Introductory Clinical Sciences

Question 1

What is inflammation?

Answer 1

A reaction to injury or infection involving cells such as neutrophils and macrophages

Question 2

Give 5 cardinal signs of inflammation.

Answer 2

1. Redness (rubor).
2. Swelling (tumor).
3. Pain (dolor).
4. Heat (calor).
5. Loss of function.

Question 3

Give a disadvantage of inflammation.

Answer 3

Inflammation can produce disease and can lead to distorted tissues with permanently altered function.

Question 4

When is inflammation bad?

Answer 4

1. Autoimmunity
2. When it’s an overreaction to the stimulus

Question 5

What is the expected outcome of acute inflammation?

Answer 5

The complete elimination of a pathogen followed by resolution of damage, disappearance of leukocytes and regeneration of tissue.

Question 6

Acute inflammation features

Answer 6

1. Sudden onset
2. Short duration
3. Usually resolves

Question 7

Give 6 causes of acute inflammation.

Answer 7

1. Microbial infections (bacteria and viruses).
2. Chemicals (corrosives, acids/alkalis).
3. Physical agents (trauma, burns, frost bite).
4. Hypersensitivity reactions (TB).
5. Bacterial toxins.
6. Tissue necrosis.

Question 8

Chronic inflammation features

Answer 8

1. Slow onset or sequel to acute
2. Long duration
3. May never resolve

Question 9

What is chronic inflammation?

Answer 9

Persistent, unresolved inflammation.

Question 10

Give 4 causes of chronic inflammation.

Answer 10

Primary chronic inflammation.
Transplant rejection.
Recurrent acute inflammation.
Progression from acute inflammation.

Question 11

Give examples of primary chronic inflammation.

Answer 11

1. Infective substances having resistance to phagocytosis e.g. TB, leprosy.
2. Endogenous materials e.g. uric acid crystals.
3. Exogenous materials e.g. asbestos.
4. Autoimmune diseases e.g. chronic gastritis, rheumatoid arthritis etc.
5. Other chronic inflammatory diseases e.g. chronic inflammatory bowel disease.

Question 12

Which one of the following is a chronic inflammatory process from its start?

A. Appendicitis
B. Cholecystitis
C. Infectious mononucleosis
D. Lobar pneumonia

Answer 12

C. Infectious mononucleosis

Question 13

What cells are involved in acute inflammation?

Answer 13

• Neutrophil polymorphs

Question 14

Give 3 endogenous chemical mediators of acute inflammation.

Answer 14

Bradykinin.
Histamine.
Nitric Oxide.

Question 15

Features of neutrophil polymorphs

Answer 15

• Short lived cells
• First on the scene of acute inflammation
• Cytoplasmic granules full of enzymes that kill bacteria
• Usually die at the scene of inflammation
• Release chemicals that attract other
  inflammatory cells such as macrophages

Question 16

What are 4 systemic effects of acute inflammation?

Answer 16

Fever.
Feeling unwell.
Weight loss.
Reactive hyperplasia of the reticuloendothelial system.

Question 17

What cells are involved in chronic inflammation?

Answer 17

Macrophages and plasma cells (B and T lymphocytes).

Question 18

Features of macrophages

Answer 18

• Long lived cells (weeks to months)
• Phagocytic properties
• Ingest bacteria and debris
• May carry debris away
• May present antigen to lymphocytes

Question 19

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

Answer 19

Multinucleate giant cell.

Question 20

What are some macroscopic features of chronic inflammation?

Answer 20

Chronic ulcer.
Chronic abscess cavity.
Granulomatous inflammation.
Fibrosis.

Question 21

Features of lymphocytes

Answer 21

• Long lived cells (years)
• Produce chemicals which attract in other inflammatory cells
• Immunological memory for past infections and antigens

Question 22

Plasma cell function and features.

Answer 22

• B cell antibody production
• Lots of endoplasmic reticulum to make protein.

Question 23

Endothelial cells features

Answer 23

• Line capillary blood vessels in areas of inflammation
• Become sticky in areas of inflammation so inflammatory cells adhere to them
• Become porous to allow inflammatory cells to pass into tissues
• Grow into areas of damage to form new capillary vessels

Question 24

What happens to the arterioles and capillary beds during inflammation?

Answer 24

In acute inflammation, the precapillary sphincters open, causing blood to flow through all capillaries. This is good in localised areas.

Question 25

Define exudate.

Answer 25

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

Question 26

Why does inflammation lead to oedema

Answer 26

- Normally, fluid leaves the arteriole end and enters through the venous end. - In acute inflammation, the sphincter is open and there is a higher pressure in the arteriole end and capillaries are more porous. - There is a net loss of fluid together with plasma protein into the extracellular space. - This leads to oedema

Question 27

Fibroblasts features

Answer 27

- Long lived cells - Produce collagenous connective tissue in scarring following some types of inflammation

Question 28

What occurs during acute appendicitis? (eg of acute inflammation)

Answer 28

– Unknown precipitating factor – Neutrophils appear – Blood vessels dilate – Inflammation of serosal surface occurs – Pain felt – Appendix either surgically removed or inflammation resolves or appendix bursts with generalised peritonitis and possible death

Question 29

What are the 4 outcomes of inflammation?

Answer 29

1. Resolution. 2. Suppuration. 3. Organisation (scar tissue formation). 4. Progression onto chronic inflammation.

Question 30

What occurs during tuberculosis? (eg of chronic inflammation)

Answer 30

– No initial acute inflammation – Mycobacteria ingested by macrophages – Macrophages often fail to kill the mycobacteria because of the cell wall – Lymphocytes appear – Macrophages appear – Fibrosis occurs

Question 31

What are granulomas?

Answer 31

A aggregation of epithelioid histocytes surrounded by lymphocytes

Question 32

What is granulation tissue?

Answer 32

Granulation tissue is composed of small blood vessels in a connective tissue matrix with myofibroblasts. It is important in healing and repair.

Question 33

What is a chronic granulomatous disease (CGD)? Give 4 examples of granulomatous disease.

Answer 33

An inherited disorder that occurs when the white blood cells (phagocytes) do not work properly. Therefore, the phagocytes cannot protect the body from bacterial or fungal infections. TB, leprosy, Crohn’s disease and sarcoidosis.

Question 34

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

Answer 34

Angiotensin converting enzyme.

Question 35

How would you treat inflammation? | List 5 things

Answer 35

- Ice - Antihistamine for insect bites: histamine drives inflammation - Aspirin, ibuprofen: inhibits prostaglandin synthetase, prostaglandins are chemical mediators of inflammation - Corticosteroids: inhibitors of inflammation down regulate chemical mediators of inflammation

Question 36

What leads to thrombus formation in arteries ?

Answer 36

Endothelial cell injury -> exposing collagen -> platelets aggregate -> Turbulent flow -> fibrinogen polymerises to fibrin -> blood clot

Question 37

What are the 3 factors that can lead to thrombosis formation?

Answer 37

1. Change in vessel wall. 2. Change in blood constituents. 3. Change in blood flow.

Question 38

Define thrombosis.

Answer 38

Formation of a solid mass from blood constituents in an intact vessel in the living.

Question 39

Give 2 reasons why thrombosis formation is uncommon.

Answer 39

1. Laminar flow. 2. Non sticky endothelial cells.

Question 40

What drug can be used to prevent Thrombosis?

Answer 40

Aspirin. Inhibits platelet aggregation

Question 41

How is COVID-19 related to thrombosis

Answer 41

- COVID virus causes massive inflammation boosting cytokines - Increases the liver's production of clotting factors - Leads to thrombosis.

Question 42

Define embolus

Answer 42

Mass of material in the vascular system able to become lodged within vessel and block it. | Most commonly, thrombus

Question 43

What are the consequences of an arterial embolus?

Answer 43

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

Question 44

What are the consequences of a venous embolus?

Answer 44

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 decreased perfusion to the lungs.

Question 45

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

Answer 45

Venous system.

Question 46

What are the effects of thrombosis and embolism

Answer 46

Can lead to ischaemia and infarction.

Question 47

Define ischaemia.

Answer 47

Decreased blood flow.

Question 48

What complication may happen if ischaemia is rectified?

Answer 48

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

Question 49

Define infarction.

Answer 49

Decreased blood flow with subsequent cell death.

Question 50

What are most organs in the body supplied by. What issue does this cause?

Answer 50

Most organs are supplied by the end arterial supply. If it blocks, can lead to infarction.

Question 51

What organs have more than one supply?

Answer 51

The lungs (bronchial arteries and pulmonary veins), liver (hepatic arteries and portal veins), and some parts of the brain (circle of Willis).

Question 52

What is the difference between resolution and repair?

Answer 52

Resolution –initiating factor removed –tissue undamaged or able to regenerate Repair –initiating factor still present –tissue damaged and unable to regenerate

Question 53

What prevents the liver from regenerating in patients with alcoholic liver disease?

Answer 53

Initiating factor not taken away (patient still drinking), leads to cirrhosis where the liver repairs instead of regenerates.

Question 54

What damages occur in lobar pneumonia and severe COVID lung damage?

Answer 54

- Pneumocytes can regenerate, but alveolar cannot. In lobar pneumonia the lungs can regenerate and can completely recover. In severe cases of Covid, the alveolar cannot regenerate, lungs can only repair.

Question 55

What are abrasion skin wounds?

Answer 55

Superficial skin wounds that have only damaged the top layer of the epidermis, will heal up normally.

Question 56

What happens when healing by 1st intention?

Answer 56

Edges by skin are closely re-approximated.

Question 57

What happens when healing by 2nd intention?

Answer 57

Occurs in traumatic wounds when skin lost and cannot heal through edges. Blood vessels have to grow in from either side. Takes longer to heal.

Question 58

Define repair.

Answer 58

* replacement of damaged tissue by fibrous tissue * collagen produced by fibroblasts

Question 59

List 3 examples of repair in the human body.

Answer 59

–heart after myocardial infarction –brain after cerebral infarction –spinal cord after trauma

Question 60

Name 6 types of cells capable of regeneration.

Answer 60

* hepatocytes * pneumocytes * all blood cells * gut epithelium * skin epithelium * osteocytes

Question 61

Name 2 type of cells that don't regenerate?

Answer 61

* myocardial cells * neurones

Question 62

Man aged 30 takes a large overdose paracetamol overdose and doesn’t come to hospital for 2 days. He spends a few days on ITU with liver failure but then recovers. What will be happening in his liver - resolution or repair?

Answer 62

Resolution! Only 1 overdose, and hepatocytes are capable of regeneration.

Question 63

A child aged 3 falls off a climbing frame onto his hand, he fractures his clavicle. He has his arm in a sling for 4 weeks and is very good about keeping it in the sling What will be happening in his clavicle - resolution or repair?

Answer 63

Resolution! The patient is keeping the sling in and osteocytes are capable of regeneration.

Question 64

A child aged 3 falls off a climbing frame onto his hand, he fractureshis clavicle. He has his arm in a sling for 4 weeks but won’t keep the sling on and moves his arm a lot What will be happening in his clavicle - resolution or repair?

Answer 64

Repair! The patient won't keep the sling on and keeps moving his arms about. Body unable to regenerate because it becomes fibrous and only repair can occur.

Question 65

Give a benefit of inflammation.

Answer 65

Inflammation can destroy invading micro-organisms in injuries and can prevent the spread of infection.

Question 66

What do viral infections result in?

Answer 66

Cell death due to intracellular multiplication.

Question 67

What does bacterial infection result in?

Answer 67

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

Question 68

Define abscess.

Answer 68

Acute inflammation with a fibrotic wall.

Question 69

Define atherosclerosis.

Answer 69

Inflammatory process characterised by accumulation of fibrolipid plaques in the intima of a vessel wall. It causes a huge amount of illness by reducing the blood flow in important areas.

Question 70

What is the time course of atherosclerosis?

Answer 70

- Birth - no atherosclerosis - Late teenage/early 20s - fatty streaks in aorta, may not progress to established atherosclerosis - 30s/40s/50s - development of established atherosclerotic plaques - 40s-80s - complications of atherosclerotic plaques e.g. thrombosis, intraplaque haemorrhage

Question 71

What is the distribution of atherosclerosis plaques?

Answer 71

It is common in high pressure systems such as aorta and systemic arteries, never in pulmonary circulation.

Question 72

What is in an atherosclerosis plaque?

Answer 72

1. Lipid core. 2. Necrotic debris. 3. Connective tissue. 4. Fibrous cap. 5. Lymphocytes.

Question 73

List 5 risk factors of atherosclerosis.

Answer 73

- Cigarette smoking - Hypertension - Poorly-controlled diabetes mellitus - Hyperlipidaemia - Lower social economic status

Question 74

What secondary preventative measure can a GP introduce to a patient post myocardial infarction, known ischaemic disease or known peripheral arterial disease? List 5 examples.

Answer 74

- Statins 80mg (primary prevention would be 20mg) - Aspirin 75mg - ACE inhibitors - Beta blockers - Control BP with anti-hypertensives

Question 75

What is the endothelial damage theory

Answer 75

- Endothelial cells are delicate, they require oxygen to produce lots of nitric oxide. - If they are in any way impaired will not produce nitric oxide and die.

Question 76

Describe the main stages involved in the formation of an atherosclerotic plaque

Answer 76

- Macrophages form foam cells from lipids in arterial wall - fatty streak formation (platelets) > intermediate lesion - Plaque protrudes into artery lumen and disrupts laminar flow - medial thinning and platelet aggregation - Secondary platelet plug forms fibrin mesh over itself and traps red blood cells - Fibroblasts form smooth muscle 'fibrous cap' over this - Continuous formation of secondary platelet plug, this is a stable atheroma - plaque stabilisation/( fibrous cap formation)

Question 77

How does cigarette smoke cause damage to the endothelial cells

Answer 77

Free radicals, nicotine and carbon monoxide can damage endothelial cells.

Question 78

How does hypertension damage the endothelial cells?

Answer 78

High blood pressure has shearing forces exerted on endothelial cells and this can lead to damage

Question 79

How does poorly-controlled diabetes mellitus damage endothelial cells.

Answer 79

Super oxide anions present and glycosylation products both cause oxidative stress and endothelial injury.

Question 80

What does cumulative damage to the endothelium lead to?

Answer 80

Endothelial ulceration -> microthrombi -> eventual development of established atherosclerotic plaques Complete block to an artery will mean no blood flow to the organ and infarction can occur.

Question 81

Give 6 examples of complications of atherosclerosis?

Answer 81

- Cerebral infarction - Carotid atheroma - Myocardial infarction - Aortic aneurysms - Peripheral artery disease with intermittent claudication - Gangrene

Question 82

What is the anatomy of a normal artery and which part of it is important with regards to atherosclerosis?

Answer 82

- Intima, media and adventitia - Intima is the most important with regards to ACS. It is formed of only a single layer of endothelium – this is involved in the immune response, releases antithrombotic molecules to prevent clots, releases vasodilators and constrictors

Question 83

Where does the left and right coronary arteries arise from?

Answer 83

The aortic sinuses

Question 84

How can occlusion of coronary arteries be detected and treated?

Answer 84

Occlusion of any of the coronary arteries can be seen on ECG and via coronary angiogram. It is diagnostic and relieving treatment. Immediate treatment can be done = coronary angioplasty = balloon & stent.

Question 85

Define apoptosis

Answer 85

Programmed cell death of a single cell.

Question 86

What is the role of p53 protein?

Answer 86

Cells can detect DNA damage using p53 protein which can then trigger apoptosis.

Question 87

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

Answer 87

p53 protein.

Question 88

How does a cell apoptose?

Answer 88

The cell triggers a series of proteins which lead to the release of caspases within the cell which can turn on apoptosis.

Question 89

Activation of what receptor can activate caspase and therefore apoptosis?

Answer 89

FAS receptor.

Question 90

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

Answer 90

Cancer; mutations in p53 mean cell damage isn’t detected.

Question 91

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

Answer 91

HIV

Question 92

Define necrosis.

Answer 92

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

Question 93

Give 5 examples of events that can lead to necrosis.

Answer 93

* Infarction due to loss of blood supply e.g. myocardial infarction, cerebral infarction * Frostbite * Toxic venom from reptiles and insects * Avascular necrosis of bone * Pancreatitis

Question 94

Give 3 differences between apoptosis and necrosis.

Answer 94

1. Apoptosis is programmed cell death whereas necrosis is unprogrammed. 2. Apoptosis tends to effect only a single cell whereas necrosis effects 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 95

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 95

C. Renal infarction. Necrosis not apoptosis

Question 96

How does the spinal cord form?

Answer 96

- Initial epithelium - Columnar base - Invagination - Tube formation and closure

Question 97

What are the types of spina bifida? | a congenital defect of the spine

Answer 97

- Spina bifida occulta - Meningocele - Myelomeningocele

Question 98

What genes control how cells migrate and differentiate?

Answer 98

Homeobox genes

Question 99

Define congenital.

Answer 99

Present at birth.

Question 100

Give an example of a disease which is congenital but not genetic.

Answer 100

Club foot.

Question 101

Why do people with Down syndrome tend to have earlier dementia?

Answer 101

This is because they have trisomy 21, this leads to excessive beta amyloid being produced which can clump together to form plaques between neurons.

Question 102

Define polygenic inheritance.

Answer 102

Polygenic inheritance refers to inheritance in which the trait is produced from the cumulative effects of many genes.

Question 103

Give an example of a congenital acquired disease.

Answer 103

Foetal alcohol syndrome.

Question 104

Is dwarfism inherited?

Answer 104

Yes, caused by genetic inheritance leading to growth hormone deficiency.

Question 105

Is gigantism inherited?

Answer 105

No, it's caused by growth hormone excess from pituitary adenoma.

Question 106

Define hypertrophy.

Answer 106

Increase in the size of a tissue due to an increase in the size of constituent cells.

Question 107

Why are cows able to grow muscle despite a grass-fed diet?

Answer 107

Mutation in the myostatin gene

Question 108

Define hyperplasia.

Answer 108

Increase in the size of a tissue due to an increase in the number of constituent cells.

Question 109

Define atrophy.

Answer 109

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.

Question 110

Define metaplasia.

Answer 110

A change in the differentiation of a cell from one fully differentiated cell type to another fully differentiated cell type.

Question 111

Give an example of a disease that demonstrates metaplasia.

Answer 111

Barrett’s oesophagus - the cells at the lower end of the oesophagus change from stratified squamous cells to columnar.

Question 112

Define dysplasia.

Answer 112

Morphological changes seen in cells in the progression to becoming cancer.

Question 113

Dysplasia is sometimes used to refer to developmental abnormalities. Give an example of this.

Answer 113

Focal cortical dysplasia.

Question 114

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

Answer 114

It can no longer divide.

Question 115

What is the limit to how many times a human cell can divide called?

Answer 115

The Hayflick limit.

Question 116

What are the effects of ageing on skin? What is the cause of it?

Answer 116

Dermal elastosis is caused by UV-B light causing cross-linking of the proteins, especially collagen, in the dermis.

Question 117

How can osteoporosis be prevented?

Answer 117

Can be prevented by hormone replacement therapy at menopause and calcium/vitamin D supplements.

