Week 5 - inflammatory arthritis Flashcards
(213 cards)
1
Q
Which genes are associated with a higher risk of rheumatoid arthritis? (LO1)
A
- HLA DRB1
- HLA DRB4
2
Q
List some environmental risk factors associated with rheumatoid arthritis. (LO1)
A
- Smoking.
- Pollution.
- Infection.
- Obesity.
- Immunisation.
- Blood transfusion.
- Previous termination of pregnancy.
- Ages 40-60.
- Females to males, 2:1.
3
Q
List some protective factors against developing rheumatoid arthritis. (LO1)
A
- Vitamin C.
- Vitamin E.
4
Q
Describe the basic epidemiology of rheumatoid arthritis. (LO1)
A
- Overall prevalence worldwide: 0.8-1%.
- Females more at risk than males.
- Both genders more at risk as they age.
- Link found between Pakistanis developing rheumatoid arthritis after moving to a western environment (England).
5
Q
Explain the link between ethnicity and the risk of developing rheumatoid arthritis. (LO1)
A
- Pima Indians - 5-6%.
- Europeans, South Americans - 0.5-1%.
- Africans, Asians - <0.4%.
6
Q
Describe the pathophysiology of rheumatoid arthritis. (LO1)
A
- An environmental factor may initiate primary inflammation in a genetically susceptible individual.
- This can occur in various tissues and trigger the immune response to citrullinated proteins.
- The resulting anti-citrullinated protein/peptide antibodies (ACPAs) are distributed through the circulation and may form immune complexes with citrullinated proteins produced in an inflamed synovium, boosting the inflammatory process.
- This will be associated with the infiltration and activation of neutrophils, macrophages and lymphocytes, cell death, extracellular DNA trap formation, activation and release of peptidylarginine deiminases (PADs), de novo citrullination and disversification of the ACPA response.
7
Q
What is meant by citrullination? (LO1)
A
- Citrullination of synovial cells in the joint is the conversion of the amino acid arginine in a protein into the amino acid citrulline.
- Increased rheumatoid factor shows loss of tolerance to citrulline.
8
Q
How is the synovium linked to the pathogenesis of rheumatoid arthritis? (LO1)
A
- An inflamed synovium is central to the pathogenesis.
- The synovium shows increased angiogenesis, cellular hyperplasia, influx of inflammatory cells, changes in the expression of cell surface adhesion molecules, and many cytokines.
- The synovial lining becomes hyperplastic, with infiltration of the sublining with mononuclear cells including T cells, B cells, macrophages, and plasma cells.
- This formation of locally invasive synovial tissue is characteristic and it is involved in causing erosions seen in rheumatoid arthritis.
9
Q
Explain how cytokines are involved in the pathogenesis of rheumatoid arthritis. (LO1)
A
- Cytokines affect all phases of the inflammatory process.
- TNF, IL-1 and IL-6 seem to be the most abundant in the joint.
- Both TNF and interleukins promote proliferation, metalloproteinase expressions, adhesion molecule expression, and further secretion of other cytokines.
- The proliferation of new blood vessels provides for the hypertrophic synovium.
- This inflammatory setting, when not treated, leads to the eventual destruction of the joint.
10
Q
Describe the presentation of rheumatoid arthritis. (LO1)
A
- PC of bilaterial, symmetrical pain and swelling of the small joints of the hands and feet lasting >6 weeks.
- Morning stiffness over 1 hour.
- Articular or extra-articular.
- Visible deformity seen in smaller joints of the hands, feet and cervical spine.
- Main joints affected: PIP, MCP, MTP, base of the thumb and big toe.
- Boutonniere deformity - PIP flexion with DIP hyperextension.
- Swan-neck deformity - PIP hyperextension, DIP hyperflexion.
- Hallux valgus or hammer-toe in the feet - can see rheumatoid nodules in both.
- Extra-articular manifestations: nodules on the skin, a pleural effusion (lungs), pericarditis (heart), tenosynovitis (muscles) or keratoconjunctivitis sicca (eyes).
11
Q
Describe a complication of rheumatoid arthritis. (LO1)
A
- Ulnar deviation due to inflammation of the MCP joints, causes the fingers to dislocate.
- As the tendons pull on the dislocated joints, the fingers tend to drift towards the ulnar side.
12
Q
How can rheumatoid arthritis presentations vary in terms of onset? (LO1)
A
- Additive - will start in one joint and spread but will continue in that initial joint.
- Insidious in 70% of patients - slow onset, rather than acute.
- Palindromic - will come and go, and flare up.
- Polymyalgic - can look polymyalgic rheumatica.
13
Q
Describe the investigations for rheumatoid arthritis. (LO1)
A
- Take a history.
- Inspect the joints for the common presentations.
- Perform full examination on the affected areas.
- Blood test - raised ESR and CRP, raised RF, raised anti-CCP, anaemia of chronic disease, neutrophilia.
- X-ray.
- DAS-28 score.
14
Q
Explain why anti-CCP is preferred to diagnose rheumatoid arthritis rather than rheumatoid factor (RF). (LO1)
A
- RF is more sensitive but less specific.
- anti-CCP is less sensitive but more specific.
- Anti-CCP is used more than RF because RF is found in other other diseases such as endocarditis, hepatitis, TB, bronchitis, cirrhosis, malignancy, ageing, and many more.
- Positive anti-CCP can be seen in 40% of seronegative patients but it’s a good predictor of erosive disease.
- Anti-CCP can be positive when RF is negative.
- Anti-CCP plays more of a pathogenic role in RA.
- Anti-CCP is positive in about 70% of patients with RA.
- RF is positive in about 60-70% of patients with RA. It is not required for diagnosis but is helpful if present.
15
Q
Explain why we use x-rays to investigate rheumatoid arthritis, especially when deformities are visible without. (LO1)
A
- Shows deviation of digits and subluxation of the MCP or MTP joints.
- RA can also lead to erosions within the bones of the joint as the synovium has become inflamed.
- Erosions are seen in around 40-73% of patients within the first year of RA.
16
Q
Describe what is meant by DAS-28. (LO1)
A
- A scoring system designed to diagnose rheumatoid arthritis.
- 28 joints are assessed on the patient and they are given a score based on multiple factors.
17
Q
List the factors used for the DAS-28 scoring system. (LO1)
A
- Tenderness of joints.
- Swelling of joints.
- ESR from bloods and general health assessment (ask the patient how active they think their disease is on a scale of 1-10).
- The feet and ankle are missed from this exam as it was designed to be quick and easy.
18
Q
Describe the management of rheumatoid arthritis. (LO1)
A
- NSAIDs - OTC, Naproxen, intermittent steroids (in that order).
- DMARDs - within 3 weeks of presentation to prevent damage to joints and soft tissues.
- 1st line DMARDS (non-biologics) - methotrexate, leflunomide, hydroxychloroquine, sulfasalazine.
- If one of these is not effective, another can be prescribed - up to 3 non-biologics can be given.
- If DAS-28 > 5.1 and 2 DMARDs are not effective, biologic DMARDs should be considered.
- Biologic DMARDS include TNF-alpha inhibitors (infliximab, adalumimab), T-cell blockers (abatacept), B-cell depletion (rituximab), IL-6 inhibitors (toclizumab), JAK inhibitors (tofacitinib).
19
Q
Describe the prognosis of rheumatoid arthritis. (LO1)
A
- If treated early and aggressively, good prognosis - achieving good disease control.
- If there’s a delay in treatment initiation or if it remains untreated, patient may be disabled within 10 years.
- Untreated RA is also associated with premature mortality, most commonly from coronary artery disease.
- Flares are common even in patients well-controlled with DMARDs. Temporary oral corticosteroids are usually adequate.
