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Sharon's Phase 2a Medicine Revision > Introduction to Clinical Sciences (ICS) > Flashcards

Introduction to Clinical Sciences (ICS) Flashcards

1
Q

Define acute inflammation

A

The initial and often transient series of tissue reactions to injury - can last few hours to few days

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2
Q

What are the 5 cardinal signs of inflammation?

A

Calor - heat
Dolor - pain
Rubor - redness
Tumour - swelling
Loss of function

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3
Q

Describe the steps involved in acute inflammatory response

A
  1. Injury to vessel endothelial cells
  2. Macrophages release prostaglandins, mast cells release histamine
  3. Histamine causes Increases in vessel calibre (gets wider) = increased vessel flow (redness and heat)
  4. Chemical mediators and histamine increased vascular permeability + formation of fluid exudate (plasma and plasma proteins) - causing swelling of tissue
  5. Swelling, prostaglandin and bradykinin (plasma protein) stimulates nerves to send pain signals to brain - pain + loss of function
  6. Formation of cellular exudate - emigration of neutrophil polymorphs (polymorphonuclear leukocytes) via chemotaxis (e.g. chemokine like IL-8 released. by macrophages recruit neutrophils) into the extravascular space and tissues
  7. Neutrophils phagocytose bacteria at the site of injury/infection (6- 24 hrs)
  8. Neutrophils also release cytokines such as interleukin-1 and tumour necrosis factor-alpha (TNFa) which cause systemic symptoms like fever
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4
Q

What type of immune cells are involved in acute inflammation?

A

Neutrophils

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5
Q

What type of immune cells are involved in chronic inflammation?

A

Macrophages and lymphocytes (T- and B- lymphocytes)

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6
Q

Describe the action of neutrophils in acute inflammation

A
  1. Migration - neutrophils migrate to the edge of the BV due to chemokines, increased plasma viscosity and slowing of flow due to injury
  2. Adhesion - Selectins on vascular endothelium bind neutrophils, causing a “rolling” action
  3. Extravasation/diapedesis - neutrophils pass through endothelial cells > basal lamina > vessel wall (cellular exudate) towards site of injury by following the gradient of inflammatory mediators
  4. Movement of neutrophils out of BV causes RBCs to also escape
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7
Q

What are the possible outcomes of acute inflammation?

A
  1. Resolution - complete restoration of tissues to normal
  2. Suppuration - formation of pus > scarring
  3. Organisation - normal tissue replaced by granulation tissue and fibrosis occurs (cardiac and neural tissue)
  4. Progression - Recurrent inflammation leads to chronic inflammation (e.g. liver cirrhosis)
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8
Q

What are granulomas?

A

Aggregates of epithelioid histocytes (i.e. macrophages)

They surround invading microorganisms to form granulomas (horseshoe shape)

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9
Q

What do granulomas secrete? And why is it important?

A

Angiotensin-converting enzyme (ACE) and increased blood levels indicate granulomatous disease

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10
Q

What disease do granulomas with central necrosis (caseating) indicate?

A

Tuberculosis (TB)

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11
Q

What diseases could noncaseating granulomas indicate?

A

Sarcoidosis, vasculitis, Crohn’s etc.

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12
Q

What is a thrombus?

A

The solidification of blood contents that form within the vascular system during life

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13
Q

What are emboli?

A

A mass of material (often from a thrombus) that can lodge in smaller vessels and result in occlusion of these vessels

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14
Q

Give an example of a thrombus

A

Deep vein thrombosis (DVT)

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15
Q

Give an example of an embolism

A

Pulmonary Embolism (PE)

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16
Q

Dalteparin

1) Use
2) MOA
3) Side effects

A

1) Type of heparin, DVT and PE

2) It potentiates the activity of antithrombin III, inhibiting the formation of both Factor Xa and thrombin by antithrombin.

3) Haemorrhage; heparin-induced thrombocytopenia; skin reactions

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17
Q

What are the 6 causes of acute inflammation?

A
  1. Microbial infections e.g. pyogenic (pus causing) bacteria
  2. Hypersensitivity reactions e.g. parasites, tubercle bacilli
  3. Physical agents e.g. trauma
  4. Chemicals e.g. acids, alkalis
  5. Bacterial toxins - lipopolysaccharide
  6. Tissue necrosis e.g. infarction
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18
Q

Define chronic inflammation

A

The subsequent and often prolonged tissue reactions to injury following the initial response

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19
Q

Describe how a thrombosis is formed

A
  1. Platelet aggregation, which starts clotting cascade
  2. Both have positive feedback loops so response is amplified
  3. Thrombosis is caused by 3 major factors (Virchow triad - hypercoagulability, reduced blood flow, endothelial injury)
  4. Typically, 2 of these factors are enough to form a thrombus
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20
Q

What is Virchow’s triad?

A

3 factors considered critical to the formation of thrombi:

  1. Reduced blood flow (AF, long-distance travel, varicose veins)
  2. Blood vessel injury (trauma, orthopaedic or major surgery, hypertension, canulation)
  3. Increased coagulability (sepsis, smoking, malignancy)
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21
Q

How is a venous thrombosis formed?

A
  1. Lower pressure in veins = no atheromas formed
  2. Thrombi tend to begin at valves as they produce turbulence by protruding into vessel lumen
  3. Valves damaged by trauma, stasis or occlusion
  4. When blood pressure falls (e.g. during surgery), blood flow slows, allowing the thrombus to form
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22
Q

What are the clinical features of an arterial thrombus?

A
  • Loss of pulse distal to thrombus
  • Area becomes cold, pale and painful
  • Gangrene might develop as result of tissue death
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23
Q

What are the clinical features of a venous thrombus?

A
  • Area becomes painful and tender due to ischaemia
  • General ischaemic pain as circulation worsens
  • Area becomes red and swollen as veins cannot drain blood away
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24
Q

Where does venous thrombosis most often occur?

A

Leg veins (95% of cases)

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25
Q

What are the main features of an arterial thrombus?

A
  • Commonly caused by atheroma (fatty streaks)
  • Formed under high pressure
  • Mainly comprised of platelets
  • Can lead to myocardial infarction/ stroke
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26
Q

What is the main treatment for arterial thrombus?

A

Anti-platelets e.g. aspirin or clopidogrel

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27
Q

What are the main features of a venous thrombus?

A
  • Commonly caused by stasis
  • Low pressure
  • Mainly comprised of RBCs
  • Can lead to DVT/PE
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28
Q

What is the main treatment for venous thrombus?

A

The initial management for a suspected or confirmed DVT or PE for most patients is treatment dose apixaban or rivaroxaban (NICE 2020).

Long term anticoagulation in VTE is a DOAC, warfarin, or LMWH for at least 3 months

3 - 6 months in active cancer

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29
Q

How does a pulmonary embolism form?

A
  1. An embolus enters the venous system often from a deep vein thrombosis
  2. It travels to the vena cava > right side of the heart
  3. It lodges somewhere in the pulmonary circulation.
  4. Loss of blood flow to lung tissue (infarction) and right ventricular strain, as RV pumps against the increased pulmonary resistance.
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30
Q

What is the effect of small pulmonary emboli?

A
  • May go unnoticed and be resolved
  • May become organised and cause damage aka “idiopathic pulmonary hypertension”
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31
Q

What is the effect of larger pulmonary emboli?

A
  • Can result in acute respiratory or cardiac problems
  • Resolves slowly with or without treatment
  • Can cause chest pain and shortness of breath as an area of the lung cannot be supplied by occluded vessel
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32
Q

What are the effects of massive pulmonary emboli?

A
  • Results in sudden death
  • Usually long thrombi from leg veins
  • Impacted (stuck) across the bifurcation of one of the major pulmonary artery
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33
Q

Why is an arterial embolism also called a systemic embolism?

A

Because if an embolus enters the arterial system, it can travel anywhere downstream of its entry point in the systemic arterial circulatory system

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34
Q

What are the 3 main causes of a systemic/arterial embolism?

A
  1. Thrombi overlying a myocardial infarct in the heart’s left ventricle
  2. Cholesterol crystals from an atheromatous plaque
  3. Atrial fibrillation
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35
Q

What stops a venous embolism from reaching systemic circulation?

A

Blood vessels in the lungs split down to capillary size, so are too small for any venous emboli to pass through

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36
Q

Where can the thrombus travel to if a mural thrombus (affecting vessel wall) forms over dead cardiac tissue as a result of myocardial infarction in the heart’s left ventricle?

A

Anywhere in the systemic circulation downstream of the thrombus’ entry point

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37
Q

Cholesterol crystals from atheromatous plaque can form thrombi that cause systemic embolism. Which areas may be affected if cholesterol crystals travel from the descending aorta?

A

Any lower limb and renal arteries

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38
Q

Define ischaemia

A

Ischaemia is the reduction in blood flow to a tissue or part of the body caused by constriction or blockage of the blood vessel supplying it

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39
Q

Define infarction

A

Infarction is the necrosis of part of a whole organ that occurs when the artery supplying it becomes obstructed

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40
Q

What are the main features of ischaemia?

A
  • Effects can be reversible
  • Duration of an ischaemic attack is brief
  • Cardiomyocytes and cerebral neurons are most vulnerable due to high metabolic demands
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41
Q

What are the main features of infarction?

A
  • Usually a macroscopic event
  • Most organs only have a single artery supplying them so susceptible to infarcts
  • Liver, brain and lungs have dual supply = less susceptible
  • Reperfusion injury = damage to tissue during re-oxygenation
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42
Q

Define atherosclerosis

A

A disease characterised by the formation of atherosclerotic plaques in the intima of large (aorta) and medium-sized arteries, such as the coronary arteries

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43
Q

What is the most important risk factor for atherosclerosis?

A

Hypercholesterolaemia (high cholesterol levels)

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44
Q

What are some other risk factors for atherosclerosis?

A
  • Smoking
  • Hypertension
  • Diabetes
  • Male gender
  • Increasing age
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45
Q

Describe the formation process of an atherosclerotic plaque

A
  1. Endothelial cell injury at site of plaque formation
  2. Inflammatory cells and lipids accumulate in arterial walls
  3. Macrophages are attracted to the site of damage and form foam cells by taking up lipids
  4. Fatty streak formation (earliest stage of atherosclerotic plaque)
  5. Platelet aggregation - plaque protrudes into lumen, disrupting laminar flow > platelets arrive at site
  6. Growth factors e.g. platelet-derived growth factor (PDGF) secreted by platelets, injured endothelium, macrophages and smooth muscle cells stimulate proliferation of smooth muscle cells on arterial intima
  7. Results in formation of fibrous cap which encloses the lipid-rich core
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46
Q

What are the constituents of an atherosclerotic plaque?

