Week 2 - Pathological Mechanisms Flashcards
1
Q
What is pathology?
A
Study of disease
2
Q
What is a disease?
A
- Abnormality of cell/tissue structure &/or function
- Loss of homeostasis
3
Q
What is another name for the mechanisms?
A
Pathogenesis
4
Q
What are the 7 categories to consider in pathology?
A
- Broad patterns- epidemiology
- Causes- aetiology
- Pathogenesis
- Nature of disease
- Complications- sequelae
- Clinical presentation
- Clinical management
5
Q
What are the 4 levels of magnification in pathology?
A
- Gross (naked-eye)
- Light microscopy
- Electron microscopy
- Molecular cell biology
6
Q
What are the levels of organisation in pathology?
A
Body –> System –> Organ –> Tissue –> Cell –> Molecules
7
Q
Describe the 3 processing in making protein?
A
- DNA polymerase: replication (DNA –> DNA)
- RNA polymerase: transcription (DNA –> RNA)
- Ribosome: translation (RNA –> Protein)
8
Q
What are the 3 normal cellular processes?
A
- Cell proliferation
- Cell growth & differentiation (specialist function)
- Cell death
9
Q
What are the 6 broad tissue types?
A
- Epithelial
- Connective tissue
- Haemato-lymphoid
- Neuro-glial
- Melanocytic
- Germ cell
10
Q
What are the 3 broad tissue types for epithelia?
A
- Squamous
- Glandular
- Solid organs ie. liver, kidney, thyroid
11
Q
What are the 6 broad tissue types for connective tissue?
A
- Fibrous
- Blood vessel
- Fat
- Muscle
- Bone
- Cartilage
12
Q
What is disease a combination of?
A
The causative agent & the body’s response to it
13
Q
Describe homeostasis in normal cells?
A
- Achieved through normal cell biological mechanisms
- Usually sense & easily adjust to mild environmental changes
14
Q
What are some external environmental changes (stresses)?
A
- Physical factors
- Chemical factors
- Infection
- Nutrition, etc
15
Q
What are some internal environmental changes (stresses)?
A
- More/less functional demand
- Hormones/metabolic
- Immune response, etc
16
Q
Define cell Atrophy?
A
Smaller/fewer cells
17
Q
Define cell hyperplasia?
A
More cells
18
Q
Define cell hypertrophy?
A
Bigger cells
19
Q
Define cell metaplasia?
A
Change from 1 mature differentiated cell type to another
20
Q
Define cell dysplasia?
A
Abnormal genetic changes which may lead to cancer
21
Q
When does cell adaptation occur?
A
If environmental change (stress) is more than can be dealt with by homeostasis, then affected cell may undergo further adaptation esp. changes in cell growth (more, less, different)
22
Q
When may the cells undergo injury?
A
If the stress is more intense, longer-lasting or of a specific type, or if the cell is very sensitive
23
Q
What 2 things can cells undergo if they are directly affected?
A
- Sub-lethal cell injury
2. Cell death
24
Q
How does the body respond to cell injury?
A
Inflammation (acute/chronic)
25
What can happen to cells affected by injury over many years?
Neoplasia
26
List the cell process from normal to cell death?
Normal --> Cell with adaptation --> Cell with reversible injury --> Cell with irreversible injury --> Cell death
27
What does the mnemonic VITAMIN CDEF stand for in the possible categories of disease?
Vascular, Infective/ Inflammatory, Traumatic, Autoimmune, Metabolic, Iatrogenic/ Idiopathic, Neoplastic, Congenital, Degenerative/ Developmental, Endocrine/ Environmental & Functional
28
Describe the 4 types of physical agents which can cause disease?
1. Mechanical trauma: stricture, adhesions, hernia, criminal
2. Temperature extremes: heat or cold
3. Ionising radiation: causes DNA damage
4. Electric shock
29
What can chemicals/ drugs do?
May damage various cell organelles & processes ie. disruption of cell membranes (osmotic damage), protein production or folding
30
What are the 4 types of chemicals/drugs that can cause disease?
1. Drugs e.g. chemotherapy (cytotoxic by
definition) , paracetamol
2. Poisons (cyanide)
3. Environmental (insecticides)
4. Occupational hazards (asbestos)
31
What are the 2 possible causes of hypoxia?
1. Anaemia
| 2. Respiratory failure
32
What does hypoxia cause?
Disrupts oxidative respiratory processes (in mitochondria) in cell & decreases ATP
33
Define ischaemia?
Reduction in blood supply to tissue
34
What is ischaemia caused by?
Blockage of arterial supply or venous drainage e.g. atherosclerosis
35
What is ischaemia a depletion of what two things?
Oxygen & Nutrients (glucose)
36
Describe the immunological reaction anaphylaxis?
Type 1 hypersensitivity: IgE mediated
37
Describe the immunological reaction auto-immune reactions?
- Type 2: antibodies directed towards antigens on cells
| - Type 3: antigen-antibody complexes and their deposition
38
Describe how genetic defects can cause disease?
- Abnormalities of gene structure or number (too many or too few)
- Leads to abnormal protein or to too much or not enough protein
39
Give 2 examples of genetic defects leading to disease?
1. Sickle cell anaemia: abnormal haemoglobin chain
| 2. Inborn error of metabolism (lack of enzyme causes build up of enzyme substrate)
40
What are the 5 questions to ask when describing pathology specimens (gross or microscopic)?
1. What is the magnification (low vs. high power image)?
2. What is the organ/tissue?
3. And/or how & what is sampled?
4. Normal/abnormal?
5. If abnormal, describe (including whether it is focal or diffuse)?
41
What are the 4 questions to ask when describing pathology specimens (gross)?
1. Size?
2. Shape?
3. Colour?
4. Texture?
42
How you would describe microscopic pathology specimens?
- If not sure, consider which tissues are present, where, & whether normal or abnormal
- Abnormalities quantitative or qualitative
- Go through systematically first if no obvious abnormality, to ensure nothing missed
43
Why should you establish disease diagnosis & severity?
Predict outcome (prognosis) & guide treatment
44
Describe inflammation?
- Universal response to tissue damage
| - Can be acute or chronic, continuum
45
What 3 things can inflammatory damage be caused by?
1. Infection
2. Necrosis
3. Trauma
46
What is the purpose of inflammation?
Destroy or control the harmful stimulus, initiate repair & restore function
47
What 4 things does the inflammatory process also have a role in?
1. Autoimmune disease
2. Atheroma
3. Cancer progression
4. Treatment
48
Describe how vascular dilatation occurs?
- Arterioles dilate increasing blood flow
- Stasis of blood flow
- Fluid passes into tissues causing swelling
49
What 3 chemical mediators are involved in vascular dilatation?
1. Histamine (mast cells)
2. Prostaglandins
3. NO
50
What 3 chemical mediators are involved in neutrophil activation?
