Mechanisms of Disease Flashcards
1
Q
Define apoptosis
A
Programmed cell death by intracellular programmes (degradation of DNA/proteins)
1
Q
Apart from TB name three other granulomatous infections.
A
-Leprosy -Cat-scratch disease -Syphilis -Chronic fungal infections -Xanthogranulomatous pyelonephritis
1
Q
Define aplasia
A
Complete failure of a specific tissue or organ to develop
2
Q
Define arteriosclerosis
A
The thickening of the walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus
2
Q
Define atheroma
A
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
3
Q
Define atherosclerosis
A
The thickening and hardening of arterial walls as a consequence of atheroma
4
Q
Define disease.
A
The consequence of failed homeostasis with consequent morphological and function disturbances
4
Q
Define chronic inflammation.
A
Chronic response to injury with associated fibrosis
4
Q
Define atrophy
A
Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells
5
Q
Define dysplasia
A
Abnormal maturation of cells within a tissue
6
Q
Define hyperplasia
A
Increase in tissue or organ size due to increased cell numbers.
7
Q
Define hypertrophy
A
Increase in tissue or organ size due to increased cell size.
7
Q
Define hypoplasia
A
Incomplete development of a tissue or organ
8
Q
Define metaplasia
A
Reversible change of one DIFFERENTIATED cell type to another.
9
Q
Define necrosis
A
Changes after cell death in living tissue
10
Q
Describe the appearance of caseous necrosis
A
It looks like cheese - contains an amorphous (structureless) debris
10
Q
Define regeneration.
A
The replacement of dead or damaged cells by functional, differentiated cells
10
Q
Describe the appearance of an arterial thrombi?
A
Pale, granular, low cell count and lines of Zahn
10
Q
Describe the appearance of a venous thrombi?
A
Deep red, soft, gelatinous and a high cell count
11
Q
Describe the basic structure of the collagen molecule
A
-Glycine every third position -3 alpha chains -Left handed triple helix -Mostly hydroxyproline and proline residues in other positions
12
Q
Describe the differences in the appearance of benign and malignant tumour to the naked eye.
A
-Benign - grow in a confined local area and so have a pushing outer margin -Malignant - irregular outer margin and shape and may show areas of necrosis and ulceration
13
Q
Describe the features of coagulative necrosis
A
-Histologically the structure is preserved creating “ghost outlines” -After this the tissue goes through acute inflammation and there is a mass immigration of phagocytes and neutrophil polymorphs -Increased eosinophilia of cytoplasm
14
Q
Describe the features of liquefactive necrosis
A
-Liquefaction of tissues -Massive neutrophil immigration
15
Q
Describe the four steps of infiltration of neutrophils.
A
- Margination - neutrophils line up at the edge of blood vessels along the endothelium 2. Rolling - neutrophils roll and begin to stick 3. Adhesion - fully stick 4. Emigration
15
Describe the mechanism of fibrous repair.
1) Inflammatory cells infiltrate the blood clot (neutrophils digest, macrophages + lymphocytes are recruited)
2) Angiogenesis occurs where capillaries/lymphatics sprout and myo/fibroblasts migrate and differentiate laying down ECM and collagen
3) Cell population falls, collagen increases and the myofibroblasts pull it together - left with a fibrous scar.
15
Describe the healing of a bone fracture.
1) Haematoma - forms from ruptured vessels within marrow cavity and periosteum. Haematoma allows for an invasion of macrophages, endothelial cells fibroblasts and osteoblasts allowing necrotic tissue to be removed and for capillaries develop.
2) Soft callus - bone is laid down in an irregular woven pattern, sometimes with islands of cartilage
3) Hard callus - Woven bone replaced with more organised lamellar
4) Remodelling - the bone is shaped by stresses of different movements N.B. a callus is described as a specialised mixture of cells
15
Describe the macroscopic appearance of atheroma
-Fatty streak (yellow bumpy lipid deposits at the intima) -Simple plaque (irregular outline, raised white/yellow colour) -Complicated plaque (thrombosis, haemorrhage, calcification or aneurysm)
16
Describe the microscopic appearance of atheroma
-Early changes - proliferation of smooth muscle cells, lots of foam cells and extracellular lipids -Later changes - fibrosis, necrosis, inflammatory cells and cholesterol clefts
17
Describe the normal structure of an artery from inside to outside.