A
  • A fully developed plaque is a lesion with a central lipid core with a fibrous cap covered by the arterial endothelium
  • Macrophages, T-lymphocytes and mast cells reside in the fibrous cap
  • The plaque is highly thrombogenic often bordered by foam cells
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47
Q

Define apoptosis

A

A process where a programmed sequence of intracellular events leads to the removal of a cell WITHOUT the release of products harmful to surrounding cells

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48
Q

Define necrosis

A

Traumatic cell death which induces inflammation and repair

Characterised by bioenergetic failure (failure to produce ATP) and loss of plasma membrane integrity

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49
Q

Describe the intrinsic pathway of apoptosis

A
  • Uses the pro- and anti-apoptotic members of the Bcl-2 family
  • Bcl-2 inhibits factors that induce apoptosis
  • Bax forms Bax-Bax dimers which leads to caspase activation > apoptosis

Ratio of Bcl-2 to Bax determines the cell’s susceptibility to apoptotic stimuli and will determine whether the cell survives or dies due to apoptosis

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50
Q

What does the intrinsic pathway of apoptosis respond to?

A

Growth factors or withdrawal of them and biochemical stressors (e.g. inflammation, hunger, injuries)

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51
Q

What is the role of p53 in the event of DNA damage in cells?

A

P53 protein, encoded by the p53 gene, can induce cell cycle arrest and initiate DNA damage repair

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52
Q

In the event that cell damage cannot be controlled, what can p53 do?

A

p53 can induce apoptosis of the cell via activation of pro-apoptotic members of the Bcl-2 family

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53
Q

Describe the extrinsic pathway of apoptosis.

A
  • Ligand (e.g. TNF-alpha, Fas-L) binding at death receptors on the cell surface
  • Receptors include tumour necrosis factor receptor-1 (TNFR1), FAS and CD95
  • Ligand-binding results in the clustering of receptor molecules on the cell surface and the initiation of signal transduction cascade
  • Caspases are activated, triggering apoptosis
  • The immune system uses this pathway to eliminate lymphocytes
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54
Q

What does apoptosis always lead to?

A

Release of capases - enzymes that trigger apoptosis!

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55
Q

Define hypertrophy

A

Increase in cell size without cell division
(e.g. muscle hypertrophy in athletes)

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56
Q

Define hyperplasia

A

Increase in cell number by mitosis (e.g. benign prostatic hyperplasia)

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57
Q

Define atrophy

A

The reduction in cell size/numbers of an organ or a cell, often by a mechanism involving apoptosis

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58
Q

Define metaplasia

A

The change in a cell from one fully-differentiated cell type to a different fully-differentiated cell type (e.g. Barret’s oesophagus)

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59
Q

Define dysplasia

A

Imprecise term for the morphological changes seen in cells in the progression to becoming cancer

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60
Q

Why does hyperplasia not occur in nerve or myocardial cells?

A

Hyperplasia can only happen in cells that divide, nerve and myocardial cells cannot divide

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61
Q

Define carcinogenesis

A

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

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62
Q

What is a neoplasm?

A

A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed i.e. a
new growth

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63
Q

What is a tumour?

A

Any abnormal swelling

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64
Q

Give 4 examples of a tumour

A
  1. Neoplasm
  2. Inflammation
  3. Hypertrophy
  4. Hyperplasia
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65
Q

What is a carcinogen?

A

An environmental agent participating in the causation of cancerous tumours

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66
Q

Define metastasis

A

The process whereby malignant tumours spread from their site of origin (the primary tumour) to form other tumours (secondary tumours) at distant sites

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67
Q

Which carcinoma NEVER metastasizes?

A

Basal cell carcinoma (type of skin cancer)

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68
Q

What do we base tumour classification on?

A
  • Behaviour (benign or metastatic)
  • Histogenesis (origin cells of tumour)
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69
Q

What are the features of an benign tumour?

A
  1. Does not invade basement membrane
  2. Exophytic (grows outwards)
  3. Low mitotic activity
  4. Circumscribed
  5. Necrosis and ulceration rare
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70
Q

What are the features of a malignant tumour?

A
  • Invades basement membrane
  • Endophytic (grows inwards)
  • High mitotic activity
  • Poorly circumscribed
  • Necrosis and ulceration common
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71
Q

Describe the different types of histogenic classifications

A
  • Epithelial cells give rise to carcinomas
  • Connective tissues give rise to sarcomas
  • Lymphoid (always malignant) and haemopoietic organs give rise to lymphomas or leukaemias
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72
Q

Describe the histological grading for tumours

A

Grade is based on the extent to which the tumour resembles its original histology

Grade 1 – Well differentiated (most closely resembles parent tissue)

Grade 2 – Moderately differentiated

Grade 3 – Poorly differentiated

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73
Q

Describe the process of metastasis

A
  1. Detachment of tumour cells from their neighbours and embolism
  2. Invasion of the surrounding connective tissue to reach conduits that allow metastasis to occur i.e. blood & lymphatic vessels
  3. Intravasation into the lumen of vessels
  4. Evasion of host defence mechanisms, such as natural killer cells in the blood
  5. Adherence to endothelium at a remote location (e.g. lungs)
  6. Extravasation of the tumour cells from the vessel lumen into the surrounding tissue
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74
Q

What are the methods by which tumours can metastasise?

A
  • Haematogenous
  • Lymphatic
  • Transcolemic (across the peritoneal cavity) spread via the potential space between the parietal and visceral peritoneum.
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75
Q

Describe the haematogenous route of metastasis

A

Spread by blood stream to form secondary tumours in the organ perfused by the blood drained from the tumour

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76
Q

Bone is a site favoured by haematogenous metastases from which 5 carcinomas?

A

BLT + KP

  1. Breast
  2. Lung
  3. Thyroid
  4. Kidney
  5. Prostate
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77
Q

Describe the lymphatic route of metastasis

A

The spread of metastatic tumours via lymphatic vessels, and might form a secondary tumour in a different organ or form secondary tumours in the regional lymph nodes

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78
Q

Give an example of a lymphatic metastasis

A

Lymphoma

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79
Q

Describe the transcolemic route of metastasis

A

Spread through pleural, pericardial & peritoneal cavities - results in a neoplastic effusion (abnormal fluid accumulation)

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80
Q

What is TNM staging?

A

A system doctors use to determine the extent of a tumour spread

T - Tumour size

N – Node (extent of lymph node involvement)

M – Metastasis (extent of metastases)

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81
Q

Give a benefit of inflammation

A

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

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82
Q

Give a disadvantage of inflammation.

A

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

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83
Q

Define carcinoma

A

Malignant epithelial neoplasm

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84
Q

Define sarcoma

A

Malignant connective tissue neoplasm

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85
Q

What is a lipoma?

A

Benign tumour of adipocytes

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86
Q

What is a rhabdomyoma?

A

Benign tumour of striated muscle

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87
Q

What is a reiomyoma?

A

Benign tumour of smooth muscle cells

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88
Q

What is a chondroma?

A

Benign tumour of cartilage

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89
Q

What is a osteoma?

A

Benign tumour of bone

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90
Q

What is an angioma?

A

Benign vascular tumour

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91
Q

What is a neuroma?

A

Benign tumour of nervous tissue

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92
Q

What is a liposarcoma?

A

Malignant tumour of adipocytes

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93
Q

What is a rhabdomyosarcoma?

A

Malignant tumour of straited muscle

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94
Q

What is a leiomyosarcoma?

A

Malignant tumour of smooth muscle cells

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95
Q

What is a chondrosarcoma?

A

Malignant tumour of cartilage

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96
Q

What is an osteosarcoma?

A

Malignant tumour of the bone

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97
Q

What is an angiosarcoma?

A

Malignant vascular tumour

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98
Q

what is a melanoma?

A

Malignant neoplasm of melanocytes

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99
Q

What is lymphoma?

A

Malignant neoplasm of lymphoid cells, all are malignant

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100
Q

What is mesothelioma?

A

Malignant tumour of mesothelial cells which line body cavities (pleura, peritoneum and pericardium) and outer surface of internal organs, secrete lubricating fluid - particularly in the lungs associated with asbestos exposure

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101
Q

What are the 5 classes of carcinogens?

A
  1. Chemical (smoking, alcohol)
  2. Viruses (Helicobacter pylori, human papillomavirus)
  3. Ionising and non-ionising radiation (UV rays, X-rays)
  4. Hormones, parasites and mycotoxins
  5. Miscellaneous (e.g. asbestos)
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102
Q

What cancer is smoking associated with?

A

Lung cancer - particularly NSCLC squamous cell carcinoma

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103
Q

What cancer is B-naphthylamine (dyes and rubber industry) associated with?

A

Bladder cancer

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104
Q

What cancer is polycyclic aromatic hydrocarbons (soot) associated with?

A

Scrotal carcinoma

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105
Q

What cancer is the Epstein-Barr virus associated with?

A

Burkitt’s lymphoma (B-cells)

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106
Q

What cancer is the human papillomavirus associated with?

A

Cervical cancer

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107
Q

Mutation in what gene causes familial adenomatous polyposis (FAP)?

A

APC (adenomatous polyposis coli) gene - a tumour suppressor gene

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108
Q

How does familial adenomatous polyposis (FAP) lead to colorectal cancer

A

FAP results in adenomas at an early age particularly in the large intestine - they undergo malignant change which almost inevitable progress to adenocarcinoma by age 35

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109
Q

Which cancers are screened for in the UK?

A

Cervical, Breast and Colorectal cancer

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110
Q

Is cancer screening primary, secondary or tertiary prevention?

A

Secondary prevention - method of early detection

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111
Q

How is cervical cancer screened for?

A

Cervical swab done every 3 years from age 25 - 49, every 5 years from 50 - 64

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112
Q

How is breast cancer screened for?

A

Mammogram every 3 years from age 50 - 71

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113
Q

How is colorectal cancer screened for?

A

Faecal immunochemical test (FIT) from age 60 - 74. This is a home test kit sent to a lab

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114
Q

Define innate immunity

A

Non-specific immunity you were born with e.g. mucus, inflammation

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115
Q

What are the features of innate immunity?

