Introduction to Clinical Sciences

Question 1

Define inflammation.

Answer 1

A local physiological response to tissue injury

Question 2

Give a benefit of inflammation.

Answer 2

It can destroy invading microorganisms thus preventing the spread of infection

Question 3

Give a disadvantage of inflammation.

Answer 3

It can produce disease

Question 4

What are the two types of inflammation?

Answer 4

Acute and chronic

Question 5

What is acute inflammation?

Answer 5

• Initial response of tissue to injury
• Early onset
• Short duration

Question 6

Which cells are involved with acute inflammation? What are their roles?

Answer 6

• Neutrophils and monocytes
• Neutrophils phagocytise pathogens, monocytes migrate to tissue and become macrophages which secrete chemical mediators for chemotaxis

Question 7

What are the 6 causes of acute inflammation?

Answer 7

• Microbial infections (bacteria, viruses)
• Hypersensitivity reactions
• Physical agents (trauma, heat, cold)
• Chemicals (corrosives, acids)
• Bacterial toxins
• Tissue necrosis

Question 8

What are the steps for acute inflammation?

Answer 8

• Vascular component: dilation of vessels
• Exudative component: vascular leakage of protein-rich fluid
• Neutrophil polymorph (the cell type recruited to the tissue)

Question 9

What is exudate?

Answer 9

A protein-rich fluid that leaks out of vessel walls due to increased vascular permeability

Question 10

What is transudate?

Answer 10

Transudate is fluid buildup caused by systemic conditions that alter the pressure in blood vessels, causing fluid to leave the vascular system

Question 11

Explain the 4 steps for neutrophil polymorph emigration.

Answer 11

1. Migration of neutrophils: due to increased plasma viscosity and slowing of flow due to injury, neutrophils migrate to plasmatic zone
2. Adhesion of neutrophils: adhesion to the vascular endothelium occurs in venules (‘pavementing’)
3. Neutrophil emigration: neutrophils pass through endothelial cells, onto the basal lamina and then the vessel wall
4. Diapedesis: RBCs may also escape from vessels, this is a passive process and indicates severe vascular injury
   Neutrophils digest the bacteria.

Question 12

What are the 4 outcomes of acute inflammation?

Answer 12

• Resolution = complete restoration of tissues to normal
• Supparation = formation of pus. This becomes surrounded by a pyogenic membrane, which is the start of healing, leads to scarring
• Organisation = replacement by granulation tissue. New capillaries grow into the inflammatory exudate, macrophages migrate and fibrosis occurs
• Progression = causative agent not removed, so progression to chronic inflammation

Question 13

Give 5 cardinal signs of acute inflammation.

Answer 13

• Rubor - redness; due to dilation of small vessels
• Calor - heat; due to increased blood flow, resulting in vascular dilation + delivery of warm blood
• Tumor - swelling; results from oedema (accumulation of fluid in extravascular space as part of the fluid exudate). Also from physical mass of inflammatory cells migrating to area
• Dolor - pain; results from stretching and distortion of tissues due to inflammatory oedema
• Loss of function

Question 14

How can acute inflammation be diagnosed histologically?

Answer 14

By looking for the presence of neutrophil polymorphs.

Question 15

Give 3 endogenous chemical mediators of acute inflammation.

Answer 15

1. Bradykinin
2. Histamine
3. Nitric oxide

Question 16

What are 4 systemic effects of acute inflammation?

Answer 16

1. Fever
2. Feeling unwell
3. Weight loss
4. Reactive hyperplasia of the reticuloendothelial system

Question 17

What causes the pain associated with acute inflammation?

Answer 17

1. Stretching and distortion of tissue due to oedema and pus under high pressure in an abcess cavity
2. Chemical mediators, e.g. bradykinin and prostaglandins, are also known to induce pain

Question 18

Describe the process of neutrophil polymorph migration into tissues as seen in acute inflammation.

Answer 18

1. Margination of neutrophils
2. Pavementing of neutrophils
3. Neutrophils pass between endothelial cells
4. Neutrophils pass through basal lamina and migrate into adventitia

Question 19

What is the role of tissue macrophages in acute inflammation?

Answer 19

They secrete chemical mediators that attract neutrophil polymorphs

Question 20

What is the role of the lymphatic system in acute inflammation?

Answer 20

Lymphatic channels dilate and drain away oedematous fluid therefore reducing swelling. Antigens are also carried lymph nodes for recognition by lymphocytes

Question 21

What is the major role of neutrophil polymorphs in acute inflammation?

Answer 21

Phagocytosis

Question 22

What does viral infection result in?

Answer 22

Cell death due to intracellular multiplication

Question 23

What does bacterial infection result in?

Answer 23

The release of exotoxins (involved in the initiation of inflammation) or endotoxins

Question 24

What is chronic inflammation?

Answer 24

• Slow onset or sequel to acute
• Long duration

Question 25

What cells are involved with chronic inflammation?

Answer 25

Macrophages, lymphocytes and plasma cells

Question 26

What cell can form when several macrophages try to ingest the same particle?

Answer 26

Multinucleate giant cell

Question 27

Give 4 causes of chronic inflammation.

Answer 27

1. Primary chronic inflammation: - Resistance of infective agent, e.g. TB - Endogenous materials, e.g. necrotic tissue - Exogenous materials, e.g. asbestos - Autoimmune conditions, e.g. Hashimoto’s - Primary granulomatous diseases, e.g. Crohn’s 2. Transplant rejection 3. Recurrent acute inflammation 4. Progression from acute inflammation

Question 28

In which type of inflammation would you see neutrophil polymorphs?

Answer 28

Acute inflammation

Question 29

What are some macroscopic appearances of chronic inflammation?

Answer 29

- Chronic ulcer - Chronic abscess cavity - Granulomatous inflammation - Fibrosis

Question 30

What are some microscopic appearances of chronic inflammation?

Answer 30

- Macrophages, lymphocytes and plasma cells - Exudation not a common feature - Evidence of continuing destruction - Possible tissue necrosis

Question 31

What are the roles of B lymphocytes, T lymphocytes and macrophages in chronic inflammation?

Answer 31

- B lymphocytes = transform into plasma cells + produce antibodies - T lymphocytes = responsible for cell-mediated immunity - Macrophages = respond to chemotactic stimuli, produce cytokines: interferon alpha and beta, IL1, 6, 8, TNF-alpha

Question 32

What is granulation tissue?

Answer 32

Granulation tissue is composed of small blood vessels in a connective tissue matrix with myofibroblasts = important for healing

Question 33

What is a granuloma?

Answer 33

An aggregate of epithelioid histiocytes

Question 34

Give examples of granulomatous diseases. What do they cause?

Answer 34

TB, leprosy, Crohn’s and sarcoidosis. They cause granulomas to develop

Question 35

What do granulomas and eosinophil presence indicate?

Answer 35

A parasite

Question 36

The activity of what enzyme in the blood can act as a marker for granulomatous disease?

Answer 36

Angiotensin converting enzyme

Question 37

Compare acute inflammation vs. chronic inflammation - onset and duration, cells involved, what these cells do and the macroscopic features.

Answer 37

- Acute inflammation: - Fast onset, short duration - Neutrophils and monocytes - Neutrophil extravasation - Rubor, calor, tumor, dolor - Chronic inflammation: - Slower onset, long duration - Macrophages, lymphocytes, plasma cells - Cellular infiltrate of lymphocytes, macrophages and plasma cells. Possible granulomas - Fibrosis, scar tissue

Question 38

What is the difference between resolution and repair?

Answer 38

- Resolution is where the initiating factor is removed and the tissue is able to regenerate - Repair is where the initiating factor is still present and the tissue is unable to regenerate. Replacement of damaged tissue by fibrous tissue, collagen produced by fibroblasts

Question 39

Name 5 types of cells that are capable of regeneration.

Answer 39

1. Hepatocytes 2. Osteocytes 3. Pneumocytes 4. Blood cells 5. Gut and skin epithelial cells

Question 40

Name 2 types of cells that are incapable of regeneration.

Answer 40

1. Myocardial cells 2. Neurones

Question 41

In skin wounds, what is healing by 1st intention?

Answer 41

When the edges of the wound are brought together, e.g. sutures

Question 42

In skin wounds, what is healing by 2nd intention?

Answer 42

Wound left open and to heal by itself

Question 43

What is an abcess?

Answer 43

Acute inflammation with a fibrotic wall

Question 44

Define thrombosis.

Answer 44

The formation of a solid mass from blood constituents in an intact vessel in the living

Question 45

Give 2 reasons why thrombosis formation is uncommon.

Answer 45

1. Laminar flow 2. Endothelial cells not 'sticky'

Question 46

What is the first stage of thrombosis formation? Why is this hard to stop?

Answer 46

- Platelet aggregation, which starts the clotting cascade of proteins in the blood - These both have positive feedback loops, so are hard to stop

Question 47

Which two granules do platelets contain? What are these involved in? Why would platelets release these?

Answer 47

- Platelets have alpha and dense granules - Alpha granules are involved in platelet adhesion, e.g. fibrinogen - Dense granules cause platelets to aggregate, e.g. ADP - Platelets are activated, releasing their granules when they come into contact with collagen. If this happens within an intact vessel, a thrombus is formed

Question 48

What are the three major factors that cause thrombosis? What is this called? How many are typically needed to form a thrombus?

Answer 48

1. Change in vessel wall 2. Change in blood constituents 3. Change in blood flow This is called Virchow's triad. Thrombosis typically formed by 2 of these factors

Question 49

Detail the steps of arterial thrombosis.

Answer 49

- An atheromatous plaque will result in a change in the vessel wall 1. Atheromatous plaque may have a fatty streak 2. Plaque grows + protrudes into lumen causing degree of turbulence in blood flow 3. Turbulence results in loss of intima cells 4. Fibrin deposited and platelet clumping occurs 5. This process is self-perpetuating, leading to the formation of the platelet layer (first layer of thrombus) 6. This layer allows for the precipitation of a fibrin mesh work in which RBCs get trapped 7. This structure protrudes further into lumen causing more turbulence + more platelet deposition 8. Thrombi grow in the direction of blood flow -\> propagation

Question 50

Detail the steps of venous thrombosis.

Answer 50

1. There is lower BP in veins and atheroma does not occur 2. Thrombi begin at valves 3. Valves produce a degree of turbulence + can be damaged, e.g. trauma, stasis 4. When blood pressure falls, flow through begins to slows, allowing for a thrombus to form

Question 51

What are the 3 clinical features of arterial thrombi?

Answer 51

1. Loss of pulse distal to thrombus 2. Area becomes cold, pale + painful 3. Possible gangrene

Question 52

What are the 2 clinical features of venous thrombi?

Answer 52

1. Tender 2. Area becomes reddened + swollen

Question 53

What are the 4 outcomes of thrombi?

Answer 53

1. Resolve 2. Organised - becomes a scar, results in slight narrowing of vessel lumen 3. Recanalisation - intimal cells may proliferate, capillaries may grow into the thrombus and fuse to form larger vessels 4. Embolus - fragments of the thrombus break off into the circulation

Question 54

Compare arterial thrombus vs. venous thrombus - what is it caused by, blood pressure, what the thrombus is made of, what can it lead to, and its treatment

Answer 54

- Arterial thrombus: - Commonly caused by atheroma - High pressure - Mainly made of platelets - Can lead to MI/stroke - Anti-platelets, e.g. aspirin - Venous thrombus: - Commonly caused by stasis - Low pressure - Mainly made of RBCs - Can lead to DVT/PE - Anti-coagulants

Question 55

What drug can be used to prevent thrombosis?

Answer 55

Aspirin

Question 56

Define embolus.

Answer 56

A mass of material (often a thrombus) in the vascular system able to lodge in a vessel and block its lumen

Question 57

What are the consequences of an arterial embolus?

Answer 57

An arterial embolus can go anywhere. The consequences could be stroke, MI, gangrene etc.

Question 58

What are the consequences of a venous embolus?

Answer 58

An embolus in the venous system will go onto the vena cava and then through the pulmonary arteries and become lodged in the lungs, causing a pulmonary embolism. This means there is a decreased perfusion to the lungs

Question 59

Define ischaemia.

Answer 59

Reduction in blood flow

Question 60

Define infarction.

Answer 60

Decreased blood flow with subsequent cell death (this is because the surrounding cells don't get enough oxygen)

Question 61

Can the effects of ischaemia be reversible? Is the duration of an ischaemic attack short or long? Which cells are the most vulnerable to an ischaemic attack?

Answer 61

- Effects can be reversible - Duration of an ischaemic attack is brief - Cardiomyocytes and cerebral neurons are most vulnerable

Question 62

What can happen if ischaemia is rectified?

Answer 62

Re-perfusion injury can occur due to the release of waste products

Question 63

Why are tissues with an end arterial supply more susceptible to infarction?

Answer 63

They only have a single arterial supply and so if this vessel is interrupted, infarction is likely

Question 64

Give 3 examples of organs with a dual arterial supply. Are these organs more or less susceptible to an infarction?

Answer 64

1. Lungs (bronchial arteries + pulmonary veins) 2. Liver (hepatic arteries + portal veins) 3. Some areas of the brain around the Circle of Willis - Organs with a dual blood supply are less susceptible to infarction

Question 65

Is infarction a microscopic or macroscopic event? What is it usually caused by?

Answer 65

Infarction is a macroscopic event usually caused by thrombosis.

Question 66

Through which blood system would an embolus have travelled if it resulted in a pulmonary embolism?

Answer 66

Venous system

Question 67

Define atherosclerosis.

Answer 67

Inflammatory process characterised by hardened plaques in the intima of a vessel wall

Question 68

What are the 3 main constituents of an atheromatous plaque?

Answer 68

1. Lipids (cholesterol) 2. Fibrous tissue 3. Lymphocytes

Question 69

Give 6 risk factors for atherosclerosis.

Answer 69

- Hyperlipidaemia = most important risk factor - Smoking - Hypertension - Uncontrolled diabetes mellitus - Increasing age - Male sex

Question 70

Why can cigarette smoking lead to atherosclerosis?