1. C5a
2. Leukotriene B4
3. Bacterial products
51
Describe how neutrophil activation occurs?
- Activation of neutrophils
- Rolling, adhesion, pass between endothelial cells
- Chemotaxis
- Phagocytosis & bactericidal
52
What 6 chemical mediators are involved in endothelial activation?
1. 5-HT
2. Histamine
3. C3a
4. C5a
5. Bradykinin
6. Leukotriene
53
Describe how endothelial activation occurs?
- Activates vascular endothelium
- Increased cell adhesion molecules --> leakiness of endothelium
- Plasma proteins travel into tissues including Immumoglobulins, Complement, Fibrinogen
54
What are the 3 vascular & cell changes that occur in acute inflammation?
1. Vascular dilatation
2. Neutrophil activation
3. Endothelial activation
55
What are the 5 clinical signs of acute inflammation?
1. Redness: caused by hyperaemia
2. Swelling: caused by fluid exudate & hyperaemia
3. Heat: caused by hyperaemia
4. Pain: caused by release of bradykinin & PGE2
5. Loss of function
56
What are the 3 different exudates that you get with inflammation?
1. Neutrophilic (suppurative/purulent)
2. Fibrinous
3. Serous
57
What are 4 factors which lead to a spread of infection?
1. Natural barriers
2. Air borne
3. Blood borne
4. Immune factors (IgA)
58
What 3 things can result from acute inflammation?
1. Resolution
2. Healing by repair
3. Chronic inflammation
59
What clinical sign can form in acute inflammation?
Abscess
60
What results in chronic inflammation?
Persisting tissue damage & ongoing acute inflammation or de novo
61
What are 3 cell infiltrates present in chronic inflammation?
1. Lymphocytes
2. Macrophages
3. Plasma cells
62
What 2 things does chronic inflammation usually lead to?
1. Fibrosis
| 2. Scarring
63
What is a subtype of chronic inflammation?
Granulomatous inflammation (specific histological appearance)
64
What is Granulomatous inflammation?
Presence of granulomas, collections of epithelioid macrophages & multinucleate giant cells
65
What are the 3 subtypes of Granulomatous inflammation?
1. Necrotising
2. Non-necrotising
3. Foreign body granulomas
66
What are the 2 types of wound healing?
1. Primary intention (simple incision, easy healing & less obvious scarring)
2. Secondary intention (dirty, infected, gaping wound with more obvious scarring)
67
Describe granulation tissue in healing?
Early blood vessels which grow in the inflammed wound
68
Does a primary or secondary intention wound have more granulation tissue during healing?
Secondary intention has more
69
What is involved in wound healing leading to fibrous scarring?
Inflammatory cells & Fibrin --> Fibrous scar
70
Describe how bone heals?
Regeneration rather than repair, callus (has osteoblasts & osteoclasts) formation
71
Give 4 reasons why we should perform a post mortem in the 21st century?
1. Confirming diagnosis/ its extent (audit of medical care)
2. Revealing diagnosis or explaining unexplainable findings (diagnostic tool)
3. Investigating possible failings in surgery or other medical care (monitor medical care)
4. Medico-legal reasons (crime, violence, suicide etc)
72
Describe a Medico-legal post mortem?
- At the instruction of the Procurator Fiscal (Scotland) or Coroner (England and Wales)
- Does not require consent of the family
73
What are forensic pathologists & what do they perform?
Sub-speciality within pathology who perform post mortem's required in certain circumstances e.g. homicide
74
What are the 2 types of background information needed from medical notes for post mortem examinations?
1. Past medical history
| 2. Summary of clinical events & treatment
75
What are the 2 types of autopsy information needed for post mortem examinations?
1. External examination
- general appearances, external disease, medical treatment
2. Internal examination
- body cavities & systems, organs examined in turn
76
What are the 2 further investigations for post mortem examinations?
1. Histology, neuropathology
| 2. Bacteriology, biochemistry etc.
77
Describe the external examination done during post mortem's?
- Identification of deceased by pathologist
- Height/weight/BMI
- Skin/hair/eye colour
78
What 3 things should you look for in an external examination during post mortem's?
1. Iatrogenic: Scars, drains, IV lines
2. Evidence of trauma
3. Jaundice, cyanosis, finger clubbing, oedema, lymphadenopathy
79
Describe Evisceration in post mortem's (internal examination)?
- Single incision from sternal notch to symphysis pubis to remove thoracic, abdominal & pelvic organs
- 2nd incision around post skull to reflect the scalp, skull is opened & brain removed
80
Who usually performs a Evisceration?
Anatomical pathology technicians
81
What happens at the end of the post mortem examination?
- Organs returned to body (minus tissue taken for microscopic assessment)
- If no death certificate has been issued, pathologist will write a death certificate
- Report sent to the PF, or for ‘consented/’Hospital’’ cases, to the patient’s GP & clinician
- Body reconstructed to permit viewing
- Body released for burial/cremation
82
Describe the layout of the medical certificate of cause of death (MCCD)?
1a. Disease or condition directly leading to death
1b. Due to, or as a consequence of,
1c. Due to, or as a consequence of,
1d. Due, to or as a consequence of,
2. Other significant conditions contributing to death, but not related to the disease or condition causing it
83
What are the 5 most frequently occurring principal causes of death, all ages, Scotland, 3 year period in 2012-2014?
1. Malignant neoplasm of bronchus & lung
2. Acute MI
3. Chronic ischaemic heart disease
4. Other chronic obstructuve pulmonary disease
5. Unspecified dementia
84
What 2 factors would you look for during a post mortem for thrombosis & infarction (vascular pathology)?
1. Thrombus in coronary artery
| 2. Dead (necrotic) muscle
85
What are the 2 potential outcomes for an MI?
1. Sudden death from arrhythmia or acute left ventricular failure
OR
2. Cardiac rupture through weakened necrotic muscle
86
Where else, apart from the heart, can you encounter thrombosis & infarction?
- Small bowel infarction due to superior mesenteric artery thrombosis
- Cerebral infarct
87
What is an embolus?
A mass of material that can move through the vascular system & is capable of blocking the lumen
88
What 4 sites can an embolus arise from?
1. Thrombus
2. Air
3. Fat
4. Amniotic fluid
89
What 3 sites can a thrombus arise from?
1. Leg veins
2. Carotid arteries
3. Inside the heart
90
What 3 sites can a thrombus embolus to?
1. Lungs
2. Brain
3. Other tissues
91
What are the 4 reasons why a blood vessel can rupture leading to haemorrhage?
1. Under high pressure
2. Congenital weakness (due to lack of elastic fibres)
3. Weakened by disease
4. Eroded into
92
What is a berry aneurysm?
Subarachnoid haemorrhage from rupture of cerebral artery aneurysm
93
What can erode a blood vessel leading to a rupture?
Ulcer
94
Describe lobar pneumonia?
- Spread through blood
- Largely confined to 1 lobe
- Lung is a grey colour (grey hepatisation)
- Severe illness
95
Describe bronchopneumonia?