A
  1. Non-specific + instinctive
  2. Response is not improved by repeat infection
  3. Rapid response (hours)
  4. Depend on phagocytes & natural killer (NK) cells
  5. Limited receptors e.g. Toll-like receptors (TLR) recognising pathogen-associated molecular patterns (PAMPs)
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116
Q

Name the immune cells involved in innate immunity

A
  • Neutrophils (most abundant WBC, extravasates to affected tissue)
  • Macrophages (detection, phagocytosis and destruction of bacteria etc. Also present antigens to T cells and initiate inflammation by releasing cytokines
  • Basophils (circulating form of mast cells, release histamine)
  • Eosinophils (IgE receptors, combats parasites)
  • Mast cells ( resident cell of connective tissue containing histamine granules)
  • Dendritic cells (APC)
  • Natural Killer cells (NK)
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117
Q

What process are neutrophils involved in?

A

Acute inflammation

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118
Q

What are the most abundant type of white blood cells?

A

Neutrophils

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119
Q

What process are macrophages involved in?

A

Phagocytosis, antigen presenting & chemokine (IL-8 recruit neutrophils) and cytokine secretion

Macrophages are formed when monocytes migrate from blood to tissue

Alveolar macrophage - Lung alveoli

Kupffer cells - Liver

Microglia - Central nervous system

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120
Q

What process are basophils involved in?

A

They are circulating forms of mast cells and release histamine - involved in analyphaxis

E.g. Allergic reactions, eczema, hay fever

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121
Q

What process are eosinophils involved in?

A

Parasitic infection
IgE receptors
Neutralise histamine therefore inhibits mast cells

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122
Q

What process are mast cells involved in?

A
  • Anaphylaxis and asthma- IgE binds to allergen, which then binds to mast cells
  • These mast cells would already be sensitized to that particular allergen and already have specific IgE bound to their surface
  • Second exposure = IgE crosslinks >causing the mast cells to release histamines, causing Sthe response e.g. bronchoconstriction
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123
Q

What process are natural killer cells involved in?

A

Release lytic granules that kill virus infected cells

  • Provide non-specific immunity against cells displaying foreign proteins such as cancer cells and virally- infected cells.
  • < 5% of circulating leukocytes.
  • NK cells can detect abnormal cells and release perforins - cytolytic proteins which create channels which allow extracellular fluid into the cells, causing them to lyse.
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124
Q

Describe the function of antigen-presenting cells?

A

These cells process and present antigens from pathogens for recognition by e.g. CD4 cells which then differentiate into T-helper cells

Main APCs are dendritic cells, but macrophages and B cells are APCs

Once T cells are exposed to an antigen, they go from naive to primed.

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125
Q

What is the complement system/pathway?

A

A complex series of interacting plasma proteins (C1 - C9) which work alongside the innate and adaptive immunity system to help destroy pathogens.

Complement system triggered by:

  • Lectin pathway, alternative pathway - pathogens
  • Classical pathway - initiated by antibody-antigen complexes

Complement system results in activation of oposinins, perpetuates inflammation and destroys pathogens.

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126
Q

What is the main function of the complement system/pathway?

A

To remove or destroy antigen, either by direct lysis or by opsonisation (process where an antigen on a pathogen becomes coated with substances (i.e. complement) that make it more easily engulfed by neutrophils and macrophages.

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127
Q

What actions can complements execute when activated by coming into contact with pathogens?

A
  • Lyse microbes directly through Membrane Attack Complexes (MACs).
  • Increase chemotaxis (C3a & C5a) - attracts neutrophils to site of infection/injury
  • Enhance inflammation
  • Induce opsonisation (C3b)
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128
Q

What are membrane attack complexes (MACs)?

A

When a group of complement proteins create a channel in pathogen’s cell membrane which causes an influx of fluids that results in lysis and thus the destruction of the pathogen

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129
Q

What are toll-like receptors (TLRs)?

A

Receptors found on macrophages, dendritic cells & neutrophils, they recognise and bind to pathogen-associated molecular patterns PAMPs (e.g. lipopolysaccharide, viral and bacterial nucleic acids and a protein in bacterial flagella

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130
Q

Give 5 examples of toll-like receptors (TLRs) and the PAMP they recognise

A

TLR-2 - gram +ve bacteria & TB

TLR-4 - lipopolysaccharides on gram -ve bacteria (important!)

TLR-5 - flagella

TLR-7 - single strand RNA

TLR-9 - non-methylated DNA

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131
Q

Describe the pathway when TLR-4 is activated by lipopolysaccharides

A
  1. TLR-4 on macrophages is activated by lipopolysaccharides on gram -ve bacteria (endotoxin)
  2. Lectins in bloodstream bind pathogen - triggering immune response
  3. Complement system activated
  4. Macrophages phagocytose the bacteria and release cytokine:
  • TNF-alpha (All of below)
  • IL1 (fever)
  • IL6 (acute phase proteins, opsonins, from the liver)
  • IL-8 (recruit neutrophils)
  • IL2 and 12 (activates NK cells))
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132
Q

Define adaptive immunity

A

Acquired defence system to destroy/prevent growth of pathogens

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133
Q

What are the features of the adaptive immunity?

A
  • Specific
  • Slower primary immune response to a pathogen not previously encountered (days - weeks)
  • Response to specific antigens
  • Memory to specific antigens (immunological memory) - faster secondary immune response
  • Cell-mediated - T-lymphocytes for intracellular microbes
  • Antibodies - B-lymphocytes for extracellular microbes
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134
Q

What is the function of Major Histocompatibility Complexes (MHC)?

A

Proteins found on cell surfaces that present antigenic peptides to T-cells. T-cells only recognise antigen that have formed a complex with that individual’s MHC

  • MHC class I molecules are found on all nucleated cells (not just professional APCs) and typically present intracellular antigens such as viruses.
  • MHC class II molecules are only found on APCs and typically present extracellular antigens such as bacteria.
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135
Q

What T-cells do MHC class I molecules interact with?

A

Cytotoxic T cells (expresses CD8)

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136
Q

On what cells is MHC class I molecule found?

A

On the surface of virtually all (nucleated) cells in the body except erythrocytes (non-nucleated)

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137
Q

What happens when cytotoxic T-cells are activated by interaction with MHC I?

A

When cytotoxic T cells (CD8) detects a foreign antigen associated with the MHC I, they will release perforin to kill the cell containing the intracellular pathogen

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138
Q

What T cells do MHC class II molecules interact with?

A

Helper T cells (CD4)

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139
Q

On what cells are MHC class II molecules found?

A

Mainly on the surface of macrophages, B cells and dendritic cells (i.e. antigen presenting cells)

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140
Q

What happens when helper T-cells are activated by interaction with MHC II?

A

When helper T cells (CD4) detect foreign antigens on the MHCII, they activate B cells to make antibodies to that specific extracellular pathogen

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141
Q

What are the main types of T-cells?

A
  • T helper cells (T helper cell 1 and 2)
  • Cytotoxic T cells
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142
Q

What is the function of T helper cells 1?

A

They mediate processes associated with cytotoxicity and local inflammatory reactions:

  1. Activate macrophages which triggers inflammation
  2. They help cytotoxic T-cells develop into effector cells to kill virally-infected target cells
  3. Induce B cells to make IgG antibodies
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143
Q

What cytokines do T-helper cells 1 release?

A

IL-2 (interleukin 2), IL12, gamma-interferon (IFN-gamma) and TNF-beta (tumour necrosis factor)

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144
Q

What are the functions of T-helper cells 2?

A
  1. Activate eosinophils and mast cells
  2. Important in helminth infections and allergies
  3. Induce B cells to make IgE which promotes the release of inflammatory mediators e.g. histamine from mast cells.

Therefore T-helper cells 2 are involved in protecting the body against free-living, EXTRACELLULAR, microorganisms

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145
Q

What does IL-4 release by T-helper cells 2 stimulate?

A

B-cell proliferation (clonal expansion)

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146
Q

What does IL-5 release by T-helper 2 cells stimulate?

A

B-cell differentiation into plasma cells, class switching to secreting all immunoglobulins

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147
Q

What cytokines do T helper cells 2 produce?

A

IL-4, -5, -6, -10, -13

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148
Q

How are cytotoxic T cells activated?

A
  • Naive CD8 T cells are activated by antigens presented via MHC class I molecules, usually derived from intracellular microorganisms, on the surface of infected cells
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149
Q

Once naive cytotoxic T-cells are activated, they become effector cytotoxic T-cells (CD8). What are the functions of cytotoxic T cells?

A
  • Effector CD8 T cells release pro-inflammatory and macrophage-activating cytokines
  • Effector CD8 T cells also release perforins and granulysin to kill infected cells by forming pores in the cell members
  • Effector CD8 T cells can also induce apoptosis by acting on the FAS molecule of the target cell
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150
Q

Once naive cytotoxic T-cells are activated, they become effector cytotoxic T-cells (CD8). What are the functions of cytotoxic T cells?

A
  • Effector CD8 T cells release pro-inflammatory and macrophage-activating cytokines
  • Effector CD8 T cells also release perforins and granulysin to kill infected cells by forming pores in the cell members
  • Effector CD8 T cells can also induce apoptosis by acting on the FAS receptor of the target cell
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151
Q

What are naive B-cells called after they are activated?

A

Plasma cells

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152
Q

How are B cells activated?

A
  1. Naive B cells present pathogen antigens on their cell surface via MHC class II. (naive B cells can only secrete IgM and IgD.
  2. The B cells then present the antigen to a T-helper 2 cell (CD4) - which has been activated by being presented with the same antigen by a different APC
  3. The T-helper cell binds to the MHC class II via its T-cell receptor (TCR)
  4. T-cell then stimulates the B cells to divide (clonal expansion) and allow B cell class switching (can produce IgMAGED) - occurs in lymph nodes
  5. The B cells differentiate into short-lived plasma cells (which produce antibodies to that same antigen) and memory cells (which will recognise the same antigen to illicit a faster immune response in the future)
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153
Q

Where do T cells maturate?

A

Thymus

T lymphocytes originate from haematopoietic stem cells within the bone marrow.

Some of these multipotent cells subsequently become lymphoid progenitor cells that leave the bone marrow and travel to the thymus via the blood.

Selection process in the thymus

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154
Q

What is thymic tolerance?

A

The process by which T-cells in the thymus are selected (I.e. which T-cells are “good”)

  • Positive selection - T cells that recognise the thymus MHC I and II as “self” - markers that tell the immune system that a particular cell is part of the host = selected for
  • Negative selection - T cells mount a response to the thymus MHC I and II = selected against
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155
Q

What does IL-5 release by T-helper 2 cells stimulate?

A

B-cell differentiation into plasma cells > release immunoglobulins

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156
Q

Where do B cell production and maturation occur?