- For patients in remission, or low disease activity who are taking biological DMARDs, discontinuing of the drugs could lead to increased risk of losing remission.
20
Q
Describe the basic epidemiology of lyme disease. (LO2)
A
- Bacterial infection caused by Borrelia burgdorferi and spread by vectors such as Ixodes scapularis (black-legged tick).
- Most common vector-borne disease in the US and Europe. One of the most common notifiable disease in the US.
- Most common in temperate regions of the Northern hemisphere.
- Majority of cases usually occur in spring and early summer as that’s when outdoor activity increases due to good weather.
- Men and women are at equal risk and all ages can be affected.
- Age groups with highest risk: 10-19 years and 50-59 years.
21
Q
Describe the presentation of lyme disease. (LO2)
A
- Erythema migrans - expanding red, ring-like rash at the site of the bite. 50-90% of lyme disease patients have it.
- Musculoskeletal: arthralgia/arthritis - monoarticular/oligoarticular, most common in knee joints.
- Neurological: cranial nerve palsy, encephalitis.
- Cardiovascular - carditis with atrioventricular blockage.
22
Q
List the clinical investigations for lyme disease. (LO2)
A
- Erythema migrans rash - enough to make a diagnosis and begin treatment.
- Myalgia.
- Fatigue.
- Fever.
- Headache.
23
Q
Describe the investigations for lyme disease in the absence of an erythema migrans rash. (LO2)
A
- Enzyme-linked immunosorbent assay (ELISA) test - positive result for Lyme disease.
- Confirmatory immunoblot test - positive result for Lyme disease.
ELISA test are used to confirm the presence of antibodies relating to a specific infectious disease.
24
Q
Describe the management of lyme disease. (LO2)
A
- Post-exposure prophylaxis - single dose of doxycycline within 72 hours of tick removal if the tick has been attached for about 36 hours.
- For erythema migrans - doxycycline for 10 days or amoxicillin, cefuroxime or phenoxymethylpenicillin for 14 days.
- For lyme arthritis - oral antibiotics (doxycycline, amoxicillin, cefuroxime, phenoxymethylopenicillin) for 28 days and NSAIDs for symptom relief.
25
Describe the prognosis of lyme disease. (LO2)
- Lyme disease is usually curable with a complete course of the appropriate antibiotics.
26
List some causes of chronic inflammation. (LO3)
- Persistent infection - most common.
- Infection with viruses, mycobacteria, parasites and fungi.
- Autoimmune disease - e.g. allergic reactions + asthma.
- Foreign material - e.g. thorn in hand.
- Carcinoma.
27
List the cells involved in chronic inflammation. (LO3)
- Macrophages are the main cell - there are two subtypes: M1 and M2.
- Lymphocytes are also involved: T-cells and B-cells.
28
List the subtypes of macrophages and explain their function. Which cytokines are they activated by? (LO3)
- M1 - pro-inflammatory - activated by bacteria or IFN-γ from T-cells.
- M2 - anti-inflammatory - activated by IL-4 or IL-13 from T-cells.
29
Describe the types of lymphocytes involved in chronic inflammation and explain their function. (LO3)
- B-cells - activated by T helper cells.
- T-cells - CD4+ helper T cells have 2 main subtypes: Th1 and Th2.
- TH1: secrete IFN-γ.
- TH2: important in allergies.
30
What is meant by granulomatous inflammation and what is it caused by? (LO3)
- The formation of granulomas: a collection of activated macrophages/epithelioid histiocytes.
- Caused by:
- Foreign material.
- Sarcoidosis.
- Crohn's disease.
- Cat scratch disease.
31
How do granulomas form? (LO3)
- Macrophages process and present an antigen to CD4+ T helper cells.
- They then secrete IL-12, causing CD4+ T helper cells to differentiate into Th1.
- Th1 secrete IFN-γ which converts macrophages into epithelioid histiocytes and giant cells.
N.B. levels of IFN-γ are helpful in indicating TB.
32
List the three stages of healing. (LO3)
- Coagulation phase.
- Inflammatory phase.
- Proliferative/granulation tissue phase.
33
List the three subtypes of tissues based on their regenerative capacity. (LO3)
- Labile - stem cells present, e.g. skin.
- Stable - can regenerate when needed, e.g. liver.
- Permanent - lack of regenerative potential, e.g. myocardial tissue.
34
Describe the coagulation phase of wound healing. (LO3)
- Started by Hageman factors coming into contact with collagen.
- This starts thrombosis (blood clotting) caused by the coagulation cascade.
35
Describe the inflammatory phase of wound healing. (LO3)
- Neutrophils, macrophages and platelets arrive.
- Neutrophils and macrophages clear out the wound.
- Platelets degranulate.
36
Describe the proliferative phase of wound healing. (LO3)
- Degranulation of platelets releases growth factors causing new cells to enter the wound.
- Proliferation of new capillaries and fibroblasts.
37
List the two types of scar with excess scar tissue and explain the difference. (LO3)
- Hypertrophic scar - excess production of scar tissue localised to the wound.
- Keloid scar - excess production of scar tissue out of proportion to the wound size - caused by excess type 3 collagen and more common in black people.
38
List the factors that can cause delayed wound healing. (LO3)
- Infection - causes more PAMPs.
- Ischaemia - reduces blood supply and healing needs blood supply.
- Foreign bodies - increase infection.
- Diabetes - can impair growth factors and cause narrowing of blood vessels - also makes blood more sugary which favours pathogens.
- Malnutrition - reduces essential elements needed: copper and vitamin C for collagen cross-linking and zinc which is a co-factor for collagenase (replaces type 3 with type 1).
39
What is meant by immune tolerance? (LO4)
- A concept which explains why we do not make antibodies against "self" antigens.
40
What is meant by immunological self? (LO4)
The identity of cells which have "self" antigens. These antigens are recognised by T cells and the immune system does not create antibodies against these antigens.
N.B. We can still make antigens against other's antigens, e.g. tissue rejection.
41
Describe acquired immunity. (LO4)
- Gene rearrangement in T and B cells is essential in acquired immunity and these are random.
- Rearrangements must be acquired after encountering foreign antigens and pathogenic antigens.
- B cells cannot make antibodies without T cell help. B cells must also present antigens to T cells to survive.
- Memory (T and B) cells can respond quickly to secondary infections.
- Plasma cells secrete antibodies.
- Th1 cells aid the effector function of antibodies.
- Th2 cells aid B cell differentiation and antibody production, e.g. after a vaccine.
42
Briefly describe antigen presentation. (LO4)
- The pathogen is phagocytosed by an antigen presenting cell, e.g. macrophage/dendritic cell.
- The pathogen is placed in a lysozyme where it is digested by proteolysis.
- The antigen is loaded onto an MHC so it can be presented to T cells.
43
What is the difference between MHC and HLA? (LO4)
Trick question:
- HLA and MHC are the same thing.
- HLA - human leucocyte antigen - humans.
- MHC - major histocompatibility complex - mice.
44
Describe the function of MHC/HLA proteins. (LO4)
They present pathogenic peptides to immune cells - usually T cells.
45
What are the two types of HLA/MHC proteins and where are they found? (LO4)
- MHC class I - most cells except neurons.
| - MHC class II - antigen presenting cells.
46
Why do we get tissue rejection even though all humans have MHC/HLA proteins? (LO4)
- The proteins which form the MHC/HLA vary between individuals.
- This is why rejection can occur if a donor and recipient aren't matched.
- The genes for MHC/HLA is >3 million base pairs on chromosome 6 and to prevent an immune response, the MHC/HLA protein must be IDENTICAL to the "self" protein.
47
List some diseases associated with mutations of HLA genes. (LO4)
Broadly, these are called autoimmune conditions. Mutations of the HLA gene leads to misidentification of the "self" antigen, leading to autoimmune disease.
