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CSP3 Flashcards

1
Q

Define hypersensitvity

A

Damage to a patient caused by the immune system

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2
Q

Define allergy

A

Subdivision of hypersensitivity

- unecessary immune response against foreign antigen (type 1 hypersensitvity)

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3
Q

Type 1 hypersensitvity

A

IgE mediated
Mast cells
Anaphylaxis

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4
Q

Type 2 hypersensitvity

A

Autoantibodies against self structures

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5
Q

Type 3 hypersensitivity

A

Immune complex mediated

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6
Q

Type 4 hypersensitvity

A

T cells and macrophages

With out without granulomas

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7
Q

Type 5 hypersensitivity

A

Stimulatory autoantibodies

Graves’

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8
Q

What stimulates mast cells?

A

Antigen binding to IgE on surface
Complement activation = C5a, C3a
Nerves = axon reflex sensory nerves, substance P
Direct stimulation

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9
Q

Diagnostic test for anaphylaxis

A

Tryptase
C4 not consumed (low)
D dimers high

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10
Q

Causes of anaphylaxis

A
  • arthropod venoms (bee, wasp, stings)
  • drugs (ABs, insulin, ACTH, suxamethonium)
  • foods (peanute, shellfish, egg, milk, latex, kiwi, alpha gliadin)
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11
Q

Differentials of anaphylaxis

A 
MI
PE
Hyperventilation
Hypoglycaemia
Phaeo
Angioedema
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12
Q

Define anaphylactoid reactions

A

Direct or indirect activation of mast cells without IgE

Still tryptase positive as involve mast cells

Same treatment as anaphylaxis

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13
Q

Triggers of anaphylactoid reactions

A

Vancomycin, NSAIDs, opiates, anaesthetic agents
Srawberries
Exercise, cold, trauma
Immune complex reactions to blood products

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14
Q

Scromboid reactions define

A

Massive ingestion of histamine from decayed mackerel/other oily fish
Tryptase negative as mast cells not involved

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15
Q

Urticaria

A

Chronic if >1 month but can be acute
Wheals/hives/raised itchy
Mast cells, histamine, leukotrienes
Dermis inflammation

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16
Q

Causes of urticaria

A

Allergic triggers
Direct contact - grass, latex
Allergic normally acute
Infections = viral, parasites
Autoimmune = vasculitis, SLE, type 3 hypersensitivity (normally chronic)
Autonomic = with heat/sweating, adrenergic with stress
Physical = sunlight/pressure/vibration/heat
Exercise: within hours of a meal
Hormonal: menstrual cycle link, steroid use
Mast cell disorders: urticaria pigmentosa
Iron/folate/B12 deficiency

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17
Q

Cold urticaria

A

Cryoglobulinaemia
Other autoimmune = SLE, leukaemia
Can cause Raynaud’s phenomenon
Can be inherited = C1AS1 gene mutation

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18
Q

Treatment of urticaria

A

Antihistamines - up to 4x recommended dose
Can add H2 antagonist (ranitidine)
Add montelukast
Progress to omalizumab (before was cyclosporin)
Treat lymphomas/autoimmune diseases accordingly

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19
Q

Non sedating antihistamines

A

Cetirizine
Loratidinde
Fexofenidine

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20
Q

Sedating antihistamines

A

Chloramphenamine

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21
Q

Define angioedema

A

Swelling of subcutaneous tissues

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22
Q

Causes of angioedema

A

Allergic (accompanied by urticaria)
Anaphylaxis/anaphylactoid syndromes
Hereditary