-Endothelium -Sub-endothelial connective tissue -Internal elastic lamina -Muscular media -External elastic lamina -Adventitia
18
Describe the process of degradation and phagocytosis in apoptosis
-Cell breaks into membrane-bound fragments that are taken up by neighbouring cells or phagocytes. -Membrane bound “apoptotic bodies” express proteins on their surface that are essential for phagocytosis by neighbouring cells.
18
Describe the process of angiogenesis in wound healing.
1) Endothelial proteolysis of basement membrane 2) Migration of endothelial cell via chemotaxis 3) VEGF causes endothelial proliferation 4) Endothelial maturation and tubular remodelling 5) Recruitment of periendothelial cells - become the pericytes and smooth muscle tissue of the blood vessel, they are important in maintaining the stability of the blood vessels.
19
Describe the systemic effects of alcohol abuse.
- Liver - alcoholic cirrhosis and acute hepatitis
- Nervous system - thiamine deficiency produces degeneration of nerve cells
- CV system - cardiac muscle degeneration causing cardiomyopathy, hypertension and arrythmias
- GI system - gastritis/pancreatitis
- Skeletal muscle - Rhabdomyolysis and chronic myopathy
20
Describe the three main stages of the change of blood flow during acute inflammation.
1. Transient vasoconstriction 2. Vasodilatation of arteries/capillaries (increased bloodflow/redness) 3. Increased permeability (exudation of protein rich fluid into tissues)
20
For benign neoplasms which effects of the growth are the most relevant?
-Local effects -Hormonal effects
21
Give a physiological and pathological example of hyperplasia
-Physiological causes - proliferative endometrium, bone marrow at altitude -Pathological Causes - thyroid goitre
22
Give a physiological and pathological example of hypertrophy
-Physiological causes - skeletal muscle and pregnant uterus (hypertrophy + hyperplasia) -Pathological causes - ventricular cardiac muscle hypertrophy, bladder smooth muscle hypertrophy
23
Give an example of one physiological and one pathological role of apoptosis.
-Physiological - Web space loss in embryogenesis -Pathological - Graft versus host disease
24
Give five functions of the extracellular matrix.
-Supports and anchors cells -Separates tissue compartments e.g. basement membrane -Sequesters growth factors -Allows communication between cells -Facilitates cell migration
25
Give the anagram commonly used for collagen synthesis and briefly outline what each letter stand for.
CHASPOGRL: -Cleavage of signal peptide -Hydroxylation of proline/lysine residues -Addition of N-linked oligosaccharides -Sulphide bond (di) formation -Procollagen - formation of triple helix -O-linked glycosylation -Golgi then exocytosis -Removal of terminal peptides (procollagen peptidase) -Lateral aggregations to form fibrils
26
Give two ways in which the immune system can damage cells?
-Hypersensitivity -Autoimmune
27
How are inflammatory cells recruited in fibrous repair?
Chemotaxis
27
How are malignant cells transported to distant sites?
1) Blood vessels (via capillaries and venules) 2) lymphatic vessels 3) Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles)
29
How can an aspirin overdose cause problems?
Stimulates respiratory centre resulting in a respiratory alkalosis. Compensatory mechanisms result in a metabolic acidosis – fall in pH indicates serious poisoning
30
How can atheroma be prevented?
-Stop smoking -Modify diet -Treat hypertension -Treat diabetes -Lipid lowering drugs
31
How can endothelial injury occur?
-Raised LDL -‘Toxins’ e.g. cigarette smoke -Hypertension -Haemodynamic stress
32
How can you diagnose alcoholic hepatitis?
-Elevated serum bilirubin -Elevated aminotransferases -Elevated alkaline phosphatase -Elevated prothrombin time
33
How can you diagnose someone with excessive alcohol intake?
-Elevated MCV - macrocytic (due to damaged bone marrow/folate deficiency) -Raised AST and ALT -Raised Gamma-GT
34
How do growth factors promote proliferation in the stem cell population?
Extracellular signals transduced into the cell. There promote expression of genes controlling cell cycle.
35
How do malignant cells take advantage of nearby non-neoplastic cells?