HLA I mutations:
- HLA B27 - Ankylosing spondylitis + other seronegative arthropathies.
HLA II mutations:
- HLA-DR3 - Rheumatoid arthritis.
- HLA-DR3/DQ2/DQ8 - Type 1 Diabetes Mellitus.
48
Briefly describe T cells loading with "self" peptides. (LO4)
- Our cells are constantly carrying out protein homeostasis which is the breakdown of proteins to maintain intracellular protein levels.
- Proteins broken down in the proteosome are called "self" peptides. These self-peptides are loaded onto MHC/HLA and presented to T cells receptors (TCRs) as "self".
- An immune response can be triggered by both the wrong antigen and the wrong MHC (organ donation).
49
Briefly describe the recognition of MHC. (LO4)
Peptide complexes by the T cell receptor triggers signal transductions which lead to gene expression. This promotes synthesis of cytokines and cell adhesion molecules, leading to an immune response.
50
B cells require T cells in order to survive and produce antibodies. How do these cells find each other? (LO4)
- Within secondary lymphoid organs, e.g. lymph nodes.
- The lymphatic system receives B and T cells from primary lymphoid organs where they are produced.
- B and T cells are stored in lymph nodes and are constantly coming across antigens until an immune response is triggered.
51
Briefly describe the process from innate immunity until antigen presentation. (LO4)
- Pathogens express PAMPs which are recognised by toll-like receptors (TLRs).
- This triggers phagocytosis and degradation of the PAMPs in the lysosome.
- A peptide is formed, bound to MHC and presented.
- The APCs change expression of cell adhesion molecules to move into the lymph vessels where they seek out T cells.
- APC presents MHC II loaded peptide, if it is not recognised as "self", the T cells start to divide.
- T cell division is why lymph nodes swell during infection.
52
What are PAMPs and which receptors correspond to them? (LO4)
Pathogen-associated molecular patterns are recognised by toll-like receptors (TLRs).
Types of pathogen-associated molecular patterns:
- Flagella - recognised by toll-like receptor 5 (TLR5).
- Lipopolysaccharides - recognised by toll-like receptor 4 (TLR4).
- Cell walls - recognised by toll-like receptor 2 (TLR2).
53
Why are dendritic cells better antigen presenting cells (APCs) than others? (LO4)
They have a larger surface area and therefore, a higher yield of MHC II bound peptides.
54
Why do the lymph nodes swell during infection? (LO4)
This is due to T cell division after recognition of the antigen as non-self in the lymph nodes.
55
Where do T cells mature? (LO4)
Thymus.
56
Where do B cells mature? (LO4)
Bone marrow.
57
Name the two parts of the selection process for T cells. (LO4)
Positive selection.
| Negative selection.
58
Describe the selection process for T cells. (LO4)
POSITIVE SELECTION:
- If the immature T cells cannot bind to MHC "self" at all, they die.
- If the immature T cells bind weakly/moderately to MHC "self" peptide, they survive.
- These cells mature and are found in the lymphatic system.
NEGATIVE SELECTION:
- If the immature T cells bind strongly to MHC "self" peptide, they die.
- If the immature T cells bind weakly/moderately to MHC "self" peptide, they survive.
59
What is meant by central tolerance? (LO4)
The elimination of self-reactive T cells in the thymus.
60
Describe the positive selection process for T cells. (LO4)
- If the immature T cells cannot bind to MHC "self" at all, they die.
- If the immature T cells bind weakly/moderately to MHC "self" peptide, they survive.
- These cells mature and are found in the lymphatic system.
61
Describe the negative selection process for T cells. (LO4)
- If the immature T cells bind strongly to MHC "self" peptide, they die.
- If the immature T cells bind weakly/moderately to MHC "self" peptide, they survive.
62
Why do T cells not attack "self" antigens? (LO4)
- T cells are produced from precursor cells.
- The precursor cells have not undergone gene rearrangement. They do not express T cell receptors and cannot bind antigens.
- Mature T cells leaving the thymus have undergone gene rearrangement but most of these cannot bind strongly to "self" antigens.
- Self-reactive T cells are suppressed and destroyed. The mature T cells must pass checks to ensure they do not react to "self". Failure of this test leads to their destruction.
- B cells rely on T cells so if the T cells are not self-reactive, B cells are normal.
63
How do diseases associated with HLA gene mutations arise? (LO4)
The mutations allow some self-reactive T cells to escape the thymus and stimulate B cells to produce self-reactive antibodies.
64
List the drugs used for the treatment of pain in rheumatoid arthritis. (LO5)
NSAIDs:
- Improves joint pain and stiffness.
- No effect on disease activity or progression.
- If one doesn't work, try another.
Corticosteroids.
- Improves pain and swelling.
- Low dose of prednisolone used before DMARDs become effective.
- Intra-articular via intramuscular administration.
- IV route for general flare up.
65
Which category of drugs are used for the prevention of damage in rheumatoid arthritis? (LO5)
Disease modifying antirheumatic drugs (DMARDs).
66
List the key features of DMARDs. (LO5)
- Suppress disease activity.
- Slow the process of joint erosion.
- Some suppress the immune system.
- Others inhibit cell replication.
- Slow-acting and take weeks to produce a clinical effect.
- If one DMARD doesn't work, you can try another or add one.
- Most DMARDS are not understood.
67
List the most common DMARDs. (LO5)
- Azathioprine.
- Cyclophosphamide.
- Ciclosporin.
- Gold.
- Hydroxychloroquine.
- Leflunomide.
- Methotrexate.
- D-penicillamine.
- Sulfasalazine.
68
List the side effects of the most common DMARDs. (LO5)
```
Azathioprine:
- GI disturbance.
- Bone marrow suppression.
Cyclophosphamide:
- Bone marrow suppression.
- Increased risk of malignancy.
- Infertility.
Ciclosporin:
- Renal impairment.
- Hypertension.
- Bone marrow suppression.
Gold:
- Rash.
- Proteinuria.
- Bone marrow suppression.
Hydroxychloroquine:
- Retinal damage.
Leflunomide:
- Hypertension.
- GI disturbance.
- Bone marrow suppression.
Methotrexate:
- GI disturbance.
- Oral ulcers.
- Raised liver enzymes.
- Pneumonitis.
- Bone marrow suppression.
D-penicillamine:
- Rash.
- Proteinuria.
- Bone marrow suppression.
Sulphasalazine:
- GI disturbance.
- Raised liver enzymes.
- Bone marrow suppression.
```
69
List the side effects of azathioprine. (LO5)
Azathioprine is a DMARD.
- GI disturbance.
- Bone marrow suppression.
70
List the side effects of cyclophosphamide. (LO5)
Cyclophosphamide is a DMARD.
- Bone marrow suppresion.
- Increased risk of malignancy.
- Infertility.
71
List the side effects of ciclosporin. (LO5)
Ciclosporin is a DMARD.
- Renal impairment.
- Hypertension.
- Bone marrow suppression.
72
List the side effects of gold as a DMARD. (LO5)
- Rash.
- Proteinuria.
- Bone marrow suppression.
73
List the side effects of hydroxychloroquine. (LO5)
Hydroxychloroquine is a DMARD.
- Retinal damage.
74
List the side effects of leflunomide. (LO5)
Leflunomide is a DMARD.
- Hypertension.
- GI disturbance.
- Bone marrow suppression.
75
List the side effects of methotrexate. (LO5)
Methotrexate is a DMARD.
- GI disturbance.
- Oral ulcers.
- Raised liver enzymes.
- Pneumonitis.
- Bone marrow suppression.
76
List the side effects of D-penicillamine. (LO5)
D-penicillamine is a DMARD.
- Rash.
- Proteinuria.
- Bone marrow suppression.