Question 118

Give 6 examples of ageing in different body parts?

Answer 118

- Wrinkling of skin (dermal elastosis) - Eyes - cataracts - Osteoporosis - Dementia - Loss of muscle (sarcopaenia) - Deafness

Question 119

Why does ageing cause osteoporosis?

Answer 119

Lack of oestrogen post menopause leading to increased bone resorption and decreased bone formation

Question 120

What are the effects of ageing on the eyes? What is the cause of it?

Answer 120

Cataracts - caused by UV-B cross-linking of proteins in the lens causing opacity.

Question 121

How can cataracts in old age be prevented and treated?

Answer 121

Can be prevented by wearing sunglasses that cut out UV light. Can be treated by replacement of the lens with a plastic implant.

Question 122

Cause of sarcopenia in old age?

Answer 122

Reduced levels of growth hormone and testosterone, increased catabolic cytokines in later life.

Question 123

How can sarcopenia be prevented?

Answer 123

Regular exercise including resistance/weight training

Question 124

What causes deafness in old age?

Answer 124

The hair cells in the cochlear do not divide so if they are damaged by high volumes they will die and not be replaced eventually producing deafness.

Question 125

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

Answer 125

C. Brain in dementia

Question 126

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

Answer 126

a) Gut or skin tissue can divide. b) Brain tissue is non dividing.

Question 127

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

Answer 127

Because BCC only invades locally and doesn’t metastasise.

Question 128

Define carcinoma.

Answer 128

Malignant epithelial neoplasm

Question 129

Why can't excision be used as a cure for leukemia?

Answer 129

Leukemia is systemic, it circulates and always spreads all around the body, therefore excision can’t be used.

Question 130

Suggest a treatment that could be used for leukemia?

Answer 130

Chemotherapy

Question 131

Where can the majority of breast carcinomas spread to?

Answer 131

Breast cancers can spread to the lymph nodes that drain the site of the carcinoma.

Question 132

Which 5 carcinomas commonly spread to bone?

Answer 132

1. Breast 2. Kidney 3. Lung 4. Prostate 5. Thyroid | PORTABLE PO=prostate, R=renal, TA=thyroid, B=breast, LE=lung

Question 133

How would you plan for treatment of breast cancer?

Answer 133

- Confirm diagnosis of breast cancer. (eg core biopsy needle) - Confirm whether it has spread to the axilla to decide whether axillary node clearance is needed. (eg ultrasound of the axilla) - Confirm whether its has spread to the rest of the body. (eg bone scan) - If cancer has spread to rest of body, systemic therapy needed. If not, then surgery with, or without axillary lymph node clearance can take place.

Question 134

Even if a tumour is completely excised, what complications may there be? What can be used to treat these patients?

Answer 134

Micro metastases could be present. Adjuvant therapy (extra treatment given after surgical excision) can be used to suppress secondary tumour formation.

Question 135

What common treatment is given to patients who have undergone lumpectomy?

Answer 135

Radiotherapy to the breast.

Question 136

What secondary treatment is given to breast cancer patients who test oestrogen receptor positive?

Answer 136

adjuvant anti-oestrogen therapy

Question 137

What secondary treatment is given to breast cancer patients who test positive for amplified HER2 gene?

Answer 137

Herceptin (Trastuzumab)

Question 138

Define carcinogenesis.

Answer 138

The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations.

Question 139

What does oncogenesis cause?

Answer 139

Cause the development of benign and malignant tumours

Question 140

What is the difference between carcinogenic and oncogenic?

Answer 140

carcinogenic = cancer causing oncogenic = tumour causing

Question 141

What percentage of cancer risk is due to environmental factors? What problems does this have?

Answer 141

85% of cancer risk is environmental Rest are chance, genetics, micro-organisms  Problems: - latent interval may last decades - complexity of environment - ethical constraints

Question 142

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

Answer 142

Skin cancer and lung cancer.

Question 143

Chemical carcinogens: what types of cancer does Beta-Naphthylamine cause?

Answer 143

Bladder cancer.

Question 144

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

Answer 144

Smoking cigarettes and mineral oils.

Question 145

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

Answer 145

Bladder cancer

Question 146

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

Answer 146

People who work in the rubber/dye industry.

Question 147

Chemical carcinogens: what types of cancer do nitrosamines cause?

Answer 147

Gut cancer

Question 148

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

Answer 148

Leukaemia; the risk is small in humans.

Question 149

Chemical carcinogens: what types of cancer does radioactive iodine cause?

Answer 149

Thyroid cancer (seen during Chernobyl)

Question 150

Name the 5 different classes of carcinogens.

Answer 150

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

Question 151

List 4 features of chemical carcinogens.

Answer 151

- No common structural features - Some act directly - Most requires metabolic conversion from procarcinogens to ultimate carcinogens - Enzyme required may be ubiquitous or confined to certain organs

Question 152

What percentage of all cancers are made up by viruses?

Answer 152

10-15% of all cancers are caused by viruses. Most oncogenic viral infections don't results in cancer.

Question 153

Name 5 viral DNA carcinogens and the cancer they cause.

Answer 153

1. Human Herpes Virus 8 (HHV8) - Kaposi sarcoma 2. Epstein Barr Virus (EBV) - Burkitt lymphoma, Nasopharyngeal carcinoma 3. Hepatitis B Virus (HBV) - Hepatocellular carcinoma 4. Human papillomavirus (HPV) - Squamous cell carcinomas of the cervix, penis, anus, head and neck 5. Merkle cell polyomavirus (MCV) - Merkle cell carcinoma

Question 154

Name 2 viral RNA carcinogens and the cancer they cause

Answer 154

1. Human T-lymphotrophic virus (HTLV-1) - Adult T-cell leukemia 2. Hepatitis C Virus (HCV) - Hepatocellular carcinoma

Question 155

Features of radiant energy carcinogens.

Answer 155

- Ionising radiation - Long term effect - Skin cancer in radiographers - Lung cancer in uranium miners (radon gas) -Thyroid cancer in Ukrainian children

Question 156

What biological agents cause cancer?

Answer 156

- Hormones such as oestrogen (mammary/endometrial cancer) and anabolic steroids (hepatocellular carcinoma) - Mycotoxins such as aflatoxin B1 (hepatocellular carcinoma) - Parasites such as Chlonorchis sinensis (cholangiocarcinoma) and Shistosoma (bladder cancer)

Question 157

Give 5 host factors that can affect cancer risk.

Answer 157

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

Question 158

Host factors - premalignant conditions. Name 3 identifiable local abnormalities which are associated with increased risk of malignancy at that site

Answer 158

- Colonic polyps - Ulcerative colitis - Cervical Dysplasia (CIN)

Question 159

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

Answer 159

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

Question 160

A 72 year old man from Singapore has smoked for all his adult life, placing the lit end of his cigarettes in his mouth. 'Reverse smoking' increases the risk of developing which cancer?

Answer 160

Oral cancer

Question 161

A 42 year old woman has recently returned from Uganda. She continued her hobby of fresh water swimming during her trip. She now complains of an itchy rash and a fever. Her doctor suspects she may have schistosomiasis. Left untreated, this parasitic infection increases the risk of which cancer?

Answer 161

Bladder cancer

Question 162

A 51 year old woman with HIV presents to her doctor with multiple purple bruise-like lesions on the skin of her face, torso and limbs. A biopsy confirms the diagnosis of Kaposi sarcoma. Which virus causes Kaposi sarcoma?

Answer 162

Human Herpes Virus 8 (HHV8)

Question 163

A 27 year old man is worried about his alcohol consumption and seeks advice about the effect it might have on his health. Which cancer can be caused by excess alcohol consumption?

Answer 163

Colon cancer

Question 164

A 32 year old man is admitted to hospital with abdominal pain. The pain is in his right iliac fossa. A scan is performed and his appendix is removed by laparoscopic surgery. The appendix is sent for histopathology examination. What is the predominant cell that the pathologist sees on microscopic examination?

Answer 164

Neutrophil polymorphs

Question 165

Pathologist finds a white area of scarring in the myocardium and takes a sample for histology. What is the predominant cell the pathologist will see in the white area?

Answer 165

Fibroblasts

Question 166

What is carcinoma in situ?

Answer 166

When the carcinoma hasn't reached the basement membrane, thus it can't enter the lymphatic system or blood vessels and cannot spread.

Question 167

What do you call carcinoma that has reached the basement membrane?

Answer 167

Invasive carcinoma

Question 168

What is micro-invasive carcinoma?

Answer 168

Carcinoma that has invaded through the basement membrane, but only by a little. Potentially, it could spread through the body, but the risk of it spreading is extremely low.

Question 169

What properties help the carcinoma invade the basement membrane? (intravasation)

Answer 169

- proteases - matrix metalloproteases - cell motility

Question 170

How does the invasive carcinoma metastasise?

Answer 170

- Tumour invades basement membrane and stroma - Tumour has to enter system (ie lymphatic vessels, venules, transcoeleomic, arteries though unlikely) - Tumour cells have to resist immune response in the lymphatic fluid or venous blood as the lymphocytes and macrophages would act against it - Tumour cells have to exit and invade the extracellular matrix and start growing

Question 171

What is required for a tumour to exit the blood stream (extravasation)?

Answer 171

- Adhesion receptors. - Collagenases. - Cell motility.

Question 172

Give 2 promoters of tumour angiogenesis.

Answer 172

1. Vascular endothelial growth factors. 2. Fibroblast growth factors.

Question 173

Give 3 inhibitors of tumour angiogenesis.

Answer 173

1. Angiostatin. 2. Endostatin. 3. Vasculostatin.

Question 174

What 3 mechanisms do tumour cells use to evade host immune defence?

Answer 174

- Aggregation with platelets - Shedding of surface antigens - Adhesion to other tumour cells

Question 175

What kind of drugs can be used in targeted chemotherapy?

Answer 175

Monoclonal antibodies (MAB) and small molecular inhibitors (SMI). MAB can be used to treat constitutive activation of receptors. SMI can be used to treat overexpression of receptors.

Question 176

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

Answer 176

Sarcoma (via venae cava -> heart -> pulmonary arteries).

Question 177

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

Answer 177

Colon, stomach, pancreas, carcinoid tumours of intestine can spread to the liver via the portal vein.

Question 178

What are the common cancers to metastasise to the bone?

Answer 178

PORTABLE Po – Prostate R – Renal Ta – Thyroid B – Breast Le – Lung

Question 179

Conventional chemotherapy: how does vinblastine work?

Answer 179

In order for cells to divide cells have to replicate. Binds to the microtubules and prevents them working.

Question 180

Conventional chemotherapy: how does etoposide work?

Answer 180

In order for cells to divide cells have to replicate. Etoposide inhibits topoisomerase II

Question 181

Conventional chemotherapy: how does ifosamide work?

Answer 181

Ifosamide binds directly to DNA inhibits DNA synthesis by cross linking

Question 182

Conventional chemotherapy: how does cisplatin work?

Answer 182

Cisplatin binds directly to DNA and inhibits DNA synthesis by cross linking

Question 183

Give an advantage and a disadvantage of conventional chemotherapy.

Answer 183

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

Question 184

What type of tumours are conventional chemotherapy good for? List 5 examples

Answer 184

Fast dividing tumours - germ cell tumours of testis – acute leukaemias – lymphomas – embryonal paediatric tumours – choriocarcinoma

Question 185

What type of tumour is conventional chemotherapy not good for?

Answer 185

Slow dividing tumours - some tumour cells increase by mitigating apoptosis.

Question 186

What is the histogenetic classification of neoplasms?

Answer 186

Histopathological tests specify tumour type by determining the cell of origin of a tumour.

Question 187

Name two genetic drivers of carcinogenesis?

Answer 187

- Proto-oncogenes: genes that promote cell growth and survival - Tumour suppressor genes: genes which inhibit cell growth and proliferation

Question 188

How would you diagnose bronchial carcinoma (small and non small)?

Answer 188

- Sputum - Radiology-guided biopsy - Bronchoscopy

Question 189

What is tumour grading and staging?

Answer 189

Tumour grading: How much the tumour cells resemble their normal counterparts Tumour staging: How much the tumour has spread. Involves assessment of lymph nodes, extent of spread to other organs and tissues.

Question 190

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

Answer 190

rhabdomyosarcoma

Question 191

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

Answer 191

Carcinoma in situ

Question 192

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

Answer 192

Adenoma

Question 193

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

Answer 193

lipoma

Question 194

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

Answer 194

adenocarcinoma

Question 195

True or False: Ovarian cancer commonly spreads in the peritoneum.

Answer 195

True

Question 196

A 27 year old woman presents to the Accident and Emergency Department with abdominal pain. She says that it started the day before when she felt non-specifically unwell and felt pain in the middle of her abdomen. She slept rather fitfully and woke up this morning with a more severe pain that had moved to her right groin region. A diagnosis of acute appendicitis is made and her appendix is removed during a laparoscopic operation. The appendix is sent to the Department of Histopathology where it is sampled and microscopic slides are produced. The Consultant Histopathologist looks at the lumen of the appendix on a high power lens on her microscope. What is the predominant type of inflammatory cell that she sees? - Eosinophil - Lymphocyte - Macrophage - Mast cell - Neutrophil polymorph

Answer 196

Neutrophil polymorph - acute inflammation

Question 197

Define neoplasm

Answer 197

An autonomous, abnormal, persistent new growth.

Question 198

What are the 3 commonest causes of cancer death in males?

Answer 198

1. Lung cancer 2. Prostate cancer 3. Bowel cancer

Question 199

What are the 3 commonest causes of cancer death in women?

Answer 199

1. Lung cancer 2. Breast cancer 3. Bowel cancer

Question 200

What is the structure of a neoplasm?

Answer 200

1. Neoplastic cells. 2. Stroma.

Question 201

Describe neoplastic cells.

Answer 201

- Derived from nucleated cells. - Usually monoclonal - Growth pattern and synthetic activity is related to the parent cell.

Question 202

Describe the stroma of a neoplasm.

Answer 202

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

Question 203

What is essential for neoplasm growth?

Answer 203

Angiogenesis.

Question 204

Why does central necrosis occur in neoplasm?

Answer 204

The neoplasm grows quickly and outgrows its vascular supply.

Question 205

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

Answer 205

1. Behavioural classification. 2. Histogenetic classification.

Question 206

What are the 5 features of a benign neoplasms.

Answer 206

- non invasive, localised - slow growth rate - well-circumscribed or encapsulated - low mitotic activity - close resemblance to normal tissue

Question 207

What is the behavioural classification of neoplasms?

Answer 207

Neoplasms can be classified as benign, malignant or borderline. Borderline tumours (e.g. some ovarian lesions) defy precise classification.

Question 208

List 4 histological features of benign neoplasms.

Answer 208

- Nuclear morphometry often normal - Necrosis rare - Ulceration rare - Growth on mucosal surfaces usually exophytic

Question 209

What are the 5 complications of benign neoplasms?

Answer 209

- Pressure on adjacent structures - Obstruct flow - Produce hormones - Transform to malignant neoplasm - Anxiety

Question 210

What are the 5 features of malignant neoplasms?

Answer 210

- Invasive - Metastases - Rapid growth rate - Variable resemblance to normal tissue - Poorly defined or irregular border

Question 211

List 5 histological features of malignant neoplasms.

Answer 211

- Hyperchromatic nuclei - Pleomorphic nuclei - Increased mitotic activity - Necrosis and ulceration common - Growth on mucosal surfaces and skin often endophytic

Question 212

List 7 complications of malignant neoplasms?

Answer 212

- Destruction of adjacent tissue - Metastases - Blood loss from ulcers - Obstruct flow - Produce hormones - Paraneoplastic effects - Anxiety and pain

Question 213

What is a papilloma?

Answer 213

A benign neoplasm of non-glandular non-secretory epithelium

Question 214

What is an adenoma?

Answer 214

Benign tumour of glandular or secretory epithelium.

Question 215

What are carcinomas of glandular epithelium called?

Answer 215

adenocarcinomas

Question 216

What is a leiomyoma?

Answer 216

A benign smooth muscle neoplasm.

Question 217

What is a neuroma?

Answer 217

A benign neoplasm of nerves.

Question 218

What is a chondrosarcoma?

Answer 218

A malignant neoplasm of cartilage.

Question 219

What is a liposarcoma?

Answer 219

A malignant neoplasm of adipose tissue.

Question 220

What is a melanoma?

Answer 220

A malignant neoplasm of melanocytes.

Question 221

What is a lymphoma?

Answer 221

A malignant neoplasm of lymphoid cells.

Question 222

What is a mesothelioma?

Answer 222

A malignant neoplasm of mesothelial cells.

Question 223

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 223

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 224

What is the neoplasm called if its cell of origin is unknown?

Answer 224

Anaplastic

Question 225

What are teratomas?

Answer 225

A teratoma is a rare type of neoplasm that may contain immature or fully formed tissue, including teeth, hair, bone and muscle.

Question 226

A 43 year old woman is referred to a gynaecologist with a history of pain during sexual intercourse and vaginal bleeding after intercourse and in between her periods. The gynaecologist takes a biopsy of the ectocervix which reveals a primary malignant neoplasm. What is the likely diagnosis?

Answer 226

Squamous cell carcinoma - As the ectocervix is lined by stratified squamous epithelium. Malignancy of stratified squamous epithelium is squamous cell carcinoma.

Question 227

A 46 year old woman undergoes an elective hysterectomy to treat severe menorrhagia (heavy period). The pathologist examining the specimen reports the presence of multiple benign smooth muscle neoplasms within the myometrium. What are these neoplasms called?

Answer 227

Leiomyomas

Question 228

A 72 year old man undergoes a biopsy of his colon. The biopsy reveals a disease process that is not neoplastic or due to an infection. What is the likely abnormality?

Answer 228

Granuloma (chronic inflammation)

Question 229

What are the 7 hallmarks of cancer?

Answer 229

- Growth self-sufficiency - Evade apoptosis - Ignore anti-proliferative signals - Limitless replication potential - Sustained angiogenesis - Invade tissues - Escape immune surveillance

Question 230

What is cancer immunosurveillance?

Answer 230

When the immune system recognises and destroys transformed cells, this is an important host protection process.

Question 231

What is cancer immunoediting?

Answer 231

Immune responses can change tumours to be hidden from recognition by the immune system and tumours can promote immune suppression

Question 232

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

Answer 232

1. Tumour specific antigens - Only found on tumour cells. - As a result of point mutations or gene rearrangement - Derive from viral antigens 2. Tumour associated antigens - Found on both normal and tumour cells, but are overexpressed on cancer cells - Developmental antigens which become derepressed. (CEA) - Differentiation antigens are tissue specific - Altered modification of a protein could be an antigen

Question 233

List 5 evidence for human tumour immunity

Answer 233

- Spontaneous regression - Regression of metastases after removal of primary tumour - Infiltration of tumours by lymphocytes and macrophages - Lymphocyte proliferation in draining lymph nodes - Higher incidence of cancer after immunosuppression, immunodeficiency (AIDS, neonates), aging, etc.

Question 234

What is tumour escape?

Answer 234

Immune responses change tumours such that tumours will no longer be seen by the immune system.

Question 235

What is immune evasion?