Answer 70

Cigarette smoking releases free radicals, nicotine and CO into the body. These all damage endothelial cells

Question 71

Why can hypertension lead to atherosclerosis?

Answer 71

A higher blood pressure means there is a greater force exerted onto the endothelial cells and this can lead to damage

Question 72

Why can hyperlipidaemia lead to atherosclerosis?

Answer 72

Direct damage to endothelial cells

Question 73

Is atherosclerosis more common in the systemic or pulmonary circulation?

Answer 73

It is more common in the systemic circulation because there is a higher pressure system

Question 74

What can be done to prevent atherosclerosis?

Answer 74

Reduce risk factors and taking low dose aspirin regularly

Question 75

What is the primary cause of atherosclerosis?

Answer 75

Endothelial cell damage

Question 76

Describe the process of atherosclerosis.

Answer 76

1. High levels of LDL in the blood. Some deposits in the tunica initima and becoome oxidised - this activates endothelial cells to attract leukocytes (ENDOTHELIAL CELL DYSFUNCTION) 2. Monocytes etc. are attracted to the site of damage (endothelium) - move to tunica intima (become macrophages) 3. Macrophages take up oxidised lipid to form foam cells (inflammatory response). These foam cells encourage plaque progression by serving as a source of pro inflammatory cytokines. They also promote the migration of smooth muscle cells from the tunica media to the tunica intima and smooth muscle cell proliferation - this causes heightened synthesis of collagen 4. Foam cells die - release lipid contents 5. Fibrous cap maintaining the plaque has to be maintained by resorption and redeposition. However, if the balance is shifted, e.g. in favour of inflammatory conditions we get a plaque rupture. This causes blood coagulation = thrombus = impedes blood flow (occludes vessel)

Question 77

What are the conditions that atherosclerosis can cause?

Answer 77

- Cerebral infarction - Carotid atheroma, leading to TIAs - MI - Aortic aneurysm (can cause sudden death) - Peripheral vascular disease - Gangrene

Question 78

Define apoptosis.

Answer 78

Programmed cell death of a single cell

Question 79

What is the role of p53 protein?

Answer 79

The p53 protein looks for DNA damage. If DNA damage is present, p53 switches on apoptosis to prevent damaged DNA from replicating

Question 80

What protein can switch on apoptosis if DNA damage is present?

Answer 80

p53 protein

Question 81

In the regulation of apoptosis, what are the 3 inhibitors and 3 inducers?

Answer 81

- Inhibitors: - Growth factors - Extracellular cell matrix - Sex steroids - Inducers: - Glucocorticoids - Free radicals - Ionising radiation - DNA damage

Question 82

Activation of which family of protease enzymes can turn on apoptosis?

Answer 82

Caspases

Question 83

Activation of what receptor can activate caspase and therefore apoptosis?

Answer 83

FAS receptor

Question 84

Describe the intrinsic pathway for apoptosis.

Answer 84

- Uses pro- and anti-apoptotic members of the Blc-2 family - Bax forms Bax-Bax diners which enhance apoptotic stimuli - The Bcl-2:Bax ratio determines the cell's susceptibility to apoptotic stimuli - Responds to growth factors and biochemical stress - p53 gene induces cell cycle arrest and initiates DNA damage repair - if damage is difficult to repair, p53 can induce apoptosis

Question 85

Describe the extrinsic pathway for apoptosis.

Answer 85

- Ligand-binding at death receptors on the cell surface - Receptors include TNFR1 and CD95 - Ligand-binding results in clustering of receptor molecules on the cell surface and the initiation of signal transduction cascade - Caspases are activated, triggering apoptosis - This pathway is used by the immune system to eliminate lymphocytes

Question 86

What is an example of a disease where there is a lack of apoptosis.

Answer 86

Cancer; mutations in p53 mean cell isn't damaged

Question 87

Give an example of a disease where there is too much apoptosis.

Answer 87

HIV

Question 88

Define necrosis.

Answer 88

Unprogrammed death of a large number of cells due to an adverse event

Question 89

What are the different types of necrosis?

Answer 89

- Coagulation necrosis = most common type, can occur in most organs, caused by ischaemia - Liquefactive necrosis = occurs in the brain due to its lack of substantial supporting stroma - Causeous necrosis = causes a 'cheese' pattern, TB is characterised by this form of necrosis - Gangrene = necrosis with rotting of the tissue, affected tissue appears black due to deposition of iron sulphide (from degraded haemoglobin)

Question 90

Give 3 examples of events that can lead to necrosis.

Answer 90

1. Frost bite 2. Avascular necrosis 3. Infarction

Question 91

Give 3 differences between apoptosis and necrosis.

Answer 91

1. Apoptosis is programmed cell death whereas necrosis is unprogammed 2. Apoptosis tends to affect only a single cell whereas necrosis affects a large number of cells 3. Apoptosis is often in response to DNA damage, necrosis is triggered by an adverse event, e.g. frost bite

Question 92

What does congenital mean?

Answer 92

Present at birth

Question 93

What does inherited mean? What does acquired mean?

Answer 93

- Inherited = caused by an inherited genetic abnormality - Acquired = caused by non-genetic environmental factors

Question 94

Define hypertrophy. Give an example.

Answer 94

- Increase in the size of a tissue due to an increase in the size of constituent cells - Muscle hypertrophy can be seen in athletes due to increased muscle mass

Question 95

Define hyperplasia. What can this only happen in? Give an example.

Answer 95

- Increase in the size of a tissue due to an increase in the number of constituent cells - This can only happen in cells that divide -\> cannot happen in myocardial cells or nerve cells - Hyperplasia of bone marrow cells can be seen in those living at high altitudes

Question 96

Define atrophy. Give an example.

Answer 96

- Decrease in the size of a tissue due to a decrease in the size of the constituent cells OR due to a decrease in the number of constituent cells - Occurs in disease, e.g. muscle atrophy

Question 97

Define metaplasia. Why does it occur? Give an example.

Answer 97

- A change in the differentiation of a cell from one fully differentiated cell type to another fully differentiated cells type - Occurs in response to alterations in the cellular environment - Barrett's oesophagus = squamous epithelium of the oesophagus can become columnar epithelium in response to stomach acid

Question 98

Define dysplasia.

Answer 98

Morphological changes seen in cells in progression to becoming cancer. The cells become more 'jumbled up'

Question 99

What limits cell growth?

Answer 99

Telomeres - found on end of chromosomes + get shorter with every cell division

Question 100

What happens to a cell when the telomere gets too short?

Answer 100

It can no longer divide

Question 101

Why do we get dermal elastosis as we age?

Answer 101

UV-B light leads to inadequate synthesis of proteins required for the correct assembly of elastic fibres

Question 102

Why do we get osteoporosis? Who is therefore more likely to get osteoporosis?

Answer 102

- Increased bone resorption caused by a LACK of OESTROGEN - Decreased bone formation caused by a LACK of OESTROGEN - Post-menopausal women most likely, so put on hormone replacement therapy

Question 103

Why do we get cataracts as we age?

Answer 103

- UV-B light - Protein cross-linking

Question 104

Why do we get deafness as we age?

Answer 104

Damage to hairs or nerve cells on the cochlea that send sound signals to the brain. When these hairs or nerve cells are damaged or missing, electrical signals aren't transmitted as efficiently, and hearing loss occurs

Question 105

Give an example of: a) a dividing tissue b) a non-dividing tissue

Answer 105

a) gut or skin tissue can divide b) brain tissue is non-dividing

Question 106

Which cancer of the skin never metastasises?

Answer 106

Basal cell carcinoma of the skin

Question 107

Why can excision only be used as a cure for basal cell carcinoma?

Answer 107

Because it never metastasises

Question 108

Where do white blood cells circulate? What does this mean for tumours of white blood cells?

Answer 108

White blood cells circulate around the body and so will any tumour of the white blood cells

Question 109

Suggest a treatment that could be used for leukaemia?

Answer 109

Chemotherapy. Leukaemia is systemic, it circulates all around the body, therefore excision can't be used

Question 110

Define carcinoma.

Answer 110

Malignant tumour of epithelial cells

Question 111

Where do carcinomas spread to?

Answer 111

Carcinomas spread to lymph nodes that drain the site of the carcinoma, e.g. breast carcinoma to axillary lymph nodes

Question 112

Where can carcinomas spread from the blood to?

Answer 112

Carcinomas can spread through the blood to bone

Question 113

Give 5 carcinomas that can spread to the bone.

Answer 113

PB KTL (lead kettle): 1. Prostate 2. Breast 3. Kidney 4. Thyroid 5. Lung

Question 114

Give an example of a carcinoma that can spread to the axillary lymph nodes.

Answer 114

Breast carcinomas

Question 115

What can still be present even if a tumour is completely excised?

Answer 115

Micro metastases

Question 116

Why is adjuvant therapy often used in the treatment of carcinomas?

Answer 116

Micrometastases are possible even if a tumour is excised and so adjuvant therapy is given to suppress secondary tumour formation

Question 117

Give an advantage and disadvantage of conventional chemotherapy.

Answer 117

- Advantage: works well for treatment against fast dividing tumours, e.g. lymphomas - Disadvantage: it is non-selective for tumour cells, so normal cells are hit too; this results in side effects such as diarrhoea and hair loss

Question 118

What kind of carcinomas would targeted chemotherapy be most effective against?

Answer 118

Slower dividing tumours, e.g. lung, colon and breast

Question 119

What is the theory behind targeted chemotherapy?

Answer 119

It exploits the differences between cancer cells and normal cells; this means it is more effective and has less side effects

Question 120

What kind of drugs can be used in targeted chemotherapy?

Answer 120

Monoclonal antibodies (MAB) and small molecule inhibitors (SMIs)

Question 121

Give an example of a malignant tumour that often spreads to the lungs.

Answer 121

Sarcoma (via venae cavae -\> heart -\> pulmonary arteries)

Question 122

Give an example of carcinomas that can spread to the liver.

Answer 122

Colon, stomach and pancreatic carcinomas can spread to the liver via the portal vein

Question 123

What is the name of the main effector cell in acute inflammation?

Answer 123

Neutrophil polymorph

Question 124

What is the name of the cells that produce collagen in fibrous scarring?

Answer 124

Fibroblasts

Question 125

Which of the following is an example of acute inflammation? A. Glandular fever B. Leprosy C. Appendicitis D. Tuberculosis

Answer 125

C. Appendicitis

Question 126

Which one of the following is a chronic inflammatory process form its start? A. Appendicitis B. Cholecystitis C. Infectious mononucleosis D. Lobar pneumonia

Answer 126

C. Infectious mononucleosis (glandular fever)

Question 127

In which of the following does granulomatous inflammation occur? A. Crohn's disease B. Acute appendicitis C. Infectious mononucleosis D. Lobar pneumonia

Answer 127

A. Crohn's disease Granulomatous inflammation is a collection of epithelioid macrophages

Question 128

Which of the following is an example of hyperplasia? A. Bodybuilder's biceps B. Enlarged left ventricle C. Benign prostate enlargement D. Wasting of quadriceps after immobilisation

Answer 128

C. Benign prostate enlargement

Question 129

Which one of the following is not an example of apoptosis? A. Loss of cells from tips of duodenal villi B. Loss of cells during embryogenesis C. Renal infarction D. Graft versus host disease

Answer 129

C. Renal infarction

Question 130

Which one of the following is an example of atrophy? A. Biceps of a bodybuilder B. Uterus in pregnancy C. Brain in dementia D. Prostate in older age

Answer 130

C. Brain in dementia

Question 131

What is the pattern of differentiation of meta plastic cells lining the bronchi of cigarette smokers?

Answer 131

Ciliated pseudostratified columnar (respiratory) epithelium to squamous epithelial cells (skin-like) This is more resistant to smoke but doesn't protect the airways

Question 132

Which one of the following is an example of necrosis? A. Loss of cells from duodenal tips B. Loss of individual cells during development C. Loss of individual cells during development D. Renal infarction

Answer 132

D. Renal infarction

Question 133

What process is defined by the formation of a solid mass of blood constituents within an intact vascular system during life?

Answer 133

Thrombosis

Question 134

Name a drug that inhibits platelet aggregation.

Answer 134

Aspirin

Question 135

What are the crystals in gout formed from?

Answer 135

Uric acid

Question 136

What is calcification in diseased tissues called?

Answer 136

Dystrophic calcification

Question 137

Which cells produce antibodies?

Answer 137

Plasma cells

Question 138

Define carcinogenesis.

Answer 138

A multistep process in which normal cells become neoplastic cells due to mutations

Question 139

What is the difference between carcinogenesis and oncogenesis? By this logic, what do carcinogenic and oncogenic mean?

Answer 139

- Carcinogenesis applies to malignant neoplasms, whereas oncogenesis applies to benign and malignant tumours - Carcinogenic = cancer causing, oncogenic = tumour causing

Question 140

What percentage of cancer risk is due to environmental factors?

Answer 140

85% environmental, 15% genetic

Question 141

Give 5 factors that can affect cancer risk.

Answer 141

1. Race 2. Diet 3. Constitutional factors (gender, age) 4. Premalignant conditions 5. Transplacental exposure

Question 142

Give an example of a situation when transplancental exposure lead to an increase in cancer risk.

Answer 142

The daughters of mothers who had taken diethylstiboestrol for morning sickness had an increased risk of vaginal cancer

Question 143

Name 5 different categories of carcinogens.

Answer 143

1. Viral 2. Chemical 3. Ionising and non-ionising radiation 4. Hormones, parasites and mycotoxins 5. Miscellaneous

Question 144

What causes skin cancer?

Answer 144

Exposure to UV light

Question 145

Chemical carcinogens: what types of cancer do polycyclic aromatic hydrocarbons cause?

Answer 145

Lung cancer and skin cancer

Question 146

Chemical carcinogens: what can expose people to polycyclic aromatic hydrocarbons?

Answer 146

Smoking cigarettes and mineral oils

Question 147

Chemical carcinogens: what types of cancer do aromatic amines cause?