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23
Q

Hereditary Angioedema Type 1

A

C1 esterase inhibitor

Restraint on complement and bradykinin pathways

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24
Q

Hereditary Angioedema Type 2

A

C1 esterase inhibitor mutation

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25
Hereditary Angioedema Type 3
Mutation of factor XII initiating bradykinin pathway and intrinsic clotting pathway
26
Acquired C1 esterase inhibitor deficiency
Angioedema but not hereditary as acquired | Autoimmune, haem malignancy, cryoglobulins, Heb C/B/Helicobacter
27
Idiopathy angioedema
Normal C1 esterase inhibitor level
28
treatment of angioedema
If allergic - same as anaphylaxis and urticaria C1 inhibitor deficiency = anabolic steroids (tranexamic acid)/C1 inhibitor IV or SC Idiopathic = tranexamic acid, icatibant SC inhibits bradykinin pathway
29
Allergic conjunctivitis, rhinitis, sinusitis
Type 1 hypersensitivity | IgE mediated
30
Antigens for allergic conjunctivitis/rhinitis/sinusitis
``` Grass pollens Tree pollens Seasonal exposure Animal danders House dust mite ```
31
Diagnosis of allergic conjunctivitis/rhinitis/sinusitis
``` Mainly History Seasonal = pollens, hayfever Skin prick IgE specific test May develop nasal polyps ```
32
Treatment for allergic conjunctivtis, rhinitis, sinusitis
Topical/systemic antihistamines Topical mast cell stabilisers Topical steroids Antigen exclusion
33
Causes of rhinitis & sinusitis
``` Infections - common Vaso-motor rhinitis Non ellergic rhinitis with eosinophilia (NARES) Drusg = alpha agonist sprays, cocaine Irritant fumes/solvents Wegner's Septal deviation/foreign bodies Late pregnancy oestrogens CSF leak ```
34
Define atopy
Genetic predisposition to make IgE antibody against common environmental antigens Associated with hayfever, childhood asthma and atopic dermatitis
35
Atopic dermatitis
``` Dry cracked itchy raised lesion Extensor surfaces first then flexures and cheeks Genetic component Filaggrin mutation IgE>1000 raised Staph infections of affected areas Increased eosinophils and mast cells ```
36
Aspirin sensitivity
Can cause angioedema Triad = asthma, nasal polyps, sinusitis Can enhance ability of other allergens to cause anaphylaxis
37
Nasal polyps
May need surgery Topical steroids Avoid aspirin and salicylates in food(tea/coffee/spices/tomatoes/cider/wine/mints)
38
Oral allergy syndrome
Itching and local swelling in oropharynx within minutes of eating Rarely progresses to urticaria & angioedema and maybe anaphylaxis IgE Type 1
39
Antigens for oral allergy syndrome
Fresh fruit/veg and cross react with pollens so often have hayfever too
40
treatment for oral allergy syndrome
Avoid foods | Cooked normally ok
41
Food allergy symptoms
``` Gut pain, bowel changes, vomiting Urticaria Angioedema Within minutes Anaphylaxis? Enteritis if eosinophillic gastropathy HISTORY crucial Skin prick tests avoidance Steroids ```
42
Latex allergy
``` Gloves, medical products, condoms Cross reactions = bananas/avacado/kiwi IgE mediated against latex protein (plant based) Contact urticaria Asthma Angioedema Anaphylaxis Rhino-conjunctivitis Skin prick Specific IgE testing ```
43
Drug allergies - penicillin
type 1 = anaphylaxis 2 = haemolytic anaemia 3 = serum sickness 4 = interstitial nephritis + erythema multiforme & Stevens Johnson
44
other drug allergies
``` Co-trimoxazole Sulphonamide Insulin = urticaria, anaphylactic like Anesthetics = measure tryptase DRESS syndrome = weeks after rash/fever/lymph, eosinophillia ```
45
Extrinsic allergic alveolitis
``` Type 3 inhaled foreign antigens occupational 6 hours after, worst at 24-48 fever, cough, SOB asthma may develop type 4 chronic exposure - interstitial pulmonary disease ```
46
Allergic bronchopulmonary aspergillosis
Type 3 & 1 Wheeze, cough, fever, haemoptysis Can dev. bronchiectasis High IgE and IgE
47
Serum sickness
``` Infused human or serum products Monoclonal AB Type 3 Fever, urticaria, vasc., lymph, poly-arthritis 7-14 days post primary exposure 1-3 days after secondary exposure ```
48
Contact hypersensitivity
``` Type 4 Nickel allergy topical drugs leather dyes chromium cement latex and rubber hair dyes/fragrance plants sunlight may be required to trigger sensitivity ```
49
Special tests overall
``` HISTORY!!! Skin prick tests Specific IgE in vitro tests Autoantibody screen Patch testing Tryptase D-dimers Complement - C3, C4, C1q, C2, C1q autoantibodies ```
50
Extracellular pathogen targets
Blood Lymph Interstitial spaces Epithelial surfaces
51
Intracellular Pathogen targets