- Spread through airways
- Tends to be more generalised
- Often develops on top of chronic lung disease
- Often terminal event in debilitated patients
96
What is endocarditis?
Infection of the heart valves
97
What is pyonephrosis?
Pus in the collecting system of the kidneys
98
Describe Meningococcus infection?
- Inhaling droplets from carrier
- Often previously healthy individual
- Often rapid illness (< 24hrs)
- Can occur in close communities
99
Describe pneumococcus infection?
- Usually from infection in the lungs
- More common in debilitated people
e. g. alcoholics
- Less rapid illness
100
Describe the post mortem appearance of peritonitis?
- Purulent exudate
- Reddening
- Purulent fluid (pus)
101
Give 2 examples of chronic inflammation & what caused them?
- Pulmonary fibrosis (from asbestos)
| - Liver cirrhosis (from alcohol)
102
Describe Alzheimers disease?
- Degenerative disease
| - Atrophy more pronounced in the frontal & parietal lobes
103
What are the 3 normal reactions to vessel injury?
1. Vasoconstriction
2. Platelet release & aggregation
3. Coagulation cascade
104
What does vasoconstriction result in?
Primary haemostatic plug --> Stable haemostatic plug
105
What does the coagulation cascade result in?
Thrombin --> Fibrin --> Stable haemostatic plug
106
What is the function of von Willebrand factor in primary homeostasis?
Binding to other proteins, in particular factor VIII & is important in platelet adhesion to wound sites
107
What is the coagulation pathway triggered by?
Tissue factor (TF)/factor VIIa complex
108
What does tissue factor (TF)/factor VIIa complex activate in the coagulation pathway?
Factor IX & Factor X
109
What does activated factor IX do in the coagulation pathway?
Coverts small amounts of prothrombin to thrombin which amplifies coagulation by activating factors V & VIII, platelets & platelet-bound factor XI
110
When is the coagulation pathway propagated?
Factor IXa binds to factor VIIIa on the surface of activated platelets, forming intrinsic tenase
111
What does intrinsic tenase activate in the coagulation pathway?
Factor X
112
What does activated factor X do in the coagulation pathway?
Binds to activated factor V to form prothrombinase, which converts prothrombin (Factor II) to thrombin (Factor IIa)
113
What happens in the final step of the coagulation pathway?
Thrombin converts fibrinogen to fibrin
114
In Virchow's Triad what are the 3 broad factors that are thought to contribute to thrombosis?
1. Hypercoagulable state
2. Vascular wall injury
3. Circulatory stasis
115
List 8 factors that could cause the hypercoagulable state in Virchow's Triad?
1. Malignancy
2. Pregnancy
3. Oestrogen therapy
4. Trauma/surgery of lower extremity, hip, abdomen or pelvis
5. IBD
6. Nephrotic syndrome
7. Sepsis
8. Thrombophilia
116
List 6 factors that could cause vascular wall injury in Virchow's triad?
1. Trauma/surgery
2. Venepuncture
3. Chemical irritation
4. Heart valve disease/ replacement
5. Atherosclerosis
6. Indwelling catheters
117
List 5 factors that could cause circulatory stasis in Virchow's triad?
1. AF
2. Left ventricular dysfunction
3. Immobility/paralysis
4. Venous insufficiency/ varicose veins
5. Venous obstruction from tumour, obesity or pregnancy
118
Describe the histopathology of arterial thrombosis?
- "White thrombus"
- Many platelets, small amounts of fibrin
- High flow rate
119
Describe the histopathology of venous thrombosis?
- "Red thrombus"
- Many fibrin with trapped red cell
- Slow/stagnant flow rate
120
What can be the 4 categories for differential diagnosis of a sore leg?
1. Trauma
2. Non-traumatic
3. Vascular
4. Skin/soft tissue infection
121
List the trauma causes of a sore leg?
- Fractures
- Dislocations
- Muscle strain/rupture
- Haematoma
122
List the Non-traumatic causes of a sore leg?
- MSK
- Osteoarthritis
- Rheumatoid arthritis
- Septic arthritis
- Gout
- Popliteal cyst
- Bursitis
123
List the skin/soft tissue causes of a sore leg?
- Cellulitis
- Abscesses
- Necrotizing fasciitis
124
List the vascular causes of a sore leg?
- Venous occlusion: DVT, superficial vein thrombosis, venous insufficiency
- Acute ischaemia: cardiac thromboembolism, peripheral arterial disease, massive DVT
- Lymphoedema
125
List 5 causes of systemic oedema leading to bilateral leg swelling?
1. Heart failure
2. Cirrhosis
3. Nephrotic syndrome
4. Malnutrition
5. Immobility
126
Describe deep vein thrombosis (DVT)?
- Thrombosis in deep venous system
| - Most commonly of leg
127
What is the origin of the popliteal vein?
Junction of the anterior tibial vein & posterior tibial vein
128
What do the superficial femoral vein & deep femoral vein join to form?
Common femoral vein
129
What does the common femoral vein become as it passes upwards above the groin?
External iliac vein
130
What is the % per-person lifetime incidence of vein thromboembolism?
~5%
131
Describe the 3 risk factors for DVT's?
1. VESSEL WALL: increased age, varicose veins, surgery
2. BLOOD FLOW: obesity, pregnancy, immobilisation, IV catheters, external vein compression
3. COMPOSITION OF BLOOD: thrombophilias, inflammatory conditions, oestrogen hormones
132
What is the likelihood of developing a vein thromboembolism in the 1st 6 weeks after surgery?
70x more likely
133
What 3 things help us confirm/exclude the diagnosis of DVT?
1. CLINICAL DECISION RULE: determine likelihood
2. BLOOD TESTS: fibrin D-dimer
3. IMAGE VENOUS SYSTEM OF LEG: compression ultrasound, venography
134
What is a D-dimer?
Test to measure the amount of dissolved thrombus (fibrinogen degradation products)
135
What is the scoring system called to measure how likely a person is of developing a DVT in A&E?
Well's Clinical Scoring System
- DVT unlikely if <2
- DVT possible if score >2
136
Describe the coagulation cascade?
Fibrinogen --> Fibrin Clot --> Fibrinogen degradation product
137
What changes fibrinogen --> Fibrin clot in the coagulation cascade?
Thrombin
138
What changes the fibrin clot --> Fibrinogen degradation product's in the coagulation cascade?
Plasmin
139
What is the diagnosis if the wells clinical score is <2 and the D-dimer test comes back negative?
- DVT very unlikely (<0.5%)
- Consider other diagnoses
- Issue patient information sheet
140
What is the diagnosis if the wells clinical score is <2 but the D-dimer test comes back positive?
Treat as DVT until confirmed or excluded by ultrasound
141
What is the diagnosis if the wells clinical score is >2 & the D-dimer test comes back either negative/positive?