77
List the side effects of sulphasalazine. (LO5)
Sulphasalazine is a DMARD.
- GI disturbance.
- Raised liver enzymes.
- Bone marrow suppression.
78
Describe the monitoring required of patients on methotrexate. (LO5)
- Full blood count, liver function test and renal function test every 4-8 weeks.
79
Describe what is meant by therapy using biologics for rheumatoid arthritis. (LO5)
- DMARDs are non-biologics.
- Biologics target inflammatory mediators of rheumatoid arthritis.
- They're widely used.
- They either target TNF-α or other cytokines at different stages.
80
List some agents inhibiting TNF-α in rheumatoid arthritis. (LO5)
- Etanerpt - soluble TNF-α receptor.
- Infliximab - monoclonal antibody against TNF-α.
- Adalimumab - monoclonal antibody against TNF-α.
81
List some drugs that manipulate other cytokines in rheumatoid arthritis. (LO5)
- Rituximab - monoclonal antibody against B-cells, used when TNF-α treatment has failed.
- Abatacept is a T-cell co-stimulation modulator.
82
List some inflammatory markers. (LO6)
- Erythrocyte sedimentation rate (ESR).
- C-reactive protein (CRP).
- Fibrinogen and fibrinogen-derived peptides.
Others:
- Urea and electrolytes.
- Liver function tests.
- Plasma viscosity.
83
List some inflammatory markers found in a full blood count. (LO6)
- Normocytic anaemia.
- Microcytic anaemia.
- Haemolytic anaemia.
- Macrocytic anaemia.
- Reactive thrombocytosis.
- WBC count.
84
Describe how normocytic anaemia can be used as an inflammatory marker. (LO6)
- May show chronic inflammation or traumatic blood loss.
- Normocytic just means low blood cell count but the cells are of normal shape and size.
- This is not due to the other type of anaemia.
85
Describe how microcytic anaemia can be used as an inflammatory marker. (LO6)
- Smaller red blood cells can be seen.
| - NSAIDs and chronic GI blood loss can contribute to this.
86
Define haemolytic anaemia and describe how it can be used as an inflammatory marker. (LO6)
- Haemolytic anaemia is the destruction of red blood cells.
| - Autoinflammatory diseases can lead to haemolytic anaemia.
87
Define macrocytic anaemia and describe how it can be used as an inflammatory marker. (LO6)
- Macrocytic anaemia means abnormally large red blood cells with too little haemoglobin.
- Autoinflammatory diseases can lead to macrocytic anaemia.
88
Describe how white blood cell (WBC) count can be used as an inflammatory marker? (LO6)
- High WBC can indicate infection, inflammation or steroid use.
- Low WBC (neutropenia) can indicate use of anti-rheumatic drugs.
89
Define reactive thrombocytosis and describe how it can be used as an inflammatory marker. (LO6)
- Reactive thrombocytosis means an abnormally high platelet count in the absence of chronic myeloproliferative disease.
- It can occur in inflammatory diseases, driven by the overproduction of thrombopoietin, IL-6, other cytokines or catecholamines in inflammation and infection.
90
What is erythrocyte sedimentation rate (ESR) and how can it be used as an inflammatory marker? (LO6)
- ESR is the rate of red blood cell sedimentation over an hour.
- It increases with higher plasma proteins, e.g. immunoglobulins and fibrinogen (one of 13 coagulation factors).
- Upper limit of ESR increases with advancing age and in overweight women.
91
What is c-reactive protein (CRP) and how can it be used as an inflammatory marker? (LO6)
- CRP is an acute phase protein made in the liver (pentraxin protein family).
- It binds to Fc receptors on monocytes and neutrophils which stimulates cytokine production.
- CRP is involved in the complement cascade.
- CRP also works as an opsonin.
- Levels of CRP rise from inflammation and infection.
- It takes 6-10 hours after inflammatory event to start increasing levels.
- Quicker response to inflammatory changed than ESR.
92
What is plasma viscosity and how does it indicate inflammation? (LO6)
- Plasma viscosity is a test for the viscosity of blood.
- It indicates the presence of acute phase proteins.
- Normal range is 1.10-1.30mPa s (millipascal second) at 37°C.
- Associated autoimmune conditions includes rheumatoid arthritis, Sjogrens, psoriatic arthritis, SLE, polymyalgia rheumatica and sarcoidosis.
93
How does fibrinogen and its derived peptides indicate inflammation? (LO6)
- Synovial fluid from rheumatoid arthritis shows soluble endogenous fibrinogen-derived peptides, e.g. significant amounts of citrulline residues and sometimes phosphorylated serine.
- Citrullinated peptides are more abundant in the synovial fluid of rheumatoid arthritis, compared to other inflammatory joint diseases.
94
How can urea and electrolytes indicate inflammation? (LO6)
- Gout or connective tissue disease can lead to renal function impairment, e.g. uric acid kidney stones affecting excretion.
95
How can results of liver function tests indicate inflammation? (LO6)
- Alkaline phosphatase is found in bone and liver.
- Can be an indicator for weak, chronic inflammation.
- Raised alkaline phosphatase could be an indicator for Paget's disease where old bone is resorbed and abnormal new bone is placed.
96
Define shared care. (LO7+LO11)
The joint participation of primary care physicians and specialist care physicians in planned delivery of care for patients with chronic conditions.
97
List the benefits of shared care. (LO7+LO11)
- Patients are not caught in miscommunication/confusion as to who is responsible for their care and do not miss any therapeutics.
- GPs may not be familiar with the correct treatments so hospital consultants can help.
- No need to be discharged and re-referred/put on waiting list to see a specialist.
- GPs paid more when they work in partnership with other professionals.
- Hospitals provide enough medication to allow GPs time to generate a prescription.
98
List some principles of shared care. (LO7+LO11)
- Approach a method of seamless prescribing - transfer of prescriptions from secondary care to primary.
- Transfer of clinical responsibility of treatment.
- Stable patients can be referred back to GP by specialist.
- Unstable patients can be referred to more specialist care.
- Local policies published to support GPs, i.e. shared care agreements.
99
Describe GMC guidance on prescribing on someone else's recommendation. (LO7+LO11)
- When acting on recommendation, it is important that you are satisfied that the prescription is needed, appropriate for the patient and within the limits of competence.
- When delegating a patient's suitability for medication, you must be confident in the person you are delegating to.
- Give the person prescribing enough information about patient to allow them to assess.
100
Describe GMC guidance on shared care prescribing. (LO7+LO11)
- Keep self informed of other medication prescribed to patient.
- Recognise serious and frequent side effects.
- Appropriate clinical monitoring arrangements in place and that patient and HCPs involved understand.
- Keep up to date with relevant guidance on medication use and management of patient's condition.
- Both specialist and GP should agree on protocol for treatment.
- Seek further guidance if unsure of your competence for continuing patient's care.
101
Explain what is meant by the treat to target (T2T) concept. (LO7)
- Strategy involving regular assessment and adjustment of therapy to achieve a well-controlled disease.
- Target of RA treatment is clinical remission and shared care does this by more patient/clinician contact.
- This leads to quick adjustments to treatment.
- Involves clear recommendations and pathways for professionals to follow.
- Partnership between clinician and patient to achieve patient-centred approach.
102
List some medications for rheumatoid arthritis that require a shared responsibility. (LO7)
DMARDS - group of drugs that stop or slow the disease process by suppressing an overactive immune system:
- Methotrexate.
- Sulphasalazine.
- Leflunomide.
Often used with pain relievers to provide fast relief of symptoms.
These are managed across the team to ensure appropriate treatment.
103
List the roles involved in rheumatology care. (LO7)
- The patient.
- Rheumatology specialist nurse.
- Doctors.
- Pain management team.
- Occupational therapists.
- Physiotherapists.