Form "cancer niches" where the normal cells provide some growth factors and proteases
36
How do neutrophils move? What chemical mediators are required?
Chemotaxis by: -C5a -LTB4 -Bacterial peptides
38
How does angiogenesis occur in fibrous repair?
Platelets, ECM and others produce angiogenic cytokines in response to hypoxia e.g. VEGF, bFGF
39
How does contact between the basement membranes & adjacent cells control the rate of cell division?
Contact inhibition - signalling through adhesion molecules inhibits proliferation in intact tissue. If this contact is lost proliferation occurs.
40
How does pain and loss of function combat injury?
Enforces rest (stops further injury)
41
How does smooth muscle proliferation occur during atheroma?
Endothelial damage leads to increased platelets and PDGF which then leads to smooth muscle proliferation
43
How does the exudation of fluid combat injury?
-Delivers plasma proteins (immunoglobins, fibrinogen, inflammatory mediators) -Dilutes toxins -Increases lymphatic drainage (so it delivers micro-organisms to phagocytes and antigens to immune system)
43
How does the body go about resolving acute inflammation using chemical mediators?
-All chemical mediators of acute inflammation have short half-lives, some can be degraded (heparinase) or inhibitors may bind (anti-proteases) -Chemical mediators may be diluted in the exudate -Lipoxins, endothelin
43
How does the fibroblast and ECM proliferation occur in fibrous repair?
Macrophages produce various pro-fibrotic cytokines, e.g. IL1, TNF alpha, TGF beta
44
How does the increased smooth muscle cause increased foam cells?
Proliferation and migration of smooth muscle takes the lipid with it. Macrophages arrive and phagocytose the fat, becoming foam cells
45
How does the infiltration of cells combat injury?
Removes pathogenic organisms/necrotic debris
45
How does vasodilatation combat injury?
-Increases delivery -Increases temperature
47
How is the vascular wall made more permeable during acute inflammation?
Chemical mediators: -Histamine, leukotrienes cause endothelial contraction which creates gaps -Cytokines IL-1 and TNF cause cytoskeletal reorganisation which creates gaps -VEGF which creates channels across endothelial cytoplasm
47
How is apoptosis initiated and executed?
-Intrinsic - Everything required is in the cell - usually due to the response to DNA damage by p53. Causes mitochondria to be more permeable, release cytochrome c, mixes with caspase 9 and APAF1 to form an apoptosome activates caspases -Extrinsic - an external ligand (TRAIL or Fas) bind to a death receptor resulting in caspase activation
48
How long can a cell survive hypoxia?
Trick question...mwhahaha Some neurones can only stand a few minutes, however, some fibroblasts in the dermis can stand hours.
48
How might fat necrosis be diagnosed? Why can you use this method?
X-rays - free fatty acids released and they react with calcium to form chalky deposits in fatty tissue
50
In general what is a neoplasm?
An abnormal growth of cells that persists after the initial stimulus is removed
51
In what cell populations can hyperplasia occur?
Labile/stable cell populations
51
In what type of cell population do germ cell neoplasms arise?
Pluripotent
52
In which three ways can chronic inflammation arise?
-Take over from acute inflammation (if damage is to severe to be resolved) -Arise anew (by some chronic low level irritation i.e. RA) -Alongside acute inflammation (when there is severe/repeated irritation)
52
Increasing tumour burden and cytokine release due to secondary neoplastic effects canlead to what presentation?
-Reduced appetite and weight loss -Cachexia -Malaise -Immunosuppression (can also be due to direct bone marrow destruction) -Thrombosis.
53
List five causes of acute inflammation.
-Microbial -Tissue necrosis -Hypersensitivity -Physical agents -Chemical agents
55
List four of the main thrombin inhibitors
Anti-thrombin III, Alpha 1 anti-trypsin, Alpha 2 macroglobulin and Protein C/S
56
List some irreversible changes of hypoxia
-Huge cystolic Ca2+ increase -Several enzymes activated resulting in cell death
57
List some reversible changes of hypoxia
-Increased anaerobic respiration producing lactate and therefore lowering pH -Low ATP means Na+ accumulates in cells -Cell swells via osmosis -Detachment of ribosomes which leads to decreased protein synthesis
58
Name some common causes of cirrhosis? (replacement of liver tissue by fibrosis, scar tissue and regenerative nodules)
-Alcohol -Infection with HBV, HCV -Fatty liver disease -Drugs and toxins
59
Name three types of giant cell and explain in which condition they are commonly seen in.