Answer 235

Tumours change the immune responses by promoting immune suppressor cells

Question 236

How can we kill tumours without killing normal cells?

Answer 236

To induce an immune response against the tumour that would discriminate between the tumour and normal cells: Adaptive immunity

Question 237

What are the two types of immunotherapy?

Answer 237

- Active immunotherapy - Passive immunotherapy -

Question 238

List 6 examples of active immunotherapy.

Answer 238

Vaccines! - Killed tumour vaccine - Purified tumour antigens - Professional APC-based vaccines - Cytokine- and costimulator-enhanced vaccines - DNA vaccines - Viral vectors

Question 239

List 2 examples of passive cancer immunotherapy.

Answer 239

- Adoptive Cellular Therapy (T cells) - Anti-tumour Antibodies (Her-2/Neu, CD20, CD10, CEA, CA-125, GD3 ganglioside)

Question 240

Features of cell-based therapy.

Answer 240

- Cellular therapies can be used to activate a patient's immune system to attack cancer. - They can also be used as delivery vehicle to target therapeutic genes to attack the tumour - They do not act directly on cancer cells. Instead, they work systemically to activate the body's immune system.

Question 241

What 2 cell types are commonly used for cell-based therapy?

Answer 241

- Dendritic cells - T cells

Question 242

Features of dendritic cells.

Answer 242

- Antigen presenting cells - Found throughout the body (0.1-0.5%) - Interstitial cells (Liver, heart, liver), Langerhans cells of the epidermis. - Detect and chew up foreign "invader" proteins and then "present" piece of the invaders on their surface.

Question 243

How would you create a dendritic cell cancer vaccine?

Answer 243

To make a DC vaccine, the blood of the cancer patient is collected and enriched to increase the population of DC.

Question 244

How would you create a T cell cancer vaccine? | eg for melanoma

Answer 244

- Tumour biopsy - Isolation: tumour fragments and tumor infiltrated lymphocytes (TILs) are isolated - Cultivation: TILs propagated on tumour fragments and cultivated - Expansion: expansion of melanoma reactive TILs - T cell infusion

Question 245

What is tumour hypoxia?

Answer 245

Hypoxia is a prominent feature of malignant tumours. The inability of the blood supply to keep up with growing tumour cells can lead to hypoxic tumour cells that have adapted to low oxygen

Question 246

What are the problems with tumour hypoxia?

Answer 246

Tumour hypoxia usually means poor patient prognosis. - Stimulates new vessel growth - Suppresses immune system - Resistant to radio- and chemotherapy (repopulate the tumour) - Increased tumour hypoxia after therapy

Question 247

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

Answer 247

Malignant tumours grow rapidly and so outgrow their blood supply

Question 248

What are the 3 types of vaccines traditionally used?

Answer 248

- whole-killed - toxoid - live attenuated

Question 249

Define passive immunisation.

Answer 249

The administration of pre-formed “immunity” from one person or animal to another person

Question 250

Limitation of passive immunisation.

Answer 250

Only humoral (antibody) mediated (will not work if cell mediated!)

Question 251

What are the advantages and disadvantages of passive immunity

Answer 251

Advantages - Gives immediate protection - Effective in immunocompromised patients Disadvantages - Short-lived - Possible transfer of pathogens - “Serum sickness” on transfer of animal sera

Question 252

Give 4 examples of passive immunisation

Answer 252

Specific Immunoglobulin (Ig) - Human Tetanus Ig (HTIG) Rapid protection of exposed individuals - Human Rabies Specific Ig - Used after exposure to rabies to give protection until vaccine becomes effective - Human Hepatitis B Ig (HBIG) - Varicella Zoster Ig (VZIG)

Question 253

What are the 3 main approaches to making a vaccine for active immunisation?

Answer 253

- Using a whole virus or bacterium - Using parts that trigger the immune system - Using just the genetic material

Question 254

List 3 features of the whole microbe vaccine

Answer 254

- Bacteria or viruses grown in vitro and inactivated using agents such as formaldehyde or Β-propionolactone. - Non-living vaccines do not cause infection, but the antigens contained in it induce an immune response that protects against infection – by non-self antigen recognition. - Non-living vaccines can also be cell-free toxoids - inactivated toxins

Question 255

List 4 problems and limitations of whole killed vaccines.

Answer 255

1. The organisms must be grown to high titre in vitro (viruses and some bacteria difficult/expensive to grow in the lab) 2. Whole pathogens can cause excessive reactogenicity (i.e., adverse reactions, excessive immunological responses) 3. Immune responses are not always close to the normal response to infection, e.g., no mucosal immunity, no CD8 Tc responses 4. Usually need at least 2 shots

Question 256

Gives examples of bacteria that have been used in active vaccine.

Answer 256

- Diphtheria - formaldehyde treated toxin - rendered a non-toxic “toxoid” - Tetanus - toxoid, causes muscle contractions/spasms - treat purified toxoid in the lab with formalin leading to loss of toxicity but NOT epitopes - Pertussis (whooping cough) - killed whole bacteria (Bordetella pertussis) given with the two above as DTP. 3-doses. UK has now moved to acellular pertussis (aP) - Cholera - heat-killed bacteria (Vibrio cholerae)

Question 257

Give examples of viruses that have been used in active vaccine.

Answer 257

Polio vaccine (Salk) - inactivated virus-IPV Influenza vaccine - inactivated virus Hepatitis A vaccine - inactivated virus Rabies vaccine - inactivated virus SARS-Co-V2 (Valneva) - inactivated virus

Question 258

How do Live Attenuated Vaccines work?

Answer 258

The organisms replicate within the host and induce an immune response which is protective against the wild-type organism but does not cause disease.

Question 259

Define attenuation.

Answer 259

Where an organism is cultured in such a way that it does not cause disease when inoculated into humans. It has lost its pathogenicity but retains its antigenicity – (i.e., shape).

Question 260

List 4 advantages of Live Attenuated Vaccines.

Answer 260

1. Immune response more closely mimics that following real infection because its not fixed – no shape change. 2. Better immune response so lower doses are required, so the scale of in vitro growth needed is lower. 3. Route of administration may be more favourable (oral). 4. Fewer doses may be required to provide protection.

Question 261

Problems and limitations of live attenuated vaccines.

Answer 261

1. Often impossible to balance attenuation and immunogenicity 2. Reversion to virulence 3. Transmissibility 4. Live vaccines may not be so attenuated in immunocompromised hosts

Question 262

Give 2 examples of live attenuated bacterial vaccines.

Answer 262

Bacille Calmette-Guérin (BCG) Mycobacterium bovis grown over many passages in vitro. Gives some protection against TB (tuberculosis) Salmonella typhi - temperature sensitive strain given orally.

Question 263

Give 3 examples of viral live attenuated vaccines.

Answer 263

Poliomyelitis (Sabin) - widely used to bring polio to the brink of eradication Vaccinia virus - used in billions of doses to eradicate smallpox due to cross-reactivity between itself and the variola virus Measles, Mumps and Rubella - 3 given together as MMR

Question 264

In this day and age, why do so many pathogens still do not have a vaccine? List 4 possible reasons.

Answer 264

- Pathogen too difficult to grow - Killed pathogen not protective (shape change) - Impossible to obtain attenuated and suitably immunogenic strain - Too many strains causing disease etc.

Question 265

Recombinant proteins are a novel approach in creating vaccines. How are they created?

Answer 265

Genetically engineered and produced from bacteria, yeast, insect or mammalian cells

Question 266

What are the advantages and disadvantages of recombinant protein vaccines

Answer 266

Advantages: Avoid the problem of having to grow pathogen in vitro Disadvantages: Major difficulties are finding a protein or proteins that are protective and generate a strong enough immune response

Question 267

Give examples of recombinant proteins

Answer 267

Hepatitis B Surface Antigen HPV vaccines Cervarix and Gardasil (HPV16 and 18) SARS-Co-V2 – Novavax (recombinant spike protein produced by moth cells in culture, these are purified, assembled into a synthetic nanoparticle for injection – 14 spike proteins per particle)

Question 268

What are synthetic peptides

Answer 268

Peptides synthesized directly using a machine - avoids the need for pathogen growth

Question 269

Problems with synthetic peptides.

Answer 269

Difficulties * Identifying protective epitopes * Inducing a strong response * Inducing a broad response

Question 270

What are live attenuated vectors – viral vector

Answer 270

Composed of a safe living attenuated viruses that have inserted genes encoding foreign antigens, which are displayed to the immune system.

Question 271

How do viral vectors work?

Answer 271

When injected the virus is taken up by an APC, the viral DNA is released and enters the nucleus. The viral DNA is transcribed to mRNA and translated to a protein – some of this spike protein is presented with MHC II on the cell surface as a foreign antigen. This is recognised by T-cells and initiates an immune response to the spike protein. The virus is replication deficient and can not replicate in human cells limiting its spread.

Question 272

What are DNA vaccines?

Answer 272

A mammalian plasmid containing DNA that encodes for the foreign protein of interest is injected directly. This requires a lipid nanocarrier to get the DNA into a human cell. The DNA goes to the nucleus, gets transcribed and the foreign protein expressed with MHC to stimulate the immune response.

Question 273

Advantages and disadvantages of DNA vaccines.

Answer 273

* Avoid the need to grow the pathogen, viral vector * No live organism involved * DNA is cheap to produce * Problem is often poor immunogenicity

Question 274

What are mRNA vaccines

Answer 274

mRNA of the target foreign protein is synthesized in vitro. It is complexed with lipid nanoparticles that stabalise and protect the mRNA from degradation and allow the mRNA to cross the plasma membrane. The mRNA is translated in the cytoplasm and the protein presented on the surface of the cell with MHC Stimulating the immune response.

Question 275

Advantages of mRNA vaccines

Answer 275

* Avoid the need to grow the pathogen, viral vector * No live organism involved * mRNA is relatively cheap to produce * Quick to make new variations of vaccine

Question 276

Features of T-Independent Antigens

Answer 276

Bacterial capsular polysaccharides cannot be processed and presented on MHC class II No T cell help Antibody response of low magnitude Low affinity Predominantly IgM Little or no boosting on secondary exposure Infants respond especially poorly and are major target group for these vaccines Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae

Question 277

Examples of conjugate vaccines.

Answer 277

Neisseria meningitidis type C polysaccharide-protein conjugate vaccine Streptococcus pneumoniae 23-valent polysaccharide vaccine or 7-valent conjugate Haemophilus influenzae type B (HiB)-Polysaccharide protein conjugate vaccine

Question 278

What are recent changes to the vaccination programme in children?

Answer 278

The addition of a pneumococcal conjugate vaccine (PCV) at 2, 4 and 13 months of age; A dose of MenC vaccine at 3 and 4 months; A booster dose of Hib and MenC vaccine (given as a combined Hib/MenC vaccine) at 12 months of age. HPV vaccine for teenage girls and boys soon BCG no longer routinely given to teenagers. Targeted on at risk infants.

Question 279

Why do people not trust vaccines?

Answer 279

Misinformation and hearsay on the internet/social media that are not based on any science Religion – its un-natural Studies linking immunisation with contraction of other diseases/conditions Japan – HPV vaccine with neurological disorders UK – MMR and autism

Question 280

Describe innate immunity

Answer 280

- 1st line of defence - Instinctive - Non-specific does not depend on lymphocytes - Present from birth - Slow response - No memory - Provides barrier to antigen

Question 281

Describe adaptive immunity.

Answer 281

Specific ‘Acquired/learned’ immunity, requires lymphocytes, antibodies. Response specific to antigen Learnt behaviour Memory to specific antigen Quicker response

Question 282

What are both innate and adaptive immunity made up of?

Answer 282

Cells and soluble factors (humoral)

Question 283

What is haematopoiesis?

Answer 283

The commitment and differentiation processes that leads to the formation of all blood cells from pluripotent haematopoietic stem cells.

Question 284

Where does haematopoiesis take place?

Answer 284

Bone marrow (10^11 new cells each day)

Question 285

How do the pluripotent haematopoietic stem cells decide what to differentiate into?

Answer 285

Stem cells in the bone marrow are stimulated by colony stimulating factors (soluble proteins) that bind to receptors on the stem cell.

Question 286

What 2 are the two pathways the pluripotent haematopoietic stem cells can split into?

Answer 286

1. Myeloid pathway 2. Lymphoid pathway

Question 287

Which 3 types of cells are polymorphonuclear leukocytes?

Answer 287

- Neutrophils (70% of wbcs in body) - Eosinophils - Basophils

Question 288

Which 3 types of cells are mononuclear leukocytes?

Answer 288

- Monocytes: differentiates into macrophages when entering tissue. - T-cells - B-cells: differentiates into plasma cells which produce antibodies.

Question 289

What process are mast cells important in?

Answer 289

Allergic reactions - have histamines

Question 290

What are natural killer cells important for? (Type of T cell)

Answer 290

Anti tumour responses

Question 291

What are dendritic cells important for?

Answer 291

Immune surveillance

Question 292

Which 3 soluble factors make up the immune system?

Answer 292

- Complement - Antibodies - Cytokines and chemokines

Question 293

Define complement.

Answer 293

Group of ~20 serum proteins secreted by the liver that need to be activated to be functional.

Question 294

What are the 3 modes of actions of complement?

Answer 294

1. Direct lysis 2. Attract more leukocytes to site of infection 3. Coat invading organisms

Question 295

What are antibodies?

Answer 295

Antibodies (also called immunoglobulins) are soluble glycoproteins that recognize and bind antigens, specifically.

Question 296

Antibodies (Ab) can also be called immunoglobulins (Ig) What are the 3 features of immunoglobulins?

Answer 296

- soluble - secreted - bound to B cells as part of B-cell antigen receptor

Question 297

What are the 5 distinctive classes of Ig?

Answer 297

IgG (IgG1-4) IgA (IgA1 & 2) IgM IgD IgE

Question 298

Describe the basic structure of an antibody (IgG).

Answer 298

Antibodies have a basic structure of four polypeptide chains – two identical light chains and two identical heavy chains. Each chain contains a variable region (fab region). The chains are held together by disulphide bonds. The C-terminal (Fc) regions of the light and heavy chains form the constant regions which determine the effector functions of an antibody.

Question 299

In an antibody what does the Fc region and Fab region bind to?

Answer 299

Fc region binds to receptors on the surface of wbcs. Fab region bind to non-self elements, they are very specific.

Question 300

Which is the most predominant Ig in the human serum?

Answer 300

IgG: accounts for 70 - 75% of Igs in human serum

Question 301

List 5 features of IgM.

Answer 301

- Accounts for 10% of Igs in serum. - Pentamer, formation requires J chain. - Mainly found in blood – too big to cross endothelium. - Mainly primary immune response, initial contact with Ag. (First responder during immune response) - The monomeric form (mIgM) is present as an antigen-specific receptor on B cells - which is important for the adaptive immune response.

Question 302

List 3 features of IgA

Answer 302

- Accounts for 15% of Igs in serum - In humans 80% of serum IgA is as a monomer (in most animals serum IgA is a dimer) - The predominant Ig in mucous secretions such as saliva, colostrum, milk, bronchiolar & genitourinary secretions Called Secretory IgA (sIgA) sIgA is held together with a J chain and a secretory component

Question 303

List 2 features of IgD.

Answer 303

Accounts for 1% of Ig in serum A transmembrane monomeric form (mIgD) is present on mature B cells

Question 304

List 5 features of IgE

Answer 304

Accounts for only ~0.05% of Ig in serum Basophils and Mast Cells express an IgE-specific receptor that has high affinity for IgE Basophils and Mast Cells are continually saturated with IgE Binding Ag triggers release of histamine by these cells Associated with hypersensitivity allergic response and defence against parasitic infections

Question 305

What is an epitope?

Answer 305

Each antibody binds to a restricted part of the antigen called an epitope.

Question 306

What are the functions of an antibody?

Answer 306

Antibodies acts as an adaptor that links a microbe to a phagocyte. 1. Neutralise toxins. 2. Opsonisation. 3. Activate classical complement system.

Question 307

What are cytokines?

Answer 307

Proteins secreted by immune and non-immune cells.

Question 308

Name 4 types of cytokines.

Answer 308

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

Question 309

Cytokines: Function of interferons (IFN)

Answer 309

Induce a state of antiviral resistance in uninfected cells & limit the spread of viral infection

Question 310

Cytokines: Function of interleukins (IL)

Answer 310

- Can be pro-inflammatory (IL1) or anti-inflammatory (IL-10) - Can cause cells to divide, to differentiate and to secrete factors - Produced by many cells, over 30 types

Question 311

Cytokines: Function of Colony Stimulating Factors (CSF)

Answer 311

- Involved in directing the division and differentiation on bone marrow stem cells – precursors of leukocytes.

Question 312

Cytokines: Function of Tumour Necrosis Factors (TNFa & b)

Answer 312

Proinflammatory molecules. Mediate inflammation and cytotoxic reactions.

Question 313

What are chemokines?

Answer 313

Chemotactic cytokines Group of approx 40 proteins that attract leukocytes to sites of infection from the bloodstream into the tissues or lymph organs by binding to specific receptors on cells

Question 314

What are the 4 subclasses of chemokines?

Answer 314

CXCL – mainly bind to neutrophils CCL – monocytes, lymphocytes, eosinophils, basophils CX3CL – mainly T lymphocytes & NK Cells XCL – mainly T lymphocytes

Question 315

What is innate immunity composed of?

Answer 315

- Physical and chemical barriers - Phagocytic cells (neutrophils and macrophages) - Blood proteins (complement, acute phase)

Question 316

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

Answer 316

- Lysozymes in tears - Skin - Low pH and commensals of vagina - Mucociliary escalator - Gastric acid

Question 317

Sometimes physical barriers are breached leading to tissue damage (trauma) or infection. This will induce an inflammatory response. What response is the body aiming for during inflammation?

Answer 317

- Coagulation: stop bleeding. - Acute inflammation (leukocyte recruitment). - Kill pathogens, neutralise toxins, limit pathogen spread. - Phagocytosis: clear pathogens/dead cells. - Proliferation of cells to repair damage. - Remove blood clot – remodel extracellular matrix to maintain homeostasis.

Question 318

What are the 3 hallmarks of inflammation?

Answer 318

1. Increased blood supply 2. Increased vascular permeability 3. Increased leukocyte transendothelial migration ‘extravasation’

Question 319

Name 3 pattern recognition receptors (PRR) that can sense microbes?

Answer 319

1. Toll-like receptors (TLR). 2. Lectin receptors. 3. Scavenger receptors.

Question 320

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

Answer 320

Innate immunity.

Question 321

What are PRR’s a receptor for?

Answer 321

PAMP's (on microbes)

Question 322

What happens when a PAMP binds to a PRR?

Answer 322

The innate immune response and inflammatory response is triggered.

Question 323

What are C-Type lectin receptors?

Answer 323

Expressed by Macrophages and DC, can recognise foreign carbohydrates.

Question 324

What are scavenger receptors?

Answer 324

They are a very large family of receptors - They mainly recognise foreign lipids on bacteria. (ie LPS in Gram -ve bacteria)

Question 325

What are toll-like receptors?

