumatic heart disease, endocarditis.
93
What is rheumatic fever?
An autoimmune condition where antibodies to Gp A streptococci cross react with antigens in the heart.
94
Common bacteria that cause endocarditis?
Strep. viridans
| Staph. aureus
95
Clinical features of Infective endocarditis?
Fever, malaise, weight loss
| New or changing murmur
96
Definition of shock?
Systemic hypoperfusion due to reduction in either cardiac output or in effective circulating blood volume.
97
What is cardiogenic shock?
Shock after MI, characterised by hypotension, associated with left ventricular failure.
98
5 different types of shock?
Cardiogenic, Hypovolemic, Septic, Anaphylactic and Neurogenic.
99
What is circulatory shock/hypovolemic shock?
Resulting from loss of plasma or blood volume, producing a reduction in preload, decreasing cardiac output.
100
What is septic shock?
Shock caused by the release of endotoxin, mostly from gram-negative bacteria.
101
What's the mechanism of septic shock caused by endotoxin?
LSP-LPB complexes bind to specific pattern recognition recognition receptors on the surface of macrophages causing cytokine secretion, specifically TNF-alpha.
TNF-alpha then stimulates the release of IL-1 and 6, tissue factor (promotes coagulation), and adhesion molecules and NO.
There is initially maintained cardiac output but then massive hypo perfusion mostly due to widespread vasodilation caused by NO.
102
What is anaphylactic shock?
Hypoperfusion caused by generalised and very pronounced IgE mediated reaction.
Histamine and other mediators cause widespread vasodilation.
103
What is neurogenic shock and what can cause it?
Uncommon and associated with widespread loss of vascular tone, can occur after spinal cord injury or anaesthesia.
104
What is vasculitis?
Inflammation of the walls of blood vessels
105
Problems associates with vasculitis, specifically arteritis?
reduced blood flow and often thrombi formation.
106
Pathological consequences that could arise from a weakened blood vessel wall?
Aneurysm and haemorrhage formation.
107
What is claudication?
Pain due to insufficient blood supply.
108
Possible causes of vasculitis?
Pathogenesis is unclear however often autoimmunity is thought to be associated.
109
What parts of the immune system can be activated by immunoglobulins?
Macrophages, neutrophils and NK cells can all be activated by the Fc receptor on their outer surface.
Complement cascade.
110
Two cellular causes of Necrosis?
Oncosis and apoptis
111
Definition of necrosis?
Overall appearance of tissue that has dies in a living body.
112
Definition of infarction?
Necrosis due to ischaemia
113
If the rate of occlusion of an end artery is slow what is likely to occur?
The formation of anatomoses, with adjacent arterial branches. This is due to secretion of cytokines when the tissue becomes ischaemic
114
What is a watershed infarction?
When there is an infarction at the boundary of two different arterial blood supplies.
115
Causes of venous infarction?
Thrombosis, vasculitis, neoplasm and torsion (twisting)
116
What are the steps of hypoxic cell injury?
Lack of oxygen
Less oxidative phosphorylation
Decreased ATP
Oxygen Free radicals
Membrane Damage
117
What is a repercussion injury?
When repercussion after ischaemia can actually cause injury through the generation of reactive oxygen species
118
3 major components of acute inflammation?
Increased vascular flow
Leakage of Plasma Proteins and neutrophils
Emigration of neutrophils to site of injury.
119
What is pneumonia?
Inflammation of the parenchyma of the lungs due to bacteria or viral infestation.
120
Four general main causes of heart failure?
Cardiac muscle impairment
Ventricular overload
Restricted ventricular filling
Exceptionally high cardiac output
121
Mechanism and examples of how cardiac muscle failure causes heart failure?
Decreased contractility due to myocyte damage, e.g. Ischaemic heart diseases, myocarditis, alcoholic cardiomyopathy.
122
Mechanism of how cardiac muscle failure causes heart failure, examples of type?
Ventricular muscle is unable to cope with increased load, and fails.
Hypertension, Stenosis or incompetence of aortic/pulmonary valves, Incompetence of Mitral or tricuspid valves.
123
Mechanism of how restricted filling of the ventricles can cause heart failure? Examples?
Insufficient blood enters the ventricles and therefore insufficient leaves the ventricles.
Mitral or tricuspid valve stenosis, Cardiac tamponade
124
Mechanism of how excessively high cardiac output causes heart failure? Examples?
Heart simply cannot keep pace with such a high demand.
Thyrotoxicosis, Arteriovenous fistula
125
What is dilation cardiomyopathy?
Dilation of both ventricles.
126
What is Hypertrophic cardiomyopathy?
Inherited condition causing massive hypertrophy of the heart, leading often to angina and sudden death.
127
Pathophysiological changes following heart failure?
1. Increased baroreceptor response
2. Activation of RAAS
3. Sympathetic stimulation of heart increases heart rate and causes more vasoconstriction.
4. ADH concentration increase, leading to more Na+ and water retention.
5. Atrial stretch release natriuretic hormones (BNP and ANP) promoting sodium secretion.
128
Leading causes of heart failure?
Hypertension and CHD.
129
Changes seen in heart failure?
Cardiac hypertrophy and dilation
Pulmonary oedema
Peripheral Oedema
Hepatic congestion
130
Common symptoms of left side heart failure?
Breathlessness or dyspnoea, at rest or on exertion.