-Langhans cells - TB -Foreign Body cells - any foreign body, commonly sutures -Touton cells - fat necrosis
61
Neoplasms originating in what area most commonly metastasise to the bone?
-Breast -Bronchus -Kidney -Thyroid -Prostate
62
Other than pancreatitis, what else can cause fat necrosis?
Also can occur after direct trauma to fatty tissue (for example breast tissue)
63
Other than thrombosis suggest other causes of embolism
-Nitrogen -Air -Amniotic fluid -Medical Equipment -Tumour cells
64
Suggest some common sites for blood borne metastasis.
-Lung -Bone -Liver -Brain
65
Suggest some common sites of atheroma
-Abdominal aorta -Coronary arteries -Carotid arteries -Cerebral arteries -Leg arteries
66
Suggest some miscellaneous systemic effects of neoplasms.
-Neuropathies affecting the brain and peripheral nerves -Skin issues (pruritis and abnormal pigmentation) -Fever -Myositis
67
What abnormal accumulations are seen under a light microscope during cell injury in alcoholic liver disease?
-Keratin deposition (Mallory's hyaline) -Fat deposition
69
What are acute-phase proteins? Give examples of some of these proteins.
Proteins that concentrations increase or decrease in response to inflammation. For example: C-reactive protein, a1 antitrypsin, haptoglobin, fibrinogen etc.
71
What are blastomas?
Occur mainly in children and are formed from immature precursor cells
71
What are amyloidosis?
A variety of conditions where normally soluble proteins become insoluble and are deposited in the extracellular space of various organs or tissues, disrupting normal function.
73
What are cells with no resemblance to any tissue called?
Anaplastic
74
What are giant cells? When does it usually occur?
Multinucleate cells made by fusion of macrophages, usually occurs during frustrated phagocytosis.
75
What are initiators of mutation? Give some of the main examples
Mutagenic agents - chemicals, infections, and radiation are the main initiators
76
What are neutrophils?
Neutrophils are a type of granulocyte and are the primary type of white blood cell involved in inflammation.
77
What are paraneoplastic syndromes?
Indirect systemic effects of neoplasms. (e.g. includeeffects of increasing tumour burden, secreted hormones etc.)
79
What are plasma cells?
Differentiated antibody-producing B lymphocytes
80
What are sarcomas?
Stromal malignant neoplasm
82
What are some of the complications of fibrous repair?
- Excessive fibrosis - Insufficient fibrosis - Excessive contraction
82
What are small clusters of malignant cells that lodge at secondary sites but fail to grow called?
Micrometastases
83
What are the 4 types of hypoxia?
-Ischaemic -Anaemic -Hypoxaemic -Histiocytic
84
What are the common effects of venous thrombi?
-Congestion -Oedema -Ischaemia -Infarction
85
What are the effects of aspirin over use?
-Acute erosive gastritis producing GI bleeding -Inhibits platelet cyclo-oxygenase producing decreased platelet aggregation which results in petechaie
85
What are the five possible outcomes of thrombosis?
-Lysis (breakdown) -Propagation (progressive spread of thrombosis, distally in arteries, proximally in veins) -Organisation (reparative process with ingrowth of fibroblasts and capillaries. ) -Recanalisation (blood flow starts again, little holes in the thrombus) -Embolism (breaks off and ends up obstructing a vessel)
86
What are the folds of the brain called?
Gyri
88
What are the four main changes in tissue during acute inflammation?
-Vasodilation -Exudation of fluid -Infiltration of cells -Pain...and loss of function
89
What are the four main effects of chronic inflammation?
-Fibrosis -Impaired function -Atrophy -Stimulation of an immune response
90
What are the four main types of necrosis?
-Coagulative -Liquefactive -Caseous -Fat necrosis
90
What are the four possible consequences of acute inflammation?
-Complete resolution -Continued acute inflammation with some chronic inflammation = abscess -Chronic inflammation and fibrous repair -Death
92
What are the functions of lymphocytes?
-B lymphocytes differentiate to produce antibodies -T lymphocytes are responsible for control and some cytotoxic functions
92
What are the functions of fibroblasts/myofibroblasts?