Answer 325

TLRs recognise Pathogen-Associated Molecular Patterns expressed by microbes. Different TLRs activate different signalling cascades depending on the pathogen being detected.

Question 326

TLRs and their targets

Answer 326

TLR2: Gram positive bacteria and mycobacteria (inc fungi) TLR4: Gram negative bacteria and lipopolysaccharides TLR5: Bacteria and flagellin TLR7: Single-strand RNA TLR9: Non-methylated DNA

Question 327

What are the 3 different activation pathways that make up the complement system? How are they activated?

Answer 327

1. Classical: Antibody bound to microbe. 2. Lectin: Mannose binding lectin bound to microbe. 3. Alternative: Complement bound to microbe.

Question 328

Which complement plasma proteins are chemoattractants that recruit leukocytes to the site of infection.

Answer 328

C3a and C5a.

Question 329

Which complement plasma proteins have opsonic properties (insert itself into the membrane of bacterium "coating it" to increase its susceptibility to ingestion by phagocytosis) when bound to a pathogen?

Answer 329

C3b, C4b.

Question 330

Which complement plasma proteins make up the membrane attack complex (MAC) and are responsible for the cytolytic function?

Answer 330

C5b-9

Question 331

What is extravasation?

Answer 331

Leukocyte (WBC) migration across the endothelium.

Question 332

What do macrophages at the tissues secrete to initiate extravasation?

Answer 332

TNF alpha.

Question 333

Describe the process of extravasation.

Answer 333

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

Question 334

Describe the process of phagocytosis?

Answer 334

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

Question 335

What are the two killing pathways present in neutrophils and macrophages?

Answer 335

- O2 dependent - O2 independent

Question 336

What is the role of NO in killing pathogens in O2 dependent killing?

Answer 336

NO leads to vasodilation and increased extravasation. This means more neutrophils etc pass into the tissues to destroy pathogens.

Question 337

Why can superoxides be used to destroy pathogens in O2 dependent killing?

Answer 337

Superoxides can be converted to H2O2 and then to hydroxyl free radicals. Hydroxyl free radicals are highly reactive and can destroy pathogens.

Question 338

What mechanisms or cells are involved in O2 independent killing?

Answer 338

Enzymes: Lysozymes Proteins: Defensins, TNF pH

Question 339

What are the advantages adaptive immunity have over innate immunity?

Answer 339

- Microbes can evade innate immunity - Intracellular viruses and bacteria ‘hide’ from innate immunity - Adaptive immunity have memory to specific antigen – ‘seen it before so faster response’

Question 340

What are the two types of adaptive immunity?

Answer 340

- Cell Mediated - T cells - intracellular microbes - Humoral (Ab) - B cells - extracellular microbes

Question 341

In which primary lymphoid tissue do T cells mature?

Answer 341

Thymus

Question 342

In which primary lymphoid tissue do B cells mature?

Answer 342

Bone marrow.

Question 343

Give examples of secondary lymphoid tissue.

Answer 343

Spleen, lymph nodes, mucosa associated lymphoid tissue - MALT.

Question 344

In which primary lymphoid tissue do antigen present cells mature?

Answer 344

Bone marrow

Question 345

Which cells are involved in cell-mediated immunity?

Answer 345

1. Antigen Presenting Cells (APC) - Macrophages - Dendritic Cell - B cells 2. T cells

Question 346

What do T lymphocytes respond to?

Answer 346

T lymphocytes only respond to intracellular presented antigens, they do NOT respond to soluble antigens.

Question 347

What is T cell selection?

Answer 347

T cell selection refers to how T cells that recognise self are killed in the foetal thymus as they mature

Question 348

T cell receptors only recognise foreign antigens under what conditions?

Answer 348

T Cell Receptor (TCR) recognises foreign antigens in association with Major Histocompatibility Complex (MHC)

Question 349

What do Major Histocompatibility Complexes MHCs do?

Answer 349

Major Histocompatibility Complex (MHC) display peptides from self OR non-self proteins

Question 350

Whare the 2 types of MHC?

Answer 350

MHC I and MHC II

Question 351

Which cells express MHC1?

Answer 351

All nucleated cells express MHC1. e.g. a virus infected or cancer cell would express MHC1.

Question 352

Which cells express MHC2?

Answer 352

Antigen presenting cells ONLY e.g. macrophages, B cells, dendritic cells.

Question 353

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

Answer 353

MHC1.

Question 354

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

Answer 354

MHC2.

Question 355

What type of T cell binds to MHC1?

Answer 355

Cytotoxic T cells (CD8).

Question 356

What type of T cells binds to MHC2?

Answer 356

Helper T cells (CD4).

Question 357

Intracellular signalling happens when a helper T cell is bound to a T cell receptor. Which interleukin is secreted?

Answer 357

IL-2. This then binds to an IL-2 receptor on the T cell and produces a positive feedback mechanism (clonal expansion) leading to division, differentiation, effector functions, and memory.

Question 358

What happens when naive T cells become activated?

Answer 358

Naive cell -> CD4 and CD 8 Any infected cell presents Ag with MHC I to a CD8 T cell CD 8: Kills intracellular pathogens directly (cytotoxic T cells) APC presents Ag with MHC II to a naïve CD4 T cell. If microenvironment has a lot of IL-12, it forms TH1 -> secretes IFNγ and IL-2 -> helps kill intracellular pathogens If no IL-12, it forms TH2 -> secretes IL-4,5,10, Antibody production

Question 359

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

Answer 359

It helps the immune response against intracellular pathogens. Secretes cytokines.

Question 360

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

Answer 360

It helps produce antibodies against extracellular pathogens. Secretes cytokines.

Question 361

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

Answer 361

It can kill cells directly by binding to antigens; they can form proteolytic granules & releases perforins and granulysin they also induce apoptosis.

Question 362

How many antibodies can each B cell make?

Answer 362

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

Question 363

What do B cells express?

Answer 363

B cells express membrane bound Ig (IgM or IgD monomer)

Question 364

What happens to B cells that recognise ‘self’?

Answer 364

They are killed in bone marrow.

Question 365

B cells can function as an APC. Describe the process of a T helper cell binding to a B cell.

Answer 365

A B-cell antibody binds an antigen -> phagocytosis -> epitope is displayed on the surface of the B-cell bound to an MHC2 -> TH2 binds to B-cells -> cytokine secretion induces B-cell clonal expansion -> differentiation into plasma cells and memory B cells.

Question 366

Give examples of PAMPs in bacteria, virus, and parasites.

Answer 366

Bacteria: - Peptidoglycan (PGN) - Lipoproteins - DNA - Flagellin - Lipopolysaccharide (LPS) Virus: - Coat protein - Nucleic acid Parasite: - GPI anchor

Question 367

What are Damage associated molecular patterns (DAMPs)

Answer 367

Endogenous molecules created to alert the host to tissue injury and initiate repair.

Question 368

Why do we not recognise our own DNA and RNA and mount an innate response?

Answer 368

Our DNA and RNA is normally located where our pattern recognition receptors (PRRs) cannot access it

Question 369

TLRs and their targets

Answer 369

TLR2: Gram positive bacteria and mycobacteria (inc fungi) TLR4: Gram negative bacteria and lipopolysaccharides TLR5: Bacteria and flagellin TLR7: Single-strand RNA TLR9: Non-methylated DNA

Question 370

What is the main function of TLR’s?

Answer 370

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

Question 371

Membrane bound PRR: Where could mannose receptors be found?

Answer 371

on macrophages (fungi)

Question 372

What is the main function of RLR’s?

Answer 372

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

Question 373

Name 3 receptors that make up the PRR family.

Answer 373

Toll-like receptors (TLR). Nod-like receptors (NLR). Rig-like receptors (RLR).

Question 374

What is the main function of NLR’s?

Answer 374

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

Question 375

What is the damage chain reaction?

Answer 375

Harmful stimulus leads to tissue damage, this causes the release of DAMPs and release TLRs and proinflammatory cytokine production. Inflammation will lead to tissue damage and lead to chain reaction of DAMP release.

Question 376

What high levels of DAMPs associated with?

Answer 376

Many inflammatory and autoimmune diseases as well as atherosclerosis and cancer.

Question 377

What is the cytokine storm?

Answer 377

- Profound increase in cytokines, chemokines & interferons - Causes severe inflammation and tissue damage - Role in sepsis, influenza, severe COVID-19 pathogenesis, etc. - Induction due to: 1. genetic makeup of the host 2. persistence of the pathogen (evasion mechanisms)

Question 378

What are the 2 main strategies of immunomodulation?

Answer 378

1. Agonists (enhance TLR signalling): - adjuvant effect (used with a primary treatment) promoting protective responses e.g. vaccines - immune stimulators - Modify adaptive immune response: bias Th and Treg responses - side-effects: potentially enhance inflammation 2. Antagonists (inhibit TLR signalling): - block binding of ligands or protein-ligand complexes to receptors / interfere with intracellular adaptor molecules of common signalling pathways - sepsis syndromes, inflammation, arthritis, etc - side-effects: potentially allow pathogen outgrowth, mutation, etc

Question 379

What is type I hypersensitivity?

Answer 379

Type I hypersensitivity is an immediate reaction to environmental antigens mediated via IgE

Question 380

What is atopy?

Answer 380

Atopy is an inherited trait for Type 1 hypersensitivity

Question 381

What are allergens?

Answer 381

Allergens are antigens that trigger allergic reactions

Question 382

What are the main steps in a Type I hypersensitivity reaction?

Answer 382

1. Sensitisation 2. Mast cell degranulation 3. Early phase response 4. Late phase response

Question 383

Define sensitisation

Answer 383

Sensitisation is the term to describe the initial event that lead to the specific IgE being developed for that allergen.

Question 384

What occurs during sensitisation?

Answer 384

1. Body is exposed to allergens. 2. Allergens are taken up by APCs, processed and expressed by MHC II where they are presented to naive T cells. 3. Naive T cells differentiate into Th2 4. Th2 cells produce IL-4 and IL-13 which activate B cells and induce them to class switch to produce IgE. 5. IgE can circulate in blood and bind to mast cells and basophils in various tissues in our body.

Question 385

What are the differences in structure between IgG and IgE?

Answer 385

IgE has 4 constant domains, while IgG only has 3 constant domains. IgG has a hinge region. IgE is more heavily glycosylated.

Question 386

What are the 3 main body surfaces that come into contact with allergens?

Answer 386

- Skin - GI tract - Lung

Question 387

What happens during mast cell degranulation?

Answer 387

1. Upon subsequent re-exposure to the allergen, the antigens can bind to the IgE on the surface of the mast cells. 2. Cross linkage of the receptors can occur through the IgEs that are bound to them. 3. This leads to mast cell degranulation and stimulates the synthesis of new cytokines.

Question 388

What happens during early phase response?

Answer 388

1. Early phase mediators such as histamine are released. 2. Histamine causes vasodilation, increased vascular permeability and broncho-constriction, causing symptoms of allergy (itch, flushing, rash, angioedema and wheeze).

Question 389

Which receptor of histamine is mainly responsible for mediating allergic reactions?

Answer 389

H1 receptor

Question 390

Clinical use of tryptase during type 1 hypersensitivity?

Answer 390

Diagnostic purposes, tryptase levels spike following allergic reaction.

Question 391

List the clinical manifestations of allergy?

Answer 391

- Itchiness - Runny nose - Hives - Sneezing - Red/watery eyes - Trouble breathing

Question 392

Systemic type 1 hypersensitivity reaction would lead to what clinical syndrome?

Answer 392

Anaphylaxis

Question 393

Type 1 hypersensitivity reaction to airways would lead to what clinical syndrome?

Answer 393

- Asthma (lower airways) - Rhinitis (upper airways)

Question 394

Type 1 hypersensitivity reaction to eyes would lead to what clinical syndrome?

Answer 394

Allergic conjunctivitis

Question 395

Type 1 hypersensitivity reaction to skin would lead to what clinical syndrome?

Answer 395

- Urticaria - Angioedema - Atopic eczema

Question 396

What happens during late phase response?

Answer 396

Recruitment of other cells would lead to a second response, prolonging the inflammatory response.

Question 397

What are the three conditions that elicit a type I hypersensitivity reaction?

Answer 397

1. Allergen characteristics 2. Host factors 3. Environmental influences

Question 398

What makes certain proteins allergenic (induce a strong IgE response)?

Answer 398

- Protease activity: Der p 1 (found in dust mites) - Surface features of protein: Ves v 5 (found in wasps) - Glycosylation pattern of protein: Ara h1 (found in peanuts) - Host factors: polymorphisms of various receptors that make them gene targets - Environmental influences

Question 399

Define pharmacokinetics.

Answer 399

The fate of a chemical substance administered to a living organism - What the body does to the drug

Question 400

When describing pharmacokinetics, ADME is used, what does it stand for?

Answer 400

Absorption route Distribution (how well distributed) Metabolism (i.e IV skips 1st pass metabolism) Excretion (hepatic or renal)

Question 401

Pharmacokinetics: What is absorption?

Answer 401

Transfer of a drug molecule from site of administration to systemic circulation

Question 402

Which routes of administration have 100% of the dose reach systemic circulation?

Answer 402

IV and IA administration. For any other route, drugs must cross at least one membrane to reach systemic circulation.

Question 403

What are the three mechanisms for drugs to permeate membranes

Answer 403

Passive diffusion through hydrophobic membrane Lipid soluble molecules Passive diffusion aqueous pores Very small water soluble drugs (eg lithium) Most drug molecules are too big Carrier mediated transport Proteins which transport sugars, amino acids, neurotransmitters and trace metals (and some drugs)

Question 404

What 2 factors affecting drug absorption?

Answer 404

Lipid solubility Drug ionisation

Question 405

What factors affect oral drug absorption?

Answer 405

- Drug ionisation. - Stomach - Intestine -First pass metabolism

Question 406

In terms of ionisation, what happens to Aspirin in the stomach?

Answer 406

Aspirin is a weak acid and so becomes less ionised in the stomach due to the low gastric pH.

Question 407

What is the advantage of aspirin becoming less ionised in the stomach?

Answer 407

This allows rapid non-ionic diffusion across the gut membrane into the plasma. Once in the plasma aspirin becomes more ionised again.

Question 408

Where are weak acid drugs and weak base drugs best absorbed?

Answer 408

Weak acids - best absorbed in stomach. Weak bases - best absorbed in intestine

Question 409

How could the stomach affect oral drug absorption?

Answer 409

- Gastric enzymes - drug molecule may be digested (peptides, proteins) Eg. insulin and biologicals - Low pH - molecule may be degraded (benzylpenicillin) - Food (full stomach will generally slow absorption) - Gastric motility (altered by drugs and disease state) - Previous surgery (eg gastrectomy)

Question 410

How could the intestine affect oral drug absorption?

Answer 410

1. Drug structure - Lipid soluble/unionised molecules diffuse down concentration gradient - Large or hydrophilic molecules are poorly absorbed 2. Medicine formulation - Capsule/tablet coating can control time between administration and drug release - Modified release controls (slows) the rate of absorption (less frequent dosing) 3. P-glycoprotein - Substrates are removed from intestinal endothelial cells back into lumen

Question 411

What is first pass metabolism?

Answer 411

Metabolism of drugs preventing them reaching systemic circulation.

Question 412

List examples of first pass metabolism.

Answer 412

Degradation by enzymes in intestinal wall Absorption from intestine into hepatic portal vein and metabolism via liver enzymes

Question 413

How can first pass metabolism be avoided?

Answer 413

By giving via routes that avoid sphlanchnic circulation (eg rectal)

Question 414

What is bioavailability (F)?

Answer 414

Proportion of administered dose which reaches the systemic circulation

Question 415

Features of bioavailability (F).

Answer 415

- Dependent on extent of drug absorption and extent of first pass metabolism - Not affected by rate of absorption - Varies with route of administration - Variation between individuals (genetic, disease states) Expressed as % or fraction (e.g 70% or 0.7)

Question 416

Pros and cons of rectal administration (PR).

Answer 416

Pros: Local administration Avoids first pass metabolism Nausea and vomiting Cons: Absorption can be variable Patient preference

Question 417

Pros and cons of inhaled administration (Inh)

Answer 417

Pros: Well perfused large surface area Local administration Cons: Inhaler technique can limit effectiveness

Question 418

Pros and cons of Sub- cutaneous administration (S/C)

Answer 418

Pros: Faster onset than PO Formulation can be changed to control rate of absorption Cons: Not as rapid as IV

Question 419

Pros and cons of Trans- dermal administration (TD)

Answer 419

Pros: Provides continuous drug release Avoids first pass metabolism Cons: Only suitable for lipid soluble drugs Slow onset of action

Question 420

Pharmacokinetics: What is distribution?

Answer 420

Drug properties will influence ability to move between compartments.

Question 421

What factors can affect distribution of drugs?

Answer 421

- Molecule size - Lipid solubility - Protein binding

Question 422

What is the volume of distribution (Vd)?

Answer 422

Theoretical volume a drug will be distributed in the body (apparent volume of distribution)

Question 423

Features of Vd.

Answer 423

Volume of plasma required to contain the total administered dose Drugs that are well distributed will have high Vd Drugs that are poorly distributed will have low Vd

Question 424

Digoxin is a small molecule, highly lipophyllic, would it be likely to have a small Vd or large Vd?

Answer 424

- Small molecule size and lipophilic so would have a large Vd Vd = 5-8L/kg

Question 425

What is the blood brain barrier (BBB)?

Answer 425

Membrane that separates foreign substances in the blood from the CNS

Question 426

What features of the BBB poses a challenge for treating CNS conditions?

Answer 426

- Continuous layer of endothelial cells with tight junctions - Efflux pumps remove water soluble molecules This allows BBB to maintain a stable environment and protects the brain, but poses a challenge for treating CNS conditions

Question 427

Ways for drugs to reach the CNS despite the presence of the BBB.

Answer 427

- High lipid solubility. e.g. Ѱ drugs usually very lipid soluble (therefore large Vd) - Intrathecal administration (e.g. baclofen in MS and spinal cord injury, chemotherapy) - Inflammation (causes barrier to become leaky)

Question 428

Pharmacokinetics: What is drug elimination?

Answer 428

the process by which the drug becomes no longer available to exert its effect on the bod

Question 429

What are the two routes of drug elimination in pharmacokinetics?

Answer 429

Metabolism: modification of chemical structure to form new chemical entity (metabolite) Excretion of unchanged drug (hydrophillic, polar molecules)

Question 430

What are the 2 phases of metabolism in drug elimination? Describe them briefly

Answer 430

Phase 1: Oxidation/reduction/hydrolysis to introduce reactive group to chemical structure. Cytochrome P450 enzymes are responsible for majority of phase 1. Phase 2: Conjugation of functional group to produce hydrophilic, inert molecule which can then be excreted

Question 431

What are the three processes for renal excretion of drugs?

