ICS Flashcards
1
Q
Causes of Acute Inflammation
A
- Microbial Infections (bacteria, virus)
- Hypersensitivity Reactions (parasites)
- Physical Agents (trauma, ionising radiation, heat, cold)
- Chemicals (acids, alkalis, reducing agents)
- Bacterial Toxins
- Tissue Necrosis (ischaemic infarction)
2
Q
Macroscopic Appearances of Acute Inflammation
A
- Redness (rubor)
- Heat (calor)
- Swelling (tumor)
- Pain (dolor)
- Loss of function
3
Q
Acute Inflammation Response Process
A
1) Vessels dilate & increase flow
2) Increase vascular permeability & formation of fluid exudate
3) Formation of cellular exudate - neutrophil polymorphism move into extravascular space
4
Q
Vascular Changes in Acute Inflammation
A
- Precapillary sphincters relax = increase blood flow
- Increased capillary hydrostatic pressure = proteins leak = increase osmotic pressure = more fluid & protein leak out
5
Q
Causes of Increased Vascular Permeability
A
1) Immediate transient - chemical mediators (histamine, bradykinin, nitric oxide etc)
2) Immediate sustained - severe direct vascular injury (trauma)
3) Delayed prolonged - endothelial cell injury (X-ray & bacterial toxins)
6
Q
Stages in Neutrophil Polymorph Emigration
A
1) Margination of neutrophils
2) Adhesion of neutrophils
3) Neutrophil emigration
4) Diapedesis
7
Q
Plasma Factors (Enzymatic Cascade Systems)
A
1) Complement
2) The Kinins
3) Coagulation factors
4) Fibrinolytic System
8
Q
Role Of Neutrophil Polymorph in Acute Inflammation
A
- Adhesion to microorganisms
- Phagocytosis
- Intracellular killing of microorganisms
- Release of lysosomal products
9
Q
Role of Mast Cells in Acute Inflammation
A
- Release histamine
- Metabolise arachidonic acid into leukotrienes, prostaglandins, thromboxanes
10
Q
Outcomes of Acute Inflammation
A
1) Resolution
2) Suppuration
3) Organisation
4) Progress to chronic inflammation
11
Q
Systemic Effects of Inflammation
A
- Pyrexia (fever)
- Constitutional symptoms (anorexia, nausea, weight loss)
- Haematological changes
- Amyloidosis
12
Q
Chronic Inflammation Definition
A
The subsequent and often prolonged tissue reactions to injury following the initial response. Lymphocytes, plasma cells and macrophages predominate
13
Q
Causes of Chronic Inflammation
A
- Primary chronic inflammation (no acute)
- Transplant rejection
- Progression from acute
- Recurrent episodes of acute
14
Q
Macroscopic Appearances of Chronic Inflammation
A
- Chronic ulcer
- Chronic abscess cavity
- Thickening of the wall of a hollow organ
- Granulomatous inflammation
- Fibrosis
15
Q
Granuloma
A
An aggregate of epithelioid histiocytes
- tuberculosis is the most commonest cause of granuloma
16
Q
Cells That Regenerate
A
- Hepatocytes
- Pneumocytes
- All blood cells
- Gut epithelium
- Skin epithelium
- Osteocytes
17
Q
Cells That Do Not Regenerate
A
- Myocardial cells
- Neurones
18
Q
Thrombosis Definition
A
The solidification of good contents that forms WITHIN the vascular system DURING life
19
Q
Clot Definition
A
Blood coagulated OUTSIDE of the vascular system during life or AFTER death
20
Q
Causes of Thrombosis
A
1) Change in vessel wall
2) Change in blood flow
3) Change in blood constituents
21
Q
Clinical Effects of Arterial Thrombosis
A
- Loss of pulse distal to thrombus
- Area becomes cold, pale & painful
- Tissue will die = gangrene
22
Q
Clinical Effects of Venous Thrombosis
A
- Area becomes tender
- Redness
- Swelling
23
Q
Thrombi Can:
A
1) Resolve
2) Organised into a scar
3) Intimal cells proliferate - capillaries grow into thrombus - vessel functions again
4) Fragments break - embolism
5) Death
24
Q
Treatment of Thrombus:
A
- LOW DOSE ASPIRIN !!!