Answer 147

Bladder cancer

Question 148

Chemical carcinogens: what types of people are more susceptible to bladder cancer caused by aromatic amine exposure?

Answer 148

People who work in the rubber/dye industry

Question 149

Chemical carcinogens: what types of cancer do nitrosamines cause?

Answer 149

Gut cancer

Question 150

Chemical carcinogens: what types of cancer do alkylating agents cause?

Answer 150

Leukaemia; the risk is small in humans

Question 151

Give 3 reasons why alcohol causes cancer.

Answer 151

1. Ethanol makes it easier for cells in the oropharynx to absorb other carcinogens 2. Ethanol increases oestrogen (carcinogen) levels 3. Alcohol's metabolite, acetaldehyde, is a mutagen

Question 152

Give 4 examples of viral DNA carcinogens.

Answer 152

1. Epstein-Barr virus 2. Human Papillomavirus 3. Hepatitis B Virus 4. Human Herpes Virus 8

Question 153

Give 2 examples of viral RNA carcinogens.

Answer 153

1. Human T lymphotrophic Virus-1 2. Hepatitis C virus

Question 154

What can B-naphthylamine cause? What is EBV linked to? What is HPV linked to? What are aflatoxins linked to? What is asbestos linked to?

Answer 154

- B-naphthylamine (dyes and rubber industry) can cause bladder cancer - EBV is linked to Burkitt's lymphoma - HPV is linked to cervical cancer - Aflatoxins (mycotoxin) linked to hepatocellular carcinoma - Asbestos has been linked to mesothelioma

Question 155

What is a tumour?

Answer 155

Any abnormal swelling. Encompasses: neoplasms, inflammation, hypertrophy, hyperplasia

Question 156

Define neoplasm.

Answer 156

An lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed

Question 157

What is a neoplasm composed of?

Answer 157

1. Neoplastic cells 2. Stroma

Question 158

Describe neoplastic cells.

Answer 158

Derived from nucleated cells. They're usually monoclonal and their growth is related to the parent cell

Question 159

Can erythrocytes become neoplastic cells?

Answer 159

No. This is because they are unnucelated

Question 160

Describe the stroma of a neoplasm.

Answer 160

Connective tissue composed of fibroblasts and collagen; it is very dense. There is a lot of mechanical support and blood vessels provide nutrition for the neoplastic cells

Question 161

What is essential for neoplasm growth?

Answer 161

Angiogenesis

Question 162

What does a neoplasm release in order to initiate angiogenesis?

Answer 162

Vascular endothelial growth factors

Question 163

Why does necrosis often occur in the centre of a neoplasm?

Answer 163

The neoplasm grows quickly and outgrows its vascular supply

Question 164

What are the advantages of classifying neoplasms?

Answer 164

It helps to determine the appropriate treatment and diagnosis

Question 165

What are the two ways in which neoplasms can be classified?

Answer 165

1. Behavioural classification (benign, malignant or borderline. Borderline tumours, e.g. ovarian lesions defy classification) 2. Histogenetic classification (cell of origin. If the origin is unknown the tumour is ANAPLASTIC)

Question 166

What are the 7 main features of benign neoplasms?

Answer 166

1. Localised 2. Non-invasive 3. Slow growth, low mitotic activity 4. Close resemblance to normal tissue 5. Normal nuclei 6. Necrosis and ulceration are rare due to slow growth 7. Exophytic growth (grows outwards)

Question 167

What are the consequences of benign neoplasms?

Answer 167

1. Pressure on adjacent structures 2. Obstruction to flow 3. Transformation into malignant neoplasms 4. Production of hormones 5. Anxiety

Question 168

What are the 7 main features of malignant neoplasms?

Answer 168

1. INVASIVE! 2. Metastasise 3. Rapid growth, high mitotic activity 4. Resemblance to normal tissue 5. Poorly defined border due to invasive nature 6. Necrosis and ulceration are common 7. Endophytic growth (grows inwards)

Question 169

What are the consequences of malignant neoplasms?

Answer 169

Destroy surrounding tissue, blood loss due to ulceration, pain, anxiety

Question 170

How do we classify tumours?

Answer 170

- Based on the specific cell or origin of the tumour: - Epithelial cells form carcinomas - Connective tissues form sarcomas - Lymphoid forms lymphomas or leukaemia

Question 171

How do we grade tumours?

Answer 171

- Grade is based on the extent to which the tumour resembles its original histology: - Grade 1 = well differentiated (most closely resembles parent tissue) - Grade 2 = moderately differentiated - Grade 3 = poorly differentiated

Question 172

What are the benign and malignant epithelial neoplasms?

Answer 172

- Benign = papilloma and adenoma - Malignant = carcinoma and adenocarcinoma

Question 173

What is a: a) papilloma b) adenoma

Answer 173

a) papilloma = benign tumour of non-glandular epithelium b) adenoma = benign tumour of glandular or secretory epithelium

Question 174

Define carcinoma.

Answer 174

MALIGNANT EPITHELIAL NEOPLASM (malignant tumour of epithelial cells)!

Question 175

Define adenocarcinoma.

Answer 175

Malignant tumour of glandular epithelium

Question 176

What are the benign connective tissue tumours?

Answer 176

- Lipoma = benign tumour of adipocytes - Rhabdomyoma = benign tumour of striated muscle - Leiomyoma = benign tumour of smooth muscle cells - Chondroma = benign tumour of cartilage - Osteoma = benign tumour of bone

Question 177

Define sarcoma.

Answer 177

Malignant connective tissue neoplasm

Question 178

What are the malignant connective tissue neoplasms?

Answer 178

- Liposarcoma = malignant tumour of adipocytes - Rhabdomyosarcoma = malignant tumour of striated muscle - Leiomyosarcoma = malignant tumour of smooth muscle cells - Chondrosarcoma = malignant tumour of cartilage - Osteosarcoma = malignant tumour of bone

Question 179

What is a melanoma?

Answer 179

A malignant neoplasm of melanocytes (EXCEPTION)

Question 180

What is a neuroma?

Answer 180

A benign neoplasm of nerves

Question 181

What is a lymphoma?

Answer 181

A malignant neoplasm of lymphoid cells (EXCEPTION)

Question 182

What is a mesothelioma?

Answer 182

A malignant neoplasm of mesothelial cells (EXCEPTION)

Question 183

Carcinomas and sarcomas are further classified according to the degree of differentiation. Is a carcinoma/sarcoma with a close resemblance to normal tissue classified as well differentiated or poorly differentiated?

Answer 183

A carcinoma/sarcoma with a close resemblance to normal tissue is classified as well differentiated. These types of neoplasms are low grade and have a better prognosis

Question 184

Define metastasis.

Answer 184

The process whereby malignant tumours spread from their site of origin to form other tumours at distant sites

Question 185

Which neoplasm never metastasises?

Answer 185

Basal cell carcinoma never metastasises

Question 186

What is it called when cancer cells have not yet made it through the basement membrane?

Answer 186

Carcinoma in situ

Question 187

What is required for a tumour to invade through a basement membrane?

Answer 187

1. Proteases 2. Cell motility

Question 188

What is it called when the tumour invades through a basement membrane?

Answer 188

Invasive carcinoma

Question 189

What is required for a tumour to enter the bloodstream (intravasation)?

Answer 189

1. Collegenases 2. Cell motility

Question 190

What is required for the tumour to exit the bloodstream (extravasation)?

Answer 190

1. Adhesion receptors 2. Collegenases 3. Cell motility

Question 191

Give 2 promotors of tumour angiogenesis.

Answer 191

1. Vascular endothelial growth factors 2. Fibroblast growth factors

Question 192

Give 3 inhibitors of tumour angiogenesis.

Answer 192

1. Angiostatin 2. Endostatin 3. Vasculostatin

Question 193

Which 3 mechanisms do tumour cells use to evade host immune defence in the blood?

Answer 193

1. Platelet aggregation 2. Adhesion to other tumour cells 3. They shed surface antigens to 'distract' lymphocytes

Question 194

Describe the process of metastasis.

Answer 194

1. Detachment of tumour cells from their neighbours 2. Invasion of the surrounding connective tissue 3. Intravasation into the lumen of vessels 4. Evasion of host defence mechanisms, such as NK cells 5. Adherence to endothelium at a remote location 6. Extravasation of the cells from the vessel lumen into the surrounding tissue 7. Tumour cells proliferate in the new environment (angiogenesis etc.)

Question 195

Which tumours more commonly metastasise to the liver?

Answer 195

Colon, stomach, pancreas, carcinoid tumours of intestine

Question 196

Which tumours more commonly metastasise to the bone?

Answer 196

Prostate, breast, thyroid, lung, kidney

Question 197

Which spread do carcinomas prefer? Which spread do sarcomas prefer?

Answer 197

- Carcinomas prefer lymphatic spread - Sarcomas prefer heamatogenous spread

Question 198

Is lymphatic metastasis common?

Answer 198

Yes

Question 199

What is tumour staging?

Answer 199

Staging is the extent of a tumour's spread. Determined by histopathological examination and clinical examination

Question 200

What is TNM staging?

Answer 200

T - refers to the primary tumour N - refers to lymph node status M - refers to metastatic status

Question 201

Which 2 cell types are involved in the response to acute inflammation? A. Neutrophils and basophils B. Eosinophils and basophils C. Neutrophils and monocytes D. Neutrophils and lymphocytes E. Lymphocytes and monocytes

Answer 201

C. Neutrophils (6-24hrs) and monocytes (24-48hrs) are the cells involved in acute inflammation. Neutrophils phagocytise pathogens while monocytes migrate to tissue and become macrophages which secrete chemical mediators for chemotaxis

Question 202

Which of these is not an outcome of acute inflammation? A. Pus formation B. Destruction C. Organisation D. Resolution E. Progression

Answer 202

B. Pus formation (also known as supparation) occurs when there is excessive exudate production during acute inflammation, organisation occurs when a tissue is replaced with granulation tissue as part of healing process, resolution is complete restoration of tissues to normal and progression to chronic inflammation

Question 203

Hypertrophy is best described as: a) Increased size of organ/tissue due to increased number of cells b) Increased size of organ/tissue due to decreased number of cells c) Increased cell growth and decreased differentiation d) Increased size of organ/tissue due to increased size of cells e) Replacement of one differentiated tissue by another

Answer 203

D. Hypertrophy is an increase in size of organ/tissue due to an increase in the size of cells (this ins due to an increase in protein synthesis and an increase in the size of intracellular organelles). Option a= hyperplasia, e.g. uterine enlargement, option b = doesn't make sense, option c = dysplasia, e.g. pre-cancer state, option e = metaplasia, e.g. Barrett's oesophagus

Question 204

In which pathological process would you expect: - Organelles to be damaged - Cell lysis - Inflammation - Altered chromatin a) Metaplasia b) Apoptosis c) Dysplasia d) Hypertrophy e) Necrosis

Answer 204

E. This is a description of cell death therefore the only answers can be B or E - apoptosis, however, is programmed cell death

Question 205

What is a malignant neoplasm of smooth muscle called? A) Adenocarcinoma B) Leiomyoma C) Rhabdomyoma D) Leiomyosarcoma E) Adenoma

Answer 205

D. An adenocarcinoma is a malignant neoplasm of glandular origin, a leiomyoma is a benign neoplasm of smooth muscle, a rhabdomyoma is a benign neoplasm of striated muscle and an adenoma is a benign neoplasm of glandular origin

Question 206

Which one of the following tumours never metastasises? A. Malignant melanoma B. Small cell carcinoma of the lung C. Basal cell carcinoma of the skin D. Breast cancer

Answer 206

C. Basal cell carcinoma of the skin

Question 207

What is the name of a malignant tumour of striated muscle?

Answer 207

Rhabdomyosarcoma. Rhabdo-myo = striated-muscle. Sarcoma = malignant + connective tissue

Question 208

Which of the following tumours does not commonly metastasise to bone? A. Breast cancer B. Lung cancer C. Prostate cancer D. Liposarcoma

Answer 208

D. Liposarcoma. Bone metastases: - Breast cancer - Lung cancer - Prostate cancer - Renal cell cancer - Thyroid cancer

Question 209

What term describes a cancer that has not invaded through the basement membrane?

Answer 209

Carcinoma in situ (still bounded by BM)

Question 210

What is the name of a benign tumour of glandular epithelium?

Answer 210

Adenoma. Adeno = glandular epithelium, oma = benign tumour

Question 211

Which one of these tumours does not have a screening programme in the UK? A. Breast cancer B. Colorectal cancer C. Cervical cancer D. Lung cancer

Answer 211

D. Lung cancer

Question 212

Which one of the following is not known to be a carcinogen in humans? A. Hepatitis C virus B. Ionising radiation C. Aromatic amines D. Aspergillus niger

Answer 212

D. Aspergillus niger (fungus)

Question 213

What is the name of a benign tumor of fat cells?

Answer 213

Lipoma

Question 214

What is the name of a malignant tumour of glandular epithelium?

Answer 214

Adenocarcinoma. Adeno = glandular epithelium, carcinoma = malignant tumour

Question 215

Which one of the following is not a feature of malignant tumours? A. Vascular invasion B. Metastasis C. Increased cell division D. Growth related to overall body growth

Answer 215

D. Growth related to overall body growth

Question 216

A transitional cell carcinoma of the bladder is a malignant tumour? A. True B. False

Answer 216

A. True

Question 217

A leiomyoma is a benign tumour of smooth muscle? A. True B. False

Answer 217

A. True. Leio = smooth muscle, muons = benign (sarcoma would have been malignant). Most common smooth muscle tumours are in the uterus - called fibroids - uterine myomas

Question 218

Radon gas is a cause of lung cancer? A. True B. False

Answer 218

A. True

Question 219

Asbestos is a human carcinogen? A. True B. False

Answer 219

A. True

Question 220

Which lifestyle factor is most likely to cause cancer? A. Drinking half a bottle of wine a day B. Being obese C. Running for 20 mins twice a week D. Smoking 20 cigarettes a day

Answer 220

D. Smoking 20 cigarettes a day

Question 221

Which tumours has the shortest median survival? A. Basal cell carcinoma of the skin B. Malignant melanoma of the skin C. Breast cancer D. Anaplastic carcinoma of the thyroid

Answer 221

D. Anaplastic carcinoma of the thyroid (2 months survival time!)

Question 222

Ovarian cancer commonly spreads in the peritoneum. A. True B. False

Answer 222

A. True

Question 223

What is the main source of histamine?