Treat as DVT until confirmed or excluded by ultrasound
142
What are the 5 possible outcomes following a DVT?
1. Painful swollen leg
2. PE
3. Recurrent vein thromboembolism
4. Venous insufficiency
5. Post thrombotic syndrome
143
At what % does compression stockings for 2 years reduce your risk of post thrombotic syndrome in DVT cases?
50%
144
What are the 5 possible outcomes following a PE?
1. Dyspneoa, chest pain, haemoptysis
2. Collapse (massive PE)
3. Death (fatal PE)
4. Recurrent venous thromboembolism
5. Chronic thromboembolic pulmonary hypertension
145
What is the likelihood of having a recurrent PE?
4-fold more likely
146
What is a paradoxical embolism?
Embolus which is carried from the venous side of circulation to the arterial side, or vice versa (RARE)
147
What are the 4 possible means of treatment for a DVT?
1. Prevent thrombus extending or embolising
2. Remove risk factors
3. Pain relief
4. Graduated elastic compression stockings
148
What are the 3 preventative treatments for a DVT?
1. Heparin (LMWH)
2. Warfarin
3. Direct Oral Anti-coagulant (direct Xa or IIa inhibitor)
149
What is the target INR for people on warfarin preventatively for DVTs?
2.5
150
How long would you give anticoagulation medication to prevent DVTs?
3-6months
151
What are the 3 oral anticoagulant agents?
1. Warfarin
2. Xa inhibitors
3. IIa inhibitors
152
List 3 Xa inhibitor drugs?
1. Rivaroxaban
2. Apixaban
3. Edoxaban
153
Give an example of a IIa inhibitor drug?
Dabigatran
154
What are the 2 parenteral anticoagulant drugs?
1. Indirect Xa inhibitor
| 2. Indirect IIa inhibitor
155
Give 2 examples of Indirect Xa inhibitor drugs?
1. Fondaparinux
| 2. Danaparoid
156
What are 3 ways to prevent venous thromboembolisms?
1. Avoid risk factors
2. Risk assess at hospital admission or surgery
3. Provide thrombo-prophylaxis when appropriate
4. Educate patients on risks & avoidance measures (early mobilisation)
157
What are the 5 key questions to ask regarding pain?
1. Character (crushing, sharp, throbbing, dull, tight, colic-like, pleuritic)
2. Location & Radiation (to left arm or jaw, through to back)
3. Duration
4. Precipitating & Relieving factors
5. Associated features (N&V)
158
List 3 musculoskeletal causes of chest pain?
1. Rib fracture
2. Muscular
3. Chondritis
159
List 2 cardiac causes of chest pain?
1. Angina
| 2. MI
160
List 3 lung causes of pleuritic chest pain?
1. Infection
2. Infarction
3. Malignant
161
List 2 vascular causes of chest pain?
1. Pulmonary embolism
| 2. Aortic dissection
162
List 2 oesophageal causes of chest pain?
1. Acid reflux (GORD)
| 2. Hiatus hernia
163
Describe the 6 stage pathogenesis of coronary artery disease (Atheromatous arterio-vascular disease)?
1. Development of atheroma/plaques
2. Progressive narrowing & stenosis of artery
3. Plaque rupture
4. Acute thrombus
5. Vascular occlusion
6. Downstream ischaemia & infarction
164
Describe the 5 stage progression of atherosclerosis in high flow arteries?
1. Monocyte adhered to epithelium
2. Monocyte migrating into intima
3. Monocyte becoming intimal macrophage
4. Macrophage foam cell
5. Dying macrophage with apoptotic bodies
165
List 6 stages of the atherosclerosis timeline?
1. Foam cells
2. Fatty streak
3. Intermediate lesion
4. Atheroma
5. Fibrous plaque
6. Complicated lesion/rupture
166
What are the 5 coronary arteries?
1. Aorta
2. Right coronary artery
3. Left coronary artery
4. Left anterior descending coronary artery
5. Circumflex coronary artery
167
List 6 risk factors for arteriosclerotic Cardiovascular Disease?
1. Smoking
2. Hypertension
3. Hyperlipdiaemia
4. Diabetes
5. Obesity
6. Family history
168
What are 5 ways to diagnose MI/ Acute coronary syndrome?
1. History
2. Clinical evidence of cardiac dysfunction
3. ECG
4. Biochemical evidence of damage (elevated troponin)
5. Visualisation of coronary arteries (cardiac catheterisation)
169
What are the 4 possible ways to treat acute coronary syndrome?
1. Prevent thrombus extension
2. Remove the thrombus
3. Widen the stenotic plaque
4. Prevent further thrombus
170
What are 2 ways that you can prevent thrombus extension in ACS treatment?
1. Anti-platelet agent (aspirin, clopidogrel)
| 2. Anticoagulant (heparin)
171
What are 2 ways that you can remove the thrombus in ACS treatment?
1. Thrombolysis (alteplase, tenecteplase)
| 2. Remove clot via catheter (percutaneous coronary intervention)
172
What are 2 ways that you can widen the stenotic plaque in ACS treatment?
1. Balloon angioplasty
| 2. Insert coronary artery stent
173
What are the 2 ways that you can prevent further thrombus in ACS treatment?
1. Anti-platelet agent
| 2. Statin
174
How old does a myocardial infarct have to be to be seen by the naked eye?
At least a day old
175
When can the 1st microscopic changes be seen in myocardial infarction?
Around 12hrs
176
What does a myocardial infarction look like after ~48hrs?
- Yellow
| - Soft tissue
177
What does a myocardial infarction look like after ~3 days?
- Haemorrhage (red) then forms yellow necrotic area
| - Very soft tissue
178
Describe an old myocardial infarct?
- Fibrous band of tissue
- Will not function as well
- ~6-8 weeks after MI
179
What are the 7 complications following an MI?
1. Death
2. Arrythmia
3. Pericarditis
4. Myocardial rupture
5. Mitral valve prolapse
6. Left ventricular aneurysm +/- thrombus
7. Heart Failure
180
What are the 2 possible musculoskeletal causes of limb weakness?
1. Myopathy
| 2. Arthropathy
181
What are the 3 possible neurological causes of limb weakness?
1. Peripheral neuropathy
2. Spinal lesion
3. Cerebral lesion
(ischaemia, inflammation, malignancy)
182
How do you investigate a suspected stroke patient?
CT scan of brain
183
What are 3 common sites for an emboli?
1. Atheromatous carotid artery
2. Left atrial thrombus
3. Left ventricular mural thrombus
184
What is the absolute stroke risk for people with AF?
5% per year
185
What are the 2 types of AF?
1. Non valvular atrial fibrillation [NVAF]
| 2. Valvular atrial fibrillation
186
What are the 3 ways to treat stroke and AF?
1. Remove thrombus (rarely)
2. Remove/correct source of thrombus
3. Address other CVD risk factors
187
What are 2 ways to remove thrombus in the treatment of stroke & AF?