(platelet aggregation inhibitor) - Warfarin (vitamin k aka clotting factor inhibitor) in severe cases
25
Embolism
An embolus is a mass of material in the vascular system able to lodge in the vessel and block the lumen
26
Venous embolism (pulmonary embolism)
Embolus travels to vena cava & lodges in pulmonary arteries.
- can't get to arterial side because blood vessels in the lungs are capillaries (can't fit through)
- lung acts as a filter
27
Small Emboli
- May go unnoticed
- May cause small permanent respiratory deficiency
- Over time this may cause idiopathic pulmonary hypertension
28
Medium Emboli
- May result in acute respiratory/cardiac problems
- Chest pain, shortness of breath, area may become infarcted
- Lung function is impaired & risk of further emboli increases
29
Massive Emboli
- Sudden death
- Usually long thrombi from leg veins
- Often impacted across bifurcation of a major pulmonary artery
30
Arterial Embolism (systemic embolism)
- Can travel to anywhere downstream
- Generally originate from heart/artheromatous plaque
- Thrombi may form on dead areas of cardiac muscle after MI
- AF can cause thrombosis in heart
31
Ischaemia
A reduction in blood flow to a tissue or part of the body caused by constriction or blockage of the blood vessels supplying it
32
Effects of Ischaemia
- Can be reversible
Depends on:
- duration of ismchaemic period
- metabolic demands of tissue (cardiac myocytes & cerebral neurones are most vulnerable)
33
Infarction
Death (necrosis) of part or the whole of an organ that occurs when the artery supplying it becomes obstructed
34
Gangrene
When whole areas of limb or a region of the gut have their arterial supply cut off and large areas of mixed tissue die in bulk
1) Dry
2) Wet
35
Other Causes of Ischaemia & Infarction (other than thrombi)
1) Spasm
2) External compression
3) Steal
4) Hyper-viscosity
5) Vasculitis
36
Spasm
Spasm of smooth muscle = transient arterial narrowing
- due to decreased NO production due to cellular injury/loss
Spasm of coronary arteries - angina
37
External Compression
- Can cause partial or total occlusion of vessels
- Done intentionally in surgery to prevent haemorrhage
- Veins are more susceptible (thin walls & low intra-luminal pressure)
38
Steal (syndromes)
- Blood diverted from vital territory
| - Uncommon
39
Hyper-viscosity
- Most effect in small vessels
| - Can occur in myeloma (due to abnormally high conc. of antibodies in plasma & cylindrical shape of RBC)
40
Vasculitis
Inflammation of vessel wall = narrow lumen
41
Apoptosis (PROGRAMMED CELL DEATH)
Physiological cellular process in which a defined and programmed sequence of IC events leads to the removal of a cell WITHOUT the release of products harmful to surrounding cells
42
Characteristics of Apoptosis
- Energy dependent
- Involved enzymatic digestion of nuclear and cytoplasmic contents
- Phagocytosis of resultant breakdown products (still within cell membrane)
43
Inhibitors of Apoptosis
1) Growth factors
2) EC cell matrix
3) Sex steroids
4) Some viral proteins
44
Inducers of Apoptosis
1) Growth factor withdrawal
2) Loss of matrix attachment
3) Glucocorticoids
4) Some viruses
5) Free radicals
6) Ionising radiation
7) DNA damage
8) Ligand binding at 'death receptors'
45
Apoptosis Pathways
```
1) Intrinsic
OR
2) Extrinsic
then both converge in
EXECUTION PHASE
```
46
Necrosis
Traumatic cell death which induces inflammation and repair - characterised by bioenergetic failure & loss of plasma membrane integrity
47
Coagulative Necrosis
- Commonest form
- Caused by ischaemia
- Macrophages digest tissue causing it to go soft
- Phagocytosis of myocardium can cause risk of ventricular rupture