Answer 223

Mast cells; the histamine is stored in the granules in their cytoplasm

Question 224

What enzymatic cascade systems does plasma contain?

Answer 224

1. The complement system 2. The kinin system 3. The coagulation system 4. The fibrinolytic system

Question 225

Describe innate immunity.

Answer 225

Non-specific, instinctive, present from birth, first line of defence. Focused around physical and chemical barriers + phagocytosis. No lymphocyte involvement

Question 226

Give examples of physical and chemical barriers used in innate immunity.

Answer 226

Physical: skin, hair, cilia, mucous membranes, digestive enzymes in mouth Chemical: stomach acid, antimicrobial molecules

Question 227

What is the function of a lysozyme?

Answer 227

It destroys bacterial cell walls

Question 228

Describe adaptive immunity.

Answer 228

Specific 'acquired' immunity, requires lymphocytes. Memory and quicker response

Question 229

Compare innate vs adaptive immunity. Include receptors, kinetics, regulation, amplification, self-discrimination, duration and memory.

Answer 229

- Innate = primitive and broad, fast, not much regulation, no amplification, no self-discrimination, short and no memory - Adaptive = highly specific (B and T cell receptors), slow, regulated, amplification, self-discrimination, long and memory

Question 230

Where do all immune cells originate? Where do B and T cells accumulate? Where are RBCs removed?

Answer 230

- All immune cells originate in the bone marrow (including B and T cells). T cells then mature in the thymus - Lymph nodes are where B and T cells can accumulate - lymphomas can cause enlarged, rubbery lymph nodes - The spleen is where RBCs are removed - leukaemias can cause splenomegaly

Question 231

Which cell do all cells originate from? Descendants of which cell can be considered the innate branch of the immune system? Descendants of which cell can be considered cells of the adaptive immune response?

Answer 231

- All stem from multipotential haematopoeitic stem cells (haemocytoblast) - Common myeloid progenitor descendants = innate branch - Common lymphoid progenitor descendants = adaptive branch

Question 232

Give examples of 3 polymorphonuclear leukocytes.

Answer 232

1. Neutrophils 2. Basophils 3. Eosinophils

Question 233

Give 3 examples of mononuclear leukocytes.

Answer 233

1. Monocytes 2. B lymphocytes 3. T lymphocytes

Question 234

What is the most abundant white blood cell? Is this innate or adaptive? Is it mononuclear or polymorphonuclear? How long does it live?

Answer 234

- Neutrophil - Adaptive - Polymorphonuclear - Short lived

Question 235

How are macrophages formed? What are their functions?

Answer 235

- When monocytes migrate from blood to tissue they become macrophages - Phagocytosis, antigen presenting, cytokine secretion (TNF-alpha, IL-1, IL-2)

Question 236

What are basophils involved in, what are they the circulating form of and what do they release? What are eosinophils involved in? Are these cells innate or adaptive?

Answer 236

- Basophils are involved in allergic reactions, eczema, hay fever. Circulating mast cells that release histamine upon IgE crosslinking Fce receptors - Eosinophils deal with parasitic infections and release ROS, eicosanoids, leukotrienes etc. - These are both innate cells

Question 237

What are mast cells involved in? What happens when IgE binds to allergens? Innate or adaptive?

Answer 237

- Important in parasitic infection and allergic reactions - IgE binds to allergen, which binds to mast cells, causing them to release histamine, causing the response, e.g. bronchoconstriction - Innate

Question 238

What is the function of Natural Killer cells? Innate or adaptive?

Answer 238

- Release lytic granules that kill virus infected cells - Innate

Question 239

What are the functions of antigen presenting cells? What are the professional antigen presenting cells?

Answer 239

- APCs process and present antigens from pathogens for recognition by cells, e.g. T cells - The main APCs are dendritic cells (egress to secondary organs to aid immune response), however macrophages and B cells are also APCs. They all present exogenous antigens in the context of MHC-II

Question 240

What is central tolerance?

Answer 240

In the human immune system, central tolerance is the process of eliminating any developing T or B lymphocytes that are reactive to self

Question 241

What is peripheral tolerance?

Answer 241

Peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease

Question 242

What is anergy? When are lymphocytes said to be anergic?

Answer 242

- Anergy is a term that describes a lack of reaction by the body's defense mechanisms to foreign substances. It is one of three processes that induce tolerance - Lymphocytes are said to be anergic when they fail to respond to their specific antigen

Question 243

How do T cells recognise antigens?

Answer 243

For T cells to recognise antigens they must be displayed by an antigen presenting cell bound to MHC I/II. T cells can't recognise soluble antigens

Question 244

What is the common T cell marker?

Answer 244

CD3

Question 245

What can T helper cells express? What do they help activate?

Answer 245

- Can express CD4 - Help activate B cells and cytotoxic T cells

Question 246

What is the function of T helper 1 (CD4)?

Answer 246

It helps the immune response against intracellular pathogens. Secretes cytokines. Cell-mediated immunity

Question 247

What is the function of T helper 2 (CD4)?

Answer 247

It helps produce antibodies against extracellular pathogens. Secretes cytokines. Humoral immunity

Question 248

What is the function of Cytotoxic T cell (CD8)?

Answer 248

Release perforins and granzymes to kill the antigens

Question 249

What is the function of Treg? What is their key cytokine?

Answer 249

Regulate the immune response. IL-10 is their key cytokine that has a mass anti-inflammatory action

Question 250

What is the function of Th17? What is their principle cytokine?

Answer 250

- Important cells at mucosal membranes - Principal cytokine is IL-17 (affects innate immune cells to produce IL-8)

Question 251

Which cells express MHC I?

Answer 251

All nucleated cells express MHC I

Question 252

Which cells express MHC II?

Answer 252

Antigen presenting cells ONLY

Question 253

Which MHC would an intracellular antigen (endogenous) lead to the expression of?

Answer 253

MHC I

Question 254

Which MHC would an extracellular antigen (exogenous) lead to the expression of?

Answer 254

MHC II

Question 255

What type of T cell binds to MHC I?

Answer 255

Cytotoxic T cells (CD8)

Question 256

What type of T cells bind to MHC II?

Answer 256

Helper T cells (CD4)

Question 257

What do B cells differentiate into?

Answer 257

Plasma cells. The plasma cells then produce antibodies

Question 258

What does a helper T cell bind to?

Answer 258

A T cell receptor which is bound to an antigen epitope which is bound MHC II on an APC

Question 259

Which interleukin is secreted when a helper T cell is bound to a T cell receptor?

Answer 259

IL-2. This then binds to an IL-2 receptor on the T cell and produces a positive feedback mechanism leading to division and differentiation

Question 260

What is the mature B cell marker?

Answer 260

CD20. Monoclonal antibodies (e.g. Rituximab) target CD20

Question 261

How many antibodies can each B cell make?

Answer 261

Each B cell can only make 1 antibody. This 1 antibody can only bind to 1 epitope

Question 262

Describe the process of a T helper cell binding to a B cell.

Answer 262

A B cell antibody binds to an antigen-\> phagocytosis-\> epitope is displayed on the surface of the B-cell bound to an MHC II-\> TH2 binds to B-cells-\> cytokine secretion induces B-cell clonal expansion-\> differentiation into plasma cells and memory B cells

Question 263

What are the 3 roles of phagocytes?

Answer 263

1. Neutralise toxins 2. Opsonisation of pathogens 3. Destroy pathogens

Question 264

Which region of an antibody binds to antigens?

Answer 264

Fab region

Question 265

Which region of an antibody binds with Fc receptors and some proteins of the complement system?

Answer 265

Fc region

Question 266

What are the 5 antibodies?

Answer 266

IgG, IgA, IgM, IgE, IgD

Question 267

What are the functions and features of IgA?

Answer 267

The mucosal antibody as a dimer. Present in colostrum and coats neonate gut

Question 268

What are the functions and features of IgM?

Answer 268

Pentameric and not entirely specific to antigen. Highest capacity to activate complement (system of plasma proteins that can be activated directly by pathogens or indirectly by pathogen-bound antibody, leading to a cascade of reactions)

Question 269

What are the functions and features of IgG?

Answer 269

Most abundant in the blood. Highly specific. Important during secondary responses. 4 subclasses. Can cross the placenta

Question 270

What are the functions and features of IgE?

Answer 270

Bound to mast cells and basophils by Fcer. Important in allergy and helminth infection. Least abundant in the blood

Question 271

What are the functions and features of IgD?

Answer 271

Not that important. Function debated in literature

Question 272

Which immunoglobulin is found in breast milk and other secretions?

Answer 272

IgA

Question 273

What are the two most common immunoglobulins?

Answer 273

IgG and IgM

Question 274

In the second exposure to an antigen, which antibody is secreted more: IgG or IgM?

Answer 274

IgG

Question 275

What are the primary lymphoid organs?

Answer 275

- Bone marrow; all immune cell origin. B cell maturation site - Thymus; T cell maturation site

Question 276

What are the secondary lymphoid organs?

Answer 276

- Lymph nodes; site of B and T cell interactions - Spleen; site of removal of RBCs and antibody-coated bacteria

Question 277

Name 4 types of cytokines.

Answer 277

1. Interferons 2. Interleukins 3. Colony stimulating factors 4. Tumour necrosis factors

Question 278

What is the function of interferons?

Answer 278

Interferons produce antiviral proteins

Question 279

What is the function of interleukins?

Answer 279

Interleukins cause cell differentiation and division

Question 280

What is the function of colony stimulating factor (CSF)?

Answer 280

Causes differentiation of bone marrow and stem cells

Question 281

What is the function of tumour necrosis factor (TNF)?

Answer 281

TNF mediates inflammation and cytotoxic reactions

Question 282

What is the function of chemokines?

Answer 282

Chemokines attract leukocytes and sites of infection

Question 283

Describe the process of phagocytosis.

Answer 283

1. Pathogen binds to neutrophil/macrophage 2. Engulfment of pathogen 3. Phagosome formation 4. Lysosome fusion - phagolysosome 5. Pathogen is destroyed

Question 284

Where are complement system plasma proteins derived from?

Answer 284

Liver

Question 285

What are the 3 main outcomes of complement system activation?

Answer 285

1. Pathogen lysis 2. Increased phagocytosis 3. Activation of leukocytes

Question 286

What is the complement system?

Answer 286

The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane

Question 287

What are the 3 complement system pathways?

Answer 287

1. Classical 2. Lectin 3. Alternative

Question 288

What activates the classical compliment pathway?

Answer 288

Antigen:antibody complex

Question 289

What activates the lectin pathway?

Answer 289

Mannose binding protein

Question 290

What activates the alternative pathway?

Answer 290

Bacterial cell walls and endotoxins

Question 291

What kind of immunity are PRR's and PAMP's associated with?

Answer 291

Innate immunity

Question 292

What are PRR's a receptor for?

Answer 292

PAMP's

Question 293

Name 3 receptors that make up the PRR family.

Answer 293

1. Toll-like receptors 2. Nod-like receptors 3. Rig-like receptors

Question 294

What is the main function of TLR's?

Answer 294

TLR's send signals to the nucleus to secrete cytokines and interferons. These signals initiate tissue repair. Enhanced TLR signalling = improved immune response

Question 295

What is the main function of NLR's?

Answer 295

NLR's detect intracellular microbial pathogens. They release cytokines and can cause apoptosis if the cell is infected

Question 296

What is the main function of RLR's?

Answer 296

RLR's detect intracellular double stranded RNA. This triggers interferon production and so an antiviral response

Question 297

TLR's are adapted to recognise damaged molecules. What characteristic do these damaged molecules often have in common?

Answer 297

They are often hydrophobic

Question 298

What kind of TLR's can be used in vaccine adjuvants?

Answer 298

TLR 4 agonists

Question 299

What happens when a PAMP binds to a PRR?

Answer 299

The innate immune response and inflammatory response is triggered

Question 300

What is extravasation?

Answer 300

Leukocyte migration across the endothelium

Question 301

What do macrophages at the tissues secrete to initiate extravasation?

Answer 301

TNF alpha

Question 302

Describe the process of extravasation.

Answer 302

1. Macrophages at tissues release TNF alpha 2. The endothelium is stimulated to express adhesion molecules and stimulate chemokines 3. Neutrophils bind to adhesion molecules; they roll, slow down and become stuck to endothelium 4. Neutrophils are activated by chemokines 5. Neutrophils pass through the endothelium to the tissue to help fight infection

Question 303

What type of cancers result from transformations in the germ line?

Answer 303

Inheritable cancers (\<10%)

Question 304

What type of cancers result from transformations in somatic cells?

Answer 304

Non-inheritable cancers (\>90%)

Question 305

What are the 7 hallmarks for cancer?

Answer 305

1. Evade apoptosis 2. Ignore anti-proliferative signals 3. Growth and self-sufficiency 4. Limitless replication potential 5. Sustained angiogenesis 6. Invade surrounding tissues 7. Escape immune-surveillance

Question 306

What are the two types of tumour antigens and where are they found?

Answer 306

1. Tumour specific antigens = only found on tumour cells 2. Tumour associated antigens = found on normal cells

Question 307

Why is hypoxia a prominent feature of a lot of malignant tumours?

Answer 307

Malignant tumours grow rapidly and so outgrow their blood supply

Question 308

What is active immunity?

Answer 308

Produced by host immune system, induced by infections or vaccines, durable effective protection, effective after initial lag period, immunological memory is present, boosted effect on subsequent dose, negative phase

Question 309

What is passive immunity?