- Clinical and health psychologists.
- Podiatry/biomechanics.
104
Explain the role of the patient in shared rheumatology care. (LO7)
- Must be able to practice good management of the disease and need to work with clinicians to know how.
- Need to know where to ask for help.
- Life-expectancy increases in patients with well-controlled disease and this is easier if treatment adherence is practised.
105
Explain the role of the pain management team in shared rheumatology care. (LO7)
- Help with polypharmacy or if patient has difficulty reducing/stopping analgesia.
- Manage chronic pain pathways.
- Help identify multifactor causes and psychological cause.
106
Explain the role of the rheumatology specialist nurse in shared rheumatology care. (LO7)
- Ensure T2T principles are applied.
- Undertake specialist tasks, e.g. escalating patients, reviewing patients, telephone clinics.
- Run escalation clinics monthly which induce clinical remission, low disease activity.
- Provide timely referral if further treatments are needed.
- Provide continuous support for patient.
- Specialist nurses and clinics are managed by a standardised protocol.
107
Explain the role of the doctors in shared rheumatology care. (LO7)
- Shared between primary and secondary care.
- Stable patient is still under specialist care but seen less frequently.
- In this time, they are monitored by the GP.
- GPs rely on quick access to specialists when issues arise, e.g. orthopaedic surgeons.
108
Why is it beneficial for a stable patient to be monitored by a GP while still under specialist care? (LO7)
- Easier to access prescription.
- Easier to access medical monitoring.
- Patient more likely to adhere to treatment.
- GPs know a lot more about patients than specialist doctors.
109
Explain the role of occupational therapists in shared rheumatology care. (LO7)
- Joint preservation - alternative ways of performing daily activity tasks.
- Find methods for conserving patient's energy.
- Help with relaxation and stress reduction.
- May provide things such as splints, insoles, etc.
- Provide home visits to identify ways to adapt the home.
110
Explain the role of physiotherapists in shared rheumatology care. (LO7)
- Joint examinations and do joint counts.
- Look at range of movements/muscle wasting.
- Provide exercise programmes, wax therapy, hydrotherapy, ultrasound and acupuncture.
- Educate patients on their joints and self-management.
111
Explain the role of clinical and health psychologists in shared rheumatology care. (LO7)
- Help manage mental health and improve poor coping strategies.
- Educate on lifestyle impact.
- Therapies such as CBT and counselling.
- Managing cognitive and behavioural functions influences interactions with health and symptoms of illness.
112
Explain the role of podiatry/biomechanics in shared rheumatology care. (LO7)
- Ensure patients have the funds and accessibility to checks and suitable footwear.
- Over 50% of patients with rheumatoid arthritis have foot deformities and care is important.
113
What is reactive arthritis? (LO8)
- Sterile joint inflammation that develops after a distant infection. Septic arthritis is inflammation at the joint.
- The immune response to the infection manifests by inflammation of one or more joints.
- It is a systemic disease.
- Previously known as Reiter's syndrome.
114
What is the characteristic triad of Reiter's syndrome? (LO8)
- Arthritis.
- Urethritis.
- Conjunctivitis.
115
Describe the basic epidemiology of reactive arthritis. (LO8)
- Numbers unclear as cases can be mild, self-limiting and therefore, go unreported.
- Incidence in Europe is estimated at 30/100,000.
- Risk is 50 times greater in people who are HLA B27 positive.
- Affects men more than women (3:1).
- Mainly affects young people (20-40 year olds).
116
Describe the pathophysiology of reactive arthritis. (LO8)
- The underlying mechanism is unknown but is potentially autoimmune.
- Triggered by a prior genitourinary or gastrointestinal infection or after surgery.
- It is immunologically mediated, rather than due to microbial invasion of the joint.
- It is also possible that there is no preceding infection. Like a subclinical infection which has no significant symptoms.
117
Reactive arthritis is classified into two categories. What are they? (LO8)
- Genitourinary.
| - Intestinal/postdysenteric.
118
Describe the genitourinary classification of reactive arthritis. (LO8)
- Usually follows a non-specific (non-gonococcal) urethritis, or less commonly, cystitis or prostatitis.
- Possible infections: chlamydia, Neisseria.
119
Describe the intestinal/postdysenteric classification of reactive arthritis. (LO8)
- In some regions, it may follow dysentery.
- Occasionally non-specific diarrhoea, occurring 10-30 days after intestinal manifestations.
- Possible infections: Salmonella, Shigella, Yersinia or Campylobacter species.
120
List some possible infections which lead to reactive arthritis. (LO8)
```
Genitourinary:
- Chlamydia.
- Neisseria.
Intestinal/postdysenteric:
- Salmonella.
- Shigella.
- Yersinia.
- Campylobacter.
Others:
- Meningococci.
- Streptococci.
- Borrelia.
- Other viruses.
```
121
List the presentations of reactive arthritis. (LO8)
Systemic symptoms:
- Malaise.
- Fatigue.
- Fever - related to reactive arthritis, not the previous infection as it will have settled already.
MSK symptoms:
- Vary in severity
- Arthralgia - could develop into disabling polyarthritis.
- Asymmetric.
- Mono/oligoarthritis.
- Large joints.
- Effusion of joint - less swollen than septic arthritis.
- Usually affecting knee or ankle and developing within weeks of the infectious episode.
- Clinically and histologically, reactive arthritis resembles rheumatoid arthritis with chronic inflammatory synovitis.
Ocular symptoms:
- Sterile conjunctivitis.
- Episcleritis.
- Keratitis.
- Corneal ulceration.
- Acute uveitis (iritis).
122
List the systematic symptoms of reactive arthritis. (LO8)
- Malaise.
- Fatigue.
- Fever - related to reactive arthritis, not the previous infection as it will have settled already.
123
List the MSK symptoms of reactive arthritis. (LO8)
- Vary in severity.
- Arthralgia - could develop into disabling polyarthritis.
- Asymmetric.
- Mono/oligoarthritis.
- Large joints.
- Effusion of joint - less swollen than septic arthritis.
- Usually affecting knee or ankle and developing within weeks of the infectious episode.
- Clinically and histologically, reactive arthritis resembles rheumatoid arthritis with chronic inflammatory synovitis.
124
List some possible skin and mucous membrane illnesses that may present with reactive arthritis. (LO8)
- Keratoderma Blenorrhagicum.
- Erythema nodosum.
- Sterile urethritis.
- Circinate balanitis.
- Cystitis.
- Prostatitis.
- Pelvis inflammatory disease.
- Lesions in the mouth.
125
List the ocular symptoms of reactive arthritis. (LO8)
- Sterile conjunctivitis.
- Episcleritis.
- Keratitis.
- Corneal ulceration.
- Acute uveitis (iritis).
126
List some extra-articular musculoskeletal manifestations of reactive arthritis. (LO8)
- Tenosynovitis - inflammation of the tendon sheath outside the tendon.
- Enthesopathy.
- Plantar fasciitis.
- Achilles tendonitis.
127
List some findings upon examination of joints with reactive arthritis. (LO8)
- Red.
- Warm.
- Shifting pattern.
- Dactylitis - painful.
- Low back pain in patients with chronic disease.
128
List some investigations for reactive arthritis. (LO8)
- FBC - check if patient is anaemia.
- U+Es - check renal function.
- LFTs - can be marginally changed due to inflammation.
- CRP and ESR - usually high in infection but the infection could've already passed for reactive arthritis.
- RF - to rule out rheumatoid arthritis.
- Urinalysis - if cannot identify underlying organisms causing infection.
- Blood culture - to identify the organism if there is one.
- HLA-B27 status - around 2/3 of ReA patients are positive for this.
129
List some synovial fluid investigations for reactive arthritis. (LO8)
- Gram stain - usually negative.