A

Bone marrow - selection process occurs

  • Positive selection - B cells with functional receptors are allowed to develop further. B cell receptor successfully binds its ligand, which induces survival signals.
  • Negative selection happens when B cells respond to self-antigens in the bone marrow and undergo apoptosis.
  • Promotes central tolerance ( eliminating any developing T or B lymphocytes that are autoreactive) and minimises the risk of autoimmune reactions when the B cells eventually mature and move to the peripheral circulation.
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157
Q

What are the different classes of antibodies (immunoglobins)?

A

GAMED

-IgG
-IgA
-IgM
-IgE
-IgD

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158
Q

Describe the features and functions of IgG

A
  • Most abundant Ig in blood
  • Important in secondary immune response (act as markers of immunological memory)
  • IgG 1, 2, 3, 4 subtypes
159
Q

Describe the features and functions of IgA

A
  • Most abundant Ig in body
  • Found on mucosal linings (GI and urinary tract) and secretions (breast milk, sweat, tears)
  • Forms dimers
160
Q

Describe the features and functions of IgM

A
  • First Ig released in adaptive response - less specific than IgG
  • Forms pentamers
161
Q

Describe the features and functions of IgE

A
  • IgE activates mast cells and basophils
  • Important n allergy and helminth infection
  • Least abundant in blood
162
Q

Describe the features and functions of IgD

A

Not that important; the function is debated in the literature

163
Q

What are 4 different hypersensitivity reactions?

A
  1. Type I - anaphylaxis
  2. Type II - cell bound
  3. Type III - antibody-antigen immune complex
  4. Type IV - delayed hypersensitivity
164
Q

Describe the mechanism of type II hypersensitivity reaction

A

IgG/M bind to antigenon host cells and activates the complement system - chemotactic and attracts neutrophils

Neutrophils release peroxidase enzymes that damage host cells by producing reactive oxygen species.

COmplement system molecules (C5b - C9) can form membrane attack complexes that create pores in the cell and destroy it
MAC at the site of the antigen-antibody complex

Examples include Goodpasture’s syndrome or penicillin reaction

165
Q

Describe the mechanism of type I hypersensitivity reaction

A

Type I (anaphylaxis) - IgE mediated. IgE binds to mast cells/basophils > histamine release > vasodilation, bronchoconstriction, facial flush, pruritus, tongue and face swelling

166
Q

Describe the mechanism of type III hypersensitivity reaction

A

Antibody-antigen complex mediated

In type III hypersensitivity reactions, antibodies bind to free soluble antigens in the blood (not cell-bound like type II)

B cells produce antibodies (immunoglobulin) - IgM initially

IgM on B cell surface cross-linked by DNA autoantigen binding

B-cell presents antigen to T-helper cells, which activates the B cell and induces class switching - can make IgG now

Antibody (IgG)-antigen complex activates the complement system - recruit neutrophils which try to phagocytose the antibody-antigen complex and release ROS toxic to cells - vasculitis mostly commonly in kidneys and joints

Examples include systemic lupus erythematosus.

167
Q

Give examples of a type I hypersensitivity reaction

A
  • Anaphylaxis
  • Atopy (e.g. asthma, eczema and hayfever)
168
Q

Give examples of a type II hypersensitivity reaction (cell bound)

A
  • Autoimmune haemolytic anaemia
  • Goodpasture’s syndrome (autoimmune disease where antibodies attack the host’s lungs and kidneys)
  • Pernicious anaemia
  • Rheumatic fever
169
Q

Give an example of a type III hypersensitivity reaction (immune complexes formation)

A
  • Systemic lupus erythematosus (SLE)
170
Q

Give examples of a type IV hypersensitivity reaction

A
  • Graft vs host disease
  • Tuberculosis
  • Multiple sclerosis
  • Guillain Barre syndrome
171
Q

Describe the mechanism of type II hypersensitivity reaction

A

IgG/M bind to antigen and activates MAC at the site of the antigen-antibody complex

172
Q

Describe the mechanism of type IV hypersensitivity reaction (delayed-type hypersensitivity)

A

T cell-mediated - T helper cell 1 and cytotoxic T cells are activated by APCs presenting antigen on their MHC class leading to an immune response

173
Q

Define pharmacodynamics

A

How a drug affects the body i.e. what does the drug do once it’s in the body?

174
Q

Define pharmacokinetics

A

What does the body do to the drug i.e. what does it do once the drug is in it? ADME

  1. Absorption/adminstration
  2. Distribution
  3. Metabolism
  4. Excretion
175
Q

Learn the haemopoiesis chart

A

Look in your notes

176
Q

Define efficacy

A

The maximum effect a drug can have in the body (i.e. the degree to how well the works on a specific receptor)

177
Q

Define potency

A

How much of a drug is needed to elicit a response in the body (measures of how well a drug works)

178
Q

Define agonist

A

A compound that binds to a receptor and activates it

Full affinity (how well it binds)

Full efficacy (how well the receptor is activated)

179
Q

Define antagonist

A

A compound that reduces the effect of an agonist

Full affinity (how well it binds)

Zero efficacy (how well the receptor is activated)

180
Q

What are the 2 types of antagonists?

A
  • Competitive inhibitors
  • Non-competitive inhibitors
181
Q

What are non-competitive inhibitors?

A

An antagonist that blocks other molecules from binding to the receptor by binding to a different part of the receptor other than the active site. This causes the active site to change shape

182
Q

In terms of pharmacokinetics, what is absorption/administration?

A

Transportation of the unmetabolized drug from the site of administration to the body circulation system

Routes of administration include oral, intravenous or inhalation etc.

Route of administration affects bioavailability

183
Q

To induce anaesthesia quickly, what characteristics should the drug have regarding its protein binding?

A

Protein binding: protein binding lowers the free concentration of a drug. Ideally, the induction drug should have low protein binding to enable a high initial plasma concentration.

184
Q

To induce anaesthesia quickly, what characteristics should the drug have regarding lipid solubility?

A

The drug should have a high lipid solubility in order for it to readily cross the blood-brain barrier and reach its site of action - BBB favours small lipid-soluble molecules.

185
Q

What is bioavailability?

A

How fast and to what extent the drug reaches systemic circulation

First-pass metabolism via the liver reduces the bioavailability of an orally administered drug

IV = 100%
IM: 100%

Other routes of administration are compared to IV

186
Q

Bioavailability: roughly how much more oral morphine is needed compared to IV morphine?

A

Due to first-pass metabolism, the oral dose of morphine needs to be twice that of intravenous morphine to have the same effect e.g. IV dose is 5mg and the oral dose is 10mg.

187
Q

Why might a doctor prescribe a lower-than-normal dose of morphine given over a longer interval for a patient with renal impairment??

A
  • Morphine is metabolised in the liver to morphine-6-glucuronide
  • More potent than morphine.
  • Excreted by the kidneys so if a patient has renal failure, it will not be as readily excreted
  • The dose and frequency of administration will need to be reduced to accommodate patient
188
Q

In terms of pharmacokinetics, what is distribution?

A

How the drug is distributed in the plasma according to its chemical properties (e.g. hydrophobicity) and size

189
Q

What is first-pass metabolism?

A

Breakdown of an orally administered drug that occurs in the intestine or liver before it reaches the systemic circulation and results in a reduction in the concentration of the drug

190
Q

In terms of pharmacokinetics, what is excretion?

A

How the body gets rid of the drug - urine or faeces

191
Q

What are the routes of administration for drugs?

A
  • Oral.
  • IV.
  • Subcutaneous.
  • Intramuscular.
  • Topical.
  • Rectal.
  • Intrathecal (spinal)
  • Sublingual/buccal.
  • Inhalation.
192
Q

What neurotransmitter is used by the parasympathetic nervous system?

A

Acetylcholine

193
Q

What neurotransmitter is used by the sympathetic nervous system?

A

Preganglionic neurotransmitter: acetylcholine
Postganglionic neurotransmitter: noradrenaline

194
Q

What are the two types of cholinergic receptors?

A
  1. Nicotinic (nAChR) - ion channel receptors
  2. Muscarinic (mAChR) - G-protein coupled receptor
195
Q

What receptors mediate the effects of the parasympathetic nervous system?

A

Muscarinic ACh receptors - the most common mAChR being M1, M2, M3

Found in heart, brain and smooth muscle cells

196
Q

What type of cholinergic receptors are found at the neuromuscular junction (NMJ) of e.g. skeletal muscle?

A

Nicotinic ACh receptors (nAChR) and they mediate the response of the somatic system at the NMJ

197
Q

Describe the process of acetylcholine synthesis, storage, release, breakdown and reuptake at the NMJ

A

Synthesis - choline acetyltransferase enzyme synthesises ACh from acetyl CoA and choline (substrate) in the neurone

Vesicle storage - ACh is then packaged into a vesicle ready to be released when the neurone is stimulated

Release - ACh is released when the neurone receives a stimulus

Breakdown - after ACh has been used it is broken down in the synaptic cleft by acetylcholinesterase AChE into choline and acetate

Reuptake - Choline is taken up into the neurone where it can be used to make
more ACh

198
Q

Which neurotransmitter does the parasympathetic nervous use?

A

Acetylcholine

199
Q

Which neurotransmitter does the sympathetic nervous system use?

A

Noradrenaline

200
Q

What are the main functions of the parasympathetic nervous system?

A

Rest & digest!

  • Constricts pupils
  • Stimulates tears
  • Stimulates salivation
  • Lowers heart rate
  • Reduces respiration
  • Constricts blood vessels
  • Stimulates digestion
  • Contracts bladder
201
Q

What are the main functions of the sympathetic nervous system?

A

Fight or flight!

  • Dilates pupil
  • Inhibits tears
  • Inhibits salivation
  • Activates sweat glands
  • Increases heart rate
  • Increases respiration
  • Inhibits digestion
  • Release of adrenaline
  • Relaxes bladder
  • Ejaculation in males
202
Q

What type of receptor is a nicotinic Ach receptor (nAChR)?

A

Ion channel receptor

203
Q

What is the agonist of a nicotinic ACh receptor (nAChR)?

A

Nicotine

204
Q

What type of receptor is a muscarinic ACh receptor (mAChR)?

A

G-protein coupled receptor

205
Q

What are the most common muscarinic receptors and where are they found?

A

M1 - brain
M2 - heart
M3 - lungs (smooth muscle cells)

206
Q

What is the agonist of a muscarinic ACh receptor (mAChR)?

A

Muscarine

207
Q

What are the adverse effects of too much muscarinic agonists (mimics action of ACh at mAChR)?

A

Cholinergic crisis :( - overstimulation at NMJ due to excess of ACh or drugs that mimics its actions

SLUDGE syndrome

Salivation
Lacrimation (tears)
Urination
Defecation
Gastrointestinal distress
Emesis (vomiting)

Nerve agents such as sarin, VX, novichok agents can cause SLUDGE syndrome

208
Q

What is the difference between noradrenaline and adrenaline?