Recruited by macrophages to make collagen which can tighten and pull damage together.
94
What are the functions of macrophages in chronic inflammation?
-Phagocytosis -Processing and presentation of antigen to immune system -Synthesis of cytokines, complement component, blood clotting factors and proteases -Control of cells via cytokine release
95
What are the grooves of the brain called?
Sulci
96
What are the main causes of cell injury and death?
-Hypoxia -Toxins -Physical agents (trauma, temperature pressure etc.) -Radiation -Micro-organisims -Immune mechanisms -Dietary insufficiencys/excesses
97
What are the main cells involved in the chronic inflammatory response?
-Macrophages -Lymphocytes -Plasma cells -Eosinophils -Fibroblasts/myofibroblasts
99
What are the most lethal features of a malignant neoplasm?
Invasion and metastasis
100
What are the three types of cells with different regeneration ability? Give an example of each.
-Labile (active cells with the normal state being cell division - high proliferation) i.e. epithelial or haematopoietic cells -Stable (resting state at G0 with varying speed of proliferation) hepatocytes, osteoblasts, fibroblasts -Permanent (unable to divide - have exited the cell cycle) neurones, cardiac myocytes
100
What are the two main factors controlling regeneration?
-Growth factors -Contact between basement membranes & adjacent cells
100
What are the three components of Virchow's triad?
-Changes in blood flow -Changes in vessel wall -Changes in blood components
101
What are the two types of gangrene? Which is more serious and why?
-Dry (coagulative necrosis) -Wet (liquefactive necrosis) Wet is worse as it is caused by infection which can spread into the blood causing septicaemia
103
What are the two types of gangrene? Which is more serious and why?
-Dry (coagulative necrosis) -Wet (liquefactive necrosis) Wet is worse as it is caused by infection which can spread into the blood causing septicaemia
104
What are the two types of infarct? Where are they common
- White (common in the kidney and spleen - end arteries)
- Red (bowel, lung, intestines)
106
What are the two types of O2 dependent killing mechanism?
-Superoxide and hydrogen peroxide -H2O2-Myeloperoxidase-halide system - produces HOCl.
107
What can be given to reverse the effects of paracetamol overdose? How does it work?
N-acetylcysteine which increases availability of hepatic glutathione
108
What changes does invasion into other tissues by carcinoma cells require?
-Altered adhesion -Altered stromal proteolysis -Altered motility
110
What complication can follow the perforation of an inflamed appendix?
Infection in the abdomen - peritonitis
111
What cytoplasmic changes are seen under a light microscope during cell injury? Are they reversible or irreversible?
-Initially reduced pink staining due to water accumulation (reversible) -Later, increased pink staining due to ribosome detachment and denaturation of proteins (irreversible)
112
What disease is commonly associated with caseous necrosis?
Tuberculosis
114
What disease is commonly associated with caseous necrosis?
Tuberculosis
115
What do blood vessels do to aid haemostasis?
Constrict to reduce the blood flow and therefore prevent blood loss
116
What do platelets do to aid haemostasis?
They adhere to the vessel wall and each other forming a platelet plug to stop blood flowing out.
116
What do foam cells secrete? What does this lead to?
Secrete cytokines causing further smooth muscle cell stimulation and recruitment of other inflammatory cells
117
What do we mean by the term in-situ and what is the inverse of that term?
No invasion of epithelial basement membrane , the opposite of this being invasive
118
What does a granuloma in Crohn's disease consist of? How is it different to one in tuberculosis?
Epithelioid macrophages and giant cells surrounded by a cuff of lymphocytes. These are distinguished from those in TB by not having any central caseous necrosis.
119
What does altered adhesion between malignant cells and stromal proteins require?
Changes in Integrin expression
120
What does altered adhesion between malignant cells require?
Reduction in E-cadherin expression
121
What does successful haemostasis depend on?
-Vessel wall -Platelets -Coagulation System -Fibrinolytic System
123
What does the term hemiplegia mean?
The paralysis of one side of the body - trunk, arm and leg of one side
124
What event may trigger acute inflammation of the appendix?
Blockage of the appendix lumen: -Faecoliths -Lymphoid hyperplasia (lots of lymphoid tissue) -Tumours
125
What four things are the local effects of neoplams due to?