- Inflammatory response
48
Liquifactive/Colliquative Necrosis
- Occurs in the brain
- Due to lack of supporting stroma
- Necrotic neural tissue may totally liquify
49
Caseous Necrosis
- Characterises tuberculosis
| - Dead tissue is structureless
50
Hypertrophy
Increase in cell size without cell division
51
Hyperplasia
Increase in cell number by mitosis
52
Atrophy
The decrease in SIZE of an organ or cell by reduction in cell size and/or reduction in cell NUMBERS
53
Metaplasia
The change in differentiation of a cell from one fully-differentiated cell type to a different fully-differentiated cell type
54
Dysplasia
Imprecise term for the morphological changes seen in cells in the progression to become cancer
55
Carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
56
Neoplasm
A lesion resulting from autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed - a new growth
57
Tumours
```
An abnormal swelling
Includes:
- neoplasm
- inflammation
- hypertrophy
- hyperplasia
```
58
Classes of Carcinogens
1) Chemicals
2) Viruses
3) Ionising & Non-ionising radiation
4) Hormones, Parasites & mycotoxins
5) Miscellaneous
59
Host Factors Influencing Carcinogenesis
- Race
- Diet
- Constitutional factors - age & gender etc
- Premalignant lesions
- Transplacental exposure
60
Oncogenes
Genes driving the neoplastic behaviour of cells
61
Activation of Oncogenes in Tumours
1) Translocation
2) Point Mutation
3) Amplification
62
Tumour Staging
T - tumour
N - node
M - metastases
63
T - Tumour
- refers to primary tumour
- suffixed by number that denotes tumour size
- number varies according to organ the tumour is on
64
N - Node
- refers to lymph node status
- suffixed by a number that denotes number of lymph nodes or groups of nodes containing metastases
E.G N0 = no nodal metastases
65
M - Metastases
- refers to anatomical extent of distant metastases
E.G. M0 = no metastases
M1 = increasing extent of distant metastases
66
Innate Immunity
- Non-specific
- Rapid response
- Instinctive
- Resistance is NOT improved by repeat infection
- Doesn't depend on lymphocytes
- Phagocytes and NK cells
67
Adaptive Immunity
- Specific 'acquired' immunity
- Requires lymphocytes (B & T)
- Antibodies
- Resistance improves with repeat infection
- Slower response
68
Neutrophils
- 65% of blood
- Lifespan of 6 hours - 12 days
- Phagocytosis
- Primary lysosomes
- Secondary granules
- Fc & complement receptors
- Secrete superoxides (toxic)
69
Monocytes
- 5% of blood
- Lifespan = months
- Differentiate into macrophages in tissues
- Phagocytose in innate immunity
- Antigen presenting in adaptive immunity
- Lysosomes
- Fc, complement receptors, PRR, TLR, mannose receptors
70
Macrophages
- Lifespan = months/years
- Phagocytose & antigen presenting
- First line of non-self recognition
- Lysosomes containing peroxidase
- Fc, complement receptors, TLR, mannose receptors
- Present antigens to T cells
71
Eosinophil
- 5% of blood
- Lifespan = 8-12 days
- Associated to parasitic infections and allergic reactions
- Granules contain major basic protein (MBP) - potent for worms
- MBP activates neutrophils
- induces histamine from mast cells
72
Basophil
- 2% of blood
- Lifespan = 2 days
- Express high affinity IgE receptors
- IgE-receptor binding = histamine release
- Parasitic infections and allergic reactions
- Can circulate the body (not fixed like mast cells)
73
Mast Cell
- Only in tissues - fixed in tissue
- Express high affinity IgE receptors
- IgE-receptor binding = histamine release
- Parasitic infections and allergic reactions
74
T Lymphocytes
- 10% of blood
- Lifespan = hours-years
- Adaptive
- Antigen presenting
- Produce cytokines
- Bind antigen through T cell receptors