Paroxysmal nocturnal dyspnoea
Orthopnoea
131
Common symptoms of left side heart failure?
Peripheral oedema
Swollen abdomen
Liver Pain
132
Clinical features of heart failure?
Cool hands and feet - peripheral cyanosis
Low systolic BP
Raised JVP
Displaced Apex beat
Peripheral oedema
133
What about the heart sounds can be used to diagnose heart failure?
If the 3rd and 4th heart sounds are heard.
134
What are the 3rd and 4th heart sounds caused by?
3rd - Blood entering the ventricles in early diastole
4th - Blood entering the ventricles in late diastole
135
What is meant by the term Glomerulanephritis?
A disease characterised by glomerular inflammation
136
What is the effect of chronic inflammation on the glomerulus?
Fibrosis occurs and the glomerulus forms a small round scar.
137
in Glomerularnephritis why does inflammation cause proteinuria, and the appearance of red cells/leukocytes in the urine?
Due to the increase in glomerular capillary permeability.
138
What two hormone's release is reduced in chronic renal failure?
EPO and Calcitrol
139
Symptoms of systemic lupus erythematosus?
```
Lethargy
Low-grade fever
Assymetrical arthritis
Rash
Evidence of nephritic syndrome
```
140
Does SLE reduce or increase the GFR?
Reduce.
141
Pathogenesis of SLE?
Immune complex deposition, these are made up of antigens (IgG) and antibodies (normally Nuclear material), and are normally removed by the bodies monocyte macrophage system, in SLE they are deposited within the capillary walls of the glomerulus
142
How is immunofluorescence for IgG performed?
An antibody to human IgG (e.g. from mouse) is placed on the section and then washed, if the antibody has bound it will not wash off, then an anti-mouse antibody is put in with a fluorescent probe attached.
143
What type of hypersensitivity is SLE?
Type III
144
In what two ways can cause the immune complexes appear in the capillary wall?
Either formed in the circulation and deposited in the walls or the antigen is deposited in the walls and then the antibody binds.
145
What is membranous glomerulonephritis?
When there are immune complexes deposited in the membrane of the glomerulus, does not cause a full inflammatory reaction but does cause nephrotic syndrome.
146
What are the pathological changes to blood vessels in diabetes?
Atherosclerosis, and microagiopathy (thickened basement membranes that are more permeable to proteins)
147
Pathophysiological changes in nephrotic syndrome?
There is a huge loss of protein due to glomerular inflammation.
The liver cannot synthesise enough protein to keep up the urinary loss, small proteins such as albumin are lost at a high rate, larger ones are not lost at such a high rate.
Hypoproteinaemia reduces plasma oncotic pressure and peripheral oedema is the result.
148
What is goodpastures syndrome?
IgG antibodies themselves bind to all of the glomerular basement membrane and initiate an inflammatory response themselves.
149
Causes of acute tubular necrosis?
Ischaemia, hypotension 'shock'
150
Normal temperature ranges? What's a good going fever?
36.5-37
151
What can you give in anaphylactic shock? why?
Adrenaline, anaphylactic shock is due to vasodilation and so adrenaline is given to counter that.
152
When is hypovelemic shock most prevalent?
Burns victims and in pelvic fractures (bleeding into the pelvic cavity occurs
153
Main clinical signs of nephrotic and nephritic syndrome?
Nephrotic: high proteinuria, hypoalbiminaemia, oedema
Nephritic: Hypertension, mild/moderate proteinuria and haematuria
154
How do you recognise First degree heart block?
Slightly extended PR interval
155
How do you recognise Second degree heart block (Mobitz I)?
The PR interval gets progressively longer until there is no transmission and then resets
156
How do you recognise Second degree heart block (Mobitz II)?
Prolonged PR interval (but stays that way) with intermittent loss of AV node conduction
157
How do you recognise third degree heart block?
No connection between P waves and QRS complex.
158
Why does the AVR chest lead have a downward deflection?
Going away so it is negative.
159
If the anterior of the heart is infarcted which leads are affected?
V3/4
160
why is 2,4 dinitrophenol poisonous?
A mitochondrial uncoupling agent - removes the electrochemical gradient and makes all the complexes in the inner mitochondrial membrane work at maximal rate. this produces heat and H2O2.
161
Following heart failure what does the body do?
Thinks it has haemorrhaged and tries to increase blood pressure (TPR) through increased sympathetic drive and activation of the RAAS pathway.
This means the heart has to work harder and it get's worse
162
What is the reason for fatigue in cardiac failure?
Decreased perfusion
163
What is the reason for SOB in cardiac failure?
Pulmonary oedema
164
What is the reason for increased central venous pressure in cardiac failure?
Due to back pressure from the pulmonary oedema
165
What diuretic would you choose to use for an old male with Left side heart failure?
Loop because it is strong, perhaps a potassium sparing one too
166
What's the danger of someone taking both a potassium sparing diuretic and someone taking an ACE inhibitor?
both can cause increased potassium retention and may lead to hyperkalaemia
167
Why do some patients develop a dry cough in response to ACE inhibitors? what can be done?
ACE is present in the lungs where is also breaks down bradykinin. If ACE is inhibited then there is more bradykinin which is an irritant.
168
In acute heart failure what drugs can you give?
Digoxin (increases heart force)
Dobutamine (B1 receptor antagonist)