1) Direct invasion and destruction of normal tissue 2) Ulceration at a surface leading to bleeding 3) Compression of adjacent structures 4) Blocking of tubes and orifices.
126
What general factors influence wound healing?
- Age - Drugs - General/specific dietary deficiencies - State of health - Cardiovascular status
127
What helps distal axons reconnect after being severed?
Neurotrophic hormones (growth factors) produced by Schwann cells which guide axonal regeneration
128
What irreversible changes are seen under an electron microscope during cell injury?
-Nuclear changes (shrinkage, dissolution and fragmentation) -Lysosome rupture (membrane damage) -Myelin figures (defects in the membrane) -Lysis of the ER (due to membrane damage)
130
What is a fistula?
An abnormal connection between two epithelium-lined organs
130
What is a councilman body?
A hepatocyte that is undergoing necrosis - an eosinophilic globule often surrounded by normal parynchyma found in the liver of individuals suffering from viral hepatitis, yellow fever, or other viral syndrome.
131
What is a granuloma? Why does it form?
A collection of lymphocytes and epitheloid histiocytes (modified, immobile macrophages). Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate.
133
What is a malignant neoplasm?
an abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue with potential to spread to distant sites
135
What is a metastasis?
A malignant neoplasm that has spread from its original site to a new non-contiguous site.
136
What is a monoclonal cell population?
A collection of cells that all originated from a single founding cell
137
What is an apotosome made from?
Cytochrome c, APAF1 and caspases 9 form an apoptosome
139
What is an embolism?
The blockage of a blood vessel by a solid, liquid or gas at a site distant from its origin
140
What is an infarct?
Ischaemia that results in necrosis
141
What is dysplasia?
A pre-neoplastic alteration in which cells show disordered tissue organisation. It is not neoplastic because the change is reversible.
142
What is fat necrosis in breast tissue commonly confused with?
Breast cancer - due to the scar left mimicing a nodule of breast cancer
143
What is fibrinolysis?
Breakdown of fibrin by plasmin
144
What is gangrene?
Necrosis that you can see
145
What is granulomatous inflammation? (this is as easy as it sounds)
Chronic inflammation with granulomas
146
What is healing by primary intention?
An incised wound with apposed edges, the epidermis regenerates and the dermis undergoes fibrous repair with minimal clot and granulation tissue. Minimal contraction and scarring as the granulation tissue turns to scar tissue.
146
What is haemostasis?
The body’s response to stop bleeding and loss of blood
147
What is healing by secondary intention?
Large wounds with unapposed edges, forms a scab (eschar) with the epidermis regenerating from the base up and a shitload of granulation tissue. This therefore produces a lot of contraction and a big ass scar.
149
What is hypoxaemic hypoxia?
A low amount of arterial oxygen due to: -Reduced absorption -Reduced oxygen at high altitudes
149
What is histiocytic hypoxia?
Hypoxia caused by the inability to utilise oxygen by oxidative phosphorylation (like in cyanide poisoning)
151
What is leukaemia?
Malignant neoplasm of blood-forming cells arising in the bone marrow
152
What is lymphoma?
Malignant neoplasms of lymphocytes, mainly affecting lymph nodes
153
What is passage beyond the R point of the cell cycle governed by?
The phosphorylation of the Retinoblastoma Protein (pRb)
155
What is Rheumatoid arthritis?
An autoimmune disease where there is a localised and systemic response. The localised chronic inflammation leads to joint destruction and the systemic immune response can affect other organs and cause amyloidosis.
155
What is pleomorphism?
Worsening differentiation of individual cells have increasing nuclear size and nuclear to cytoplasmic ratio, more mitotic figures and increasing variation in size and shape of cells and nuclei.
157
What is streptokinase?
A fibrinolytic therapy used to active plasminogen
158
What is the importance of endothelial cells in fibrous repair?
Angiogenesis
159
What is the clinical appearance of acute inflammation? (those 4 words)
-Rubor (redness) -Tumor (swelling) -Calor (heat) -Dolor (pain) and loss of function
160
What is the function of an apotosome?
Part of the initiation phase of apoptosis. The apoptosome leads to caspase activation and ultimately to apoptosis
161
What is the function of Bcl-2 in apoptosis?