1. Thrombolysis
| 2. Carotid end-arterectomy
188
What are the 3 ways to remove / correct source of thrombus in the treatment of stroke & AF?
1. Anticoagulation (warfarin or Direct Oral AntiCoagulant)
2. Revert to sinus rhythm (cardioversion)
3. Replace defective heart valve
189
What are 2 other CVD risk factors that can be addressed in the treatment of stroke & AF?
1. High blood pressure
| 2. Hyperlipidaemia
190
What do atheroma look like in post-mortems?
Yellow plaques attached to interior of vessel wall
191
What does a recent cerebral infarct look like?
Red
192
What does a cardiac abscess look like macroscopically?
Green area
193
What is margination of leucocytes?
Free-flowing leukocytes exit the central blood stream & initiate leukocyte & endothelial cell interactions by close mechanical contact
194
Describe Vasodilatation during acute inflammation?
- Increased flow
- Allows mediators in
- Due to Nitric oxide & histamine
195
Describe increased vascular permeability in acute inflammation?
- Endothelial contraction
- Mediated by bradykinin, histamine & substance P
- Quick & transient
196
What does exudate fluid do during acute inflammation?
Takes cells & mediators to the site of injury
197
What is exudate rich in?
Proteins
198
Describe the vascular changes which occur in acute inflammation?
Chemotaxis --> Margination --> Rolling --> Adhesion --> Migration
199
What are the inflammatory chemicals adhered to?
Selectins
200
What migrates during the vascular changes of acute inflammation?
Integrins
201
What 4 inflammatory markers are attracted during chemotaxis in acute inflammation?
1. Neutrophils
2. Bacterial products
3. Complement
4. Chemokines
202
What are the 5 cellular derived (intracellular granules or synthesised) chemical mediators in inflammation?
1. Vasoactive amines (histamine & serotonin)
2. Arachidonic acid metabolites (prostaglandins)
3. Nitric oxide
4. Cytokines (TNF, IL-1 – acute phase response)
5. Interferons (macrophages)
203
What are the 2 functions of nitric oxide in inflammation?
1. Inhibits platelet aggregation
| 2. Blocks mast cell degranulation
204
What are the 2 plasma protein derived (secreted from liver in inactive state) chemical mediators in inflammation?
1. Complement (opsonisation/membrane attack complex)
| 2. Coagulation & Kinin Systems
205
What are the 5 other chemical mediators in inflammation?
1. Cascades
2. G-coupled protein receptors to bacterial products
3. Opsonisation
4. Phagocytosis
5. Termination
206
What do toll-like receptors do?
Bind bacterial & viral components & then cause further chemical stimulation
207
Describe the 3 factors in inflammation termination?
1. Short-lived mediators
2. Anti-inflammatory cytokines
3. Neural impulses
208
How can a local infection spread?
- Remain at initial site
- Spread to local lymph nodes via draining lymphatics
- Five cardinal signs!
209
What 2 ways can a systemic infection spread?
1. Haematogenous: spread through blood/lymph to cause SIRS
| 2. Track through tissue to form abscess/infection elsewhere ie. psoas abscess
210
What is the spreading of infection controlled by?
How virulent the organism is, the host condition i.e. immunosuppression, low protein levels, poor vascular supply & treatment given
211
List the factors testing in the NHS Sepsis screening tool?
- Is infection known/ suspected?
- Resp rate >20 bpm
- Heart rate > 90 bpm
- Temp <36oC or >38oC
- WCC <4x10*9/l or >12x10*9/l
- Altered mental state?
- Glucose >7.7mmol/L
212
What are the 3 outcomes of acute inflammation?
1. Resolution (complete restoration or tissue to normal)
2. Healing by fibrosis
3. Progression to chronic inflammation
213
List what 4 factors can result in the resolution of acute inflammation?
1. Minimal tissue damage
2. Occurs in tissue with regenerative capacity i.e. skin
3. If cause is rapidly removed or destroyed
4. Good vascular drainage
214
List what 3 factors can result in acute inflammation healing by fibrosis?
1. After substantial tissue damage
2. Tissue incapable of regeneration
3. Abundant fibrin exudate
215
List what 2 factors can result in acute inflammation progressing to chronic inflammation?
1. Persistent stimulus
| 2. Tissue destruction leading to ongoing inflammation
216
What are 3 possible causes of an inflammatory infiltrate rich in eosinophils?
1. Parasitic infection
2. Drug reactions
3. Allergy
217
Describe what excess production of eosinophils causes in hypereosinophilia syndrome?
- Drive inflammatory process within the myocardium which damages the myocytes in subendocardial distribution
- Fibrosis ensues
218
What does hypereosinophilia syndrome present with clinically?
Restrictive cardiomyopathy
219
What can neutrophil polymorphs be due to?
Tissue damage leading to ischaemia
220
What are the 5 beneficial effects of acute inflammation?
1. Dilution of toxins by oedema fluid
2. Increased entry of antibodies & drug transport
3. Fibrin traps micro-organisms
4. Delivery of nutrients
5. Stimulation of immune response
221
What are the 3 detrimental effects of acute inflammation?
1. Digestion of normal tissues
2. Swelling e.g. epiglottitis
3. Inappropriate response e.g. type I hypersensitivity response
222
What could the diagnosis be for someone with moderate erythema & granularity in the distal large bowel during a colonoscopy?
IBD
223
How can we define chronic inflammation?
- Persistent & lacks resolution when inflamed tissue is unable to overcome the effects of the injurious agent
- Persists for weeks, months, or years
224
What is chronic inflammation characterised by?
Infiltrates of lymphocytes, plasma cells & macrophages
225
What is the histological difference between Crohn's disease & Ulcerative colitis?
- CROHNS: granulomas
| - UC: architectural changes
226
What are the 2 predominant cell types in granulomatous inflammation?
1. Activated macrophages with a modified appearance (epithelioid macrophages)
2. Giant cells (formed from fused epithelioid macrophages)
227
What disease is so-called caseous necrosis characteristic of?
Tuberculosis
228
What is the formation of granulomas a manifestation of?
T cell mediated immune reaction (delayed hypersensitivity reaction)
229
What results in macrophage activation during an inflammatory response?
Antigen is presented to CD4+ T cells which in turn produce IFN gamma & other cytokines
230
What are the 5 important factors to consider in the clinical history of a patient with oral ulceration?
1. Drugs
2. Trauma
3. Viral infection
4. Connective tissue disorder
5. Immunosuppression
231
What is syphilis caused by?
Treponema pallidum
232
What is predominant histologically in syphilis?
Plasma cell rich infiltrate
233
What is the acute response to syphilis driven by?
Neutrophils, complement & IgG, IgA, IgM immune complexes (derived from plasma cells)
234
What 2 immune cells are important in chronic disease?
1. CD4+ T cells
| 2. Macrophages
235
What is the response to syphilis if CD4+ T cells are low (HIV)?