Answer 431

1. Glomerular filtration - 20% of plasma filtered - Free/unbound drug molecules - Very large molecules excluded 2. Active tubular secretion - 80% of renal blood flow passes on to peritubular capillaries - Can clear protein bound drugs - Most effective renal clearance mechanism 3. Passive reabsorption - Diffusion down the concentration gradient from tubule into peritubular capillaries - Hydrophobic drugs will diffuse easily - Highly polar drugs will be excreted

Question 432

A 66 year old woman is admitted to the medical ward after a fall. She is a heavy drinker and is showing signs of alcohol withdrawal. She is prescribed lorazepam to control her withdrawal symptoms. What property allows it to cross the blood brain barrier? A) substrate for CYP3A4 B) Avoids first pass metabolism C) Highly protein bound D) Large molecule E) Highly lipid soluble

Answer 432

E) Highly lipid soluble

Question 433

List 6 examples of how ageing impacts the immune response in the molecular level.

Answer 433

- Genomic instability - Telomere shortening - Epigenetic alteration - Loss of proteostasis - Compromised autophagy ( body's cellular recycling system) - Mitochondrial dysfunction

Question 434

List 3 examples of how ageing impacts the immune response in the cellular level.

Answer 434

- Cellular senescence - Stem cell exhaustion - Altered intercellular communication

Question 435

List an example of how ageing impacts the immune response in the systemic level.

Answer 435

Nutritional dysregulation

Question 436

What is immunosenescence?

Answer 436

The state of dysregulated immune function that contributes to the increased susceptibility of the elderly to infection and possibly to autoimmune disease and cancer.

Question 437

Interventions to reduce immunosenescence in the elderly.

Answer 437

Modifications to lifestyle: - Physical activity - Caloric restriction - Maintaining optimal nutrition Pharmacological interventions: - Statins

Question 438

What is meant by ‘first order kinetics’?

Answer 438

First order: Rate of elimination is proportional to the plasma drug concentration (processes involved in elimination do not become saturated) A constant % of the plasma drug is eliminated over a unit of time.

Question 439

What is meant by ‘zero order kinetics’?

Answer 439

Zero order: Rate of elimination is NOT proportional to the plasma drug concentration (metabolism processes become saturated) A constant amount of the plasma drug is eliminated over a unit of time

Question 440

What is clearance (CL)?

Answer 440

Efficiency of irreversible elimination of a drug from the systemic circulation

Question 441

Single modified release oral dose vs single oral dose.

Answer 441

Modified release formulations usually require less frequent dosing.

Question 442

Features of Half life (t1/2)

Answer 442

- Dependent on clearance (CL) of drug from body by all eliminating organs (hepatic, renal, faeces, breath) - Dependent of volume of distribution (Vd) - A drug with large Vd will be cleared more slowly than a drug with a small Vd - Not dependent on drug dose or drug formulation - A drug will be 97% cleared from the body after 5 x half lives (considered ‘cleared’ in clinical practice)

Question 443

What are single or STAT doses useful to treat?

Answer 443

Acute conditions, effects will usually wear off after a few minutes - hours

Question 444

When is continuous IV infusions used?

Answer 444

Critical care patients Antibiotics Unfractionated heparin General anaesthetics

Question 445

Pharmacokinetics: What is the steady state?

Answer 445

When the rate of drug input is equal to rate of drug elimination

Question 446

Why is the steady state important?

Answer 446

Aim for Css which lies between the Maximum safe concentration (MSC) and minimum effective concentration (MEC)

Question 447

Waiting to reach the steady state may be detrimental. What can we do to speed up the time to steady state?

Answer 447

Using a loading dose.

Question 448

Give 2 examples of zero order drugs

Answer 448

Ethanol, phenytoin

Question 449

Pharmacokinetics: What is tmax and cmax

Answer 449

Cmax= maximum plasma concentration tmax= time taken to reach Cmax

Question 450

A 66 year old woman is admitted to ED with SOB and haemoptysis. CTPA confirms bilateral PEs. She is prescribed an IV loading dose of unfractionated heparin 5000 units followed by an IV continuous infusion. What effect will the loading dose have on the heparin pharmacokinetics?

Answer 450

Reduce time to steady state plasma concentration (Css)

Question 451

Define pharmacogenetics

Answer 451

The use of genetic and genomic information to tailor pharmaceutical treatment to an individual.

Question 452

Benefits of medicine use through genomics.

Answer 452

improved patient outcomes, cost efficiency

Question 453

Most drug targets are proteins. List 4 drug targets.

Answer 453

- Enzymes - Receptors - Transporters - Ion channels

Question 454

What is a receptor?

Answer 454

A component of a cell that interacts with a specific ligand* and initiates a change of biochemical events leading to the ligands observed effects.

Question 455

Receptors are the principal means by which chemicals communicate. List three chemicals receptors can communicate with.

Answer 455

- Neurotransmitters: acetylcholine, serotonin - Autacoids (local) Greek "autos" (self) and "acos" (relief): cytokines, histamine - Hormones: testosterone, hydrocortisone

Question 456

List 4 examples of receptors involved in drug reactions.

Answer 456

Ligand-gated ion channels nicotinic ACh receptor G protein coupled receptors beta-adrenoceptors Kinase-linked receptors receptors for growth factors Cytosolic/nuclear receptors steroid receptors

Question 457

Features of G protein coupled receptors

Answer 457

GPCRs are the largest and most diverse group of membrane receptors in eukaryotes. Ligands include light energy, peptides, lipids, sugars, and proteins.

Question 458

How is G coupled protein receptor activity regulated?

Answer 458

Their activity is regulated by factors that control their ability to bind to and hydrolyse guanosine triphosphate (GTP) to guanosine diphosphate (GDP)

Question 459

Give an example of a GPCR.

Answer 459

Muscarinic and β2 adrenoceptor.

Question 460

What do the majority of GPCRs interact with?

Answer 460

GPCR's usually interact with adenylate cyclase or phospholipase C

Question 461

How do kinase-linked receptors work?

Answer 461

Kinases are enzyme that catalyze the transfer of phosphate groups between proteins - process is known as phosphorylation. The substrate gains a phosphate group ”donated” by ATP Transmembrane receptors activated when the binding of an extracellular ligand causes enzymatic activity on the intracellular side. 

Question 462

How do steroid hormones/nuclear receptor work?

Answer 462

Work by modifying gene transcription

Question 463

Give an example of a drug which targets nuclear receptors.

Answer 463

Tamoxifen (Breast Cancer) acts as a selective oestrogen receptor modulator (SERM), or as a partial agonist of the oestrogen receptors - Used in ER+ cancers. 

Question 464

Give examples of how imbalance of chemicals and receptors can lead to pathology.

Answer 464

Imbalance of chemicals allergy; increased histamine Parkinson’s; reduced dopamine Imbalance of receptors myasthenia gravis; loss of ACh receptors Mastocytosis (Mast cells); increased c-kit receptor

Question 465

What is an agonist and antagonist?

Answer 465

Agonist a compound that binds to a receptor and activates it Antagonist a compound that reduces the effect of an agonist

Question 466

What is the two state model of receptor activation?

Answer 466

Describes how drugs activate receptors by inducing or supporting a conformational change in the receptor from “off” to “on”.

Question 467

Describe the shape of a log concentration response curve.

Answer 467

Sigmoidal

Question 468

What does EC50 tell us about a drug?

Answer 468

Its potency!

Question 469

Would a drug with a lower EC50 have a lower or greater potency?

Answer 469

Greater potency.

Question 470

Define affinity, efficacy/intrinsic activity (IA) and potency

Answer 470

Affinity: -How well a ligand binds to receptor Efficacy/IA: -How well a ligand ACTIVATES a receptor Potency: -Relative strength of the drug (potency is solely comparative, i.e drug A vs B. Efficacy, is what % of bound drugs activate the receptor)

Question 471

Role of antagonist

Answer 471

Antagonists reverse the effects of agonists.

Question 472

Difference between competitive and non-competitive antagonism.

Answer 472

Competitive antagonists bind to the same site as the agonists, while in non-competitive antagonism, the antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor

Question 473

What are factors governing drug action?

Answer 473

Receptor-related affinity efficacy Tissue-related receptor number signal amplification

Question 474

Do agonists and antagonists display efficacy and affinity?

Answer 474

Agonists Have affinity and efficacy Antagonists Have affinity but zero efficacy

Question 475

What is the effect of fewer receptors on receptor response?

Answer 475

Some agonists needs to activate only a small fraction of the existing receptors  to produce the maximal system response. (Partial agonists don't have receptor reserve).

Question 476

What is inverse agonism?

Answer 476

When a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. (negative activity)

Question 477

What is tolerance?

Answer 477

Tolerance (slow) - reduction in agonist effect over time - continuously, repeatedly, high concentrations

Question 478

What is desensitization?

Answer 478

Desensitization (rapid) - uncoupled - internalized - degraded

Question 479

Use of the terms specificity and selectivity in drug interactions.

Answer 479

Selective is a better term to describe activity as no compound is ever truly specific.

Question 480

What are the two types of enzyme inhibitors.

Answer 480

Irreversible inhibitors - usually react with the enzyme and change it chemically (e.g. via covalent bond formation). Reversible inhibitors - bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, the enzyme-substrate complex, or both.

Question 481

Give an example of an enzyme that acts as drug products

Answer 481

- Streptokinase - tPA

Question 482

How do statins work?

Answer 482

HMG-CoA reductase inhibitors Block the rate limiting step in the Cholesterol pathway

Question 483

What is the renin-angiotensin-aldosterone system?

Answer 483

Renin-angiotensin-aldosterone system is a major blood pressure regulating mechanism. The system increases blood pressure by increasing the amount of salt and water the body retains

Question 484

How does inhibition of angiotensin converting enzyme help lower blood pressure?

Answer 484

Inhibiting ACE reduces ATII production and therefore causes a reduction in blood pressure

Question 485

Angiotensin converting enzyme can be hijacked. Give an example of when this could happen.

Answer 485

SARS-CoV-2 uses ACE2 as an entry receptor

Question 486

Enzymes can target multiple steps in biosynthetic pathways such as in Parkinson's disease. Treatment is through multiple enzymatic inhibitor drugs. This includes: L-DOPA, Peripheral DDC Inhibitor, Peripheral COMT Inhibitor, Central COMT Inhibitors, Mono Amine Oxidase B Inhibitors. How much each of these drugs help the management of Parkinson's,

Answer 486

L-DOPA is a precursor for neurotransmitter biosynthesis. Peripheral DDC Inhibitor blocks DDC in the periphery generating more for the CNS pathway Peripheral COMT Inhibitor prevents breakdown of L-DOPA generating more for the CNS pathway Central COMT Inhibitors function within the CNS to keep Dopamine levels up Mono Amine Oxidase B Inhibitors prevents Dopamine breakdown and increases availability

Question 487

What non enzymatic inhibitor drug can be used to help management Parkinson's disease?

Answer 487

Central Dopamine Receptor Agonists Antagonise dopamine receptors

Question 488

How and where do loop diuretics work?

Answer 488

They act on the ascending loop of henle and inhibit NKCC2 channels, this stops Na, K and Cl reabsorption.

Question 489

Name a loop diuretic.

Answer 489

Furosemide - acts on Na+/K+/2Cl- transporter (NKCC2).

Question 490

Name 3 TNF blockers.

Answer 490

1. Etanercept (TNF alpha specific).2. Infliximab.3. Adalimumab.

Question 491

List 2 naturally occurring opioids.

Answer 491

- Morphine - Codeine

Question 492

List 3 simple chemically modified opioids

Answer 492

diamorphine (heroin), oxycodone, dihydrocodeine

Question 493

List 4 synthetic opioids.

Answer 493

- Pethidine - Fentanyl - Alfentanil - Remifentanil

Question 494

10 mg of morphine orally is equal to how many mg in s/c, IM, IV?

Answer 494

5mg! 50% of oral morphine is metabolised by first pass metabolism.

Question 495

Which route of administration is the quickest between sub-cutaneous, IM and IV?

Answer 495

IV>IM>Sub-cutaneous

Question 496

What are the 4 opioid receptors?

Answer 496

MOP KOP DOP and NOP

Question 497

What are the relative potencies of diamorphine morphine and pethidine? (5mg of diamorphine)

Answer 497

Diamorphine 5 mg Morphine 10 mg Pethidine 100 mg

Question 498

What do opioids act on?

Answer 498

- CNS + GI tract receptors - Resp centres of the brain (pontine)

Question 499

Side effects of opioids

Answer 499

- Addiction - Constipation - Nausea and vomiting - Respiratory distress/depression

Question 500

How long does opioid withdrawal last?

Answer 500

- Starts within 24 hours - Lasts about 72 hours

Question 501

What to do for opioid induced respiratory depression?

Answer 501

- Call for help - ABC (check airway, breathing, circulation) - Naloxone - IV is fastest route - Titrate to effect - don’t have to give it all at once - once you’ve injected a drug you can’t get it back! - Short half-life of naloxone - beware drug addict overdoses in A&E

Question 502

Codeine is a pro-drug what does this mean?

Answer 502

Needs to be metabolised by cytochrome CYP2D6 to morphine to work. - 10% of people don’t have cytochrome CYP2D6 that converts it, codeine will have no effect in these people. - 5% of people have too much of the enzyme, these individuals may be at increased risk of respiratory depression with codeine

Question 503

What is morphine metabolised to?

Answer 503

Morphine 6 glucuronide.

Question 504

In renal failure, what may morphine 6 glucuronide lead to?

Answer 504

Morphine 6 glucuronide is renally excreted. In renal failure it will build up and may cause respiratory depression

Question 505

What should patients with renal failure use instead of morphine?

Answer 505

Oxycodone

Question 506

Parasympathetic (Ach) responses

Answer 506

- Rest + digest - Pupil constricts - Lower heart rate - Bronchoconstritction - Increased GI motility and secretion - Detrusor muscle contracts - Penis points (erect)

Question 507

Sympathetic (NAd) response

Answer 507

- Fight or flight - Pupil dilates - Increased heart rate - Bronchodilation - Decreased GI motility and secretion - Detrusor muscle relaxes - Penis shoots (ejaculation)

Question 508

Sympathetic nervous system receptors

Answer 508

alpha 1 (postsynaptic) - vasoconstriction alpha 2 (presynaptic) - negative feedback suppresses norad release beta 1 - increased heart rate and contractility beta 2 - bronchodilation

Question 509

When does a pharmacodynamic interaction occur?

Answer 509

Occurs when drugs have an effect on the same target or physiological system

Question 510

When does a pharmacokinetic interaction occur?

Answer 510

Occurs when a drug affects the pharmacokinetics (absorption, distribution, metabolism or excretion) of another drug

Question 511

Features of a pharmacodynamic interactions.

Answer 511

* Pharmacodynamic interactions are either synergistic or antagonistic * Due to drugs acting on the same drug receptor(s) or physiological system * Generally predictable (related to pharmacology of drug) * Highly selective drugs are less likely to be problematic

Question 512

72 year old female prescribed amitriptyline (for nerve pain) and solifenacin (for bladder spasm) Solifenacin is a highly selective antagonist for M3 receptors M3 receptors widespread (bladder, CNS, salivary glands, GIT) Amitriptyline increases serotonin and NA in synaptic cleft. Poor specificity for target, also antagonist at M3 receptors This leads to amplified anticholinergic effects (dry mouth, constipation, flushed+dry skin, delirium) In the above scenario is the pharmacodynamic interaction synergistic or antagonistic?

Answer 512

Synergistic interaction

Question 513

54 year old male prescribed atenolol (ß antagonist) for hypertension and salbutamol (ß2 agonist) for asthma Experiencing wheeze This is due to an antagonist reaction between the two drugs. Explain how?

Answer 513

Salbutamol agonist at ß2 receptors (located in bronchial smooth muscle) Atenolol cardioselective ß blocker (cardioselective antagonist at ß1 receptors but also antagonist at ß2) Atenolol and salbutamol compete at ß2 receptors Results in incomplete agonist effect and reduced bronchodilation/increased bronchospasm

Question 514

34 year old male prescribed morphine (pain relief) and lorazepam (anxiety) Increased sedation This is due to a synergistic reaction between the two drugs. Explain how?

Answer 514

Morphine agonist at MOP, KOP and DOP opiate receptors Benzodiazepines potentiate actions of GABA (inhibitory CNS neurotransmitter) MOP and KOP agonism and GABA transmission cause sedation Different mechanisms within the CNS Results in increased risk of sedation

Question 515

48 year old female prescribed methadone (opioid misuse) and ciprofloxacin (antibiotic) Complaining of dizziness and palpitations This is due to synergistic reaction between the two drugs. Explain how?

Answer 515

Methadone agonist at MOP, KOP and DOP opiate receptors Ciprofloxacin quinolone antibiotic Methadone and ciprofloxacin block voltage gated K channels Results in increased risk of QT prolongation and Torsades de Pointes

Question 516

51 year old female prescribed amlodipine (hypertension) and ramipril (hypertension) This will result in a synergistic reaction between the two drugs. Explain how, and whether this is beneficial or not?

Answer 516

Amlodipine: dihydropyridine calcium channel blocker reduces Ca2+ influx into vascular smooth muscle Ramipril: ACE inhibitor inhibits conversion of angiotensin I to angiotensin II Both lead to reduced vasoconstriction Results in increased risk of hypotension (may be beneficial) In practice: CCBs and ACEIs are used in combination in management of hypertension

Question 517

Pharmacokinetic drug interactions: What mechanisms of a drug could affect the absorption of another drug?

Answer 517

1. Drugs which alter pH of GI tact 2. Formation of insoluble drug complexes 3. P-glycoprotein induction/inhibition

Question 518

How can a drug which causes changes in GI Tract pH affect absorption of another drug?

Answer 518

Changes in pH will alter the proportion of ionised and unionised drug

Question 519

Famotidine (H2 antagonist) increases stomach pH and reduces absorption of ketoconazole (antifungal). In practice what can be done to prevent this?

Answer 519

In practice: If taking famotidine, oral ketoconazole should be taken with an acidic drink

Question 520

How can complex formation affect absorption?

Answer 520

Insoluble drug complexes will not be absorbed and will be retained in the GIT

Question 521

doxycycline and iron can form complexes which will not be absorbed. In practice what can be done about this?

Answer 521

In practice: separate administration of doxycycline and oral iron by 2-3 hours

Question 522

How can a drug causing P-glycoprotein induction/inhibition affect the absorption of another drug?

Answer 522

P-glycoproteins (P-gp) are drug transporter proteins widely distributed in body Excretory function to remove toxic substances (incl drugs) out of cells Amongst other locations - situated in intestinal lumen to reduce absorption

Question 523

Pgp inhibitors and inducers lead to increased or decreased level of Pgp substrates Carbamazepine = Pgp inducer Upregulates P-gp and therefore reduces the absorption of P-gp substrates Carbamazepine significantly reduces rivaroxaban levels (note interaction also occurs due to CYP3A4 induction) In practice what can be done about this?

Answer 523

NOTHING. In practice: combination can lead to anticoagulant treatment failure, therefore concurrent use is contraindicated

Question 524

Pharmacokinetic drug interactions: What issues could occur during distribution of a drug? Give an example.

Answer 524

Only unbound drug will be distributed from plasma volume. Interactions can occur when drugs compete for protein binding Warfarin is highly protein bound (~99%) 1% unbound and pharmaceutically active Amiodarone displaces warfarin from albumin to create unbound warfarin molecules Change of 99% bound to 98% bound = free drug doubles from 1% to 2%

Question 525

What enzymes are responsible for majority of phase 1 metabolic reaction

Answer 525

Cytochrome P450 (CYP450) enzymes

Question 526

What are inducer drugs?