A
  • Noradrenaline (NAd) is a neurotransmitter
  • Adrenaline (Ad) is a hormone
209
Q

Describe the synthesis pathway for noradrenaline and adrenaline

A

Tyrosine > L-DOPA > dopamine > noradrenaline > adrenaline

210
Q

What are the different classes of adrenergic receptors?

A

Alpha:
- Alpha-1
- Alpha-2

Beta:
- Beta-1
- Beta-2
- Beta-3

211
Q

Where in the body are alpha 1 receptors found and what effects do they mediate?

A

O - blood vessels
N - neck of bladder
E - eye

Effects
- Vasoconstriction
- Pupil dilation
- Bladder contraction

212
Q

Where in the body are alpha 2 receptors found and what effects do they mediate?

A

Presynaptic nerve terminals - inhibitory receptors responding to adrenaline and noradrenaline

Effect is the presynaptic inhibition of noradrenaline (e.g. blood sugars low = alpha-2 in pancreas stimulated to reduced noradrenaline release = less insulin release from pancreas)

TWO = Terminals Weaning Off

213
Q

Where in the body are beta 1 receptors found and what effects do they mediate?

A

Heart, kidneys - response to noradrenaline

Effects:

  • Increased force of heart contraction (positive inotropic
    effect)
  • Increased heart rate
  • Increased electrical conduction in heart
  • Increased renin release from kidneys
  • Increased BP
214
Q

Where in the body are beta 2 adrenergic receptors found and what effects do they mediate?

A

Lungs, blood vessels, GI tract - response to noradrenaline and adrenaline

Effect is smooth muscle relaxation leading to bronchodilation, vasodilation, reduced GI motility

215
Q

Where in the body are beta 3 adrenergic receptors found and what effects do they mediate?

A

Adipose tissue, bladder
Effect is increased lipolysis and relaxation of bladder

216
Q

What is an adverse drug reaction (ADR)?

A

Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug. It has to be noxious and unintended

217
Q

What are the 5 different types of ADRs?

A

ABCDE

Type A - Augmented
Type B - Bizarre
Type C - Chronic
Type D - Delayed
Type E - End of use

218
Q

What are the characteristics of a type A (augmented) ADR?

A
  • Most common
  • An extension of the clinical effect
  • Predictable
  • Dose related
  • Self-limiting
219
Q

Give examples of drugs that cause type A ADRs

A
  • Diuretic causing dehydration
  • Anticoagulant causing bleeding
  • Drug for hypertension causing hypotension
220
Q

What are the characteristics of a type B (bizarre) ADR?

A
  • Unexpected
  • Unrelated to dosage and not expected from known pharmacological action
  • Unpredictable
  • Mostly immunological mechanisms
  • Hypersensitivity
221
Q

Give an example of a drug that causes type B ADRs

A
  • Heparin causing hair loss
  • Penicillin causing allergic reaction?
222
Q

What are the characteristics of a type C (chronic) ADR?

A
  • Occurs after long term therapy
  • May not be immediately obvious with new medicines
223
Q

Give an example of a drug that causes type C ADRs

A

Steroids can cause hyperglycemia which may result in diabetes

224
Q

What are the characteristics of a type D (delayed) ADR?

A

Also occurs after a long period of time after treatment - many years

Common to see patients developing an ADR 20-30 years after treatment

225
Q

What are the characteristics of a type E (end of use) ADR?

A
  • Relatively long term use (days/weeks)
  • Withdrawal reactions
  • Serious complication of stopping related to clinical effect
226
Q

Give an example of a drug that causes type E ADRs

A

Opioids - stopping abruptly causes withdrawal syndrome

227
Q

What questions do we need to ask patients in order to determine which type of ADR they are experiencing?

A
  • Is it predictable from the mechanism of action? Does it seem dose-related? - Type A (Augmented)
  • Is there a history of allergy? - Type B (Bizarre)
  • Has the patient been using the medication for a long time? - Type C (Chronic)
  • Has the patient uses a drug in the past that could be causing a problem now? - Type D (Delayed)
  • Is the patient withdrawing from a medicine? - Type E (End of Use)
228
Q

What is the MHRA yellow card scheme?

A

The system for recording adverse incidents with medicines and medical devices in the UK

Patients can report through the yellow card website, app or phone

229
Q

What type of adverse drug incidents need to reported to the yellow card scheme?

A

All serious suspected ADRs for established medicines and vaccines need to be reported, even if the effect is well recognised:

  • Fatal
  • Life-threatening
  • Disabling
  • Results in prolonged hospitalisation

Particularly suspected ADRs:

  • in children
  • in patients that are over 65
  • to biological medicines and vaccines
  • associated with delayed drug effects and interactions
  • to complementary remedies such as homeopathic and herbal products
230
Q

What are the different types of opioids?

A

Naturally occurring opioids - from the opium poppy
Morphine
Codeine (weak)

Simple chemical modifications (1900s)
Diamorphine (heroin)
Oxycodone
Dihydrocodeine

Synthetic Opioids (1950s on)
Fentanyl (very potent)

Synthetic Partial Agonists
Buprenorphine

231
Q

Which drug is given to patients who overdosed on opioids?

A

Naloxone - opioid receptor antagonist

232
Q

Describe the routes of administration for opioids

A
  • Oral
  • Parenteral (into the body but outside GI tract) - IV, subcutaneous & intramuscular
  • Patient Controlled Analgesia (clicker)
  • Epidural / CSF
  • Trans-dermal patches for lipid soluble drugs (e.g. fentanyl)
233
Q

Why do we need to double the morphine dose if giving it orally compared to parenterally?

A

Because 50% of oral morphine is metabolised by first pass metabolism in the liver!

10mg oral morphine = 5mg parenteral morphine (IV, subcutaneous, intramuscular)

234
Q

Briefly describe how opioids work

A
  • Opioids use the body’s natural pain modulation pathways - endorphins (endogenous morphine) and enkephalins
  • They bind to opioid receptors, G-protein coupled receptors that act via secondary messengers.
  • They inhibit the transmission of pain signals from spinal cord to the brain and change pain perception to cause euphoria
235
Q

Briefly describe how opioids work

A
  • Opioids use the body’s natural pain modulation pathways - endorphins (endogenous morphine) and enkephalins
  • They bind to opioid receptors, G-protein coupled receptors that act via secondary messengers.
  • They inhibit the release of pain transmitters at spinal cord and midbrain and change pain perception to cause euphoria
236
Q

Rank the potency of heroin, morphine and pethidine

A

The following dose of each drug is needed to elicit the same effect:

5mg heroin (most potent) = 10mg morphine = 100mg pethidine (least potent)

237
Q

Define side effect in relation to a drug/medication

A

Side effect is an unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment

238
Q

What are the common side effects of ACE inhibitors?

A
  • Bradykinin accumulation in lungs cause dry cough - switch to angiotensin receptor blockers
  • Dilates afferent arterioles in the glomerulus - leading to worsened kidney function > AKI

-

239
Q

Briefly describe the mechanism of action of ACE inhibitors

A

ACE inhibitors used to treat heart failure and high blood pressure and are often prescribed to people following a heart attack

They block the action of ACE to prevent the conversion of angiotensin I to angiotensin II.

Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion - so blocking its action > reduced peripheral vascular resistance > lowers blood pressure

240
Q

Briefly describe the mechanism of action of ACE inhibitors

A

ACE inhibitors used to treat heart failure and high blood pressure and are often prescribed to people following a heart attack

They block the action of ACE to prevent the conversion of angiotensin I to angiotensin II.

Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion - so blocking its action > reduced peripheral vascular resistance > lowers blood pressure

241
Q

Briefly describe the mechanism of action of NSAIDs (non-steroidal anti-inflammatory drugs)

A
  • NSAIDs are cyclooxygenase (COX) inhibitors which then prevents production of prostaglandins.
  • Mucus secretion is stimulated by prostaglandins
  • COX-1 needed for prostaglandin synthesis
  • COX-2 inhibition is useful, COX-1 inhibition causes the adverse effects such as reducing the mucosal defence in stomach
242
Q

What are the common side effects of NSAIDs?

A

As NSAIDs reduce the mucosal defence, it can cause GI upset, GI bleeding, renal impairment and peptic ulcers

243
Q

Briefly describe the mechanism of action of loop diuretics.

A
  • Inhibit Na+/K+/Cl- cotransporter in ascending loop of Henle
  • Usually all 3 are absorbed in the kidneys and water follows
  • Blocked= less water reabsorbed

E.g. Furosemide, bumetanide

244
Q

What are common side effects of loop diuretics?

A

Dizziness; electrolyte imbalance (hyponatraemia, hypochloraemia, hypokalaemia), fatigue; hypotension

245
Q

Briefly describe the mechanism of action of thiazide diuretics

A

Thiazides inhibit Na+/Cl- co-transporters in the distal convoluted tubule of the nephron > prevents reabsorption Na+ and water > lower extracellular fluid volume > lower blood pressure

E.g. Bendroflumethiazide

246
Q

What are some common side effects of thiazide diuretics?

A
  • Hyponatraemia
  • Hypokalaemia
  • Cardiac arrhythmias
  • Impotence in men
247
Q

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

A

Potassium-sparing diuretics (e.g. spironolactalone) are weak alone but often used in combination with another diuretic. Used to treat hypokalaemia caused or loop or thiazide diuretics

Spironolactone is an antagonist of aldosterone and prevents the reabsorption of sodium (and therefore water) by binding to and blocking aldosterone-dependent epithelial sodium channels (ENaC) at the distal convoluted tubule > sodium and water excretion > potassium retention

248
Q

What are some side effects of K+ sparing diuretics?

A
  • GI upset
  • Dizziness, hypotension, hyperkalemia (discontinue)
249
Q

What are the common indications for beta-blockers?

A

First line for ischaemic heart disease, chronic heart failure, atrial fibrillation, supraventricular tachycardia (SVT)

Hypertension - when other treatments are insufficient

250
Q

Briefly describe the mechanism of action of beta-blockers

A

Beta-blockers are antagonista of and act on beta-1 adrenergic receptors in the heart and reduce force of contraction, heart rate and speed of conduction in the heart

251
Q

What are the common indications for protein pump inhibitors (PPIs)?

A
  1. Prevention and treatment of peptic ulcer disease
  2. Symptom relief of GORD
  3. Helicobacter pylori infection in combo with amoxicillin and clarithromycin
252
Q

Briefly describe the mechanism of PPIs

A

PPIs reduce gastric acid secretion by irreversibly inhibiting H+/K+-ATPase in gastric parietal cells

253
Q

What are some common side effects of PPIs?