- Polarised light microscopy - to rule out crystal arthritis.
- Culture - should be sterile for most cases.
130
List some culture investigations for reactive arthritis. (LO8)
- Faeces - especially when patient has GI symptoms, e.g. diarrhoea.
- Urine.
- Urethral.
- Cervical.
- Throat.
- Blood/serology.
131
List some differential diagnoses for reactive arthritis. (LO8)
- Septic arthritis - need to aspirate joint if in doubt and culture synovial fluid.
- Crystal arthritis (gout).
- Psoriatic arthritis/spondyloarthropathies.
132
Describe the management of reactive arthritis. (LO8)
- NSAIDs.
- Corticosteroids - during acute flare or if NSAIDs don't work.
- DMARDs - only when steroids fail and it's needed to prevent joint destruction.
133
Describe the prognosis of reactive arthritis. (LO8)
- Generally good, self-limiting in weeks.
| - Reoccurrences may happen without previous infection.
134
List the different classes of spondyloarthropathies. (LO9)
Spondyloarthropathies is an umbrella term for a variety of conditions:
- Axial spondyloarthritis.
- Reactive arthritis.
- Psoriatic arthritis.
- Enteropathic arthritis.
- Undifferentiated spondyloarthritis.
135
Which genes are associated with the inheritance of spondyloarthritis? (LO9)
- Most arthritis runs in the family.
- Very few of them are directly inherited.
- Many are associated with HLA:
1. HLA DR4 - reactive arthritis, giant cell arteritis.
2. HLA B27 - ankylosing spondylitis, spondyloarthropathies.
136
List the HLA B27 associated spondyloarthropathies. (LO9)
- Psoriatic arthritis.
- Ankylosing spondyloarthritis.
- Undifferentiated spondyloarthritis.
- Juvenile spondyloarthritis.
- Irritable bowel disease (IBD) associated arthritis.
- Reactive arthritis.
- Acute anterior uveitis (inflammation of the uvea in the eye).
137
List some of the associated features of HLA B27 spondyloarthropathies. (LO9)
- Sacroiliitis.
- Enthesitis (inflammation of tendons).
- Spondylitis (ascending).
- Peripheral joint involvement.
- Inflammatory eye disease.
- Aortitis, valve disease, heart block.
- Upper lobe fibrosis of the lung.
- Psoriasis, keratoderma, balanitis (inflammation of the penis).
138
Describe the association of the HLA B27 gene with spondyloarthropathies. (LO9)
- Present in 8% of British Caucasian population.
- 95% of patients with radiographic axial spondylitis are HLA B27 positive.
- 5% of HLA B27 positive patients develop MSK symptoms.
139
What is ankylosing spondylitis? (LO9)
- Fusion of vertebrae.
- Starts in the sacroiliac joints.
- Sacroiliitis with pain and stiffness due to new bone formation.
- On x-rays - bamboo spine (appearance due to ankylosis of lumbar spine bones).
- Classified using New York Classification.
140
Describe the New York classification with relation to ankylosing spondylitis. (LO9)
```
Grade 0 - normal.
Grade 1 - suspicious.
Grade 2 - minimal sacroiliitis.
Grade 3 - moderate sacroiliitis.
Grade 4 - ankylosis (fusion of the bones) - visible as bamboo spine on x-rays.
```
141
Describe the diagnostic criteria for ankylosing spondylitis. (LO9)
Clinical:
- Lower back pain and stiffness >3 months. Improves with exercise and is relieved on rest.
- Limited movement of lumbar spine in both sagittal and frontal planes.
- Limitation of chest expansion relative to normal values correlated for sex and age.
X-ray:
Sacroiliitis grade 2 bilaterally OR grade 3-4 unilaterally. (New York classification).
These features do not show up on an x-ray but they do on an MRI.
- Bone marrow oedema.
- Sacroiliitis with pain, stiffness and new bone formation.
142
What is axial spondyloarthritis? (LO9)
Axial spondyloarthritis is the name given to the clinical presentation of ankylosing spondylitis with x-ray findings of below grade 2 on the New York classification system (relatively normal x-ray). For a diagnosis of axial spondyloarthritis, the pain must persist for >3 months and be worse at rest, better with exercise.
For example: A patient comes in with lower back pain, better with exercise, worse with rest and a normal x-ray. This patient has axial spondyloarthritis.
143
Describe the epidemiology of spondyloarthritis. (LO9)
- Ankylosing spondylitis typically affects young men (<40).
- 95% of affected patients are under 40. 5% of affected patients between 40-45 years of age.
- Males twice as likely to get it.
- Around 1% of the population has ankylosing spondylitis.
- Progression of disease is slow which can sometimes delay the diagnosis.
144
List the presentation of inflammatory back pain (spondylitis). (LO9)
- Gradual onset.
- Early morning pain and stiffness.
- Pain improves with movement.
- Pain is worse at rest.
- No radicular signs/symptoms (pain originating from the spine) - no symptoms of nerve compression, e.g. sciatica.
145
List the long-term features of ankylosing spondylitis. (LO9)
- Constitutional symptoms:
1. Fatigue.
2. Fever.
3. Weight loss.
4. Anaemia.
5. Raised ESR in up to 20% of patients.
- Stiffness can lead to functional issues, e.g. difficulty driving.
- >20 year old patients are at increased risk of lung fibrosis, aortitis and heart problems.
- 10% develop psoriasis.
- 40% develop uveitis/iritis.
- 5% develop inflammatory bowel, peripheral joints, chest wall problems.
146
Describe the pathogenesis and radiological findings of ankylosing spondylitis. (LO9)
- Bone marrow oedema.
- Erosions.
- Bone - shiny corners, syndesmophytes, ossification.
- Bamboo spine.
147
Describe the investigations for ankylosing spondylitis. (LO9)
- FBC - ESR, CRP.
- Spinal x-ray.
- MRI.
148
Describe the management of ankylosing spondylitis. (LO9)
- Monitoring of disease activity.
- Physiotherapy.
- NSAIDs.
- Biologics (anti-TNF, Secukinumab (AS specific)).
- DMARD - only if peripheral joints are involved.
149
What is reactive arthritis? (LO9)
- Also known as Reiter's syndrome.
- Sterile (non-infective) joint inflammation that develops after a distant infection.
- Systemic effects - triad of symptoms.
- Triggering infection is usually in the throat, urogenital or GI tract, e.g. STI or gastroenteritis.
- Can occur with NO preceding infection.
150
What is meant by the triad of Reiter's syndrome symptoms? (LO9)
1. Conjunctivitis.
2. Urethritis.
3. Arthritis.
Remember:
Can't see, can't pee, can't climb a tree.
151
Describe the epidemiology of reactive arthritis. (LO9)
- 30-40 per 100,000.
- Affects 20-40 years olds.
- 65% of affected are HLA B27 positive.
- Male: female, 1:1.
- Disease tends to be more chronic. Severe is HLA B27 positive.
152
Describe the clinical features/history of reactive arthritis. (LO9)
Family history.
History of infection up to 2 weeks before onset:
- GI - salmonella, shigella, yersinia, C. jejuni.
- Urogenital - chlamydia, gonorrhoea.
- Other - meningococci, streptococcus, borrelia, viruses.
153
List the systemic symptoms of reactive arthritis. (LO9)
- Malaise.
- Fever.
- Fatigue.
154
List the joint symptoms of reactive arthritis. (LO9)
- Arthralgia.
- Asymmetric.
- Mono/oligoarthritis.
- Large joints more commonly affected.
- Knee effusion.
- Red/warm to touch.
- Shifting pattern.
- Dactylitis.
- Low back pain in chronic disease.
155
List the extra-articular symptoms of reactive arthritis. (LO9)
- Tenosynovitis.
- Enthesopathy.