Answer 309

Passive with no host participation, usually pooled antibodies transferred into host, transient and less effective, no lag period + effective immediately, no memory present, subsequent doses do not boost immunity due to elimination, no negative phase

Question 310

Give 2 advantages of passive immunity.

Answer 310

1. Immediate effect 2. Useful treatment for acute dangers, e.g. snake venom

Question 311

Give 3 disadvantages of passive immunity.

Answer 311

1. Short term 2. No immunological memory produced 3. Reaction is possible

Question 312

Describe the first immune response to initial exposure.

Answer 312

1. Innate immune response 2. IgM predominates 3. Low affinity

Question 313

Give 3 disadvantages of inactivated vaccines.

Answer 313

1. Inactivated vaccines tend to only activate the humoral response; there is a lack of T cell involvement 2. The response is often weak 3. Boosters are needed so patient compliance may be poor

Question 314

Describe the second immune response following exposure to a pathogen encountered before.

Answer 314

1. Rapid and larger than the first 2. High affinity IgG 3. Adaptive immunity, T cell help

Question 315

Give 3 advantages of live vaccines.

Answer 315

1. Very effective, prolonged and comprehensive 2. Immunological memory produced 3. Often only 1 vaccine is needed

Question 316

Give 2 disadvantages of live vaccines.

Answer 316

1. Immunocompromised patients may become ill 2. Vaccines often need to be refrigerated which can be a problem in remote areas

Question 317

Give 2 advantages of inactivated vaccines.

Answer 317

1. There is no risk of infection 2. Storage is less critical

Question 318

What is the role of an adjuvant?

Answer 318

An adjuvant is a substance added to a vaccination to stimulate an immune response. They convince your immune system that you're infected

Question 319

What can be used as an adjuvant?

Answer 319

Toxoids, proteins, chemicals (aluminium salts) etc.

Question 320

What are the 5 features of an ideal vaccine?

Answer 320

1. Safe 2. Induces a suitable immune response 3. Shouldn't require repeated boosters 4. Generates immunological memory 5. Stable and easy to transport

Question 321

Give 3 advantages of active immunity.

Answer 321

1. Produced immunological memory 2. Produces high affinity antibodies 3. It produces a persistent protective response against pathogens

Question 322

Give 3 advantages of transplantation.

Answer 322

1. Improved quality of life 2. Improved survival rates 3. Cost effective

Question 323

Why are immunosuppressive agents needed to prevent rejection?

Answer 323

Transplanted organs are recognised as non-self and therefore are seen as a threat

Question 324

What are the consequences of transplant rejection?

Answer 324

Fibrosis and scarring

Question 325

What are the two types of immune response in humans? A) Immunological tolerance B) Immune surveillance C) Innate and acquired D) Intrinsic and extrinsic E) Overt and covert

Answer 325

C) Innate and acquired

Question 326

What cell type is described below? These are the most abundant white blood cell in humans and are characterised by the multi-lobed shape of their nucleus. A) Macrophage B) Neutrophil C) Eosinophil D) Mast cell E) Fibroblast

Answer 326

B) Neutrophil

Question 327

Which antigen presenting cell is considered a professional at activating lymphocytes? A) Neutrophils B) Mast cells C) Macrophages D) Dendritic cells E) Monocyte

Answer 327

D) Dendritic cells

Question 328

Which of the following is not a component of innate immune mechanisms? A) Mucosa B) Inflammatory mechanisms C) Antibody production D) Skin E) Antimicrobial peptides

Answer 328

C) Antibody production

Question 329

Antigen presenting cells process and present antigens for recognition by: A) Neutrophils B) Red blood cells C) Eosinophils D) T cells

Answer 329

D) T cells

Question 330

Which of the following are features of the adaptive immune response A) Does not require prior contact with the pathogen B) It works with B and T lymphocytes C) Lacks specificity D) Distinguishes "self" from "non-self" E) Enhanced by complement

Answer 330

B) It works with B and T lymphocytes

Question 331

Complements are the proteins that are involved in the clearance of antigen/bacteria. Which of the following is not part of the Elimination phase of complement activation? A) Opsonisation B) Production of interferons C) Target cell lysis D) Chemoattraction of leukocytes E) Phagocytosis

Answer 331

B) Production of interferons

Question 332

Which of the following are administered as a live attenuated vaccine in the UK? A) Hepatitis A B) Tetanus C) MMR D) Flu E) BCG (TB)

Answer 332

C) MMR and E) BCG (TB)

Question 333

Polysaccharide vaccines are composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. These vaccines are available for the treatment of which of the following diseases? A) Pneumococcal disease B) Influenza type b C) Rabies D) Salmonella Typhi E) Meningococcal disease

Answer 333

A) Pneumococcal disease D) Salmonella Typhi E) Meningococcal disease

Question 334

Influenza vaccine is targeted towards 'at risk' groups in the UK. Which of the following are classified as 'at risk'? A) Asthmatics B) 16 years old C) Diabetics D) The obese of any age E) 6 months of age and over

Answer 334

E) 6 months of age and over

Question 335

Which of the following is not an organ-specific auto-immune disease? A) Type 1 diabetes mellitus B) Graves disease C) Ulcerative colitis D) Hashimoto’s thyroiditis E) Sjogren's syndrome

Answer 335

C) Ulcerative colitis

Question 336

Which of the following are classical PAMPs? A) Flagellin, a protein found in bacterial flagella B) Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria C) Peptidoglycan, found in bacterial cell walls D) Lipoarabinomannan of mycobacteria E) Interleukin 12

Answer 336

A) Flagellin, a protein found in bacterial flagella B) Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria C) Peptidoglycan, found in bacterial cell walls D) Lipoarabinomannan of mycobacteria

Question 337

What is the role of the Major Histocompatibility Complex (MHC)?

Answer 337

To present antigen showing self or non-self on the cell surface

Question 338

What compound prevents excessive activation of the classical complement pathway?

Answer 338

C1 inhibitor. C1 inhibitor leads to a negative feedback loop

Question 339

Which complement plasma proteins have opsonisec properties when bound to a pathogen?

Answer 339

C3b and C4b

Question 340

What is the function of MAC in a pathogens' membrane?

Answer 340

MAC is a leaky pore channel. Ions and water pass through the channel and disrupt the intracellular microbe environment -\> microbe lysis

Question 341

Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes?

Answer 341

C3a and C5a

Question 342

Define allorecognition.

Answer 342

The ability of an organism to distinguish its own tissues from those of another. Recognition of non-self antigens

Question 343

What are the consequences of transplant rejection?

Answer 343

Fibrosis and scarring

Question 344

Define xenotransplantation.

Answer 344

Transplantation of tissues from one species to another

Question 345

Define pharmacokinetics.

Answer 345

The action of the body on the drug (how it's broken down)

Question 346

What are the 4 stages of pharmacokinetics?

Answer 346

ADME: - Absorption - Distribution - Metabolism - Excretion

Question 347

Define pharmacodynamics.

Answer 347

The action of the drug on the body

Question 348

What are the main routes of administration?

Answer 348

- Oral → first pass metabolism - IV → directly into systemic circulation - Subcut → has to diffuse through the subcut fat, so absorbed more slowly - IM → muscle tissue is vascular so rapidly absorbed - Topical → directly onto the skin/mucosa. Avoids first pass metabolism, slowly absorbs into circulation - Rectal → can be used when patient is unable to tolerate oral route. Highly vascular tissue so absorbs quickly - Intrathecal → into the spinal column so it will reach the CSF - Sublingual/buccal → avoids first pass metabolism and rapidly enters circulation. Drugs like GTN - Inhalation → passes through the trachea into the lungs. Good if this is the target site of the drug

Question 349

In the absorption phase of pharmacokinetics, how do drugs pass through membranes?

Answer 349

- Unless given straight into the blood stream, drugs cross membranes by: - Passive diffusion - Facilitated diffusion - Active transport - Endocytosis

Question 350

In the absorption phase of pharmacokinetics, do all of the drugs make it into the circulation? Why? What is this called?

Answer 350

- Not all - This is because the gut and liver metabolise drugs given orally before reaching the circulation - This is called first pass metabolism

Question 351

What is bioavailability? What is the bioavailability of IV drugs assumed to be?

Answer 351

- The amount of drug taken up into systemic circulation in proportion to the amount administered - The bioavailability of IV drugs is assumed to be 100%

Question 352

Define the distribution phase of pharmacokinetics.

Answer 352

The journey of the drug through the bloodstream into the target tissue

Question 353

What does the distribution of drugs depend on?

Answer 353

- BLOOD FLOW to area - MOLECULAR WEIGHT/SIZE - LIPOPHILICITY - lipophilic drugs can penetrate the cell membrane easily - Permeability of capillaries (some capillaries have slit junctions that allow drugs through, e.g. in liver) - BLOOD-BRAIN BARRIER/BLOOD TESTICLE BARRIER - Binding to proteins. If they are bound to albumin in the blood, distribution will be SLOWED because drugs must be FREE FROM ALBUMIN to cross membranes

Question 354

In the distribution phase of pharmacokinetics, what do drugs target?

Answer 354

- Cellular receptors - Enzymes (ramipril is an ACE inhibitor which blocks angiotensin converting enzyme) - Membrane ion channels (e.g. lidocaine blocks sodium ion channels) - Membrane transporters (proton pump inhibitors like omeprazole inhibit membrane transporters)

Question 355

Define the metabolism phase of pharmacokinetics.

Answer 355

Drugs are broken down so that they can be eliminated

Question 356

What is the main route of drug elimination? What can it not eliminate?

Answer 356

- Kidney is the main route of elimination - It can't eliminate lipid soluble drugs

Question 357

What is the role of the liver in drug metabolism?

Answer 357

The liver converts lipid soluble drugs into water soluble drugs so they can be excreted by the kidney. This happens in two stages

Question 358

What are the two stages of drug metabolism in the liver?

Answer 358

- Phase 1 = make drug hydrophilic (Cytochrome P450 catalysed) - Phase 2 = if it is still to lipophilic, make the drug polar, e.g. acetylation

Question 359

Can drugs change or inhibit the action of cytochrome p450? Is there more than one Cytochrome P450 enzyme?

Answer 359

- Yes. Drugs can alter the activity of Cytochrome P450 enzymes, so can alter the metabolism of other drugs - There are many Cytochrome P450 enzymes

Question 360

What is an inducer? Give an example.

Answer 360

An inducer will increase Cytochrome P450 activity, and speed up the metabolism of other drugs - may result in sub therapeutic dose. Example = phenytoin

Question 361

What is an inhibitor? Give an example. What are the two types?

Answer 361

- An inhibitor will decrease Cytochrome P450 activity and reduce the metabolism of other drugs - may result in toxicity. Example = amiodarone - The competitive inhibitor binds to the active site and prevents the substrate from binding there. The noncompetitive inhibitor binds to a different site on the enzyme (allosteric site); it doesn't block substrate binding, but it causes other changes in the enzyme so that it can no longer catalyse the reaction efficiently

Question 362

Give examples of inducers.

Answer 362

- Anti-epileptics: phenytoin, carbamazepine - Rifampicin - St John's Wort - Chronic alcohol intake - Smokers (CYP1A2)

Question 363

Give examples of inhibitors.

Answer 363

- Ciproflaxacin, erythromycin - Isoniazid - Amiodarone - Allopurinol - Anti-fungal: ketoconazole, fluconazole - SSRI: fluoxetine, setraline - Sodium valproate - Acute alcohol

Question 364

In the rate of elimination of drugs, what do first order and zero order mean?

Answer 364

- First order = catalysed by enzymes, rate of metabolism directly proportional to drug concentration - Zero order = enzymes saturated by high drug doses, rate of metabolism constant, e.g. ethanol, phenytoin

Question 365

In the excretion phase of pharmacokinetics, how are most drugs excreted? How about the rest?

Answer 365

- Most drugs are excreted by the kidneys in urine - Some are also excreted by the liver in the bile and then faeces

Question 366

What happens to the doses/drugs if a patient has renal failure?

Answer 366

They may need to be altered

Question 367

What is pKa?

Answer 367

- A number that shows how strong or weak an acid is, lower value = stronger acid - The pH at which a drug is 50% protonated and 50% non-protonated (ratio 1:1) - Example: if aspirin has a pKa of 3.8 and the pH of the GI tract is 4.8, there is a 1:10 ratio. This means that 10% of the drug will be lipid soluble at this pH

Question 368

What is the effect of an increase in pH on a weak acid?

Answer 368

The weak acid will become more ionised

Question 369

What is the effect of an increase in pH on a weak base?

Answer 369

The weak base will become less ionised

Question 370

What is the effect of a decrease in pH on a weak acid?

Answer 370

The weak acid will become less ionised

Question 371

What is the effect of a decrease in pH on a weak base?

Answer 371

The weak base will become more ionised

Question 372

Explain what would happen to the bioavailability of aspirin if gastric pH increased.

Answer 372

The bioavailability would decrease. Aspirin would be more ionised and so wouldn't diffuse across the gut into the plasma as rapidly this would mean aspirin uptake would decrease

Question 373

Write an equation for the volume of distribution (Vd).

Answer 373

Vd = amount of drug administered/concentration of drug in plasma

Question 374

If a drug had a high Vd what would that tell us about the drug?

Answer 374

This would indicate that the drug was highly lipid soluble and that most of the drug had moved into the intracellular space, less was in the plasma

Question 375

What is the relationship between plasma concentration and Vd?

Answer 375

Plasma concentration is inversely proportional to Vd

Question 376

Give the two definitions for clearance.

Answer 376

1. The volume of plasma from which a drug is completely removed per unit time 2. The rate at which plasma drug is eliminated per unit plasma concentration

Question 377

Write an equation for renal clearance.

Answer 377

Renal clearance = Rate of appearance in urine / plasma concentration

Question 378

What are the two ways by which drugs can be eliminated in the kidneys?

Answer 378

1. Glomerular filtration 2. Active secretion

Question 379

What are the possible dangers of kidney damage with regards to renal clearance?

Answer 379

Kidney damage results in decreased renal clearance and so there is danger of accumulation, over dosage and toxicity

Question 380

What compound do many lipid soluble drugs combine with to increase their hydrophilicity?