Answer 526

- Increase Cytochrome P450 activity and speed up metabolism of other drugs

Question 527

List examples of inducer drugs

Answer 527

PCARBS Phenytoin Carbamazepine Alcohol (chronic use) Rifampicin Barbiturates (St John's Wort) Sulfonylureas and smoking

Question 528

What are drugs which decrease CYP450 activity and decrease metabolism of other drugs called? Give an example.

Answer 528

Inhibitor drugs Macrolides (clarithromycin, erythromycin) Azoles (fluconazole) Grapefruit juice

Question 529

Pharmacokinetic drug interactions: What issues could occur during elimination of a drug? Give an example.

Answer 529

Competition for renal tubular secretion. Drugs are transported by OAT (organic anion transporters) and OCT (organic cation transporters. Methotrexate (MTX) is 80-90% excreted unchanged by the kidneys Secreted into renal tubule by OAT NSAIDs compete with MTX for secretion by OAT leading to reduced MTX elimination MTX toxicity: cirrhosis, fatal blood dyscrasias, renal damage (acute renal failure)

Question 530

How does grapefruit juice affect CYP450? And what drugs might this impact on?

Answer 530

Grapefruit juice is a CYP450 inhibitor, it affects CYP3A4 specifically and increases the bioavailability of some drugs e.g. warfarin, statins

Question 531

Eating foods high in which vitamin can affect the action of warfarin?

Answer 531

High in vitamin K - opposes warfarin

Question 532

Why should cranberry juice be avoided by patients taking warfarin?

Answer 532

Cranberry juice is a CYP2C9 inhibitor

Question 533

Milk can affect absorption of some drugs such as doxycycline, levothyroxine, ciprofloxacin, how?

Answer 533

Milk can affect absorption of some drugs due to insoluble complex formed with Ca

Question 534

It is important to identify and avoid drug interactions. What types of drugs are considered high risk?

Answer 534

Obtain complete drug history (DHx) Enzyme inducers, inhibitors and substrates Drugs with a narrow therapeutic index High risk/critical medicines New drugs (e.g. biologics) - little data

Question 535

It is important to identify and avoid drug interactions. What indicators are there for patients considered high risk?

Answer 535

Polypharmacy Kidney or liver impairment Extremes of age

Question 536

Mr K (86 year old male) is brought to A&E by his daughter after falling at home and hurting his wrist. He has recently started taking codeine for pain relief. Which of his regular medicines would interact with codeine to increase his risk of falls? 1. Aspirin 2. Metformin 3. Morphine 4. Omeprazole 5. Ramipril

Answer 536

3. Morphine - duplicated agonism at opioid receptors.

Question 537

Define adverse drug reaction (ADR)

Answer 537

A response to a medicinal product, or combination of medicinal products, which is noxious and unintended

Question 538

List some examples of the impact of ADR on patients.

Answer 538

* Reduced Quality of life * Poor compliance * Reduced confidence in clinicians and the healthcare system * Unnecessary investigations or treatments

Question 539

List some examples of the impact of ADR on the NHS

Answer 539

* Increased hospital admissions * Longer hospital stays * GP appointments * Inefficient use of medication

Question 540

How can ADRs be classified using the ABCDE system?

Answer 540

A = Augmented B = Bizarre C = Chronic/continuing D = Delayed E = End of use/withdrawal F = Failure of treatment G = Genetic

Question 541

Type A ADR features

Answer 541

Most common type of ADR (80%) Exaggerated effect of drugs pharmacology at a therapeutic dose Often not life threatening Dose dependent and reversible upon withdrawing the drug

Question 542

Give an example of a Type A ADR

Answer 542

* AKI with ACE inhibitors * Bradycardia with betablockers * Hypoglycaemia with gliclazide, insulin * Respiratory depression with opiates * Bleeding with anticoagulants

Question 543

Type B ADR features

Answer 543

* Not related to pharmacology of drug * Not dose related * Can cause serious illness or mortality * Symptoms do not always resolve upon stopping drug

Question 544

Give an example of a Type B ADR.

Answer 544

* Anaphylaxis with penicillins * Tendon rupture with quinolone antibiotics * Steven Johnson Syndrome with IV vancomycin

Question 545

Type C ADR features

Answer 545

ADRs that continue after the drug has been stopped

Question 546

Give an example of a Type C ADR

Answer 546

* Osteonecrosis of the jaw with bisphosphonates * Heart failure with pioglitazone

Question 547

Type D ADR features

Answer 547

ADRs that become apparent some time after stopping the drug.

Question 548

Give an example of a Type D ADR

Answer 548

Leucopenia with chemotherapy

Question 549

Type E ADR features

Answer 549

ADR develops after the drug has been stopped.

Question 550

Give an example of a Type E ADR

Answer 550

* Insomnia after stopping benzodiazepine * Rebound tachycardia after stopping beta-blocker * Nasal congestion after stopping xylometolazine nasal spray

Question 551

Type F ADR features

Answer 551

* Unexpected treatment failure * Could be due to drug-drug interaction or drug-food interaction * Poor compliance with administration instructions

Question 552

Give an example of a Type F ADR

Answer 552

* Failure of oral contraceptive pill due to St John’s Wort * Failure of DOAC due to enzyme inducer (eg carbamazepine) * Failure of bisphosphonate due to taking with food

Question 553

What is the DoTS method of classifying ADR

Answer 553

Do = Dose-relatedness T = Timing: ADRs which can develop during any time during treatment (often due to clinical changes in the patient). S = Susceptibility More complex than ABCDE, but provides more detail. Useful for those working in pharmacovigilance, undertaking research or developing medicines

Question 554

DoTS: What are the three ADRs that could occur at different stages of doses.

Answer 554

Hypersusceptibility: ADRs at subtherapeutic doses (eg anaphylaxis with penicillins) Collateral effects (side effects): ADRs at therapeutic doses (eg hypokalaemia with loop diuretic) Toxic effects: ADRs at subpratherapeutic doses (eg liver damage with paracetamol)

Question 555

DoTS: Certain patient groups/populations may have a specific susceptibility to ADRs from a drug. Give factors which may make people more susceptible.

Answer 555

Age (anticholinergics in elderly patients) Gender (metoclopramide in females) Disease states (eg diclofenac in CVD) Physiological states (eg phenytoin in pregnancy)

Question 556

What systems are in place to allow identification of ADRs?

Answer 556

Pre-clinical testing (computer models, cells and toxicity testing in animals) Clinical trial data (pre-marketing evaluation) Post marketing surveillance Pharmacovigilance

Question 557

ADRs can be reported to the MHRA using the Yellow Card system. Which of the following ADRs is an augmented type ADR? * Treatment failure of warfarin due to dietary consumption of vitamin K * Neurodevelopmental disorder in child of patient taking sodium valproate * Constipation in patient taking morphine sulphate * Rebound tachycardia in patient after stopping atenolol * Angioedema in patient taking amoxicillin

Answer 557

* Constipation in patient taking morphine sulphate

Question 558

Outline the steps taken if it is suspected that a patient has an ADR to a certain drug?

Answer 558

1. Assess if ADR requires treatment (reversal, symptom management) 2. Take a history 3. Review medication history 4. Review ADR profile of suspected drug (BNF, SPC) 5. Modify dose, stop or swap 6. Document allergy/ADR in patient record (including nature of reaction) 7. If criteria met…report

Question 559

What are the different types of hypersensitivities mediated by?

Answer 559

Type 1 – IgE mediated drug hypersensitivity Type 2 – IgG mediated cytotoxicity Type 3 – Immune complex deposition Type 4 – T cell mediated

Question 560

Features of Type 2 hypersensitivity

Answer 560

Type 2 reactions – Antibody-antigen complex formation - Antibody-antigen complex formation Drug or metabolite combines with a protein Body treats it as foreign protein and forms antibodies (IgG, IgM) Antibodies combine with the antigen and complement activation damages the cells e.g. methyl-dopa-induced haemolytic anaemia, pemphigus

Question 561

Features of Type 3 hypersensitivity

Answer 561

Type 3 reactions – Antibody-antigen complex deposition Antigen and antibody form large complexes and activate complement Small blood vessels are damaged or blocked Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process Includes glomerulonephritis, vasculitis,

Question 562

Features of Type 4 hypersensitivity

Answer 562

Type 4 reaction – Lymphocyte mediated Antigen specific receptors develop on T-lymphocytes Subsequent admin, adminstration leads to local or tissue allergic reaction E.g. contact dermatitis E.g. Stevens Johnson syndrome (TEN)

Question 563

Main features of anaphylaxis

Answer 563

Exposure to drug, immediate rapid onset Rash (absent in 10-20%) Swelling of lips, face, oedema, central cyanosis Wheeze / SOB Hypotension (Anaphylactic shock) Cardiac Arrest

Question 564

Features of non immune anaphylaxis

Answer 564

Due to direct mast cell degranulation. Some drugs recognised to cause this No prior exposure Clinically identical

Question 565

Management of anaphylaxis

Answer 565

1. Commence basic life support. ABC (airway, breathing, circulation) 2. Remove the trigger if possible - Stop the drug if infusion 3. Adrenaline IM 500 micrograms (300mcg epi-pen) 4. High flow oxygen 5. IV fluids – aggressive fluid resuscitation If anaphylactic shock may need IV adrenaline with close monitoring Antihistamines not first line treatment but can be used for skin symptoms Corticosteroids no longer recommended

Question 566

How does adrenaline work?

Answer 566

Adrenaline acts on alpha 1, alpha 2, beta 1 and beta 2 receptors. Vasoconstriction - increase in peripheral vascular resistance, increased BP and coronary perfusion via alpha1-adrenoceptors Stimulation of Beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart Reduces oedema and bronchodilates via beta2-adrenoceptors Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators

Question 567

Risk factors for hypersensitivity

Answer 567

Medicine factors: Protein or polysaccharide based macro molecules Host factors: Females > Males – we don’t know why EBV, HIV Prev drug reactions Uncontrolled asthma Genetic factors: Certain HLA groups Acetylator status

Question 568

For a patient to have allergy for a drug, what criteria do they have to fulfil?

Answer 568

Does not correlate with pharmacological properties of the drug No linear relation with dose (tiny dose can cause severe effects) Reaction similar to those produced by other allergens Induction period of primary exposure Disappearance on cessation Re-appears on re-exposure Occurs in a minority of patients on the drug

Question 569

Define refractory anaphylaxis.

Answer 569

No improvement in respiratory or cardiovascular symptoms despite 2 appropriate doses of intramuscular adrenaline.

Question 570

Define commensal.

Answer 570

Organism which colonises the host but causes no disease in normal circumstances

Question 571

Morphological term for round shaped bacteria?

Answer 571

Cocci

Question 572

Morphological term for rod shaped bacteria?

Answer 572

Bacilli

Question 573

Features of typical bacteria structure

Answer 573

- Cell wall - Chromosome of circular double stranded DNA - Outer membrane - Inner membrane - Pili - Capsule

Question 574

What are Gram positive bacteria bacterial cell envelope's made up of?

Answer 574

Capsule Peptidoglycan Lipoteichoic acid Cytoplasmic membrane

Question 575

How do Gram negative bacteria's cell envelope differ from Gram positive?

Answer 575

Gram negative bacteria have a Lipopolysaccharide (ENDOTOXIN) cell wall, an outer membrane, lipoprotein, periplasmic space, and an inner membrane

Question 576

What colour does Gram positive bacteria stain?

Answer 576

Violet

Question 577

What colour does Gram negative bacteria stain?

Answer 577

Red

Question 578

Under what environments can bacteria survive in?

Answer 578

1. Temperature <-800C to + 80C (1200C for spores) 2. pH <4-9 3. Water/dessication 2 hours – 3 months (>50 years for spores) 4. Light UV

Question 579

What are the four phases used to describe bacterial growth?

Answer 579

- LAG phase - Exponential LOG phase - Stationary phase - Death phase

Question 580

What are the two bacterial toxins that bacteria can produce?

Answer 580

ENDOTOXIN Component of the outer membrane of bacteria, eg lipopolysaccharide in Gram negative bacteria EXOTOXIN Secreted proteins of Gram positive and Gram negative bacteria

Question 581

Differences between endotoxins and exotoxins.

Answer 581

Exotoxin: * Composed of proteins * Action is specific * Heat labile * Strong antigenicity * Produced by both Gram +ve and -ve * Can convert to toxoids Endotoxins: * Composed of lipopolysaccharide * Action is non specific * Heat stable * Weak antigenicity * LPS Gram -ve * Cannot convert to toxoids

Question 582

What can lead to genetic variation in bacteria (antibiotic resistance)?

Answer 582

Mutations: - deletion - insertion - base substitution Gene transfer: - Transformation eg via plasmid - Transduction eg via phage - Conjugation eg via sex pilus

Question 583

What is meant by obligate intracellular bacteria?

Answer 583

Bacteria that cannot be cultured in media, requires a host cell to replicate.

Question 584

Give examples of obligate intracellular bacteria.

Answer 584

- Chlamydia - Coxiella - Rickettsia

Question 585

Give an example of a slow growing bacteria.

Answer 585

TB

Question 586

Give an example of a fast growing bacteria.

Answer 586

E.coli and S.aureus.

Question 587

Give 2 functions of pili.

Answer 587

1. Help adhere to cell surfaces 2. Plasmid exchange.

Question 588

Give an example of a gram negative aerobic diplococci?

Answer 588

Neisseria e.g. N.meningitidis and N.gonorrhoeae.

Question 589

Give two examples of gram positive cocci?

Answer 589

Staphylococcus and streptococcus.

Question 590

What type of organism would you stain with Ziehl Neelsen?

Answer 590

Mycobacteria e.g. TB.

Question 591

What test can be done to distinguish between staphylococcus and streptococcus?

Answer 591

The catalase test; detects the presence of catalase enzyme using hydrogen peroxide. Staph = catalase + ve. Strep = catalase - ve.

Question 592

How would you describe the arrangement of staphylococci?

Answer 592

Clusters of cocci.

Question 593

How would you describe the arrangement of streptococci?

Answer 593

Chains of cocci.

Question 594

Pain in shoulder, elevated temperature MRI scan, disc infection and osteomyelitis C6 &C7, Blood cultures grow Gram positive cocci in clusters. What is the likely bacterial infection? How is it treated?

Answer 594

Staphylococcus aureus; flucloxacillin 3 months

Question 595

What test could be done to further distinguish between staphylococci bacteria.

Answer 595

Coagulase test; looks at whether a fibrin clot is produced. Staphylococci aureus = coagulase +ve All other staph bacteria = coagulase -ve

Question 596

What is the normal habitat of Staphylococci?

Answer 596

Nose and skin

Question 597

How is Staph. aureus spread?

Answer 597

Spread by aerosol and touch - carriers and shedders

Question 598

Virulence of factors of Staph. aureus

Answer 598

Pore-forming toxins (some strains) a - haemolysin & Panton-Valentine Leucocidin Proteases Exfoliatin Toxic Shock Syndrome toxin (stimulates cytokine release) Protein A (surface protein which binds Ig’s in wrong orientation)

Question 599

S.epidermidis is coagulase -ve. How may they cause infections?

Answer 599

They are opportunistic Infections in debilitated, prostheses (opportunistic) Main virulence factor - ability to form persistent biofilms

Question 600

How might S.saprophyticus cause infections?

Answer 600

Acute cystitis haemagglutinin for adhesion urease

Question 601

Wound received to shoulder 3 days later spreading inflammation Fever, malaise Swab culture showed Gram positive cocci in chains. What is the bacteria involved likely to be? How could it be treated?

Answer 601

Streptococcus pyogenes Penicillin sensitive

Question 602

What test could be done to distinguish between different streptococci?

Answer 602

Blood agar haemolysis. Beta- complete lysis e.g. S.pyogenes Haemolysins O & S Alpha- partial, greening e.g. S.intermedius non (or Gamma) - no lysis e.g. some S.mutans

Question 603

What further test can be done for those streptococci in the β haemolysis group?

Answer 603

Serogrouping; detecting carbohydrate cell surface antigens. e.g. lancefield grouping.

Question 604

In Lancefield grouping, what are the members of Group A and Group B?

Answer 604

Group A - S.pyogenes; important pathogen Group B - S.agalactiae neonatal infections

Question 605

S.pyogenes virulence factors

Answer 605

Exported factors Enzymes Hyaluronidase - spreading Streptokinase - breaks down clots C5a peptidase - reduces chemotaxis Toxins Streptolysins O&S - binds cholesterol Erythrogenic toxin - SPeA – exaggerated response Surface factors Capsule - hyaluronic acid M protein – surface protein (encourages complement degradation)

Question 606

Infections caused by S.pyogenes

Answer 606

Wound infections >> cellulitis, puerperal fever Tonsillitis & pharyngitis Otitis media Impetigo Scarlet fever Complications rheumatic fever glomerulonephritis

Question 607

Chains of purple cocci are seen on a gram film. They show alpha haemolysis when grown on blood agar. They don’t grow near the optochin disc. What bacteria is likely to have caused this?

Answer 607

Streptococcus pneumonia.

Question 608

How can you differentiate streptococci pneumoniae from other streptococci?

Answer 608

The optochin test can differentiate streptococci pneumoniae from other streptococci. Pneumococci are sensitive and so a clear area would be seen.

Question 609

What illnesses can S.pneumoniae cause?

Answer 609

pneumonia, otitis media, sinusitis, meningitis

Question 610

Predisposing factors for S.pneumoniae infections

Answer 610

impaired mucus trapping (e.g. viral infection) hypogammaglobulinaemia asplenia

Question 611

S.pneumoniae virulence factors

Answer 611

1. Capsule polysaccharide (84 types), antiphagocytic polyvalent vaccine 2. Inflammatory wall constituents teichoic acid (choline) peptidoglycan 3. Cytotoxin pneumolysin

Question 612

What can Viridans group streptococci cause?

Answer 612

Some cause dental caries & abscesses Important in infective endocarditits S. sanguinis, S. oralis Cause deep organ abscesses (e.g. brain, liver)

Question 613

Haemolysis of Viridans group streptococci

Answer 613

alpha- haemolytic (or non-haemolytic)

Question 614

Features of bacillus anthracis

Answer 614

Gram positive bacilli Spore forming - pneumoniae, skin infection

Question 615

Corynebacterium diphtheriae clinical feature?

Answer 615

Thick greyish pseudo membrane on tonsils

Question 616

Virulence factors of Clostridia

Answer 616

Spore forming Survive in environment Produce toxins

Question 617

What does C. tetani cause?

Answer 617

Tetanus

Question 618

What does C. botulinum cause?

Answer 618

Botulism

Question 619

What does C. difficile cause?

Answer 619

antibiotic associated diarrhea pseudomembranous colitis

Question 620

LPS (‘endotoxin’) forms the outer leaflet of the outer membrane of Gram -ves, what is the LPS comprised of?