Cytoplasmic | Vesicular
52
When does adaptive immune response begin?
Innate immune response begins first | Then reaches threshold where pathogen level increases where adaptive is activated
53
Immune response from a cute
- wound bleeds washing out foreign bodies - resident macrophages and injured tissue initiate inflammatory response - interleukins and cytokines activated- specificaly IL1,6,8 and TNFalpha
54
How are interleukins actiavted?
TLR recognise pathogen features
55
TLR1 & 2
Gram positive bacterial products yeast
56
TLR3
dsRNA
57
TLR4
LPS | Gram negative
58
TLR5
Flagellin
59
TLR6
Complex | With TLR2
60
TLR7 & 8
ss RNA
61
TLR9
bacterial DNA
62
What do interleukins then do?
``` Inflammation Driving innate immune response Fluid enters site Clot forms sealing wound NK cells, neutrophils, macrophages and IgM attracted ```
63
How does innate immunity initiate adaptive
Dendritic cells phagocytose bacterial antigen | Become APC
64
How does a dendritic cell mature?
Immature releases LPS which is detected by TLR4 | Moves from tissues to lymph nodes
65
What do dendritic cells do once matured?
Activate naive T cells binding to them via MHC | CD4+ differentiate to either Th1 or Th2 effector cells
66
CD4+ to Th1
Via IL12
67
CD4+ to Th2
Via IL4
68
What produces IL4
Parasitic worms via IgE
69
What produces IL12
Dendritic cell
70
Function of Th1 cells?
Produce IFNgamma which: cell mediated immunity helps cytotoxic T cells and macrophages
71
Function of Th2 cells?
Produce IL4,5,13 Humoral Immunity Help B cells for antibody production via plasma cell production
72
TB Leprosy
``` Th1 dominant response IFN-gamma Activated macrophages Low organism number Limited disease ```
73
Lepromatous Leprosy
``` Th2 dominant response IL4,5,13 Hyperglobulinemia High no. of organisms Disseminated disease ```
74
Cutaneous leishmaniasis
boils Th1 dominant limited
75
Visceral lieshmaniasis
Black Fever Th2 dominant Disseminated
76
Miliary TB
Th2 dominant | Disseminated
77
Memory cells
Fraction of activated T and B cells become memory cells Provide long lasting immunity Stored in bone marrow and lymph nodes
78
Features of bronchial asmtha
Mucus hypersecretion Airway inflammation Bronchial hyper-responsiveness Acute attacks of SOB and airway obstruction due to SM contraction
79
2 phases of asthms
``` 1 = early bronchospasm 2 = late inflammation ```
80
Spasmogens examples asthma early phase
Histamine | Methacholine
81
Histological asthma chages
Goblet cell hyperplasia Thick sub-basement membrane Cellular infiltrate
82
IgE production is asthma
Dendritic cells present allergen to T and B cells at LN | - T helper switch to B cells via IL4,13 and CD14 on B cells bind to ligand on T cells
83
Role of IgE in asthma
Binds to IgE receptors on mast cells via FcR1 | Binds to low affinity receptors on lymphocytes, eosinophils, platelets and macrophages via FcR2
84
Role of mast cells
Release mediators: - histamine - leukotrienes - cytokines
85
Early effects of mediators
bronchospasm OEdema Airflow obstruction
86
Late effects of mediators
Airway inflammation Airway obstruction Airway hyper-responsiveness
87
Eosinophils
- originate in bone marrow - IL3 and 5 regulate - leukotriene source - contain proteins which damage epithelium
88
Terminal differentiation of eosinophils
By GM-CSF & IL5 - IL5 prolongs survival - Increased IL5 associated with tissue eosinophilia - Anti-IL5 therapy = mepolizumab, reslizumab
89
Lymphocytes
Surface activation markers CD4+ Th1 - IL2 and IFNgamma Th2 - IL4,5,6,9,13
90
GATA-3 mRNA
TF confined to Th2 in asthmatics
91
Factors favouring Th1 phenotype
Presence of older siblings Early exposure to day care TB, measles, Hep A Rural environment
92
Factors favoring Th2 phenotypes
``` Widespread AB use Western lifestyles Urban environment Diet Sensitization to house dust mites and cockroaches ```
93
Define immunodeficiency
Suboptimal resistance to infectious disease | Primary & secondary
94
Primary immunodeficiency
Genetically mediated = X linked agammaglobulaemia, Di George Idiopathic = Common variable immune deficiency
95
Secondary Immunodeficiency
``` Infections = AIDS Malignant = lymphoma, myeloma, leukaemia Metabolic = DM Trauma = burns Treatment caused = cytotoxic drugs, glucocorticoids, irradiation AB loss = nephrotic syndrome ``` - more common than primary
96
B lymphocyte & AB deficiency
``` Pneumococcus Haemophilus Staphylococcus Moraxella Strep Neisseria Mycoplasma Enteroviruses Norovirus Rhinovirus ``` ``` Otitis Media Sinusitis LRTI Meningitis Septicaemia Septic arthritis Osteomyeltiis Abscess ```
97