Relatively poor response
236
Describe the histological appearance of oesophageal candidiasis?
- Exudate
- Ulceration
- Plasma cell infiltrate
- Inflammatory debris on surface
- Neutrophil polymorphs in keratin layer
237
What are pleomorphic cells?
Cells with variation in their size
238
Describe how tumours can evolve in the presence of Epstein-Barr virus (EBV) infection?
- Inflammatory cells recruited in response to EBV infection
- Ligands on the tumour cells (PDL1) allow them to evade this inflammatory response
- CD8+ T cells bind to the tumour cells via ligand & negatively regulates their activation & proliferation
239
Why is there an increase in histamine during anaphylaxis?
Because its being released by mast cells
240
What is Systemic mastocytosis?
Mast cells accumulate in internal tissues & organs which release histamine and cause symptoms of rash & itch
241
What happens when mast cells infiltrate the bone marrow, spleen, liver & lymph nodes?
Lead to suppression of the normal functions of these organs
242
What can Systemic mastocytosis be caused by?
Mutation in CD117
243
What can Systemic mastocytosis be treated with?
Imatininb (CD117 inhibitor)
244
List 7 potential causes of cell injury?
1. Physical agents
2. Chemicals/drugs
3. Infections
4. Hypoxia/ischaemia
5. Immunological reactions
6. Nutritional imbalance
7. Genetic disease
245
Cell injury may be ______ or ______?
- Reversible
| - Irreversible
246
Describe reversible causes of cell injury?
- Changes due to stress in environment
| - Return to normal once stimulus removed
247
Describe irreversible causes of cell injury?
- Permanent
| - Cell death, usually necrosis, follows
248
What 3 factors does the threshold between reversible & irreversible cell injury depend on?
1. Type
2. Duration
3. Severity of injury
249
What can damage to the mitochondria cause?
Disrupted aerobic respiration/ATP synthesis
250
What can damage to the cell membrane cause?
Disrupted ion concentrations esp. increased calcium ions
251
What can damage to the cytoplasm (including ribosomes) cause?
Disrupted enzyme & structural protein synthesis & architecture
252
What can damage to the nucleus cause?
Disrupted DNA maintenance & DNA damage
253
What is oxidative stress caused by?
Reactive oxygen species (free radicals)
254
Describe the 2 ways in which oxidative stress can occur?
1. Normally formed in small amounts as a by- product of respiration
2. Formed pathologically by absorption of radiation, toxic chemicals, hypoxia etc
255
What makes oxidative stress more damaging?
Lack of antioxidants
256
List the 5 different types of reversible (less severe) cell injury?
1. “Cloudy swelling”
2. Cytoplasmic blebs
3. Disrupted microvilli
4. Swollen mitochondria
5. “Fatty change”
257
Describe the reversible “Cloudy swelling” type of cell injury?
Osmotic disturbance, loss of energy-dependent Na pump leads to Na influx & build up of intracellular metabolites
258
Describe the reversible “Fatty change” type of cell injury?
Accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism, especially in liver
259
List the 5 difference types of irreversible cell injury?
1. Swelling of endoplasmic reticulum & loss of ribosomes
2. Lysosome rupture
3. Membrane blebs
4. Swelling of mitochondria
5. Nuclear condensation
260
Describe the 2 different forms of cell death?
1. NECROSIS which is uncontrolled & due to external stimuli (always pathological)
2. APOPTOSIS which is “programmed” & controlled (usually physiological, can be pathological)
261
What is the main difference between necrosis and apoptosis?
Whether cell contents leak out or not
262
Give an example of necrosis?
Infarction (loss of blood supply)
263
Describe the histological changes during necrosis?
- Cell swelling, vacuolation & disruption of membranes of cell & its organelles including mitochondria, lysosomes & ER
- Release of cell contents including enzymes --> adjacent damage & acute inflammation
- DNA disruption & hydrolysis
264
What is Karyolysis?
- Nuclear fading
| - Chromatin dissolution due to action of DNAases & RNAases
265
What is Pyknosis?
- Nuclear shrinkage
| - DNA condenses into shrunken basophilic mass
266
What is Karyorrhexis?
Pyknotic nuclei membrane ruptures & nucleus undergoes fragmentation
267
Describe early necrosis morphology under the microscope?
- Nuclei are papers & more ill-defined
- Cytoplasm looks bigger & paler
- Immune cells are present
268
Describe late necrosis morphology under the microscope?
- No structure
| - Wasted away tissue
269
Describe coagulative necrosis?
Firm, tissue outline retained
270
What are the 2 types of coagulative necrosis?
1. Haemorrhagic: due to blockage of venous drainage
| 2. Gangrenous: larger area especially lower leg
271
Describe Colliquitive necrosis?
Tissue becomes liquid & its structure is lost
| e.g. infective abscess, cerebral infarct
272
Describe Caseous necrosis?
- Combination of coagulative & colliquitive, appearing “cheese-like”
- Classical for granulomatous inflammation, esp TB
273
Describe fat necrosis?
Due to action of lipases on fatty tissue
274
What are the 4 different types of necrosis?
1. Coagulative
2. Colliquitive
3. Caseous
4. Fat
275
What are the 2 types of effects of necrosis?
1. Functional (depends on the tissue/organ)
| 2. Inflammation (release of cell contents activates inflammation & causes damage)
276
Describe the 2 types of inflammatory effects that necrosis has?
1. ACUTE with removal of stimulus & then healing and repair
2. CHRONIC with persistence of stimulus & chronic inflammation
277
What does apoptosis require?
Energy & distinct pathways involved
278
What does apoptosis NOT cause?
Inflammation but may be caused by immunological mechanisms
279
List the 5 different types of apoptosis physiological aetiologies?
1. Embryogenesis
2. Hormone dependent involution
3. Cell deletion in proliferating cell populations to maintain constant cell number (epithelium)
4. Deletion of inflammatory cells after inflammatory response
5. Deletion of self-reactive lymphocytes in thymus
280
List the 3 different types of apoptosis pathological aetiologies?
1. Viral infection (cytotoxic T-lymphocytes)
2. DNA damage
3. Hypoxia/ischaemia
281
Describe the morphology of apoptosis?
- Cell shrinkage
- Chromatin condensation (unlike
necrosis)
- Membranes of cell & mitochondria remain intact (unlike necrosis)
- Cytoplasmic blebs form & break off to form apoptotic bodies which are phagocytosed by macrophages
282
What is Chromatin condensation?
Packaging up of nucleus
283
What is the pathway of necrosis?
Normal --> Reversible swelling --> Irreversible swelling --> Disintegration
284
What is the pathways of apoptosis?
Normal --> Condensation (cell blebbing) --> Fragmentation --> Secondary necrosis
285
Define depositions?
Abnormal accumulation of substances
286
What are the 3 potential locations for depositions?