- Plantar fasciitis.
- Achilles' tendonitis.
- Keratoderma blenorrhagicum.
- Erythema nodosum.
- Sterile urethritis/circinate balanitis/cystitis/prostatitis.
- Conjunctivitis.
- PID (pelvis inflammatory disease).
- Abdominal pain + diarrhoea.
156
List the eye-related symptoms of reactive arthritis. (LO9)
- Unilateral/bilateral.
- Sterile conjunctivitis.
- Episcleritis.
- Keratitis.
- Corneal ulceration.
- Acute uveitis (iritis).
157
Describe the investigations for reactive arthritis. (LO9)
Aspirate the joint if unsure to rule out septic arthritis as the presentation is very similar.
Urinalysis.
Autoantibodies, HLA B27.
Eye test.
X-rays.
Culture:
- Faecal.
- Urine.
- Urethral.
- Cervical.
- Throat.
- Blood.
Blood:
- FBC.
- U+Es.
- LFT.
- CRP.
- ESR.
- RF.
158
Describe the management of acute reactive arthritis. (LO9)
- Analgesia.
- NSAIDs.
- Steroids.
- Rest.
- Splinting.
- Rehab.
- Antibiotics if prior infection if persisting.
159
Describe the management of chronic reactive arthritis. (LO9)
- NSAIDs.
- Physiotherapy.
- DMARDs.
- Urgent referral for eye issues.
- Treat skin conditions as psoriasis.
160
Describe the prognosis of reactive athritis. (LO9)
- Self-limiting within weeks.
- Can recur - specifically eye issues and urogenital symptoms.
- Back pain/arthralgia can be chronic.
161
What is psoriatic arthritis? (LO9)
- 1-3% of population.
- 20% of patients develop arthritis first, then psoriasis.
- Male:female, 1:1.
- Nail lesions are more predictive of arthritis - 90% of patients with nail lesions develop arthritis.
162
Describe the pattern of disease for psoriatic arthritis. (LO9)
- 30-40% have asymmetrical oligoarthritis.
- 30% have symmetrical polyarthritis.
- 10-15% have predominantly DIP joint symptoms.
- 10-20% have spondyloarthritis.
- <10% have mutilans - disappearance of bone tissue, described as "opera glass hand" or "telescopic finger".
163
Describe the management of psoriatic arthritis. (LO9)
- NSAIDs.
- SZP, MTX, LFN, CyA, apremilast.
- Biologics, e.g. anti-TNF, ustekinumab.
- Physiotherapy.
- Occupational therapy.
- Education.
- Management of skin plaques.
164
Describe the presentation of psoriatic arthritis. (LO9)
- Pencil-in-cup appearance on x-rays.
| - Nail changes - pitting, onycholysis (separation of nail from nail bed).
165
What is enteropathic arthritis? (LO9)
- Mainly due to IBD (Crohn's disease and ulcerative colitis).
- Risk of spondylitis is 30% higher in IBD patients.
- Identical presentation to ankylosing spondylitis.
- The presence of enteropathic arthritis with IBD is independent of severity/presence of bowel symptoms.
- Polyarthritis is usually asymmetrical large joints + dactylitis.
- Associated with other extra-intestinal manifestation of IBD: uveitis, mouth ulcers, gum hyperplasia, primary sclerosing cholangitis, kidney stones, arthritis, erythema nodosum, pyoderma gangrenosum.
166
Define polyarticular joint pain. (LO10)
Pain and swelling affecting five or more joints or joint groups.
167
List common causes of polyarticular joint pain. (LO10)
Rheumatoid arthritis:
- Symmetrical.
- Small and large joints.
- Upper and lower limbs.
Viral arthritis:
- Symmetrical.
- Small joints.
- May be associated with rash and prodromal illness.
- Self-limiting.
Osteoarthritis:
- Symmetrical.
- Targets PIP, DIP and first CMC joints in hands.
- Knees, hips, back and neck.
- Associated with Heberden's and Bouchard's nodes.
Psoriatic arthritis:
- Asymmetrical.
- Targets all joints and entheses.
- Associated with nail pitting/onycholysis.
- Dactylitis.
168
Describe the presentation of polyarticular joint pain. (LO10)
Skin, nails and mucous membranes:
- Urticaria.
- Erythemas.
- Nodules.
- Oral ulcers.
- Psoriasis.
Heart, lung:
- Aortic valve/root disease.
- Interstitial lung disease.
Abdominal organs:
- Urethritis.
- Haematuria.
- Hepatosplenomegaly.
General:
- Fever.
169
List some differential diagnoses of polyarthritis. (LO10)
- Rheumatoid arthritis.
- Psoriatic arthritis.
- Axial spondyloarthropathies.
- Osteoarthritis.
170
Describe the location and pattern of joint pain for rheumatoid arthritis. (LO10)
- Metacarpophalangeal (MCP) joints.
- Proximal interphalangeal (PIP) joints.
- Metatarsophalangeal (MTP) joints.
- Symmetrical.
171
Describe the location and pattern of joint pain for psoriatic arthritis. (LO10)
- Proximal interphalangeal (PIP) joints.
- Distal interphalangeal (DIP) joints.
- Entheses and larger joints.
- Asymmetrical pattern.
172
Describe the location and pattern of joint pain for axial spondyloarthritis/ankylosing spondylitis. (LO10)
- Spine.
- Sacroiliac joints.
- Entheses.
- Large peripheral joints.
- Asymmetrical.
173
Describe the location and pattern of joint pain for osteoarthritis. (LO10)
- Proximal interphalangeal (PIP) joints.
- Distal interphalangeal (DIP) joints.
- First carpometacarpal (CMC) joints - base of the thumb.
- Knees.
- Hips.
- Lumbar and cervical spine.
174
What initial investigations can be carried out for polyarticular joint pain? (LO10)
Blood:
- Haematology.
- Biochemistry.
- Erythrocyte sedimentation rate.
- C-reactive protein.
- Viral serology.
- Immunological screening.
Ultrasound/MRI to check synovitis.
175
What is the initial management of polyarticular joint pain? (LO10)
- NSAIDs and analgesics.
- Systemic glucocorticoids - if severe pain or extreme impact on function.
- DMARDs required if rheumatoid arthritis.
176
What are the 5 cardinal features of acute inflammation? (LO12)
1. Calor (Heat).
2. Rubor (Redness).
3. Tumor (Swelling).
4. Dolor (Pain).
5. Functio Laesa (Loss of Function).
177
List 4 causes of acute inflammation. (LO12)
1. Infection.
2. Tissue necrosis.
3. Foreign bodies.
4. Immune reactions.
178
How specific is the immediate response to a pathogen? (LO12)
The immediate response activates the innate immune system and therefore has limited specificity.
179
Name 3 cell types which act as sentinel cells in tissues ready to react to invading microorganisms or to cell damage. (LO12)
1. Macrophages.
2. Dendritic cells.
3. Mast cells.
180
What are the molecules which pathogens and damaged cells produce which can activate cells of the innate immune system? (LO12)
PAMPS and DAMPS (Pathogen Associated Molecular Patterns and Damage Associated Molecular Patterns).
181
What is the main cytokine produced by sentinel cells when they are activated by DAMPs and PAMPs? (LO12)
Interleukin 1 (IL-1).
182
List the 5 steps of acute inflammation (the 5 R's). (LO12)
```
Recognition (of the injurious agent).
Recruitment (of leucocytes).
Removal (of the agent).
Regulation (of the response).
Resolution.
```
183
What is the difference between a cytokine and a chemokine? (LO12)
Cytokines are proteins produced by many cell types that can mediate and regulate inflammatory reactions. Cyto means cell and kine refers to kinesis or movement. Chemokines are chemotactic cytokines. These are produced as a chemical cloud which spreads out from the source of inflammation and can attract specific white blood cells.