Prevents cytochrome c release from mitochondria, therefore inhibits apoptosis
162
What is the importance of inflammatory cells in fibrous repair?
-Removal of debris (by neutrophils and macrophages) -Chemical mediators (lymphocytes and macrophages)
163
What is the main difference between Crohn's disease and Ulcerative colitis? (both types of inflammatory bowel disease)
-Crohn's disease is transmural so results in strictures and fistula -Ulcerative colitis is superficial and results in diahorrea and bleeding
164
What is the main target for radicals? What does this result?
Lipids in the membrane - results in lipid peroxidation and autocatalytic chain reaction (creates more radicals)
165
What is the process early in female embryogenesis whereby one allele is randomly inactivated in each cell?
Lyonisation
166
What is the process of malignant cells leaving a vessel called?
Extravasation
168
What is the process that affects distal nerve fibres that have been severed called?
Wallenian degeneration
169
What is the purpose of acute inflammation?
This is the response of living tissue to limit damage/injury to tissue
170
What is the risk of increased intercranial pressure?
Intercranial haematoma (bleed in the brain) leading to cerebral oedema.
171
What is the role of thrombin in the clotting cascade?
Positively feeds back on factors V, VIII and XI
173
What is the significance of the hydroxyproline residues in the collagen molecule? How are they formed?
Formed from hydroxylation of proline (Prolyl Hydroxylase) and forms many interchain H-bonds
174
What is the significance of the proline residues in the collagen molecule?
Prevents the peptide moving into a different structure than the extended α-chain conformation
175
What is the spread of malignant cells via fluid in the body cavities known as?
Transcoelomic spread
176
What is tuberculosis caused by? How does it cause disease?
Mycobacteria (especially M. tuberculosis) which causes disease by persistence and induction of cell-mediated immunity
178
What local complications can be caused by swelling?
Blockage of tubes (in the bile ducts, intestine etc.)
178
What local complications can be caused by excessive exudate?
-Compression (cardiac tamponade etc.) -Serositis
179
What local factors influence wound healing?
- Type/size/location of wound - Apposition/movement - Blood supply - Infection - Foreign material - Radiation
180
What main things cause granulomas to arise?
-Hypersensitivity to mildly irritant foreign material -Infections (e.g. mycobacteria in TB/leprosy) -Sarcoidosis -Wegener's granulomatosis -Crohn's disease
180
What must malignant cells do to get from a primary site to a secondary site?
1) Grow and invade at the primary site 2) Enter a transport system 3) Grow at the secondary site to form a new tumour. N.B. At all points the cells must evade destruction by immune cells.
182
What nuclear changes are seen under a light microscope during cell injury? Are they reversible or irreversible?
-Clumped chromatin (reversible) -Shrinkage (pyknosis), fragmentation (karryohexis) and dissolution (karryolysis) - (irreversible)
183
What often covers areas of acute inflammation? (fancy word for pus)
Fibropurulent exudate
185
What reversible changes are seen under an electron microscope during cell injury?
-Swelling (due to messed up Na+/K+ pump) -Clumped chromatin (due to low pH) -Autophagy (due to needing more energy) -Ribosomes pop off (no energy to keep them) -Cytoplasmic blebs (cell swelling)
186
What structural changes that you can see under a light microscope accompany apoptosis?
-Single cells or small clusters -Intensely eosinophilic -Dense nuclear fragments -Cell shrinkage -Chromatin condensation -Nuclear fragmentation -Phagocytosis by macrophages NO INFLAMMATION
187
What structural changes that you can see under an electron microscope accompany apoptosis?
Cytoplasmic blebs - producing fragmentation into membrane-bound apoptotic bodies NO INFLAMMATION
188
What three processes make up apoptosis?
-Initiation -Execution -Degradation and phagocytosis
189
What two things are required for Prolyl Hydroxylase to function correctly?
-Vitamin C -Fe 2+ ions
190
What two things determine the site of a secondary tumour?
1) Regional drainage i.e. lymphatics to the lymph nodes, blood to the next capillary bed and for transcoelomic spread this is predictably to other areas in the coelomic space or to adjacent organs 2) Cross-talk between malignant neoplasms and organ microenvironments (Stephen Paget)
191
What type of cell is mainly present in chronic gastritis?