Answer 620

- Lipid A, the toxic portion of LPS that is anchored in the outer leaflet of the outer membrane. - Core (C) antigen (core oligosaccharide), short chain of sugars, some are unique to LPS. - Somatic (O) antigen (O-polysaccharide), a highly antigenic repeating chain of oligosaccharides.

Question 621

Which three main aerobic Gram negative bacteria rod groups are there?

Answer 621

1. Coliforms 2. Vibrio 3. Pseudomonads

Question 622

Coliform features

Answer 622

Enterobacteriaceae or Enterobacteria Rod-shaped Motile (most) Peritrichous flagella Facultatively anaerobic Colonise the intestinal tract

Question 623

What kind of bacteria is MacConkey agar used with?

Answer 623

Gram negative bacilli.

Question 624

What is MacConkey agar?

Answer 624

MacConkey agar contains bile salts, lactose and pH indicator. If an organism ferments lactose, lactic acid will be produced and the agar will appear a red/pink colour.

Question 625

Name 2 gram negative bacilli that will give a positive result with MacConkey agar.

Answer 625

1. E.Coli. 2. Klebsiella pneumoniae.

Question 626

What category of bacteria does shigella fall under?

Answer 626

Gram negative bacilli.

Question 627

Does shigella give a positive result with MacConkey agar?

Answer 627

No. Shigella does not ferment lactose and so gives a negative result.

Question 628

Does e.coli give a positive result with MacConkey agar?

Answer 628

Yes. E.coli does ferment lactose and so you would see a red/pink colour indicating a positive result.

Question 629

How can you distinguish between gram negative bacilli (salmonella, shigella and e.coli)?

Answer 629

Xylose Lysine Deoxycholate (XLD): - e. coli +ve results turn phenol red in media yellow - shigella cannot ferment lactose remains red - salmonella cannot ferment lactose, but reduce thiosulphate to produce hydrogen sulphide (black)

Question 630

Which type of e.coli would you associate with causing travellers diarrhoea?

Answer 630

Enterotoxigenic e.coli (ETEC).

Question 631

Principal infections caused by pathogenic E. coli

Answer 631

Wound infections (surgical) UTIs Gastroenteritis Travellers’ diarrhoea Bacteraemia Meningitis (infants) – rare in UK

Question 632

Why are there pathogenic strains of e.coli?

Answer 632

Due to the acquisition of genes from other bacteria.

Question 633

What are the symptoms of shigella infection?

Answer 633

Severe bloody diarrhoea (bacillary dysentery) and frequent passage.

Question 634

How is shigella passed on?

Answer 634

Via contaminated food/water or from person to person.

Question 635

What bacteria is responsible for salmonellosis?

Answer 635

S.enterica.

Question 636

Name the 3 forms of salmonellosis.

Answer 636

1. Gastroenteritis.2. Enteric fever.3. Bacteraemia.

Question 637

What causes gastroenteritis?

Answer 637

Frequent cause of food poisoning, 6-36 hour incubation period.

Question 638

What causes enteric fever?

Answer 638

Frequent cause of poor quality drinking water/poor sanitation Systemic disease

Question 639

Describe the pathogenesis of enteric fever.

Answer 639

1. Endocytosis.2. Migration to the basolateral membrane. 3. Survival in macrophage -> systemic spread.

Question 640

What infections are caused by p. auruginosa?

Answer 640

Acute infections (due to multiple toxins): 1. Localised - Burn/surgical wounds - UTI - Keratitis 2. Systemic (bacteraemic -> sepsis) - neutropenic patients (leukaemia, chemotherapy, AIDS) 3. ICU patients (ventilator acquired pneumonia) - leading cause of nosocomial pneumonia Chronic infections: 1. Cystic fibrosis (CF) patients

Question 641

What are the symptoms of v.cholerae?

Answer 641

Most severe diarrhoeal disease. Huge volumes of watery stools (no blood or pus).

Question 642

Why is v.cholerae so dangerous?

Answer 642

Release of cholera toxin causes huge amounts of water loss which can result in hypovolemic shock and severe dehydration, this can lead to death.

Question 643

Why would you need to be infected with a large amount of v.cholerae to show symptoms of the disease?

Answer 643

The optimum pH for v.cholerae growth is 8; alkaline. It is therefore very sensitive to the pH of the stomach.

Question 644

Why bacteria is the most common cause of food poisoning in the US and UK?

Answer 644

Campylobacter - causes mild to severe diarrhoea, often with blood

Question 645

How would you grow haemophilus influenzae?

Answer 645

On chocolate agar as it requires haem and NAD.

Question 646

What diseases can haemophilus influenzae cause?

Answer 646

Mostly opportunistic infections: Meningitis and pneumonia.

Question 647

Virulence determinants of H. influenzae

Answer 647

Capsule, LPS

Question 648

What diseases can Helicobacter pylori cause?

Answer 648

Major role in gastritis and peptic ulcer disease (80-90% of ulcers)

Question 649

What disease can Bordetella pertussis cause?

Answer 649

Pertussis (whooping cough) - Highly contagious Non-specific flu-like symptoms (~7 d), followed by paroxysmal coughing

Question 650

Name the bacteria that can cause legionnaires disease?

Answer 650

Legionella pneumophila

Question 651

Who might be susceptible to infection by legionella?

Answer 651

Immunocompromised individuals.

Question 652

What problems are there with treating the anaerobic bacteroides?

Answer 652

Opportunistic - tissue injury Often present in polymicrobial infections with enterobacteria, thus require specific anti-anaerobe antibiotics

Question 653

What are the main Gram negative cocci groups?

Answer 653

Veillonella Neisseria

Question 654

What are the two medically important species of neisseria?

Answer 654

N.meningitidis and N.gonorrhoeae.

Question 655

Describe the pathogenesis of N.meningitidis.

Answer 655

Crosses nasopharyngeal epithelium and enters blood stream. Can cause asymptomatic bacteraemia or septicaemia. If the bacteria crosses the BBB it can cause meningitis.

Question 656

What are the consequences of N.gonorrhoeae infection?

Answer 656

STI - rectal, vaginal or oral inflammation.

Question 657

What are the three main groups of Gram negative spirochaetes?

Answer 657

Borrelia Treponema Leptospira

Question 658

Describe the flagellum of a spirochaete.

Answer 658

Spirochaete's have an endoflagellum, it propels bacterium in a corkscrew motion

Question 659

Name the spirochaete that is responsible for causing lyme disease.

Answer 659

B.burgdorferi.

Question 660

Name the spirochaete that is responsible for causing syphilis.

Answer 660

T.pallidum.

Question 661

Describe the three stages of syphilis.

Answer 661

1. Primary stage: localised infection. 2. Secondary stage: systemic - skin, lymph nodes etc. 3. Tertiary stage: CV syphilis and neuro syphilis.

Question 662

Can you grow chlamydia on agar?

Answer 662

No, chlamydia is an obligate intracellular parasite.

Question 663

How can you detect chlamydia?

Answer 663

Cannot culture in bacteriological media, thus can only be detected by serum antibodies or PCR.

Question 664

What are the 2 developmental stages of chlamydia's unique growth cycle?

Answer 664

1. Elementary bodies (infective). 2. Reticulate bodies (intracellular multiplication).- Reticulate bodies are converted back into elementary bodies and are released. The cycle continues.

Question 665

Which bacteria is responsible for chlamydia?

Answer 665

c.trachomatis

Question 666

Name 2 bacteria in the chlamydophila genre.

Answer 666

1. C.pneumoniae - respiratory tract infection 2. C.psittaci - associated with birds.

Question 667

Give an example of mycobacteria.

Answer 667

M.tuberculosis (TB). M.leprae (leprosy).

Question 668

Why are Mycobacteria resistant to Gram stain?

Answer 668

High lipid content with mycolic acids in cell wall makes Mycobacteria resistant to Gram stain

Question 669

What staining is used for Mycobacteria?

Answer 669

Ziehl-Neelsen stain

Question 670

Challenges of treating and diagnosing TB?

Answer 670

1. Thick lipid rich cell wall making immune cell killing and penetration of drugs challenging 2. SLOW growth - Gradual onset of disease - Takes much longer to diagnose - Takes longer to treat

Question 671

What is pulmonary tuberculosis?

Answer 671

Granulomas forms around bacilli that have settled in apex

Question 672

How does TB infect us?

Answer 672

- Aerosol transmission - Primary TB in lung - Latent TB can remain for decades Can spread beyond lungs

Question 673

What does our body do to protect us from TB?

Answer 673

- Primarily controlled by macrophages - Requires a CD4 T cell response to be controlled - Involves many cells of immunity- formation of granulomas - Granuloma stability controls reactivation of TB

Question 674

How are Mycobacteria adapted to evade the immune system?

Answer 674

Mycobacteria can withstand phagolysosome killing and escape to the cytosol. Mycobacteria can form granulomas - when they become unstable can result in the break out of systemic disease

Question 675

What is a rapid diagnosis method for detecting M. tb?

Answer 675

Nucleic acid detection

Question 676

How can you use the immune response as a diagnosis test?

Answer 676

Tuberculin skin test (mantoux)

Question 677

Standard treatment for TB?

Answer 677

- Isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), ethambutol (ETA) for two months - Isoniazid and rifampicin for four more months

Question 678

List the resistance mechanisms of TB

Answer 678

Drug inactivation: Mtb produces beta-lactamase Drug titration: Target overproduction Alteration of drug target: Missense mutations Altered cell envelope: Increased permeability and drug efflux

Question 679

XDR-TB: resistant to four commonly used TB drugs. How would you treat these strains?

Answer 679

BPaL regimen for 6 months However this could fail as well

Question 680

Define what a virus is.

Answer 680

An infectious, obligate intracellular parasite Comprising genetic material (DNA or RNA) surrounded by a protein coat and/or a membrane

Question 681

List an example of a non-enveloped virus

Answer 681

Adenovirus Parvovirus

Question 682

List an example of an enveloped virus

Answer 682

HIV Influenza

Question 683

How do viruses replicate?

Answer 683

1. Attachment to specific receptor 2. Cell entry 3. Host cell interaction + replication 4. Assembly of virion 5. Release of new virus particles

Question 684

How do viruses cause disease?

Answer 684

a) Direct destruction of host cells b) Modification of host cell c) “Over-reactivity” of immune system d) Damage through cell proliferation e) Evasion of host

Question 685

Give an example of a virus that causes damage by direct destruction of host cells.

Answer 685

Poliovirus -> host cell lysis and death after a viral replication period of 4 hours

Question 686

Give an example of a virus that causes damage by modification of host cell.

Answer 686

Rotavirus -> atrophies villi and flattens epithelial cells, this leads to decrease of small intestine s.a, nutrients not absorbed, hyperosmotic state, profuse diarrhoea

Question 687

Give an example of a virus that causes damage by 'over-reactivity' of immune system.

Answer 687

Hepatitis B SARS-CoV-2

Question 688

Give an example of a virus that causes damage by cell proliferation.

Answer 688

human papillomavirus -> cervical cancer

Question 689

How can a virus evade of host defences on a cellular level?

Answer 689

Cellular level: - Herpesviridae - latency - Measles, HIV - cell-cell spread

Question 690

How can a virus evade of host defences on a molecular level

Answer 690

Molecular level: - Influenza, HIV, rhinovirus - antigenic variability - Herpesviridae - prevention of host cell apoptosis - Downregulation of interferon and other intracellular host defence proteins - Herpesviridae, measles, HIV - Interference with host cell antigen processing pathways

Question 691

Why do viruses vary wildly in the range of clinical syndromes they can cause?

Answer 691

- Different host cells and tissues that they can infect - Different methods of interaction with the host cell

Question 692

What is meningitis?

Answer 692

Inflammation of the meninges (membranes) which cover the brain and spinal cord

Question 693

Give an example of meningitis caused by bacteria

Answer 693

meningococcus, pneumococcus

Question 694

Given an example of meningitis caused by virus

Answer 694

coxsackievirus, echovirus, herpes virus, mumps virus, influenza, HIV etc

Question 695

List some non infectious causes of meningitis

Answer 695

- Medications such as antibiotics, NSAIDs - Cancers such as melanoma, lung cancer - Autoimmune diseases such as SLE, Behcet's disease

Question 696

What are the two main manifestations of Neisseria meningitidis?

Answer 696

Meningitis: a localised infection of the meninges, with “local” symptoms Septicaemia : a systemic infection with widespread signs, and generalised organ damage

Question 697

What kind of bacteria is Neisseria meningitidis?

Answer 697

Gram negative diplococci

Question 698

Symptoms of meningococcal meningitis

Answer 698

- Fever - Stiff neck - Headache - Confusion - Increased sensitivity to light - Nausea and vomitting

Question 699

What is Brudzinski's neck sign?

Answer 699

When neck flexion causes the individual to flex their hips and knees automatically, typical sign in patients with meningitis

Question 700

Meningococcal septicaemia symptoms

Answer 700

Fever and chills Fatigue Vomiting Cold hands and feet Severe aches or pain in the muscles, joints, chest, or abdomen Rapid breathing Diarrhoea Non blanching rash (petechiae) In the later stages, a dark purple rash (purpura)

Question 701

Meningococcal septicaemia can cause Disseminated Intravascular Coagulation (DIC). What is this?

Answer 701

Activation of coagulation pathways that results in formation of intravascular thrombi (clots) and depletion of platelets and coagulation factors. These clots can cause arterial occlusions leading to gangrene of extremities & auto-amputations (spontaneous detachment of an appendage from the body)

Question 702

What are some long term consequences of Meningococcal meningitis ?

Answer 702

Deafness or partial hearing loss (34%), seizures (13%), motor deficits (12%), cognitive impairment (9%), blindness (6%), Amputations (8% of children, 3% of adults)

Question 703

How would you make a diagnosis for Meningococcal meningitis?

Answer 703

- Blood sample for blood culture & PCR - CSF for microscopy, culture and PCR - Throat swab for culture

Question 704

Features of yeast

Answer 704

Single celled organisms that divide by budding

Question 705

Features of mould

Answer 705

Form multicellular hyphae and spores

Question 706

What are dimorphic fungi?

Answer 706

Fungi which can exist as both yeasts and moulds, switching between the two when conditions suit

Question 707

Why are most fungi unable to cause human infection?

Answer 707

Inability to grow at 37 degrees Innate and adaptive immune response

Question 708

Why are there limited options for antifungal drugs? Which part of the fungi do these drugs target?

Answer 708

Fungi are eukaryotic which limits options for selective toxicity. DNA/RNA synthesis is similar to mammalian. Antifungal drugs usually target - cell wall and ergosterol containing plasma membrane. Some drugs may target protein synthesis.

Question 709

Risk factors for mucosal candidiasis

Answer 709

immunosuppression, diabetes antibacterial therapy and mucosal disruption

Question 710

Treatment of mucosal candidiasis

Answer 710

Treatment with topical or oral azoles

Question 711

How are dermatophyte infections transmitted?

Answer 711

Human-human or animal-human transmission

Question 712

How would you treat dermatophyte infections?

Answer 712

Treatment is usually with topical or oral azoles or terbinafine

Question 713

Give an example of a dermatophyte

Answer 713

Trichophyton spp., Microsporum spp. Epidermophyton floccosum

Question 714

Which fungi can cause severe infections in healthy hosts in endemic areas?

Answer 714

Dimorphic fungi. These are fungi that can exist as both yeast and mould; they are yeast in tissues but mould in vitro

Question 715

Give an example of a dimorphic fungi

Answer 715

Coccidioides immitis

Question 716

Late manifestations of Coccidioides

Answer 716

1. Cavitatory lung disease may result in pleuritic pain or cough or become colonised by Aspergillus 2. Orthopaedic Asymetrical chronic arthritis with effusion or vertebral osteomyelitis 3. Cutaneous ulcers and abscesses 4. Cervical lymphadenopathy 5. Intracranial – chronic meningitis- BAD

Question 717

What usually causes invasive candidiasis?

Answer 717

infection of prosthetic devices or intra-abdominal disease

Question 718

What does Cryptococcus cause?

Answer 718

Cryptococcus causes acute or chronic meningitis in patients with reduced cell mediated immunity

Question 719

How would you investigate for Cryptococcus?

Answer 719

CSF microscopy with India ink

Question 720

Who would typically develop invasive aspergillosis?

Answer 720

Invasive aspergillosis is normally associated with profound immunocompromise but is increasingly recognised in patients with severe viral infection

Question 721

How would you treat invasive aspergillosis?

Answer 721

Voriconazole

Question 722

What are Mucoraceous moulds (zygomyctes) ?

Answer 722

Mucoraceous moulds (zygomyctes) are rare but cause devastatingly rapidly progressive infections that cross tissue planes. Mucoraceous moulds need aggressive antifungal therapy and surgery for optimal outcomes

Question 723

What does pneumocystis jirovecii cause?

Answer 723

Pneumocystis jirovecii causes a pneumonitis with severe hypoxia in the immunocompromised

Question 724

What are protozoa?

Answer 724

Single celled eukaryotic organisms

Question 725

What is African Trypanosomiasis? What is it caused by?

Answer 725

"sleeping sickness" Caused by Trypanosoma brucei gambiense and rhodesiense - spread by Tsetse fly bite - Chancre - Flu like symptoms - CNS involvement - (sleepy, confusion, personality change) - Coma and death

Question 726

What is American Trypanosomiasis? What is it caused by?

Answer 726

“Chagas Disease” Caused by Trypanosoma cruzi - spread by Triatomine bug Acute: - Flu like symptoms Chronic: - Cardiomyopathy - Megaoesophagus - Megacolon

Question 727

What is Leishmaniasis? What is it caused by?

Answer 727

Caused by Leishmania spp Spread by the bite of the sandfly >20 species that affect humans - Cutaneous & Mucocutaneous * ulceration and destruction - Visceral * Fever * Weight loss * Massive splenomegaly * Hepatomegaly * Anaemia * High fatality without treatment

Question 728

How is Trichomonas vaginalis transmitted?

Answer 728

Sexually transmitted - Most common non-viral STI

Question 729

How is Trichomonas vaginalis treated?

Answer 729

Treated with Metronidazole

Question 730

How is Giardiasis spread? What does it cause?

Answer 730

Faeco-oral spread - Diarrhoea

Question 731

How is Giardiasis treated?

Answer 731

Treated with Metronidazole

Question 732

What is Amoebiasis caused by?

Answer 732

Entaemoeba histolytica Faeco-oral spread

Question 733

How is Amoebiasis treated?

Answer 733

Metronidazole

Question 734

What is Cryptosporidiosis caused by? How is it spread?

Answer 734

Cryptosporidium spp Waterborne

Question 735

What is Toxoplasmosis caused by? How is it spread?

Answer 735

Toxoplasma gondii Ingestion of contaminated food and water/feline faeces

Question 736

What are the 5 classifications of amoeba?

Answer 736

1. Flagellate i.e Trypanosoma, Leishmania, Giardia 2. Amoeba i.e Entaemoeba histolytica 3. Sporozoa i.e Cryptosporidium, Toxoplasma gondii, Plasmodium 4. Microsporidia 5. Cilliates i.e Balantidium coli

Question 737

How is malaria transmitted?