Answer 380

Glucuronic acid

Question 381

Define hepatic extraction ratio (HER).

Answer 381

The proportion of a drug removed by one passage through the liver

Question 382

What is the limiting factor when a drug has a high HER?

Answer 382

Hepatic blood flow, perfusion limited

Question 383

What is the limiting factor when a drug has a low HER?

Answer 383

Diffusion limited. A low HER is slow and not efficient

Question 384

What happens to high and low HER drugs when enzyme induction is increased?

Answer 384

The clearance of low HER drugs increases. There is minimal effect on high HER drugs

Question 385

Give 4 properties of the 'ideal drug'.

Answer 385

1. Small Vd 2. Drug broken down effectively by enzymes 3. Predictable dose:response relationship 4. Low risk of toxicity

Question 386

What is GFR?

Answer 386

GFR stands for glomerular filtration rate. GFR is a measure of how well your kidneys filter blood

Question 387

What is creatinine clearance? How is it measured?

Answer 387

- Volume of blood plasma cleared of creatinine per unit of time. Used to estimate GFR, since glomeruli freely filter creatinine - Done by comparing serum creatinine with urine creatinine

Question 388

What is the gate-control theory of pain?

Answer 388

The gate control theory of pain asserts that non-painful input closes the nerve "gates" to painful input, which prevents pain sensation from traveling to the central nervous system

Question 389

Pharmacodynamics is what the drug does to the body. It is the effect on cellular receptors via signal transduction. What is signal transduction, what are some receptors, and what does it lead to?

Answer 389

- Binding of a drug to extracellular or intracellular receptors - Via a variety of receptors: ligand-gated ion channels, G protein-coupled receptors etc. - Either leads to amplification or down-regulation of signals

Question 390

Give an example of a ligand gated ion channel.

Answer 390

Nicotinic ACh receptor

Question 391

Give an example of a G protein-coupled receptor.

Answer 391

Muscarinic and beta-2 adrenoreceptor

Question 392

Give an example of a kinase linked receptor.

Answer 392

Receptors for growth factors

Question 393

Give an example of a cytosolic/nuclear receptor.

Answer 393

Steroid receptors

Question 394

What is the shape of a log dose-response curve?

Answer 394

Sigmoidal

Question 395

What is EC50? What does it tell us about a drug? Would a drug with a lower EC50 have a lower or greater potency?

Answer 395

- EC50 is the concentration of a drug that gives half the maximal response - It tells us its potency - Greater potency

Question 396

What does Emax tell us about a drug?

Answer 396

Its efficacy

Question 397

Which is more efficacious, a full against or partial agonist?

Answer 397

A full agonist is more efficacious because it can give an 100% response

Question 398

Would an antagonist shift a dose-response curve to the left or right?

Answer 398

The antagonist would shift the dose-response curve to the RHS. The drug therefore becomes less potent

Question 399

How do we calculate Intrinsic Activity (IA)?

Answer 399

Intrinsic Activity = Emax of partial agonist / Emax of full agonist

Question 400

What is receptor reserve?

Answer 400

Some agonists need to activate only a small fraction of the existing receptors to produce the maximal system response

Question 401

What is an agonist? Give an example.

Answer 401

- Agonists bind to a receptor and activate it - Mimics endogenous substance - Can be FULL (causes same response as endogenous substance) or PARTIAL - Example: salbutamol is a beta 2 agonist

Question 402

What is an antagonist? Give an example.

Answer 402

- Antagonists bind to receptor and prevents its activation - Can be reversible or irreversible (if covalent bind forms) - Antagonist can also bind at another site to the main active site (allosteric site) - Example: propranolol (hypertension) is a beta blocker

Question 403

What does the term affinity mean?

Answer 403

Affinity is how avidly a drug binds its receptor

Question 404

Define efficacy.

Answer 404

The maximum effect a drug can have in the body

Question 405

Define potency.

Answer 405

How much of a drug is needed to elicit a response in the body

Question 406

Define specificity.

Answer 406

Specificity is the measure of a receptors ability to respond to a single ligand

Question 407

Define selectivity.

Answer 407

Selectivity refers to a drug's ability to preferentially produce a particular effect

Question 408

Define bioavailability.

Answer 408

The fraction of the drug that reaches the systemic circulation unaltered

Question 409

Define first pass metabolism.

Answer 409

Metabolism of the drug by the gut and liver before it reaches the bloodstream

Question 410

What does a narrow therapeutic index mean? Give examples of drugs with a low therapeutic index.

Answer 410

- A narrow therapeutic index/range means there is an increased chance of toxicity + a decreased chance of an affective dose - Examples: digoxin, theophylline, lithium, phenytoin, gentamicin + vancomycin

Question 411

How is paracetamol metabolised?

Answer 411

- Paracetamol is mostly converted to non-toxic metabolites via Phase II metabolism. Here, it conjugated with sulfate and glucuronide, with a small portion being oxidised via the Cytochrome P450 enzyme - Cytochromes P450 2E1 and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cytsteine and mercapturic acid conjugates

Question 412

What happens to paracetamol metabolism in the case of a paracetamol overdose?

Answer 412

- Phase II metabolic pathways become saturated + more paracetamol is shunted to the Cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration - NAPQI remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocytes damage and death, leading to acute liver necrosis

Question 413

How do we manage a paracetamol overdose?

Answer 413

- Activated charcoal should be considered if patient pares to within 1 hour of ingestion of \>150mg/kg paracetamol - Ingestion in last 8 hours, wait 4 hours from ingestion then measure plasma level and send for analysis. Paracetamol plasma \<4 hours after ingestion can't be interpreted. If the results suggest acute liver injury = IV N-acetylcysteine - If the overdose was staggered (\>1 hour), treatment nomogram is unreliable + based on paracetamol levels and further blood tests - Liver transplant may be required. Need often based on low blood pH, high blood lactate, poor blood clotting, or significant encephalopathy

Question 414

Give an example of a proton pump inhibitor.

Answer 414

Omeprazole

Question 415

Give an example of a statin.

Answer 415

Simvastatin

Question 416

Give an example of an ACE inhibitor.

Answer 416

Enalapril

Question 417

Give an example of a COX inhibitor.

Answer 417

Aspirin and paracetamol

Question 418

Give an example of a beta-2 adrenoceptor agonist.

Answer 418

Salbutamol

Question 419

Give an example of a beta-1 adrenoceptor blocker.

Answer 419

Atenolol

Question 420

Give an example of a Ca2+ channel blocker.

Answer 420

Amlodipine

Question 421

Give an example of a broad spectrum antibiotic.

Answer 421

Amoxicillin

Question 422

Give an example of an opiate analgesic.

Answer 422

Tramadol

Question 423

What do most drugs target?

Answer 423

Proteins, e.g. ligand gated ion channels, GPCR, kinase linked, cytosolic/nuclear

Question 424

What is the effect of fewer receptors on drug potency?

Answer 424

Fewer receptors will shift the dose-response curve to the RHS, this means drug potency will be reduced

Question 425

What is the effect of fewer receptors on receptor response?

Answer 425

Receptor response is still 100% due to receptor reserve (partial agonists don't have receptor reserve)

Question 426

Approximately 60% of the body is comprised of water. In an average 70kg male this constitutes 42L of water. Approximately how many litres of water would you expect to find in the following compartments of this patient: intracellular, extracellular, plasma?

Answer 426

- Intracellular = 28L - Extracellular = 14L - Plasma = 3L

Question 427

Name 3 drug targets.

Answer 427

Receptors, enzymes, transporters

Question 428

What do they terms afferent and efferent mean?

Answer 428

- Afferent = carries signals towards the brain or spinal cord - Efferent = carries signals away from the brain or spinal cord

Question 429

What do the terms adrenergic and cholinergic mean?

Answer 429

- Adrenergic = relating to adrenaline or noradrenaline and their receptors - Cholinergic = relating to acetylcholine and its receptor

Question 430

How is the nervous system divided?

Answer 430

- Central nervous system (brain and spinal cord) + peripheral nervous system (connects CNS to muscles and organs) - PNS into efferent and afferent - Efferent into autonomic nervous system (controls internal organs) and somatic nervous system (controls skeletal muscles) - Autonomic nervous system into sympathetic and parasympathetic (+ enteric)

Question 431

Which neurotransmitter do cholinergic receptors bind to?

Answer 431

Acetylcholine

Question 432

What are the two types of cholinergic receptors?

Answer 432

- Muscarinic receptor - Nicotinic receptor

Question 433

What do preganglionic neurons release? Which nervous system(s) is this in? What does this neurotransmitter bind to?

Answer 433

- Preganglionic neurons in both the sympathetic and parasympathetic nervous system release acetylcholine (ACh) - Binds to nicotinic receptors

Question 434

What do most postganglionic neurons release? What are these known as? What do these bind to? Which nervous system is this in?

Answer 434

- Most postganglionic neurons release adrenaline (epinephrine) and noradrenaline (norepinephrine) - These are collectively called catecholamines - These bind to adrenergic receptors - This is in the sympathetic nervous system

Question 435

What are the 5 effects of the sympathetic nervous system?

Answer 435

- IMPORTANT: - Increased HR, increased CO, vasoconstriction - Bronchodilation - Reduced GI motility + secretions - Reduced bladder detrusor activity - Increased sweating and reduced salivation

Question 436

In the parasympathetic nervous system, what do postganglionic neurons release? What does this neurotransmitter bind to?

Answer 436

- Postganglionic neurons in the parasympathetic nervous system release acetylcholine - Acetylcholine binds to muscarinic receptors on the target organ cells

Question 437

What are the 5 effects of the parasympathetic nervous system?

Answer 437

- Decreased HR, decreased CO, vasodilation - Bronchoconstriction - Increased digestion - Increased bladder detrusor activity - Reduced sweating

Question 438

How are cholinergic drugs divided?

Answer 438

- Cholinergic agonists = either mimic or enhance the action of ACh at the neuromuscular junction - Cholinergic antagonists = inhibit the action of ACh (enhances SNS activity)

Question 439

What can cholinergic agonists be divided into?

Answer 439

- Direct-acting agents - Indirect-acting agents split into competitive (reversible) and non-competitive (irreversible)

Question 440

Direct-acting agents are synonymous with what term?

Answer 440

Cholinomimetics

Question 441

How are cholinergic antagonists divided?

Answer 441

Competitive antagonists and non competitive antagonists

Question 442

Cholinergic antagonists are synonymous with which terms?

Answer 442

Cholinergic antagonists are synonymous with the terms anticholinergics, parampatholytic, antimuscarinics or antinicotinics

Question 443

How do cholinergic agonists work? Give examples.

Answer 443

- Cholinergic agonists mimic ACh and bind to ACh receptors - Examples: carbachol (constricts pupil), bethanechol (increases smooth muscle tone in GI and GU tract) + pilocarpine (stimulate saliva secretion)

Question 444

How do indirect-acting cholinergic agonists work? Give examples.

Answer 444

- Indirect-acting cholinergic agonists inhibit acetylcholinesterase (AChE), increasing the concentration of ACh available at the synapse - Examples: neostigmine, pyridostigmine (myasthenia gravis, reverse anaesthesia), donepezil, rivastigmine, galantamine (boost cholinergic activity in Alzheimer's)

Question 445

How do nicotinic antagonists work? Give examples.

Answer 445

- Nicotinic antagonists compete with ACh for binding to the nicotinic receptor - Examples: curare, pancuronium (relax skeletal muscles during surgery)

Question 446

How do muscarinic antagonists work? Give examples.

Answer 446

- Compete with ACh for binding to the muscarinic receptor - Examples: atropine, scopolamine, belladonna alkaloids (treat bradycardia, diarrhoea, bladder spasms, dilate bronchi, reduce secretions, dilate pupils)

Question 447

What do catecholamines help trigger?

Answer 447

Catecholamines released from postganglionic neurons in the SNS, so help to trigger the fight or flight response

Question 448

Where are adrenergic receptors located?

Answer 448

Adrenergic receptors are located in the plasma membrane of the cells of the target organs

Question 449

What type of receptors are adrenergic receptors? Why?

Answer 449

- Adrenergic receptors are one type of GPCR as they work directly with intracellular G proteins - They bind to a GDP molecule when they're inactive + to GTP when they're active

Question 450

What are the different types of adrenergic receptors?

Answer 450

Alpha-1, alpha-2, beta-1 + beta-2

Question 451

What are the functions of alpha-1 adrenoreceptor?

Answer 451

Smooth muscle contraction (ONE): - O = blood vessels - N = neck of bladder, prosate and stomach - E = eyes

Question 452

What are the functions of alpha-2 adrenoreceptor?

Answer 452

- Inhibition of presynaptic nerve terminals - TWO (terminal weaning off): - Inhibition of noradrenaline release, inhibition of acetylcholine release + inhibitor of insulin release

Question 453

What are the functions of beta-1 adrenoreceptor?

Answer 453

- Beta 1 = 1 heart - heart and kidneys: - Tachycardia, increased lipolysis, increased myocardial contractility + increased release of renin

Question 454

What are the functions of beta-2 adrenoreceptors?

Answer 454

- Beta-2 - 2 lungs. Smooth muscle relaxation in the lungs, blood vessels, GI tract, bladder, uterus, and liver: - Vasodilation, decreased peripheral resistance, bronchodilation, increased muscle and liver glycogenolysis, increased release of glucagon + relaxed uterine smooth muscle

Question 455

What is the mechanism of action for alpha agonists?

Answer 455

Alpha-adrenoceptor agonists (α-agonists) bind to α-receptors on vascular smooth muscle and induce smooth contraction and vasoconstriction, thus mimicking the effects of sympathetic adrenergic nerve activation to the blood vessels

Question 456

What is the mechanism of action for beta agonists?