A
  • Prolonged use in the elderly can increased risk of fractures
  • GI disturbances
  • Headaches
  • Reduced host deference against infection e.g. Clostridium difficile
254
Q

Briefly describe the mechanism of action of opioids

A

E.g. morphine (naturally-occurring) and oxycodone (synthetic)

Opioids activate the opioid μ (mu) receptors in the CNS, which result in reduced neuronal excitability and pain transmission.

They also act on the medulla to decrease respiratory drive and thus calms the “fight and flight” response

255
Q

What are some side effects of opioids?

A
  • Respiratory depression > reverse with naloxone
  • Nausea and vomiting
  • Constipation
  • Itching
  • Tolerance
  • Dependence
  • Withdrawal reaction
256
Q

Describe how to carry out a gram stain

A

“Come In And Stain”
Crystal violet dye (purple)
Iodine - binds to crystal violet and fixes it to cell wall
95% Ethyl Alcohol - decolouriser
Safranin - counterstain (pink)

Gram +ve bacteria retain crystal violet = purple

Gram -ve bacteria decolourise and are stained with safranin = pink

257
Q

What results will the gram stain show if the bacteria is gram positive?

A

Gram-positive bacteria = multi-layered peptidoglycan wall

Gram positive: purple

258
Q

What results will the gram stain show if the bacteria is gram negative?

A

Gram-negative bacteria = single layer of lipopolysaccharide membrane

Gram Negative: piNk

259
Q

What bacteria is blood agar used to culture (sheep blood)?

A

Streptococcus

260
Q

What bacteria is chocolate agar used to culture (cooked blood)

A

Fastidious Neisseria (e.g. Neisseria gonorrhoeae)

261
Q

What bacteria is Xylose Lysine Deoxycholate (XLD) agar used to culture?

A

Salmonella and Shigella

If present, they both turn red on the medium, but Salmonella will show up as black dots

262
Q

What bacteria do MacConkey agar differentiate between?

A
  • MacConkey agar contain red dyes and lactose.
  • Only gram-negative bacilli can grow on MacConkey agar
  • Used to differentiate:
    lactose-fermenting - turns pink/red e.g. e.coli
    non-lactose-fermenting - turns white/transparent e.g. salmonella
263
Q

Describe how to carry out the catalase test

A

Add hydrogen peroxide 3% (H2O2) to a small sample of pure colony

264
Q

When carrying out the catalase test, bubbles indicate the presence of which genus of bacteria?

A

Staphylococcus = catalase +ve

If bubbles are produced = catalase +ve bacteria present as catalase catalyses the following reaction:

2H2O2 => 2H2O + O2 (gas bubbles)

265
Q

If the catalase test does not produce any bubbles when added to a colony, which genus of bacteria is likely to be present?

A

Streptococcus = catalase -ve

266
Q

Describe how to carry out the coagulase test

A

Apply rabbit plasma to a small sample of pure colony. Observe for fibrin clot clumps - coagulase is an enzyme that clots blood plasma

267
Q

What bacteria do the coagulase test differentiate between?

A

Staphylococcus aureus - coagulase +ve
Coagulase Negative Staphylococcus (CONS) - coagulase -ve

268
Q

Give examples of Coagulase Negative Staphylococcus (CONS)

A

S. epidermis
S. saprophyticus

269
Q

What is the haemolysis test?

A

Detects the presence of alpha or beta-haemolysin in the bacteria being tested.

Haemolysin is an enzyme that breaks down red blood cells

Used for classifying different types of streptococci

270
Q

Describe how the haemolysis test is carried out

A

Bacteria are cultured on blood agar

Alpha-haemolytic - greenish/brown discolouration surrounding colonies indicates partial breakdown of RBCs

Beta-haemolytic - clear zone surrounding colonies indicating complete lysis of RBCs

Gamma haemolysis - no haemolysis

271
Q

If the haemolysis test identifies the presence of alpha-haemolytic bacteria, what further test is carried out?

A

Optochin test

272
Q

If the haemolysis test identifies the presence of beta-haemolytic bacteria, what further test is carried out?

A

Lancefield test - differentiate beta haemolytic bacteria by detecting surface antigens, each antigen is given a letter:

  • A, C, G - tonsillitis & skin infection
  • B - neonatal sepsis & meningitis
273
Q

Give two examples of alpha-haemolytic bacteria

A

Strep pneumoniae & strep viridans

274
Q

Give two examples of beta-haemolytic bacteria

A

Strep pyogenes (tonsillitis and skin infections) & strep agalactiae (neonatal sepsis and meningitis)

275
Q

What bacteria does the optochin test differentiate between?

A

Streptococcus pneumoniae and other alpha-haemolytic streps

S. pneumoniae- susceptible to optochin
All other alpha-haemolytic streps - resistant to optochin

276
Q

Why might the Ziehl-Neelsen stain be used instead of gram stain?

A

Gram stain can differentiate MOST bacteria

  • But mycobacteria e.g. TB are acid-fast bacilli that DO NOT take up the gram stain
  • Instead they take up a stain called Ziehl-Neelsen
277
Q

What colour will mycobacterium show up as if dyed with Ziehl-Neelsen stain

A

-Mycobacterium is an acid-fast bacilli (resistant to decolourisation) and show as red

278
Q

What colour will E.coli show up as if dyed with Ziehl-Neelsen stain

A

-E.coli is an non acid-fast bacilli and show as blue

279
Q

How is the optochin test carried out?

A
  • Optochin is a chemical
  • Filter paper disc containing optochin is placed in the petri dish
  • If the bacteria is susceptible (S. pneumoniae) = clear ring around the optochin as the bacteria could not grow
  • If the bacteria is resistant (all other alpha-haemolytic streps) = bacteria surrounds the optochin disc
280
Q

How is the optochin test carried out?

A
  • Optochin is a chemical
  • Filter paper disc containing optochin is placed in the petri dish
  • If the bacteria is susceptible (S. pneumoniae) = clear ring around the optochin as the bacteria could not grow
  • If the bacteria is resistant (all other alpha-haemolytic streps) = bacteria surrounds the optochin disc
281
Q

How does the structure of gram-negative bacteria differ from that of gram-positive bacteria?

A

Cell wall = extra layer outside cell membrane on bacteria to protect the cell from osmotic lysis

Gram +ve have many layers of peptidoglycan forming cell wall

Gram +ve = thicker cell wall

Gram-negative bacteria cell wall have 2 layers:

  • inner peptidoglycans (thinner)
  • Outer phospholipid bilayer containing lipopolysaccharide (endotoxin that immune system react to)

Gram -ve = thinner cell wall

Gram +ve do not have LPS

282
Q

Describe the structure of gram negative bacteria

A

Inner membrane (cell membrane) > inter-membrane space (cell wall made of peptidoglycan) > outer membrane

283
Q

Describe the structure of gram positive bacteria

A

Inner membrane (cell membrane) > cell wall composed of many layers of peptidoglycans

284
Q

What the two major genus of gram-positive bacteria

A
  • Streptococci (chains)
  • Staphylococci (clusters)
285
Q

What are some examples of gram-negative bacteria?

A

Escherichia coli - commensal
Shigella
Salmonella

286
Q

What are the 12 major classes of antibiotics?

A

“The Queens Guidance Counsellor Said Antibiotics Can Protect Many (if not) Most Royal Members”

Tetracycline
Quinolone/Fluoroquinolone
Glycopeptide
Cephalosporin (beta-lactam)
Sulfonamides
Aminoglycoside
Carbapenem (beta-lactam)
Penicillin (beta-lactam)
Macrolides
Monobactam (beta-lactam)
Rifampicin
Metronidazole

287
Q

GIve an example of an antibiotic from each of the classes

A

“The Queens Guidance Counsellor Said Antibiotics Can Protect Many (if not) Most Royal Members”

Tetracycline - tetracycline/doxycycline

Quinolone/Fluoroquinolone - ciprofloxacin

Glycopeptide - vancomycin

Cephalosporin - cefotaxime

Sulfonamides - sulfamethoxazole

Aminoglycoside - gentamicin

Carbapenem - meropenem

Penicillin - amoxicillin

*Macrolides - clarithromycin

Monobactam - aztreonam

Rifampicin - rifampcin

Metronidazole - metronidazole

288
Q

Describe the mechanism of action of tetracycline/doxycycline and what pathogens or diseases they target

A

Mechanism: inhibition of the 30s ribosomal subunit - preventing translation
Both gram +ve and -ve - broad spectrum, examples:

  • Staph aureus (+ve)
  • Strep pyogenes (+ve)
  • Strep viridians (+ve)
289
Q

Describe MOA of quinolone/fluoroquinolone (e.g. Ciprofloxacin) and what diseases or pathogens they target

A

Mechanism- inhibition of DNA synthesis (topoisomerase II and IV) in bacteria

Both Gram + and -

  • Strep viridians (+ve)
  • strep pyogenes. (+ve)
  • Pseudomonas auerginosa (-ve)
290
Q

Describe MOA of glycopeptide (e.g. vancomycin) and diseases and pathogens they target

A

Mechanism: inhibits synthesis of bacterial cell wall does not affect mammalian cells as no cell wall

Gram positive (Strep, staph)

Severe staph. infections e.g. MRSA/ C. Difficile

291
Q

Describe MOA of cephalosporin (beta-lactam) (e.g. cefotaxime) and the disease/pathogens they target

A

Part of the beta-lactam class of antibiotics, interferes with cell wall assembly consisting of peptidoglycans by inhibiting transpeptidase enzyme > weakens cell wall > lysis of the bacteria

Both Gram + and -

Hypersensitivity reactions

  • Staph. Aureus,
  • Streptococci
  • Nisseriae
  • Haemophilus influenza
  • Coliforms.
292
Q

Does sulfonamides target gram + or - bacteria or both?

A

Both

Used for pneumocystis pneumonia treatment and prophylaxis

293
Q

Aminoglycoside: MOA and use (e.g. gentamicin)

A

Mechanism: inhibits protein synthesis by 30s ribosomal subunit inhibition

Staph aureus - severe sepsis

294
Q

Carbapenem MOA and use (e.g. imipenem)

A

Beta-lactam - interferes with cell wall assembly consisting of peptidoglycans by inhibiting transpeptidase enzyme > weakens cell wall > lysis of the bacteria.