Answer 737

Transmitted by bite of female anopheles mosquito. 5 species: Plasmodium falciparum Plasmodium ovale Plasmodium vivax Plasmodium malariae Plasmodium knowlesi

Question 738

What test to diagnose malaria?

Answer 738

Blood film test Malaria parasites can be identified by examining under the microscope. Thin (tells you species and parasite count) and thick (low resolution, tells you if you have malaria) blood films.

Question 739

Symptoms of malaria?

Answer 739

Chills Headache Myalgia Fatigue Diarrhoea Vomiting Abdo pain FEVER

Question 740

What are the 4 signs of malaria?

Answer 740

- Anaemia - Jaundice - Hepatosplenomegaly - 'Black water fever'

Question 741

What does Plasmodium falciparum cause that results in 'complicated malaria'?

Answer 741

OBSTRUCTED MICROCIRCULATION - Caused by infected RBCs ability to adhere to endothelial cells

Question 742

What are features of Complicated Malaria?

Answer 742

- Cerebral malaria - ARDS/Pulmonary oedema - Renal failure - Sepsis - Bleeding/Anaemia

Question 743

Treatment for complicated malaria?

Answer 743

- IV artesunate (IV quinine + doxycycline)

Question 744

Treatments for uncomplicated malaria?

Answer 744

Chloroquine.

Question 745

What 2 species of the plasmodia genus lie dormant, form hypnozoites in the liver and cause late relapse of malaria? How is it treated?

Answer 745

P.ovale and p.vivax. Primiquine to eliminate

Question 746

What is Aciclovir used for?

Answer 746

Anti-herpesvirus drug Typically used to treat or prevent HSV1 HSV2 VZV infection.

Question 747

What is Aciclovir's mechanism of action?

Question 748

What is are antibiotics?

Answer 748

Antibiotics are molecules that work by binding a target site on bacteria

Question 749

How do antibiotics work?

Question 750

Beta lactam antibiotics...

Answer 750

don't work as well on Gram negative bacteria and aren't useful for eukaryotic cells.

Question 751

Metronidazole and ciprofloxacin

Answer 751

Inhibit bacteria's nucleic acid synthesis

Question 752

What are we trying to achieve with antibiotics?

Answer 752

Antibiotics give time and support for the immune system to deal with an infection.

Question 753

How are bacteria pathogenic?

Answer 753

1. Attach and enter 2. Local spread 3. Multiply 4. Evade host defences 5. Shed from body

Question 754

Consequences of bacteria being pathogenic on the human body

Answer 754

1. Direct: destroy phagocytes or cells in which bacteria replicate. 2. Indirect: Inflammation - e.g. nectroic cells, immune pathology - e.g. antibody. 3. Exotoxin - protein production. Endotoxin - Gram negative 4. Diarrhoea

Question 755

Bactericidal antibiotics

Answer 755

- The agent kills the bacteria. - Kills more than 99.9% in 18-24 hrs - Antibiotics that inhibit cell wall synthesis - Useful in endocarditis. - Difficult to treat meningitis.

Question 756

Bacteriostatic antibiotics

Answer 756

- Prevents the growth of bacteria. - Kills more than 90% in 18-24 hrs - Antibiotics that inhibit protein synthesis, DNA replication or metabolism. - Reduce toxin production (i.e. endotoxin)

Question 757

What is mininum inhibitory concentration (MIC)?

Answer 757

Minimum Inhibitory Concentration (MIC) is the lowest concentration (expressed as mg/L or μg/μL) of an antimicrobial agent that inhibits the visible in-vitro growth of microorganisms. The MIC test determines the antimicrobial activity of a test agent against a specific bacteria.

Question 758

What determines the efficacy of an antibiotic?

Answer 758

Drug must occupy an adequate number of binding sites, which is related to its conc within the microorganism. Antibiotic should be able to remain at the binding site for sufficient period of time.

Question 759

The two major determinants of anti bacterial effects are...

Answer 759

the conc and time the antibiotic remains on these binding sites.

Question 760

Time dependent killing antibiotics

Answer 760

Key parameter is the time that serum conc remain above the MIC during the dosing interval. E.g. beta lactams (penicillins, cephalosporins, carbapenems, monobactams), clindamycin, macrolides, oxazolidinones

Question 761

Concentration dependent killing antibiotics

Answer 761

Key parameter is how high the conc is above MIC. E.g. aminoglycosides, quinolones

Question 762

The antibiotic reaching and staying on the site of bacterial infection depends on...

Answer 762

pharmacokinetics.

Question 763

What is the appropriate or available route of administration of antibiotics?

Question 764

How do antibiotics not work?

Answer 764

1. Bacteria can change the molecular configuration of antibiotic binding site or masks it e.g. flucloxacillin and rifampicin 2. The antibiotic is destroyed or inactivated e.g. Penicillins and cephalosproins hydrolysed by bacterial enzyme "Beta lactamase" 3. Prevent antibiotic stress 4. Remove antibiotic from bacteria

Question 765

Intrinsic resistance of bacteria against antibiotics?

Question 766

Acquired resistance of bacteria against antibiotics?

Question 767

Carbapenems

Question 768

What is the duration of a normal course of antibiotics?

Answer 768

5-7 days

Question 769

Is an antibiotic safe to prescribe? What do we need to consider?

Answer 769

- What pathogen/bacteria are we treating? - Bioavailability of the drug - How are we administering the drug? - Age of the patient - Side effects - Intolerance, allergy, anaphylaxis - Renal and liver function - Pregnancy and breastfeeding - Risk of C.difficile - Drug interactions

Question 770

Beta lactams are

Answer 770

cell wall/peptidoglycan weapons

Question 771

Beta lactams inhibitors

Answer 771

Amoxicillin-clavulanate Piperacillin-tazobactem

Question 772

What antibiotics work on Gram positive bacteria?

Answer 772

Thick cell wall therefore need beta lactams (simple cell wall weapon).

Question 773

What does MRSA stand for?

Answer 773

Methicillin-resistant Staph. aureus

Question 774

Vancomycin

Answer 774

Does not cross BBB or the eyes so not useful for infections there.

Question 775

Glycopeptides are cell wall weapons

Answer 775

Vancomyosin and Teicoplanin - IV

Question 776

What antibiotics work for Gram negative bacteria?

Answer 776

- Can use beta-lactams but aren't as useful. - Cefuroxime - IV. Do not cover anaerobic bacteria. - Co-amoxiclav (Augmentin) oral and IV. - Piperacillin/tazobactem - Meropenem - IV restricted at STH

Question 777

Case 1: 23-year old woman attends with dysuria, frequency and cloudy urine for 36 hours

Answer 777

**Likely diagnosis** Urinary tract infection (lower) Bacteria: gram negatives (E. coli, proteus, klebsiella) And gram positives (staph saprophyticus) **Samples** Consider urine culture if ? Resistance ✓ Children, pregnancy, men, > 65s, sepsis/pyelonephritis, catheter **Management** Self care + back-up antibiotics Immediate antibiotic treatment Nitrofurantoin for 3 days

Question 778

Case 2: 66 year old woman 3 day history of fevers and nausea Leg = hot, red, swollen

Answer 778

**Likely diagnosis** Cellulitis usually lower limbs - unilateral Red, hot, painful, tender skin Spreading Systemic symptoms Bacteria: S. aureus and β haemolytic strep (Group A, C & G) ** Samples** Bacterial swab for culture Blood cultures ** Management** Antibiotics PO or IV flucloxacillin Penicillin allergy: clarithromycin or clindamycin Duration ~ 7 days

Question 779

Why is infection prevention and control important?

Answer 779

300,000 healthcare associated infections (HCAI) in England per year Estimated 9% of in-patients have a HCAI Cost approx. £1 billion per year Cause or contribute to estimated 20,000 deaths Estimated 75% of healthcare workers infected at work

Question 780

Which pathogens do we consider when it comes to infection prevention and control?

Answer 780

**Bacteria** Methicillin resistant S.aureus Clostridium difficile Multi-drug resistant gram negatives Glycopeptide resistant enterococci Group A streptococcus Mycobacterium tuberculosis **Viruses** Influenza Norovirus SARS-CoV-2 HIV Hep B Hep C Varicella Zoster Virus Viral haemorrhagic fevers **Other** Candida Auris Creutzfeldt–Jakob disease

Question 781

Infection vs colonisation

Answer 781

Infect: verb affect (a person, organism, etc.) with a disease-causing organism We are more bacterial cells than human cells – COLONISATION

Question 782

How do we prevent and control infections?

Answer 782

Ensure policies are kept. Identification of risks: - Routes and modes of transmission - Virulence of organisms - ease of spread, likelihood of causing infection, consequences of infection if it occurs - Some diseases have higher R rate i.e. Measles has R rate of 20 which means it can spread to 20 other people. Minimise risks

Question 783

How do you identify a risk of an infection?

Answer 783

Risk factors e.g. recent return from Sierra Leone with fever Screening e.g. MRSA admission screening Clinical diagnosis e.g. cough and cavity on chest x-ray Lab diagnosis Carbapenemase Producing Enterobacteriaceae in urine

Question 784

Routes of transmission

Answer 784

1. Patient A > environment > Patient B 2. Patient A > staff > Patient B

Question 785

What are CPEs?

Answer 785

Carbapenemase-producing Enterobacteriaceae

Question 786

What do CPEs include?

Answer 786

Include E. coli, Klebsiella, Proteus, Serratia, Enterobacter

Question 787

Where do CPEs colonise?

Answer 787

Colonisers of large bowel, skin below waist and moist sites Most common causes of UTI, intra-abdominal infection

Question 788

What is carbapenemase?

Answer 788

Enzyme which inactivates carbapenem antibiotics

Question 789

MRSA

Answer 789

Methicillin resistant Staph aureus Staph aureus is a common skin and nasal commensal Most strains are susceptible to flucloxacillin and other beta-lactem antibiotics. MRSA was first described in 1971 Huge increase in numbers of cases in 1990s and 2000s

Question 790

Norovirus

Answer 790

High attack rates amongst close contacts Low infecting dose Uncontained vomiting and diarrhoea Short lived immunity only Staff and patients at risk Able to persist in the environment Relatively resistant to conventional cleaning

Question 791

Clostridium difficile

Answer 791

Produce bacterial spores, leads to prolonged hospital stays, toxic megacolon. Water is the only thing that removes the spores. Need to wash hands with soap and water. The antibiotics use to treat it begin with "C"

Question 792

What are endogenous infections?

Answer 792

Infections caused by patients own bacterial flora Important in hospitalised patients, especially those with invasive devices or surgical patients

Question 793

How can you prevent endogenous infections?

Answer 793

Good nutrition and hydration Antisepsis/skin prep where indicated Good theatre practice Remove lines and catheters as soon as clinically possible Change from IV to oral treatment whenever appropriate

Question 794

What are some simple things that you can do to protect patients from infections?

Answer 794

Hand Hygiene is the single most effective method of preventing cross infection (Can be hand washing and/or alcohol gel) Personal protective equipment e.g. gloves, aprons, masks etc. Disposal of sharps

Question 795

What are the two blood tests used to monitor HIV infection?

Answer 795

1. CD4 count - measure of immune function 2. HIV viral load test

Question 796

What is the UNAIDS goal by 2020?

Answer 796

90/90/90 *90% diagnosed. *90% on anti-retroviral treatment. *90% viral suppression, undetectable viral load.

Question 797

What is the Fast-Track Cities initiative goal by 2030?

Answer 797

*95/95/95 *95% diagnosed, 95% on treatment, 95% virally suppressed. *200,000 new infections per year *zero discrimination

Question 798

Did the UK achieve the 90/90/90 target?

Answer 798

YES! :D achieved by 2018

Question 799

HIV transmission routes

Answer 799

*Sexual *Vertical

Question 800

Prevention of HIV?

Answer 800

*Condoms *Post exposure prophylaxis (PEP) (72 hrs) *Oral pre-exposure prophylaxis (PrEP) *Male circumcision *Testing STIs *Treatment as prevention (TasP)

Question 801

What are the steps that should be taken following HIV diagnosis?

Answer 801

- Discuss soon after diagnosis - length of 'look back' depends on individual circumstances - Document discussion of safer sex practices, PEPSE, PreP for their partner

Question 802

What is U=U?

Answer 802

Undetectable = untransmittable

Question 803

Why is HIV testing important?

Answer 803

- Access to appropriate treatment and care - Reduction in morbidity an mortality - Reduction of vertical transmission - Reduction of sexual transmission - Public health/partner notification - Cost-effective

Question 804

What scenarios would you test for HIV?

Answer 804

*Clinician initiated testing triggered by clinical indicators of immuno-suppression disease/seroconversion *Routine screening in high prevalence locations *Routine screening Antenatal screening *Screening in high risk groups *Patient initiated requests for testing

Question 805

Why do doctors not test for HIV?

Answer 805

*They don't think of HIV *Underestimate the risk of HIV in their patients *Failure to recognise HIV as a modifiable prognostic indicator *Misconception they need pre-test counselling *Misunderstanding of the implications for insurance, etc *Fear of offending the patient

Question 806

What is the most common opportunistic infection seen in HIV patients?

Answer 806

Pneumocystis pneumonia (PCP) Caused by the Pneumocystis jirovecii fungal infection Symptoms: fevers, SOB, dry cough, pleuritic chest pain, exertional drop in oxygen saturations

Question 807

Common medical conditions where you should consider the possibility of HIV.

Answer 807

- Flu-like illness, rash - Blood dyscrasias eg low platelets - Multi-dermatomal shingles - Lymphadenopathy - Weight loss or diarrhoea, night sweats, PUO

Question 808

What method of HIV screening test is preferred?

Answer 808

*Venous blood sample is preferred. *4th generation HIV tests include p24 antigen and will detect the vast majority of infections at 4 weeks (if negative, repeat at 7 weeks if high index of suspicion) *High sensitivity and selectivity

Question 809

HIV is a retrovirus what does this mean?

Answer 809

It is an RNA virus which uses reverse transcriptase (RT) to make a DNA copy that becomes integrated into the DNA of the infected cell.

Question 810

Where did HIV come from?

Answer 810

HIV-1 is similar to SIV in chimps from central Africa, and probably arose there HIV-2 closely resembles SIV isolated from West African sooty mangabey monkeys

Question 811

Why is it hard to create a vaccine for HIV?

Answer 811

HIV-1 mutates rapidly, as it is error-prone and replicates rapidly. The tried and tested vaccine strategies that we have used for other organisms (live attenuated or killed vaccines) are deemed too risky for HIV

Question 812

HIV genome structure

Answer 812

Small RNA virus ~10KB Retrovirus family Lentivirus: long incubation period

Question 813

Briefly describe the mechanism of HIV replication.

Answer 813

1. GP160 binds to CD4 receptors. 2. Viral caspid, enzymes and nucleic acids are uncoated and released into the cell. 3. RNA is converted into DNA using reverse transcriptase. 4. Viral DNA is integrated into cellular DNA by intergrase. 5. Viral DNA is transcribed into viral proteins. 6. Splicing. 7. New HIV cells 'bud' from CD4.

Question 814

What is the CD4+ count when someone is diagnosed with having AIDS?

Answer 814

CD4+ <200.

Question 815

Where in the cell can HIV drugs target?

Answer 815

1. Reverse transcriptase inhibitors. 2. Protease inhibitors. 3. Fusion/entry inhibitors. 4. Integrase inhibitors.

Question 816

How are some people resistant to HIV-1 infection?

Answer 816

Homozygous 32bp deletion in the CCR5 gene.

Question 817

What are the 4 main phases in the natural history of untreated HIV?

Answer 817

1. Acute primary infection. 6-12 weeks 2. Asymptomatic phase. 1-15+ years 3. Early symptomatic HIV. 4. AIDS.

Question 818

Why does the immune response to HIV-1 fail to clear the virus?

Answer 818

*CD4 T helper cells are lost from early in infection as these are the cells HIV infects first. *Cytotoxic CD8 cell response fails when "immune exhaustion" sets in. *Antibodies fail to bind to virus due to heavily glycosylated envelope spike. *Virus can change quickly and evade antibody recognition

Question 819

Which regions are seeing the most rapid rise in new HIV infections?

Answer 819

Eastern European and central Asia

Question 820

List 3 social-economic impact of HIV/AIDS in Africa?

Answer 820

*Significant impact on life expectancy *Loss of economically-productive adults (including health-care workers) *Increased spending on healthcare (particularly as ART drug use becomes more widespread) *Distortion of health-care spending *Change in social structure: orphans cared for by elderly grandparents *Stigma of HIV infection persists

Question 821

Who is most at risk of acquiring HIV?

Answer 821

In the modern world HIV incidence among adolescent girls and young women (aged 15-24) are the highest.

Question 822

What are the three methods of paediatric HIV-1 transmission?

Answer 822

*In utero - transplacental, mostly during third trimester *Intra partum - exposure to maternal blood and genital secretions during delivery *Breast milk - ingestion of large amounts of contaminated milk

Question 823

How does male circumcision work to prevent HIV infection?

Answer 823

By removing foreskin, circumcision reduces the ability of HIV to penetrate due to keratinization of the inner aspect of the remaining foreskin.

Question 824

What signs and symptoms might you see when someone is in the acute primary infection phase of HIV?

Answer 824

Symptoms usually start within 2-4 weeks of infection *Similar to glandular fever/flu *Abrupt onset of non-specific symptoms e.g. fever, rash, sore throat, Weight loss, myalgia, V+D, headache, lymphadenopathy

Question 825

What signs and symptoms might you see when someone is in the clinical latent phase of HIV?

Answer 825

No symptoms May notice some enlarged lymph nodes *persistent generalised lymphadenopathy

Question 826

What signs and symptoms might you see when someone is in the early symptomatic phase of HIV?

Answer 826

Unexpected medical conditions that are recurring with no clear underlying cause.

Question 827

What is the usual treatment for PCP?

Answer 827

High dose co-trimoxazole.

Question 828

What does it mean when a patient has HIV and TB?

Answer 828

Regardless of CD4 count they would be considered to have AIDS.

Question 829

Name 3 CNS diseases associated with HIV.

Answer 829

1. Mass lesions e.g. primary CNS lymphoma, cerebral toxoplasmosis. 2. Meningitis e.g. pneumococcal, cryptococcal. 3. Opthalmic lesions e.g. CMV, toxoplasmosis, choroidal tuberculosis etc.

Question 830

What cancers does HIV increase the risk of?

Answer 830

HIV increases the risk of any cancer that is associated with a virus Human Herpesvirus 8 -> Kaposi’s sarcoma Epstein Barr Virus -> Lymphomas Human Papillomavirus -> Cervical, anal, penile carcinoma Hepatitis B/C -> Hepatocellulcar carcinoma

Question 831

What symptoms are there in someone with Kaposi's sarcoma?

Answer 831

Single or multiple lesions, usually on the skin

Question 832

What is HAART?

Answer 832

Highly active anti-retroviral therapy where 3 drugs that act on different points in the replication cycle are taken together.

Question 833

What happens when a patient starts HAART?

Answer 833

*Viral load decreases rapidly. *CD4 count begins to increase.

Question 834

What factors increase the chances of HIV developing drug resistance?

Answer 834

1. Non adherence 2. Drug-drug interactions