75
B Lymphocytes
- 15% of blood
- Lifespan = hours-years
- Adaptive
- Antigen presenting
- Differentiates into plasma cells
- In blood, lymph nodes & spleen
76
Natural Killer (NK) Cells
- 15% of lymphocytes
- Expresses CD56
- In spleen and tissues
- Recognise and kill virus infected cells and tumour cells - via apoptosis
77
Dendritic Cells
- Antigen presenting
- Adaptive
- Induce primary immune response in inactive/resting T cells
- Produce cytokines
- Promote B cell activation and differentiation
- Found in skin (Langerhan's cells), lining of nose, lungs, stomach, intestines
78
Soluble Complement Factor
A complex series of interacting plasma proteins which form a major effector system for antibody-mediated immune reactions
79
Purpose of Complement Pathway
To remove/destroy antigens - by direct lysis or by opsonisation
80
Opsonisation
Process by which an antigen becomes coated with substances (complement) that make it more easily engulfed by phagocytic cells (macrophages have special receptors for specific complement proteins)
81
Clinical Indications Related to Complement
- Recurrent infections in children (pulmonary)
- Swelling in hands/face
- Fatigue
- Butterfly-shaped rash on face
- Fever, tachycardia after blood transfusion
- Morning urine colour
82
Complement Activation
1) Activation of C3 component
| 2) Activation of the lytic pathway
83
Routes of Cleaving C3 (generate C3 convertases)
1) Classical pathway
2) Alternative pathway
3) Lectin pathway
84
Classical Pathway
- Antibody bound to microbe
- Antibody dependent activation
- Ab INdependent polyanions, gram-negative bacteria or bound-C reactive protein reactions directly with C1
- Complement proteins: C1 (C1q, C1r, C1s), C4 & C2
- IgM = more efficient activator of C1q than IgG
85
Alternative Pathway
- Complement binds to microbe
- Consists: factor D, B, properdin (factor p), C3
- Doesn't need Ab, C1, C4, C2)
- Microbial cell surfaces (endotoxin, bacterial cell walls - gram negative bacteria)
- Innate defence (performs in the absence of pre-formed specific antibody)
86
Lectin Pathway
- Ab independent activation
- Consists: mannose-binding lectin , MASP-1, MASP-2, C4, C2
- MBL binds to mannose on bacterial cell walls, yeast walls, viruses = activates
87
Opsonisation
Process by which an antigen becomes coated with substances (complement) that make it more easily engulfed by phagocytic cells (macrophages have special receptors for specific complement proteins)
88
Clinical Indications Related to Complement
- Recurrent infections in children (pulmonary)
- Swelling in hands/face
- Fatigue
- Butterfly-shaped rash on face
- Fever, tachycardia after blood transfusion
- Morning urine colour
89
Complement Activation
1) Activation of C3 component
| 2) Activation of the lytic pathway
90
Routes of Cleaving C3 (generate C3 convertases)
1) Classical pathway
2) Alternative pathway
3) Lectin pathway
91
Classical Pathway
- Antibody bound to microbe
- Antibody dependent activation
- Ab INdependent polyanions, gram-negative bacteria or bound-C reactive protein reactions directly with C1
- Complement proteins: C1 (C1q, C1r, C1s), C4 & C2
- IgM = more efficient activator of C1q than IgG
92
Alternative Pathway
- Complement binds to microbe
- Consists: factor D, B, properdin (factor p), C3
- Doesn't need Ab, C1, C4, C2)
- Microbial cell surfaces (endotoxin, bacterial cell walls - gram negative bacteria)
- Innate defence (performs in the absence of pre-formed specific antibody)
93
Lectin Pathway
- Ab independent activation
- Consists: mannose-binding lectin , MASP-1, MASP-2, C4, C2
- MBL binds to mannose on bacterial cell walls, yeast walls, viruses = activates