Both Gram + and -

Broad spectrum

Severe infection
Sepsis
Peritonitis

295
Q

Penicillin: MOA and use

A

Beta-lactam inhibits cell wall synthesis > weakens cell wall > lysis of the target bacteria

Penicillin G - gram positive
Ampicillin - both
Methicillin - both

Narrow spectrum: benzylpenicillin; active against streptococci

Moderate spectrum: amoxicillin; active against a range of Gram-positive and Gram negative bacteria

-Penicillins resistant to staphylococcal b-lactamase = flucloxacillin

296
Q

Macrolides (clarithromycin) MOA and use

A

MOA: Inhibition of 50S ribosome subunit leading to inhibition of protein systhesis

Gram positive

Used in streptococcal and staphylococcal soft tissue infections; respiratory infections including those caused by Mycoplasma pneumoniae, Legionella

297
Q

monobactam (beta-lactam) MOA and use

A

MOA : inhibition of cell wall synthesis
Gram negative
Not on guide so dont need to know

298
Q

What are trimethoprim used for?

A

Trimethoprim:

  • Used for UTIs
  • Inhibition of folic acid synthesis and causes folate deficiency.
  • Do not use in pregnancy
299
Q

Rifampicin MOA and use

A

MOA: binds to and inhibits bacterial RNA polymerase

Both Gram+ and -

Used in combination with isoniazid, pyrazinamide and ethambutol in treatment of TB

300
Q

Metronidazole MOA and use

A

MOA: causes DNA strand breaks and dysregulates DNA synthesis
Both Gram+ and -

Used to treat anaerobic infections and dental
infections

301
Q

Which classes of antibiotics work by inhibiting bacterial cell wall synthesis?

A

Glycopeptide
Cephalosporin
Carbapenem
Penicillin
Monobactam

302
Q

Which classes of antibiotics work by inhibiting synthesis of the bacterial 30s ribosomal subunit - preventing translation?

A

Tetracycline
Aminoglycoside

303
Q

Which classes of antibiotics work by inhibiting synthesis of the bacterial 50s ribosomal subunit - preventing translation?

A

Macrolides

304
Q

Which class of antibiotics work by inhibiting DNA synthesis (topoisomerase II and IV) in bacteria?

A

Quinolone/Fluoroquinolone

305
Q

Which class of antibiotics work by inhibiting folate synthesis in bacteria?

A

Sulfonamides

306
Q

Which class of antibiotics work by inhibiting RNA polymerase in bacteria - preventing transcription?

A

Rifampicin

307
Q

Which class of antibiotics work by damaging bacterial DNA?

A

Metronidazole

308
Q

Which three classes of antibiotics are the beta-lactams?

A

Penicillin
Cephalosporins
Carbapenems

309
Q

Cefuroxime

1) Use
2) MOA
3) Side effects

A

Use: gram-positive and negative infections, hospital-acquired pneumonia

MOA: cefuroxime is a cephalosporin, which are antibacterials that attach to penicillin binding proteins to interrupt cell wall biosynthesis, leading to bacterial cell lysis and death.

Side effects: Abdominal pain; diarrhoea; dizziness

310
Q

Co-amoxiclav

1) Use
2) MOA
3) Side effects

A

1) infection due to beta-lactamase-secreting bacteria

2) Co-amoxiclav is a penicillin. They are bactericidal and act by interfering with bacterial cell wall synthesis

3) Diarrhoea; hypersensitivity; nausea

311
Q

Erythromycin

1) Use
2) MOA
3) Side effects

A

1) Infection (e.g. impetigo, cellulitis)

2) Macrolide - inhibtes synthesis of the bacterial 50s ribosomal subunit - preventing translation

3) Appetite decreased; diarrhoea; dizziness

312
Q

Rifampicin

1) Use
2) MOA
3) Side effects

A

1) Endocarditis and tuberculosis alongside other drugs

2) Inhibits bacterial DNA-dependent RNA polymerase

3) Nausea; thrombocytopenia; vomiting

313
Q

Describe how bacteria can develop resistance to beta-lactam antibiotics through mutations in the transpeptidase gene

A

Transpeptidases (specifically penicillin binding protein) help crosslink the peptidoglycans on bacterial cell wall

Beta-lactam antibiotics work by binding and disrupting these transpeptidases - thus breaking the cell wall

However, some bacteria have developed antibiotics resistance by mutations in their transpeptidase gene, the resulting shape change means the transpeptidase no longer bind to the antibiotics molecules

314
Q

Describe how bacteria can develop resistance to beta-lactam antibiotics through producing beta-lactamase

A
  • Some gram-negative bacteria can produce beta-lactamase - an enzyme which hydrolyses beta-lactam antibiotic molecules.
  • They can share the gene that encode for beta-lactamase with other bacterial cells, thus spreading antibiotic resistance
315
Q

Which gene enables MRSA (Methicillin Resistant Staphylococcus Aureus) to be resistant to beta-lactam antibiotics?

A

resistance gene mecA

316
Q

What protein does mecA encode for?

A

Penicillin-binding protein 2a (PBP2a) - which builds bacterial cell wall by crosslinking amino acids on the peptidoglycans

317
Q

How does penicillin-binding protein 2a (PBP2a) enable MRSA to be resistant to beta-lactams?

A

PBP2a does not bind penicillin, therefore confers resistance to all beta-lactam antibiotics and methicillin

318
Q

What are the 5 main microorganisms that cause UTIs?

A

Remember KEEPS!

Klebsiella
E.coli (80 - 90% cases)
Enterococcus
Proteus mirabilis
Staph saprophyticus (common in young women)

319
Q

What are the symptoms or signs of a lower UTI?

A

Symptoms

Dysuria (painful urination)
Urgency
Increased frequency
Cloudy/foul-smelling urine

SIgns
Haematuria (blood in urine - micro/macro)
Suprapubic tenderness

320
Q

What are the symptoms of an upper UTI?

A

Fever
Confusion
Loin tenderness
History of lower UTI symptoms

321
Q

WHat are the investigations/tests used to diagnose UTIs?

A

1st line: Urine dipstick: nitrite and leukocyte positive

Midstream urine and culture if dipstick positve: gold standard for Dx of the causative agent, urinalysis - white cells and microscopic haematuria

322
Q

What is the length of antibiotics treatment for women with simple lower UTIs?

A

3 days

323
Q

What is the length of antibiotics treatment for women with an UTI who have immunosuppression, abnormal anatomy or impaired kidney function?

A

5 - 10 days

324
Q

What is the length of antibiotics treatment for men, pregnant women and catheter related UTIs?

A

7 days

325
Q

What antibiotics is given to someone with an UTI who is NOT pregnant?

A

Oral Nitrofurantoin or Trimethoprim

326
Q

What antibiotics is given to a pregnant woman someone with an UTI?

A

First-line = nitrofurantoin

DO NOT use trimethoprim as it inhibits folate synthesis and can harm the foetus

327
Q

Why is nitrofurantoin NOT given to pregnant women in their third trimester?

A

Nitrofurantoin is linked with haemolytic anaemia in the newborn

Give amoxicillin instead if not allergic

328
Q

Define virus

A

an infectious, obligate intracellular pathogen comprising of genetic material (DNA/RNA) surrounded by a protein coat and/or membrane

329
Q

Define pathogen

A

Organism that causes or is capable of causing disease

330
Q

Define commensal

A

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

331
Q

Define opportunist pathogen

A

Microbe that only causes disease if host defences are compromised

332
Q

Define virulence

A

The degree to which a given organism is pathogenic.

333
Q

Define asymptomatic carriage

A

When a pathogen is carried harmlessly at a tissue site where it causes no disease

334
Q

What are the differences between bacteria and viruses?

A

Bacteria: has cell wall, DNA, RNA and organelles. Considered living and NOT dependent on host

Virus: no cell wall, no organelles, contain only DNA or RNA. Not living and dependent on host

335
Q

Describe the steps in a virus’ life cycle

A
  1. Attachment
  2. Cell entry
  3. Genome interaction
  4. Genome replication
  5. Assembly
  6. Exit
336
Q

What happens in the attachment stage of the virus life cycle?

A

Virus binds to host cell receptors e.g. gp120 on HIV binding to CD4 on T cells

337
Q

What happens in the cell entry stage of the virus life cycle

A

Viral “core” containing nucleic acids, enzymes for replication and negotiation of host cell defences are released into the host cell cytoplasm

Outer protein coat not released

338
Q

What happens in the genome interaction stage of the virus life cycle?

A

Virus uses cell materials including enzymes, amino acids, nucleotides for their own replication and to evade host cell defences.

Some viruses like HIV produce proviral DNA that integrates itself into the host genome

339
Q

What happens in transcription and translation stage of the virus life cycle?

A
340
Q

What happens in the genome replication stage of the virus life cycle?

A

Once the viral nucleic acids are in the host cell, transcription or translation of the viral genome is initiated. This process results in synthesis of viral nucleic acids, proteins and genome.

341
Q

What happens in the assembly stage of the virus life cycle?

A

This is where the virus puts itself together and encapsulate their genome into a shell called a capsid

Can occur in:
- nucleus e.g. herpesvirus
- cytoplasm e.g. polio virus
- cell membrane e.g. influenza virus

342
Q

What happens in the exit stage of the virus life cycle?

A

This is where the progeny leave the host cell, few enter but millions exit because of replication :(

Different viruses leave in different ways:

  • By bursting open (lysis) of cell e.g. rhinovirus
  • By ‘leaking’ (exocytosis) from the cell over time e.g. HIV & influenza
343
Q

Name the two bacteria that most commonly cause bacterial meningitis in adults and children

A

Neisseria meningitidis (meningococcus)
Streptococcus pneumoniae (pneumococcus)

344
Q

Name the bacteria that most commonly cause bacterial meningitis in neonates.

A

Lancerfield group B strep (GBS) = strep agalactiae - usually lives harmlessly in mother’s vagina

345
Q

Name the viruses that most commonly cause viral meningitis

A

Herpes simplex virus 1/2 (HSV 1/2)
Enterovirus
Varicella zoster virus (VZV)

346
Q

Name the virus that most commonly cause encephalitis

A

Herpes simplex virus - HSV 1 95% cases
Children: Herpes simple type-1 (HSV-1) from cold sores
Neonates: Herpes simple type-2 (HSV-1) from genital herpes contracted during birth

347
Q

Name the two types of bacteria that most commonly cause cellulitis (infection of skin and soft tissues underneath)

A
  • Staphylococcus aureus
  • Group A streptococcus (mainly strep pyogenes)
348
Q

What is the first-line antibiotics used to treat cellulitis?

A

Flucloxacillin - oral or IV

349
Q

What some alternatives to flucloxacillin in treatment of cellulitis?