Lymphocytes
192
What type of cell is mainly present in Leishmaniasis (a protozoal infection)?
Macrophages
193
What type of cell is mainly present in rheumatoid arthritis?
Plasma cells
194
What type of inflammation is commonly associated with caseous necrosis?
Granulomatous
195
What type of necrosis does the brain go under after an infarct?
Liquefactive
196
What type of necrosis is common in ischaemic cell death?
Coagulative
197
What type of necrosis is common when there are loads of neutrophils? Why?
Liquefactive as the neutrophils release shitloads of proteolytic enzymes
199
What type of neoplasm ends in a carcinoma?
Malignant
200
What type of neoplasm ends in an -oma?
Benign
201
When are free radicals produced?
-Chemical/radiation injury -Ischaemic-reperfusion injury -Cellular ageing -High oxygen concentrations
202
When do the changes seen in hypoxia become irreversible?
-Huge cystolic Ca2+ increase -Several enzymes activated resulting in cell death Mechanism poorly understood (what's new?!)
203
When do the symptoms of paracetamol OD usually present?
After 36-96 hours
205
Where is liquefactive necrosis commonly seen? Why?
The brain as it is a fragile tissue without support from a robust collagenous matrix
205
Which chemical mediator is most important during phagocytosis?
C3b
207
Which enzyme converts oxygen radicals to hydrogen peroxide?
Superoxide dismutase (SOD)
208
Which enzyme is required to turn ethanol to acetaldehyde? What else is required?
Alcohol dehydrogenase with CYPZE1 and catalase
209
Which factor turns fibrin into a cross linked fibrin clot
Activated factor xIII (factor 13)
210
Which is the most dangerous (badass) free radical?
OH•
211
Which neoplasms do not produce metastases?
Benign
212
Why are alcoholics particularly susceptible to paracetamol overdose?
Lower reserves of glutathione means it is easier to saturate.
213
Why are skin grafts used?
Produces apposed edges - less scaring and granulation tissue
214
Why can metaplasia occur due to smoking? What type of cell change takes place?
Change in epithelium to be more suited to new environment, to make it more robust. Pseudostratified Ciliated → Squamous cells (more robust)
215
Why do inflamed appendices appear plumper than usual?
Oedema
216
Why do malignant cells have altered protease ability? Which proteases are most notably altered?
The cells must degrade basement membrane and stroma to invade. Matrix metalloproteinases (MMPs)
217
Why do you get fibrosis of the gall bladder wall in chronic cholecystitis?
Repeated obstruction by gall stones leads to recurrent acute inflammation and therefore fibrosis of the gall bladder wall
218
Why does a red infarct occur? (5 reasons)
-Dual blood supply -Rich anatomoses -Loose tissue (shit support for capillaries) -Congestion of tissue (congestive cardiac failure) -Raised venous pressure
219
Why does a white infarct occur?
The occlusion of an end artery (the sole source of blood to an area)
220
Why is angiogenesis important for wound healing?
-Provides access to the wound for inflammatory cells and fibroblasts -Delivery of oxygen and other nutrients
221
Why is fat necrosis commonly seen in pancreatitis?
Pancreatitis causes release of lipases from injured pancreatic acinar cells. Lipases act on fatty tissue of pancreas and fat elsewhere in the abdominal cavity causing fat necrosis.
222
Why is NAPQI a big problem?
It binds with sulphydryl groups on liver cell membranes, eventually causes hepatocyte necrosis and liver failure.
223
Why is the transition of a carcinoma cell to one able to invade other tissues called EMT?
Epithelial-to-mesenchymal transition (EMT) occurs appears more like a mesenchymal cell than an epithelial cell. This allows it to invade other tissues
224
Why is there oedema during acute inflammation?
Increased permeability of the vessel wall leads to proteins flowing into the interstitum
225
Why might the appendix have a fibrous tip in older people?
Recurrent abscess formation
226
Why might there be a high white blood cell count (leukocytosis) after acute inflammation?
-IL-1 and TNFa produce an accelerated release of WBCs from marrow -Macrophages + T lymphocytes produce colony-stimulating factors
227
Why might there be fever after acute inflammation?
Endogenous pyrogens (IL-1 and TNFa) are produced