Answer 456

Beta-2 agonists act directly on beta-2 receptors, causing smooth muscle relaxation and dilatation of the airways

Question 457

What are agonists for: a) alpha-1 b) alpha-2 c) beta-1 d) beta-2 e) indirect

Answer 457

a) decongestants (phenylephrine) b) centrally-acting vasodilator, e.g. clinicians, alpha-methyldopa c) inotropes (epinephrine, dopamine, dobutamine) d) SABA/LABA e) cocaine, amphetamine

Question 458

What are antagonists for: a) alpha-1 b) alpha-2 c) beta-1 d) beta-2

Answer 458

a) tamsulosin, doxazosin b) yohimbine c) selective/non-selective beta-blockers d) non-selective beta-blockers

Question 459

Where does Tamsulosin exert its greatest effect?

Answer 459

Tamsulosin is a selective alpha-1-adrenoreceptor antagonist that exerts its greatest effect in the prostate and bladder, where these receptors are most common

Question 460

Based on the fact that alpha-1-adrenoreceptors are most common in the prostate and bladder, name a condition that Tamsulosin could be used to treat.

Answer 460

Tamsulosin is indicated for the treatment of benign prostate hypertrophy. Antagonism of these receptors leads to relaxation of smooth muscle in the prostate and detrusor muscles in the bladder, allowing for better urinary flow

Question 461

Define tolerance.

Answer 461

A reduction in the effect of a drug overtime. This can be due to continuous use of repeatedly high concentrations

Question 462

What is the mechanism of a Type 1 hypersensitivity reaction? Give an example.

Answer 462

- Type 1 = antigen reacts with IgE bound to mass cells - Example = anaphylaxis

Question 463

What is the mechanism of Type 2 hypersensitivity? Give examples.

Answer 463

- Type 2 = IgG or IgM binds or antigen on cell surface - Examples: haemolytic anaemia, Goodpasture's syndrome, pernicious anaemia, rheumatic fever

Question 464

What is the mechanism of Type 3 hypersensitivity?

Answer 464

- Free antigen and antibody (IgG, IgA) combine - Examples: systemic lupus erythematosus, post-streptococcal glomerulonephritis

Question 465

What is the mechanism for Type IV hypersensitivity? Give examples.

Answer 465

- T-cell mediated - Examples: tuberculosis/tuberculin skin reaction, graft versus host disease, multiple sclerosis, Guillain-Barré syndrome

Question 466

What are the signs and symptoms of anaphylaxis?

Answer 466

- CVS = vasodilation, increased vascular permeability, lowered BP - Respiratory = dyspnoea due to bronchoconstriction, mucus production - Skin = rash, swelling - GI = pain, vomiting

Question 467

What is the mechanism of anaphylaxis? How can we treat anaphylaxis?

Answer 467

- IgE binds antigen which then cross-links FceRI (high affinity IgE receptor) on mast cells and basophils leading to massive degranulation and histamine release - The resuscitation council’s algorithm for anaphylaxis says: 1. ABCDE 2. Check for obvious potential diagnosis 3. Call for help 4. Adrenaline 5. Establish airway / high flow O2 / IV fluid challenge / chlorphenamine / hydrocortisone - IM ADRENALINE (1st line) - opens airway and blood vessels helping to reverse the effects of anaphylaxis. 500 MICROGRAMS (0.5 mL) OF 1:1000 IM - IV FLUIDS - fluid loss from increased vascular permeability. Signs of shock, vasodilation and a low BP - CHLORPHENAMINE is an antihistamine which takes 15-20 mins to work. Histamine release is the cause of anaphylaxis so this helps reverse the effects - HYDROCORTISONE is a corticosteroid, its benefit in anaphylaxis is still unproven but aims to stop a biphasic reaction, reduce the symptom recurrence, and wheezing

Question 468

How does autoimmunity develop?

Answer 468

- Thymic education - Tregs - CD4 activation against autoantigen

Question 469

What is the difference between primary immunodeficiency and secondary immunodeficiency?

Answer 469

- Primary immunodeficiency = those born with intrinsic defects in their immune system, rare and mostly genetic disorders - Secondary immunodeficiency = these are acquired and referred to generally as immunosuppression. Drug induced, cancers of the bone marrow and blood cells, AIDS

Question 470

A 34-year-old male comes into the GP complaining of haemoptysis. He notes that he wakes up at night due to waking up in a pool of sweat and mentions he recently returned from a holiday in Pakistan. The GP suspects tuberculosis. Which of the following cytokines is primarily responsible for activating macrophages? a) IL-2 b) IL-4 c) TNFα d) IL-1β e) IFN-γ

Answer 470

E. INF gamma is the main activator of macrophages. IL-2 is secreted by macrophages. IL-4 is involved in B-cell differentiation. IL-1β is a pyrogen

Question 471

A 5-year-old girl is brought to the GP after repeated episodes of allergic rhinitis and eczema. Which cytokine is involved in atopy and, amongst other things, causes class switching of immunoglobulins to IgE? a) IL-4 b) IL-17 c) IL-5 d) IL-1β e) IFN-γ

Answer 471

A) IL-4 is the key cytokine for allergic inflammation and has multiple roles in allergy and asthma including; IgE class switching, Th2 polerisation, Increases VCAM-1 expression, promotes eosinophils to enter tissues, and mucous secretions.

Question 472

An infant presents to hospital with a fever, shortness of breath and a cough producing yellow sputum. She has had many previous admissions due to similar infections and has been diagnosed with a deficiency in mannose binding lectin (MBL). Which substance is failing to trigger a complement cascade reaction in this patient? a) IgE b) IgM c) C3 Convertase d) Pathogen surface carbohydrates e) Membrane attack complex

Answer 472

D. Mannose is a carbohydrate found on bacterial cell walls but not human cells. The lectin pathway of the complement system is triggered when MBL binds to mannose on bacteria. a and b are incorrect as antibodies activate the classical complement pathway. C3 convertase and the membrane attack complex are downstream components of the complement system and therefore do not trigger the cascade

Question 473

A 13-year-old boy has been brought to the GP by his dad after having a sore throat and a cough for the last week. After an examination, the GP concludes that he likely has a viral infection that will resolve without other treatment. Which immune cells are responsible for directly combating this type of infection through apoptosis? a) Basophils b) Plasma Cells c) T helper cells (CD4) d) Neutrophils e) Cytotoxic T-cells (CD8)

Answer 473

E) CD8 T cells are responsible for inducing apoptosis in virally infected cells. Cytotoxic T cells are responsible for inducing apoptosis. T helper cells produce cytokines for promoting the immune response. Basophils are a sign of chronic inflammation and produce histamine. Neutrophils (macrophages) kill extracellular microbes through phagocytosis and not apoptosis. T helper cells release cytokines to alter the immune response.

Question 474

A 10-year-old boy presents with an itchy rash on his elbows. The rash is red and there are excoriation marks. He has a past history of hay fever and has generally dry skin. The GP diagnoses him with eczema and he is prescribed hydrocortisone. Which antibody is responsible for mediating type 1 hypersensitivity? a) IgG b) IgA c) IgM d) IgE e) IgD

Answer 474

D) IgE is the antibody responsible for type I hypersensitivity

Question 475

A 38-year-old male attends the human immunodeficiency virus (HIV) clinic for routine blood tests for monitoring of his condition. The number of which of the following cells is used to measure the progression of disease in HIV positive patients? a) Neutrophils b) B Cells c) NK cells d) CD4 T cells e) CD8 T cells

Answer 475

D) CD4+ T cells are the specific cell tropism for HIV are is correlated to disease progression. HIV uses CD4 to enter CD4+ cells. Other immunological changes are seen but are not correlated clinically with progression. The following immunological changes are seen in progressive HIV: ●Reduction in CD4 count ●Increase B2-macroglobulin ●Decreased IL-2 production ●Polyclonal B-cell activation ●Decrease NK cell function ●Reduced delayed hypersensitivity responses

Question 476

A 34-year-old man is referred to the gastroenterologist due to persistent epigastric pain and nausea. He returned travelling from south-east Asia ten weeks ago. Blood tests reveal iron deficiency anaemia, and faecal microscopy reveals the presence of hookworm eggs. Which immune cell is responsible for the defense against helminths? a) Basophils b) Eosinophils c) Neutrophils d) Macrophages e) Dendritic Cells

Answer 476

B) Eosinophils are the innate response to helminth infection. Basophils could be thought of as circulating mast cells that secrete histamine. Neutrophils are the principle cell in acute inflammation and are particularly good at combating pyogenic (pus forming) bacteria. Macrophages serve a similar role to neutrophils but also antigen present and are present in chronic inflammation. Dendritic cells are antigen presenting cells that serve as a joining of the adaptive and innate immunity.

Question 477

A 14-year-old boy complains of a 3-day history of fatigue, aches and pains, and fever. Upon examination his temperature is 38ºC and his tonsils are inflamed. He is suspected to have a bacterial infection which will be fought by his adaptive immune system. Which of the following cell-surface proteins are found on cytotoxic T-cells? a) CD4 b) CRP c) MHC I d) CD 8 e) MHC II

Answer 477

D) CD8 is the identifying surface marker for cytotoxic T cells. CD4 is the marker for T helper cells. CRP is an acute phase protein raised during infection and inflammatory responses. MHC I and MHC I are antigen presenting molecules.

Question 478

A 24-year-old lady collapses after being stung by a wasp. You run to her aid and find marked facial oedema and a loud wheeze. You suspect anaphylaxis. Which type of immunoglobulin (Ig) is associated with this kind of reaction? a) IgG b) IgA c) IgM d) IgE e) IgD

Answer 478

D) IgE is the principle antibody involved in type 1 hypersensitivity.

Question 479

Which of the following is not a component of the innate immune system? A.Complement system B.Toll-like receptors C.Macrophages D.T helper cells E.C-reactive protein

Answer 479

D. T helper cells

Question 480

Which of the following statements about the adaptive immune system is false? ## Footnote * MHC class I is found on all nucleated cells * MHC is coded for on Chromosome 6 * Treg cells are involved in regulating autoimmunity * B cells undergo monoclonal expansion in the thymus * Active immunisation involves harnessing the adaptive immune system

Answer 480

B cells undergo monoclonal expansion in the thymus

Question 481

Which of the following is a Type III hypersensitivity reaction? * Tuberculosis * Goodpasture’s Disease * Systemic Lupus Erythematosus * Contact Dermatitis * Anaphylaxis

Answer 481

Systemic Lupus Erythematosus

Question 482

Which of the following antibodies is implicated in asthma? * IgG * IgA * IgM * IgE * IgD

Answer 482

IgE

Question 483

Which of the following antibodies is implicated in the secondary response to infection? * IgG * IgA * IgM * IgE * IgD

Answer 483

IgG

Question 484

You are an F1 at A/E. A young boy has come in with signs of anaphylaxis after eating food containing peanuts. He has a peanut allergy. * Give 2 signs/symptoms on general inspection you might see * The boy has a known peanut allergy. What drug might he be carrying around? * Give 2 drugs that can be used to treat Anaphylaxis. What is the route of administration?

Answer 484

* Rash (urticaria), swollen lips (angioedema) * Noradrenaline (Epipen) * IV Hydrocortisone, IV Chlorphenamine

Question 485

Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes etc?

Answer 485

C3a and C5a

Question 486

Define allorecognition.

Answer 486

The ability of an organism to distinguish its own tissues from those of another. Recognition of non-self antigens

Question 487

Describe the immune responses to detection of graft antigens.

Answer 487

1. Innate immune response is activated 2. T cell mediated cytotoxicity 3. Ab mediated cytotoxicity 4. Hypersensitivity 5. Tolerance

Question 488

Give 6 ways of preventing transplant rejection.

Answer 488

1. Manage risk factors 2. Tissue typing 3. Cross match 4. Immunosuppressive agents 5. Sensitisation and desensitisation 6. Tolerance

Question 489

Why is it important to get the balance right when using immunosuppressive agents?

Answer 489

Too much = infection Too little = rejection

Question 490

What is involved in tissue typing?

Answer 490

1. Blood group matching 2. HLA typing

Question 491

What is atopy?

Answer 491

The tendency to develop allergies

Question 492

What happens to IgE receptors when a 'threat' is identified?

Answer 492

The receptors cross-link

Question 493

Which compound causes blood vessel dilation and vascular leakage in an allergic response?

Answer 493

Histamine

Question 494

Which complement proteins: a) are involved in the formation of MAC b) increase chemotaxis c) are involved in opsonisation?

Answer 494

a) C3b, C5b-C9 b) C3a, C5a c) C3b

Question 495

What are the exogenous ligands for: a) TLR1/2 b) TLR3 c) TLR4 d) TLR5 e) TLR9

Answer 495

a) gram positive lipopeptides b) double-stranded RNA c) LPS d) flagellin e) CpG DNA

Question 496

What is VDJ recombination?

Answer 496

The process by which T + B cells randomly assemble different gene segments (VDJ) in order to generate unique receptors

Question 497

What is an adverse drug reaction? How is it different from a side effect?

Answer 497

- An adverse drug reaction is an unwanted or harmful reaction following administration of a drug - A side effect is different because side effects can be beneficial

Question 498

Give 4 risk factors for ADRs.

Answer 498

1. Female 2. Genetic factors 3. Allergies 4. Polypharmacy

Question 499

Why are drug interactions such a big problem today?

Answer 499

1. Ageing population 2. Polypharmacy 3. Increased use of over the counter drugs

Question 500

Give 2 drug related risk factors for drug interactions.

Answer 500

1. Narrow therapeutic index 2. Steep dose-response curve

Question 501

What are the types of adverse drug reactions according to the Rawlins Thompson classification?

Answer 501

- Type A (augmented) = very common, predictable, often dose related - Type B (bizarre) = unpredictable, not dose dependent - Type C (chronic) = occurs after long term therapy - Type D (delayed) = occurs many years after treatment - Type E (end of use) = withdrawal reaction after long-term use - Type F (failure of therapy)

Question 502

When there is suspected anaphylaxis, what is the first thing we do?

Answer 502

- ABCDE = airways, breathing, circulation, disability, exposure - Then raise legs if breathing not impaired - IM adrenaline - Stop infusion of drugs if they have been given any (could be causing the anaphylaxis)

Question 503

What are the two types of NSAIDs? What do they both do?