1. Intracellular
2. Extracellular
3. Connective tissue
287
What are the 2 different compositions of depositions?
1. Normal endogenous substances
| 2. Exogenous (foreign) material
288
What are 2 normal endogenous substances?
1. Normal products of metabolism, including protein, lipid, & carbohydrate
2. Pigments (some deposits are both product & pigment)
289
What are 2 Exogenous (foreign) materials?
1. Pigments
| 2. Industrial material
290
What are 5 examples of intracellular endogenous depositions?
1. Melanin
2. Haemosiderin
3. Bile
4. Lipid, including cholesterol
5. “Storage diseases” especially in liver e.g. alpha-1-antitrypsin
291
What are 3 examples of extracellular endogenous depositions?
1. Amyloid
2. Fibrosis
3. Calcium
292
What are 3 examples of intracellular exogenous depositions?
1. Tattoo pigment
2. Carbon (anthracosis)
3. Asbestos
293
Describe the nature of amyloid endogenous depositions?
Organisation (abnormal folding) of soluble protein fibrils into specific abnormal, insoluble aggregates
294
What does amyloid depositions resemble on morphology?
Fibrosis but without prior inflammation
295
What can amyloid depositions be stained by & how does it appear?
Congo Red: fibrils have a specific structure which the stain intercalates & shows pink
296
How does the congo red stain of amyloid appear under polarised light?
“Apple- green birefringence”
297
What are the 2 forms of amyloid accumulation?
1. Systemic: widespread
| 2. Localised: one place
298
What are 3 ways that amyloid can occur?
1. Excessive production/ accumulation of a normal
protein
2. Production/accumulation of an abnormal protein
3. Tendency of protein to misfold (i.e. abnormal)
299
What is amyloid deposition an example of?
Accumulation of abnormal protein (alzheimer's, genetic variants)
300
What is AL amyloid?
Immunoglobulin light chain
| - Produced in B-cell neoplasms e.g. multiple myeloma
301
What is AA amyloid?
Serum amyloid associated protein (anormal
| acute phase protein)
302
Where is AA amyloid produced?
- In liver
| - In prolonged chronic inflammation e.g. rheumatoid arthritis
303
Give 3 examples of the clinical effects of amyloid on specific organs (kidney, heart, brain)?
1. Kidney: renal impairment or failure
2. Heart: heart failure
3. Brain: dementia
304
What is amyloid important in?
Systemic pathology especially in kidney, osteo-articular system & brain
305
Give an example of an acute sub-lethal cell injury (deposition)?
Steatosis in liver caused by alcohol & reversible on abstinence
306
What is lipofuscin?
- Brown “wear & tear” or “age” pigment in liver
- Endogenous breakdown product
- May also deposit in heart & other organs
307
Describe the stained appearance of excess iron deposited in the liver?
Stained blue with Perl’s stain (“Prussian blue reaction”)
308
What is excess iron in the liver called?
Haemosiderosis
309
What 2 circumstances would Haemosiderin (iron, brown) be deposited in macrophages?
1. After haemorrhage
| 2. Congestion of blood vessels
310
Describe the appearance & location of carbon depositions in the lungs?
Black carbon in lines on lung serosal surface, in lymphatics
311
When would carbon depositions be higher in the lungs?
If smoker or from a city
312
What are the 2 pathological types of calcification (deposition of calcium salts)?
1. Dystrophic
| 2. Metastatic
313
Describe dystrophic calcification?
Deposition in abnormal tissue with normal serum calcium
314
Describe metastatic calcification?
- Deposition in normal, living tissue with raised serum calcium
- Often in connective tissue of blood vessels
- Can compromise tissue function
315
What are 2 potential causes of raised serum calcium?
1. Increased levels of parathyroid hormone
| 2. May be systemic effect with cancer
316
What are the primary & secondary causes of increased levels of parathyroid hormone?
- Primary: parathyroid gland tumour
| - Secondary: kidney disease
317
What do depositions cause?
Cell degeneration
318
What 3 things are present in the lung hilum?
1. Pulmonary arteries
2. Pulmonary veins
3. Main bronchi
319
Describe the anatomy of the left lung?
Divided into 2 lobes by the oblique fissure
320
Describe the anatomy of the right lung?
Divided into 3 lobes by the horizontal & oblique fissures
321
What is the branching of trachea called?
Carina
322
Describe the lung coverings?
- Pleura
- 2 layers
- Inner layer: visceral
- Outer layer: parietal
323
How are lung fissures formed?
Invagination of the visceral pleura
324
How much fluid may the space between visceral & parietal pleura contain?
15mls
325
What does the bronchi divide further into?
Bronchopulmonary segments
326
List the 6 important invisible/obscure structures in a chest X-ray?
1. Sternum
2. Oesophagus
3. Spine
4. Fissures
5. Pleura
6. Aorta
327
Describe the location of the trachea compared to the aorta?
Passes to the right of the aorta so may be slightly off midline to the right
328
What bronchus is more vertical?
Right main bronchus (aspiration)
329
Describe the appearance of oblique fissures in a lateral view?
Overlie each other & are not always seen in their entirety
330
What is another name for the accessory fissure in the lung?
Azygous fissure
331
How common is the accessory/azygous fissure?
1-2% of individuals
332
What is contained within the azygous fissure?
Azygous vein with pleura wrapped around it
333
When is the pleura visible on X-ray?
When abnormal
334
What is the costophrenic recess formed by?
Hemidiaphragm & the chest wall
335
What does the costophrenic recess contain?
Rim of the lung base which lies over the diaphragm
336
What is the costophrenic angle formed by?
Lateral chest wall & the diaphragm
337
Is the right or left hemidiaphragm slightly higher than the other?
Right is higher
338
Where is the liver located?
Beneath the right hemidiaphragm & the stomach bubble is seen below the left
339
What makes up the right border of the heart?
Right atrium
340
What makes up the left border of the heart?
Left ventricle
341
What is the normal heart volume no more than?
60% cardio thoracic ratio
342
What is the aortic knuckle?
The left lateral edge of the aorta as it arches backwards over the left main bronchus
343
What does the aortic knuckle continue as?
Descending aorta
344
Where does the aorto-pulmonary window lie?
Between the arch of aorta & the pulmonary artery
345
What is the right edge of the trachea seen as?
Right para-tracheal stripe
346
What is the right para-tracheal stripe normally less than?
3mm
347
Where is a common place for lung cancer/mass/nodes?
Right para-tracheal stripe
348
What side of the trachea is less well defined?
Left side
349
What are hilar points formed by?
Descending upper lobe veins & the lower lobe pulmonary arteries (not always clearly visible)
350
When are hilar lymph nodes visible in chest X-rays?
Only when enlarged
351
Where can lung cancer pain occur?
In the shoulder
352
Describe the appearance of posterior and anterior ribs on a chest X-ray?
- POSTERIOR: run horizontal
| - ANTERIOR: less obvious & run at an angle
353
What are the 5 emergency indications for chest X-rays?