184
List the 5 important mediators of acute inflammation. (LO12)
1. Hageman factor (Factor XII).
2. The complement system.
3. Mast cells.
4. Arachidonic acid metabolites.
5. Toll-like receptors.
185
What is the Hageman Factor? (LO12)
This is a factor produced by the liver as an inactive protein. It circulates in the blood stream until it is activated by exposure to collagen.
186
What is the link between the clotting system and the inflammatory system? (LO12)
Hageman factor activates the coagulation cascade and also activates the kinin system.
187
What are the 3 main functions of bradykinin? (LO12)
1. Vasodilation.
2. Increased vascular permeability.
3. Pain.
188
What is the Complement System? (LO12)
A system of pro-inflammatory proteins produced by the liver which circulate as inactive precursors until they are activated by 1 of 3 pathways.
189
Name the 3 complement system activation pathways and explain how they are activated. (LO12)
1. Classical pathway. Activated by antigen binding to IgG or IgM which activates C1.
2. Alternative pathway. Activated by microbial components directly.
3. Mannose-binding lectin pathway. Activated by mannose-binding lectin binding to mannose on the surface of a bacterium.
190
List 4 consequences of complement system activation. (LO12)
1. Formation of anaphylatoxins (C3a, C4a + C5a) which cause histamine to be released from mast cells. C5a is a chemotactic + activation agent for neutrophils, monocytes, eosinophils and basophils.
2. Opsonisation. C3b is the main opsonin (an 'eat-me' signal for neutrophils and macrophages which have C3b receptors).
3. Cell lysis. The final stage of the complement cascade results in the formation of a membrane attack complex (C5b, C6, C7, C8 and C9) flooding the cell with water and ions and causing lysis.
4. Immunoglobulin clearance. Removal of immune complexes from the circulation.
191
List 3 ways in which mast cells can be activated (LO12)
1. Tissue trauma.
2. Complement components C3a and C5a.
3. Cross-linking of IgE bound to the mast cell surface by antigen.
192
Describe the consequences of mast cell activation (LO12)
Mast cells contain pre-formed histamine granules which can be quickly released causing blood vessels to dilate and to leak. Mast cells also cause a delayed response by producing leukotrienes.
193
What enzyme is required to generate arachidonic acid from membrane phospholipids and what drug class can stop this reaction? (LO12)
Phospholipase A2 and steroids.
194
What enzymes are required to generate Prostaglandins from Arachidonic acid and name 2 drugs which can block these enzymes? (LO12)
Cyclooxygenase 1+2 (COX 1+2) and Aspirin/Non-steroidal anti-inflammatory drugs.
195
What is produced when 5-lipooxygenase acts on Arachidonic acid? (LO12)
Leukotrienes.
196
List 4 effects of prostaglandin production in the context of acute inflammation. (LO12)
1. Vasodilation.
2. Increased vascular permeability.
3. Pain (PGE2).
4. Fever (PGE2).
197
List 4 consequences of leukotriene production in the context of acute inflammation. (LO12)
1. Vasoconstriction.
2. Bronchospasm.
3. Increased vascular permeability.
4. Attraction and activation of neutrophils (LTB4).
198
How do steroids reduce inflammation? (LO12)
Corticosteroids are broad-spectrum anti-inflammatory agents that reduce the transcription of genes encoding phospholipase A2, COX-2, proinflammatory cytokines (interleukin-1 and tumour necrosis factor) and iNOS.
199
What are Toll-like receptors? (LO12)
These are receptors present on macrophages and dendritic cells which can be activated by PAMPs. TLR activation upregulates NF-ƙß which activates immune response genes producing cytokines. TLRs are also present on cells of adaptive immunity (lymphocytes).
200
List 4 mediators which can cause redness and heat (rubor and calor). (LO12)
1. Histamine.
2. Prostaglandins.
3. Bradykinin.
4. Nitric oxide.
201
What causes fever in the context of acute inflammation? (LO12)
Pyrogens (eg. lipopolysaccharide) cause macrophages to release interleukin 1 (IL-1) and tumour necrosis factor (TNF) which increase COX activity in perivascular cells of the hypothalamus. This causes production of PGE2 which raises the temperature set point.
202
What causes the swelling seen in acute inflammation? (LO12)
Histamine (from mast cells) causes endothelial cells to contract and endothelial cells can also be disrupted. This results in leakage of fluid from post-capillary venules into the interstitial space.
203
What is oedema? (LO12)
An excess of fluid in the interstitial tissue or serous cavities. Can be an exudate (a fluid high in protein containing cell debris) or a transudate (a fluid low in protein).
204
What is pus? (LO12)
A purulent exudate which is an inflammatory exudate rich in leucocytes (mostly neutrophils), the debris of dead cells and in many cases microbes.
205
What causes pain in the context of acute inflammation? (LO12)
Bradykinin and PGE2 sensitise sensory nerve endings.
206
Describe the 5 steps which neutrophils follow to get from the post-capillary venule to the site of infection. (LO12)
1. Margination.
2. Rolling (selectins on endothelial cells weakly bind to sialyl Lewis X on neutrophils).
3. Adhesion (mediated by adhesion molecules eg. ICAM and VCAM strongly binding to integrins on neutrophils).
IL-1 and TNF induce the expression of selectins and adhesion molecules.
4. Transmigration (histamine contracts endothelial cells allowing neutrophils to squeeze through the gaps, helped by PECAM1 (CD31)).
5. Chemotaxis (neutrophils are attracted by bacterial products, IL-8, C5a and LTB4).
207
Describe the steps involved in phagocytosis. (LO12)
Consumption of pathogens is enhanced by opsonins/eat me signals (IgG and C3b). Phagocytosis involves binding to receptors on the neutrophil membrane, engulfment and fusion of phagocytic vacuoles with lysosomes. This is followed by destruction of ingested particles within the phagolysosomes by lysosomal enzymes and by reactive oxygen and nitrogen species. In activated leucocytes, cytoplasmic components of the phagocyte oxidase enzyme assemble in the membrane of the phagosome to form the active enzyme which catalyses the conversion of oxygen into superoxide and hydrogen peroxide. Myeloperoxidase which is present in the granules of neutrophils converts hydrogen peroxide into hypochlorite. Microbiocidal reactive oxygen species and nitric oxide then kill the ingested microbes.
208
What is the consequence of myeloperoxidase deficiency? (LO12)
There is defective conversion of hydrogen peroxide to hypochlorite. This leads to an increased risk of candida infection. The conversion of oxygen to hydrogen peroxide remains intact.
209
Which inflammatory cell predominates in acute inflammation and which can be raised in a full blood count in the setting of acute inflammation, such as in the setting of an acute bacterial infection? (LO12)
Neutrophil.
210
Which cell dominates 3 days after acute inflammation begins? (LO12)
Macrophage.
211
How do macrophages kill organisms? (LO12)
They ingest via phagocytosis helped by opsonins (C3b) and destroy phagocytosed material using enzymes (lysozyme) in secondary granules (Oxygen-independent killing).
212
List 3 organs which mediate the systemic protective effects seen in acute inflammation and the cytokines which mediate these effects. (LO12)
1. Brain. Fever (mediated by TNF, IL-1 and IL-6).
2. Liver. Production of acute phase proteins (mediated by IL-1 and IL-6).
3. Bone marrow. Leukocyte production (mediated by TNF, IL-1 and IL-6).
213
List the 4 possible outcomes to acute inflammation. (LO12)
1. Resolution and healing (mediated by IL-10 and TGF-beta).
2. Continued acute inflammation (mediated by IL-8 with persistent pus production).
3. Abscess formation.
4. Chronic inflammation (macrophages present antigen to activate CD4+ helper T-cells).