Answer 503

- Non-selective NSAIDs = competitive reversible inhibitors of COX1 and 2, e.g. ibuprofen, naproxen - COX2-selective NSAIDs = selectively inhibit COX2, e.g. celecoxib

Question 504

What is the role of COX?

Answer 504

- COX is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins - thromboxanes play a role in platelet adhesion, prostaglandins cause vasodilation - COX1 plays a role in maintaining GI mucosa lining, kidney function + platelet aggregation - COX2 inducibly expresses during an inflammatory response (therefore COX-2 selective NSAIDs should provide anti-inflammatory relief without compromise the gastric mucosa)

Question 505

What is the action of NSAIDs?

Answer 505

Cyclooxygenase (COX) inhibitors → prevents production of prostaglandins. COX-2 inhibition is useful, COX-1 inhibition causes the adverse effects

Question 506

What are the anti-platelet effects of aspirin?

Answer 506

Aspirin irreversibly inhibits COX1/2 = decreased thromboxane A2 = decreased platelet aggregation = increased bleeding time

Question 507

What are the anti-platelet effects of clopidogrel and ticlodipine?

Answer 507

They are metabolised in the liver to active compounds which covalently bind to the ADP receptor on platelets and dramatically reduce platelet activation

Question 508

What are the anti-platelet effects of dipyridamole?

Answer 508

Dipyridamole inhibits phosphodiesterase, which inactivates cyclic AMP. It also stimulates prostacyclin release and inhibits thromboxane A2 formation. This leads to decreased platelet aggregation and vasodilation

Question 509

What is the purpose of anti-coagulants?

Answer 509

Anti-coagulants act at different points within the coagulation cascade to prolong clotting time

Question 510

Where do the intrinsic and extrinsic coagulation cascade pathways converge? What does this lead to?

Answer 510

Factor Xa. This leads to fibrin activation

Question 511

What are some direct inhibitors of Factor Xa? What could be a side effect?

Answer 511

- Apixaban, Betrixaban, Edoxaban, Rivaroxaban - Side effect = bleeding

Question 512

What does heparin activate?

Answer 512

Heparin activates antithrombin (decreased thrombin and Factor Xa)

Question 513

What is the purpose of warfarin?

Answer 513

- Anti-vitamin K = decreased FII (prothrombin)/VII/IX/X and Protein C/S - Increased time for the blood to clot

Question 514

Give examples of thrombolytics. What do they do? What are they used for? Give a side effect.

Answer 514

- Activate Plasminogen, which forms the cleaved product Plasmin. Plasmin is a proteolytic enzyme that is capable of breaking cross-links between fibrin molecules, which provide the structural integrity of blood clots. Increased PT - Examples: Alteplase/Tenecteplase (tPA), Streptokinase - SE: Bleeding

Question 515

How do loop diuretics work? What are they used for? Give examples.

Answer 515

- Loop diuretics act at the ascending limb of the loop of Henle and reversibly INHIBIT THE NA+/K+/CL- COTRANSPORTER, inhibiting the reabsorption of sodium and chloride ions. This reduces the hypertonicity of the renal medulla, thus inhibiting water reabsorption by the collecting ducts - Loop diuretics are indicated for the treatment of hypertension and oedema often caused by ischaemia heart disease or chronic kidney disease - SEs = hypokalaemia (as less K+ absorbed) - Loop diuretic examples: FUROSEMIDE, BUMETANIDE

Question 516

How do thiazide diuretics work? What are they used for? Give examples. Give side effects.

Answer 516

- Thiazide diuretics - INHIBIT NA+/CL- CONTRANSPORTER IN THE DCT. Less Na+ reabsorbed = less water follows - Thiazide diuretics are indicated for hypertension and heart failure, as well as nephrogenic DI - Examples: BENDROFLUMETHIAZIDE, INDAPAMIDE - SE: hypokalaemia (more Na+ in the DCT where it can be exchanged for K+ so more K+ lost in the urine), alkalosis hypochloraemic, diarrhoea, hyperglycaemia, hyperuricaemia

Question 517

What is the mechanism of action for K+ sparing diuretics?

Answer 517

Inhibit reabsorption of Na+ and water in ENaC channels in DCTs leading to Na+ and water excretion and K+ retention = hyperakalaemia

Question 518

What is the action of spironolactone? What is it used to treat? Give side effects.

Answer 518

- Spironolactone = ALDOSTERONE ANTAGONIST - Binds competitively to the aldosterone receptor at the aldosterone-dependent sodium-potassium exchange site. This promotes sodium and potassium retention - Spironolactone is indicated to treat a number of condition including heart failure, hypoaldosteronism, hypertension, and nephrotic syndrome - SE: HYPERKALAEMIA, drowsiness, dizziness, nausea, vomiting

Question 519

What is the dosage of oral morphine:IM morphine?

Answer 519

Oral is double, 10:5mg. This is because oral drugs have a lower bioavailability and have to undergo first pass metabolism

Question 520

What is the mechanism of action for antidiabetic drugs?

Answer 520

These agents work by closing potassium channels on the surface of beta cells, which causes an influx of calcium ions into the cells and a consequent outflow of insulin from cellular storage vesicles

Question 521

What is the mechanism of action for adrenaline?

Answer 521

- Epinephrine acts on alpha and beta receptors and is the strongest alpha receptor activator. - Through its action on alpha-adrenergic receptors, epinephrine minimises the vasodilation and increased the vascular permeability that occurs during anaphylaxis, which can cause the loss of intravascular fluid volume as well as hypotension. Epinephrine relaxes the smooth muscle of the bronchi and iris and is a histamine antagonist, rendering it useful in treating the manifestations of allergic reactions and associated conditions - Through its action on beta-adrenergic receptors, epinephrine leads to bronchial smooth muscle relaxation that helps to relieve bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis

Question 522

What is the mechanism of action for ACE inhibitors?

Answer 522

Block the action of ACE and prevent angiotensin I being converted to angiotensin II, so no aldosterone secreted and no vasodilation etc.

Question 523

What is the mechanism of action for PPIs?

Answer 523

Proton pump inhibitors (PPIs) irreversibly inhibit H+/K+-ATPase pump in gastric parietal cells to reduce H+ (acid) secretion

Question 524

What is the mechanism of action for anaesthetics?

Answer 524

In general the anaesthetics inhibit or block excitatory ligand-gated ion channels and enhance the sensitivity of inhibitory ion channels such as γ-aminobutyric acid A (GABAa) receptor that function as inhibitory CNS receptors

Question 525

What is the mechanism of action for opioids?

Answer 525

Activation of mu receptors in the CNS

Question 526

What is the action of antihistamines?

Answer 526

H1 receptor antagonist. Prevents release of histamine from storage granules in mast cells which cause allergic reaction symptoms

Question 527

What are the side effects of these drugs: a) NSAIDS b) Anti-histamines c) Beta-2 agonists d) ACE-INHIBITORS e) PPIs f) OPIOIDS g) Diuretics?

Answer 527

a) NSAIDs → GI upset, GI bleeding, renal impairment b) Anti-histamines → older ones can cross BBB and cause sedation. Many H1 receptors in vomiting centre, so can act as anti-emetics too! c) Beta-2 agonists → can agonise B2 receptors in other tissue → fight or flight response (sweating, tachycardia etc.) d) ACE-i → DRY COUGH DUE To BRADYKININ!!! Dilates afferent glomerular arteriole, so worsens kidney function e) PPI → prolonged use in elderly can increase risk of fracture f) Opioids → RESPIRATORY DEPRESSION → GIVE NALOXONE!! N&V, constipation, tolerance and withdrawal. g) Diuretics → spironolactone can cause hyperkalemia (remember it’s potassium sparing), they can all cause increased frequency and dehydration

Question 528

What is diamorphine? How does it work? Which class of drug does it fall under?

Answer 528

- Diamorphine is a painkiller - It behaves as an agonist at a complex group of receptors (the μ, κ and δ subtypes) that are normally acted upon by endorphins - It is an opioid

Question 529

What are the side effects, indications, contra-indications and interactions of diamorphine?

Answer 529

- Side effects: biliary spasm, circulatory depression, intracranial pressure increased, mood altered, postural hypotension (frequency not known). For opioids (common): arrhythmias, confusion, constipation, dizziness, drowsiness, dry mouth, euphoric mood - Indications: acute pain, chronic pain not currently treated with a strong opioid analgesic, acute pulmonary oedema, myocardial infarction - Contra-indications: delayed gastric emptying, phaeochromocytoma. Opioids: acute respiratory depression, comatose patients, head injury, raised intercranial pressure - Interactions: alcohol, buprenorphine, isocarboxazid, naltrexone

Question 530

What are the side effects, indications, contra-indications and interactions of paracetamol?

Answer 530

- Side effects: thromobocytopenia (rare). With rectal use: anorectal erythema (common) - Indications: mild to moderate pain, pyrexia, acute migraine - Contra-indications: before administering, check when paracetamol last administered and cumulative paracetamol dose over previous 24 hours, body-weight under 50 kg, chronic alcohol consumption, chronic dehydration, chronic malnutrition, long-term use - Interactions: alcohol, dapsone, flucloxacillin, imatinib, phenindione, prilocaine

Question 531

What is ramipril?

Answer 531

Ramipril is an ACE inhibitor used to treat high blood pressure, heart failure, and diabetic kidney disease

Question 532

What are the side effects, indications, contra-indications and interactions of ramipril?

Answer 532

- Side effects: gastrointestinal disorders, increased risk of infection, muscle spasms - Indications: hypertension, symptomatic heart failure, prophylaxis after myocardial infarction in patients with clinical evidence of heart failure (started at least 48 hours after infarction), nephropathy - Contra-indications (these are CAUTIONS): concomitant diuretics, diabetes, patients of Black African or African-Caribbean descent, aortic or mitral valve stenosis - Interactions: aliskiren, allopurinol, azathioprine, everolimus, lithium,

Question 533

What is salmeterol?

Answer 533

Salmeterol is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms

Question 534

What are the side effects, indications, contra-indications and interactions of salmeterol?

Answer 534

- Side effects: muscle cramps (common), nervousness, skin reactions (uncommon) - Indications: reversible airways obstruction in patients requiring long-term regular bronchodilator therapy, asthma, COPD - Contra-indications (these are cautions for beta-2 agonists): arrhythmias, cardiovascular disease, diabetes, hypertension, hyperthyroidism, hypokalaemia, susceptibility to QT-interval prolongation - Interactions: amifampridine, amiodarone, amisulpride, apomorphine, clarithromycin, erythromycin, lithium

Question 535

What is suxamethonium chloride? How does it work?

Answer 535

- Suxamethonium chloride is a medication used to cause short-term paralysis as part of general anaesthesia - Suxamethonium acts by mimicking acetylcholine at the neuromuscular junction but hydrolysis is much slower than for acetylcholine; depolarisation is therefore prolonged, resulting in neuromuscular blockade

Question 536

What are the side effects, indications, contra-indications and interactions of suxamethonium chloride?

Answer 536

- Side effects: arrhythmias, bradycardia, flushing, involuntary muscle contractions, myoglobinuria, post-procedural muscle pain, rash - Indications: neuromuscular blockade (short duration) during surgery and intubation - Contra-indications: hyperkalaemia, low plasma-cholinesterase activity, major trauma, neurological disease, personal or family history of congenital myotonic disease or malignant hyperthermia, prolonged immobilisation, severe burns, skeletal muscle myopathies - Interactions: betamethasone, hydrocortisone, prednisolone

Question 537

What is tramadol?

Answer 537

Tramadol is an opioid pain medication used to treat moderate to moderately severe pain

Question 538

What are the side effects, indications, contra-indications and interactions?

Answer 538

- Side effects: fatigue (common), postural hypotension (uncommon) - Indications: moderate to severe pain, postoperative pain - Contra-indications: acute intoxication with alcohol/analgesics/hypnotics/opioids, compromised respiratory function, uncontrolled epilepsy - Interactions: buprenorphine, carbamazepine, fluoxetine

Question 539

Answer 539

C. One or more alternative genes coding for the same trait found at the same locus on homologous chromosomes

Question 540

Answer 540

C. 50%

Question 541

Answer 541

C. 50%

Question 542

Answer 542

C. 50%

Question 543

Answer 543

C. Trisomy 21

Question 544

Answer 544

C. Convulsions

Question 545

Answer 545

B. Calf atrophy

Question 546

Answer 546

C. Commonly affects the Alpha chain in haemoglobin

Question 547

Answer 547

C. Trachea

Question 548

Answer 548

C. It consists of chondrocytes and fibroblasts surrounded by type I collagen

Question 549

Answer 549

D. Internal elastic lamina

Question 550

Answer 550

A. Tunica intima

Question 551

Answer 551

B. Merkel

Question 552

Answer 552

C. Neutrophil

Question 553

Answer 553

E. Podocytes

Question 554

Answer 554

E. Transmit electrical impulses

Question 555

Answer 555

B. Are multinucleated

Question 556

Answer 556

B. Kupffer cells

Question 557

What are the antibodies for: a) rheumatoid arthritis b) SLE c) Sjorgen syndrome, SLE d) Antiphospholipid syndrome, SLE e) primary biliary cirrhosis f) Hashimoto thyroiditis g) Goodpasture syndrome h) Coeliac disease i) Microscopic polyangiitis, Churg-Strauss syndrome j) Granulomatosis with polyangiitis k) Type 1 diabetes mellitus

Answer 557

a) Rheumatoid factor (anti-IgG), anti-CCP b) ANA, anti-dsDNA, Anti-Sm c) anti-SSA (Ro) and SSB (La) d) anti-phospholipid e) anti-mitochondrial f) anti-thyroid peroxidase, anti-thyroglobulin g) anti-basement membrane h) anti-gliadin IgA, anti-endomysial IgA, anti-transglutinase IgA i) P-ANCA j) C-ANCA k) anti-glutamic acid decarboxylase

Question 558

What are the different toll-like receptors, their ligand, and their origin?

Answer 558