1. Acute respiratory symptoms
2. Chest pain
3. Septic Screen
4. Acute abdomen
5. Post central line / chest drain insertion
354
What are the elective indications for chest X-rays?
1. Persistent/chronic respiratory symptoms
2. Pre-operative work up
3. Metastatic screen
4. TB contacts
355
What are the 4 technical factors to take into consideration when interpreting an X-ray?
1. PA vs AP
2. Rotation
3. Inspiration
4. Penetration
356
Describe a PA X-ray?
- X-rays penetrated through the back to the front of the patient
- Standard projection
- Heart is closer to the film & less magnified
357
What are all X-rays in the PICU?
- Portable
| - AP view
358
How do you work out the degree of inspiration from a chest X-ray?
- Count the ribs
- Highlight anterior versus posterior
- Should be 9- 10 posterior ribs & 6 anterior ribs
359
How do you tell if a patient is rotated on a chest X-ray?
Highlight tear drops ie spinous processes & that they are equidistant from clavicles
360
What indicates good chest X-ray exposure?
Not being able to see the vertebra through the heart shadow
361
Describe how the silhouette sign in chest X-rays are formed?
Normal adjacent anatomical structures of differing densities form a crisp silhouette or contour
362
What does a loss of specific contour (silhouette sign) in a chest X-ray help to determine?
Position of the disease process
363
What lobe lie adjacent to the right heart border?
Right lung middle lobe
364
What can determine the heart size?
PA radiograph
365
What are the 3 types of cellular pathology?
1. Autopsy (post-mortem exanimation)
2. Histopathology (tissues)
3. Cytopathology (cells)
366
What are the 2 types of specimens taken in cytology?
1. Smears
| 2. Aspirates
367
What are the 3 types of specimens taken in small tissue biopsies?
1. Prostate chips
2. Bladder chips
3. Punch biopsies
368
What is the purpose of specimens?
Diagnostic and/or treatment (e.g. removal of effusion, colectomy)
369
Describe the types of exfoliative cytology?
- Fluid cytology including effusions
| - Scrape, smear & brush cytology (including cervical)
370
Describe the types of fine needle aspiration cytology sample (FNA)?
- Direct ie. sampling surface lumps on skin,
head & neck, breast, lymph nodes
- Under ultrasound (US) guidance, as above plus endoscopic ultrasound (EUS)
371
What are the 3 different types of pathology specimens?
1. Cytology samples
2. Small tissue biopsies
3. Larger tissue resections
372
What are the 2 different types of cytology samples?
1. Exfoliative cytology
| 2. Fine needle aspiration (FNA)
373
What are the 3 different types of histology samples?
1. Small biopsies
2. Excision biopsy
3. Resection
374
What are the 3 different types of small biopsy histology samples?
1. Mucosal
2. Needle core
3. Incisional ie. skin punch
375
What 2 things can needle core biopsy sample (histology)?
1. Diffusely abnormal organ e.g. liver
| 2. Focal lesion e.g. liver, breast, prostate
376
What can excision biopsy sample (histology)?
Full skin lesion
377
Give an example of a smaller histological resection?
Appendicectomy
378
Give examples of a larger histological resection?
Lung, limb amputation, hysterectomy & oophorectomy, prostatectomy
379
Describe how the small and large specimens are examined & described?
- LARGE: gross examination & macroscopic description
| - SMALL: trimmed & described by biomedical scientist then placed in cassettes
380
Describe the gross examination, description & trim of larger specimens?
- Includes “inking” of specimen “resection margins”
- Orientation
- Macroscopic description aided
by Biomedical Scientist
381
Describe tissue processing in diagnostic pathology?
- From water-based formalin through graded alcohols to xylene then wax
- Different cycles used (2hr, 4hr, 15hr, Brain & Breast)
382
What does formalin do during tissue processing?
Fixes tissue
383
What does H&E stand for?
Haematoxylin & Eosin
384
Describe the appearance of Haematoxylin stain?
- Dark blue
| - Nuclei
385
Describe the appearance of Eosin stain?
- Pink
| - Cytoplasm
386
What are 3 other stains which may be required during diagnostic pathology of a specimen?
1. Special stains
2. Immunohistochemistry (IHC)
3. Molecular test (FISH)
387
What is the turnaround timescale for an urgent pathological problem?
<1 week
388
What is the turnaround timescale for other pathological problems?
<4 weeks
389
What is the most routine diagnostic stain?
Standard H&E
390
Describe the 4 particular features that "special" stains are used to demonstrate?
1. Mucin in epithelial cells for adenocarcinoma classification
2. Normal elastic tissue in vessels
3. Depositions e.g. fibrous tissue
4. Infections e.g. bacterial, fungal
391
Describe Immunohistochemistry (IHC)?
Staining technique which yields brown staining of specific proteins (may be cytoplasmic, membranous &/or nuclear)
392
List the 4 applications of Immunohistochemistry (IHC)?
1. Tumour diagnosis & classification
2. Prediction of cancer prognosis
3. Prediction of cancer treatment benefit e.g. ER & HER2 in breast cancer
4. Diagnosis of infectious disease
393
What are the 3 comparisons to look at in molecular pathology?
1. Somatic (tumour) versus germ-line (blood)
2. Tissue sections versus tissue extracts, for different techniques
3. Quantitative changes versus qualitative changes
394
What does FISH demonstrate?
Large-scale qualitative changes in DNA ie. chromosomal translocations, amplifications, deletions
395
What is FISH useful for in somatic (tumour) DNA?
Tumour classification & prediction of treatment benefit
396
What does PCR stand for?
Polymerase chain reaction
397
What type of tissue sample can FISH technique be used on?
Tissue sections
398
What does PCR demonstrate?
Large-scale quantitative changes in DNA ie. clonality in lymphoma for diagnosis and classification
399
What type of tissue sample can PCR technique be used for?
Tissue extracts
400
What does NGS stand for?
Next generation sequencing
401
What does NGS demonstrate?
Small-scale qualitative or quantitative changes in DNA ie. sequence mutations including “actionable mutations”
402
What type of tissue sample can NGS technique be used for?
Tissue extract
403
What are the 5 categories for classifying breast lesions?
1. Palpation
2. Mammography
3. Ultrasound
4. FNA (fine needle aspiration cytology)
5. Core biopsies
404
Breast tumours which have a ____ lesion are at a worse prognosis?
HER2 positive
405
What does ER and PR stand for in regards to breast lumps?
- ER: Oestrogen receptor
| - PR: Progesterone receptor
406
What would be the 3 forms of treatment plan for someone with infiltrative carcinoma with ductal carcinoma & widespread infiltration of lymphovascular channels?
1. Neoadjuvant systemic chemotherapy
2. Left mastectomy with left axillary clearance
3. Adjuvant chemotherapy +/- radiation therapy +/- Herceptin +/- endocrine therapy