A

Clarithromycin

350
Q

Define protozoa

A

Microscopic unicellular eukaryotes, can be free-living or parasitic

351
Q

Briefly describe malaria

A

Malaria is an infectious disease caused by members of the Plasmodium family of protozoan parasites.

352
Q

Which 4 species of the Plasmodium family cause malaria?

A
  • P. falciparum (most common and dangerous - 75% cases in UK)
  • P. ovale
  • P. vivax
  • P. malariae
353
Q

How is malaria spread?

A

The bite of the female Anopheles mosquitoes
Infection is acquired when feeding on an infected human

354
Q

What are the steps in the life cycle of Plasmodium

A

Differs between species but generally:

Sporozoites > Merozoites > Trophozoites > Schizonts > Merozoites

355
Q

Describe how sporozoites enter and infect a human

A

A female anopheles mosquito sucks up infected blood, the malaria in the blood reproduce in the mosquito gut producing thousands of sporozoites

Mosquito bites another human > sporozoites injected > sporozoites travel to liver of newly infected person

356
Q

Which two plasmodium species can lay dormant as hypnozoites in the liver for a few years after infection?

A

P.vivax
P.ovale

357
Q

What happens after sporozoites enter the liver of the newly infected person?

A

They mature into merozoites which enter blood and infect RBCs > reproduce over 48 hours > RBCs rupture > release more merozoites into blood > haemolytic anaemia

People infected with malaria therefore have high fever spikes every 48 hours

358
Q

Define fungi

A

Eukaryotic organism with cell wall made of chitin and glucan

Clinically usually opportunistic

359
Q

What are two main species of fungi that cause disease?

A

Candida albicans
Aspergillus fumigatus

360
Q

What disease does Candida albicans cause?

A

Thrush - vaginal and oral

Sepsis (candidiasis)

Line/catheter infections

Can kill rapidly if untreated

361
Q

What disease does Aspergillus fumigatus cause?

A

Lung infections, allergic disease.

Usually affect those with weakened immune system or underlying lung conditions

Poor prognosis but kills slowly

362
Q

What is the treatment for fungal diseases?

A

Generally difficult to treat as fungi are eukaryotic like human cells.

Usually antifungal drugs that target fungal cell wall/plasma membrane

E.g. azole group (e.g. Fluconazole, Clotrimazole & ketoconazole)

363
Q

Describe what happens in a newborn baby check and when it occurs

A

Within the first 72 hours of life

  • Physical examination
  • Heel prick test - newborn screening

The purpose:

  • Screen for congenital abnormalities that will benefit from early intervention
  • To make referrals for further tests or treatment as appropriate
  • To provide reassurance to the parents
364
Q

What happens in a newborn physical examination?

A

The HCP checks the baby’s eyes, heart, hips and testicles (in boys) to detect any problems

A newborn hearing screen is conducted as well.

365
Q

What condition does the heel prick test screen for?

A

Carried out when the baby is 5 days old, and screens for:

  • Sickle cell anaemia
  • Cystic fibrosis
  • Congenital hypothyroidism
  • Inherited metabolic disease (e.g. phenylketonuria)
  • Severe combined immunodeficiency (SCID) (in some areas of England)
366
Q

When does the postpartum check occur?

A

When the baby is 6 - 8 weeks of age

367
Q

What happens at the postpartum check?

A

The GP will ask mum questions to assess her and the baby’s health - physical symptoms, psychological problems, social problems, sex & contraception

368
Q

What vaccination is given when the baby is 8 weeks old?

A

6-in-1vaccination against:

  • Diphtheria
  • Hepatitis B
  • Hib (Haemophilus influenzae type b)
  • Polio
  • Tetanus
  • Whooping cough (pertussis)
369
Q

What are the routes of administration for paracetamol for babies and children

A

Oral, rectal (PR) and IV

370
Q

What investigations/tests are used to diagnose viral diseases?

A

Serology testing (detects antibodies against virus) - ELISA (enzyme-linked immunosorbent assay), immunofluorescence, complement fixation

Viral detection - EM, PCR (quick, easy and cheap when you suspect a particular virus)

Diagnostic swabs - green swabs for viral infections and black charcoal swabs for bacterial infection - differentiate between the different sources of infection

371
Q

What diseases does the Epstein-Barr virus most commonly cause?

A

Infectious mononucleosis (glandular fever)

372
Q

IM is usually accompanied by pharyngitis with tonsillar exudates (liquid with yellow pus). What is a DDx for pharyngitis?

A

Streptococcal pharyngitis caused by S.pyogenes - EBV pharyngitis is usually clinically indistinguishable from strep. pharyngitis

373
Q

IM is usually accompanied by pharyngitis with tonsillar exudates (yellow purulent lining over tonsils). What is a DDx for pharyngitis?

A

Streptococcal pharyngitis - EBV pharyngitis is usually clinically indistinguishable from strep. pharyngitis

Exclude S.pyogenes infection using black charcoal swabs

374
Q

Green viral swabs cannot diagnose EBV. What investigations/tests are used instead?

A

Primary investigations:

  • FBC: may show more than 20% atypical/reactive lymphocytes or a lymphocytosis - available in hours
  • Monospot test (heterophile antibodies): tested in the 2nd week of symptoms to confirm the diagnosis
375
Q

What signs and symptoms might a patient with IM/EBV infection present with?

A

Symptoms:

  • Tonsillitis
  • Cough
  • Fever

Signs:

  • Splenomegaly
376
Q

What is the management plan for IM?

A

Conservative. However, hospital admission if the patient has stridor (high-pitched sound on auscultation indicating airway obstruction), dehydration or difficulty swallowing fluids, or a complication such as a splenic rupture.

1st line: conservative measures: oral fluids and paracetamol/ibuprofen for pain and fever relief

Avoid heavy lifting: for the first month of the illness to reduce the risk of splenic rupture.

377
Q

What disease does cytomegalovirus (CMV) cause?

A

CMV colitis/gastroenteritis - inflammation of GI tract due to CMV infection.

Characteristic “owl-eye” inclusion bodies under the microscopy

378
Q

What condition does CMV colitis/gastroenteritis indicate?

A
  • As usually asymptomatic, if CMV infects healthy patients, it is an AIDS defining illness
379
Q

What is the management plan for CMV disease?

A

Mild, self-limiting illness is usually managed conservatively.

Intravenous ganciclovir (Antiviral) is the first-line antiviral treatment of severe CMV disease, including severe colitis and pneumonitis

380
Q

Treatment for DVT: describe the MOA of heparin in relation to the coagulation cascade

A
  • It is a glycosaminoglycan
  • Binds to antithrombin and increases its activity (antithrombin inactivates several factors of the coagulation cascade - factor IIa (thrombin) and factor Xa)
  • Monitor with activated partial thromboplastin time (APTT), aim ratio 1.2-2.8
  • Given by continuous infusion
381
Q

Treatment of DVT: what is low molecular weight heparin?

A
  • Smaller molecule compared to heparin, less variation in dose, and renally excreted
  • Affects instinct pathway, activates antithrombin - inactivates factor Xa and IIa (thrombin)
  • Once daily, weight-adjusted dose given subcutaneously
  • Used for treatment and prophylaxis, preferred over heparin as reduced risk of heparin-induced thrombocytopenia) and generally more convenient to use
382
Q

Treatment of DVT: describe the MOA of warfarin in relation to the coagulation cascade

A
  • Warfarin affects the extrinsic pathway, and it is a vitamin K antagonist. Therefore it inhibits vitamin K-dependent clotting factor synthesis - factors X, IX, VII and II (1972)
  • Difficult to use, need to monitor
  • Measure INR (international normalised ratio, derived from prothrombin time (PT))
  • Target range: 2-3, higher range: 3-4.5
383
Q

Treatment of DVT: describe the MOA of DOACs (e.g. apixaban, rivaroxaban) in relation to the coagulation cascade

A
  • Directly-acting Oral Anticoagulants
  • Affects intrinsic pathway, direct inhibitor of activated factor X (factor Xa)
  • No blood tests or monitoring
  • Side effects: anaemia; asthenia (weakness); constipation; diarrhoea
  • teratogenic
384
Q

Dobutamine

1) Use
2) MOA
3) Side effects

A

1) Inotropic support in infarction, cardiac surgery, cardiomyopathies

2) Dobutamine is a cardiac stimulant which acts on beta1 receptors in cardiac muscle and increases contractility.

3) Arrhythmias; bronchospasm; chest pain

385
Q

What is a vaccine?

A

Controlled and safe exposure to part of a pathogen that is immunogenic and will induce immunological memory with little to no harm to the host.

A lot of vaccines have an initial “prime” dose followed by a “boost dose”.

An ideal vaccine will induce both T and B memory cells.

386
Q

What is the role of an adjuvant?

A

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

387
Q

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

A

TLR4 agonist (mimics lipopolysaccharide)

388
Q

Give 3 advantages of live (attenuated) vaccines

A
  • Live/attenuated vaccines contains the live pathogen with reduced virulence
  • Very effective, prolonged and comprehensive.
  • Immunological memory produced.
  • Often only 1 vaccine is needed.
389
Q

Give 3 disadvantages of live (attenuated) vaccines

A
  • Immunocompromised patients may become ill.
  • Vaccines often need to be refrigerated which can be a problem in remote areas.
390
Q

Give 2 advantages of inactivated vaccine

A

Vaccines consisting of the pathogens that have been grown in culture and then killed to destroy disease-producing capacity

  • No risk of infection
  • Storage method is less critical
391
Q

Give 2 disadvantages of inactivated vaccine

A
  • Inactivated vaccines tend to only activate the humoral response; there is a lack of T cell involvement.
  • Boosters are needed and so patient compliance may be poor.
392
Q

What can be used as an adjuvant?

A

Toxoids (inactivated toxins), proteins, chemicals (aluminium salts) etc.

393
Q

What are the 5 features of an ideal vaccine?

A

1) Safe.
2) Induces a suitable immune response.
3) Shouldn’t require repeated boosters.
4) Generates immunological memory (T and B cell response)
5) Stable and easy to transport.

394
Q

Aspirin MOA, Use, Side effects

A

Aspirin works by IRREVERSIBLY inhibiting Cox and prevents the
breakdown of arachidonic acid into prostaglandin H2. It is non-selective
for Cox-1 and Cox-2.

Used in secondary prevention of CVD (75mg)

Management of unstable angina, non-STEMI, STEMI, acute ischaemic stroke (300mg)

Secondary prevention of ischaemic stroke (not associated with AF) (75mg)

Side effects: general: asthma attack, bronchospasm

Specific: oral use = dyspepsia, haemorrhage

Sharon's Phase 2a Medicine Revision (10 decks)

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