X Linked Agammaglobulaemia
- no antibodies - no B lymphocytes - defective tyrosine kinase gene for B lymphocytes - very rare - boys> - 2nd 6m of life with chest infections/ear/sinusitis - will get worse infections if not treated -> bronchiectasis - die in childhood or early adulthood if not treated - can also get viruses
98
Treatment of X linked agammaglobulaemia
AB replacement - almost all IgG AB when necessary Then normal lifespan
99
Common Variable Immune Deficiency
- not common - any time presents - small degree of inherited - B lymph normal/low/absent - low AB - impaired immunisation response - T lymph may be affected - autoimmunity associated?/granulomatous disease? - get infections like X linked - severity depends on AB levels - Need AB replacement ASAP
100
Isolated AB class deficiency
IgA = low or absent with normal IgG and IgM - at any time - often healthy otherwise - RTI, intestinal infections - v. rare IgM inherited deficiencies, aut recessive in consanguineous families
101
Secondary AB deficiency causes
- drugs - nephrotic syndrome = urine low - protein losing enteropathy = loss into bowel lumen - malignancies = lymphomas (with T lymp defect) - cytotoxic therapy + immunosuppressive = with T lymph deficiency and neutrophil deficiency - rituximab = B lymphocyte depletion so specific AB deficiency
102
Fungi causing T lymphocyte deficiency
``` Pneumocystis jeroveci Candida Cryptococcus Histoplasma Skin ```
103
Protozoa causing T lymphocyte deficiency
Cryptosporidium = diarrhoea | Toxoplasma
104
Viruses causing lymphocyte deficiency
Herpes Simplex, Zoster CMV EBV HHV 8
105
Mycobacteria causing T lymphocyte deficiency
Atypical
106
Di George Syndrome
Primary T lymph deficiency cause - chromosome 22 partial deletion - pharyngeal 3rd & 4th arch defects - no thymus or parathyroids - vessel abnormalities - facial abnormalities - complete thymus absence = complete T lymph absence - often incomplete thymus = T lymph gradually improves with age
107
Nucleoside phosphorylase and adenine deaminase deficiency
T lymph deficiency primary cause | - enzymes specific to T lymph
108
AIDS
- caused by HIV - T lymph deficiency - retrovirus - CD4 targeted - now antiretroviral treatment
109
Diagnostic test of AIDS
AB to HIV p24 viral antigen HIV RNA
110
Neutropenia
- oral soreness/gingivitis/pharyngitis - then URTI/LRTI - soft tissue infections and abscess - septicaemia
111
Bacteria causing neutropenia
Gram negative aerobic rods = pseudomonas, E Coli, entrobacteria, enterococci Non beta haemolytic strep Staph - epidermidis, saprophyticus
112
Fungi causing neutropenia
Candida spp. Aspergillus spp. Dermatophyte fungi
113
Primary causes of neutropenia
``` Rare genetic syndromes: Cyclical neutropenia Severe congenital neutropenias Kostmann syndrome Chronic benign neutropenia ```
114
Secondary causes of neutropenia
``` Marrow aplasia Haem malignancies Drugs - cytotoxic therapy Autoimmune - anti-neutrophil AB Infections ```
115
Chronic granulomatous disease
Neutrophil function defects - X linked recessive - boys - childhood presentation - pneumonia/infective arthirits/abscess/skin infections - end as granulomas
116
Test for chronic granulomatous disease
Nitroblue tetrazolium test OR Dihydrorhodamine test Normal phagocytes decolourise dyes, patients' do not
117
Treatment fro chronic granulomatous disease
AB IFN Bone marrow transplant
118
Leukocyte Adhesion Deficiency (LAD)
``` Very rare aut recessive CD18 deficiency Associates with CD11 forming beta 2 integrin (neutrophil adhesion molecule) Failure of umbilical cord to slough ```
119
Test for LAD
CD11/18 expression measured
120
Treatment for LAD
AB | Bone marrow or stem cell transplant
121
Possible mechanisms for diabetes causing infections
Neutrophil function impaired Microcirculation impaired Body fluids more nutritious for bacteria
122
Complement defects
Genetic Lupus like picture Meningitis danger Often healthy individual
123
Low C3
Bacterial infections
124
Tests for complement defects
C3 and C4 routine C1q C2 Factors H,I,B
125
Angioedema
ACEi can cause
126
Absent/small spleen
Congenital Infarcted in SC Hyposplenism in coeliac Removed for hereditary spherocytosis and lymphoma, trauma, idiopathic thrombocytopenia, hypersplenism
127
Typical infections causing absent/small spleen
``` Septicaemia Pneumococcus Haemophilus Meningococcus Malaria ```
128
Treatment for absent/small spleen
Prophylaxis AB = pen V or macrolide Vaccines - pneumococcal, meningococcal, Haem Infl. Better before splenectomy Carry INFO CARD
129
Defects of anatomical innate immune system
``` CF Bronchiectasis Urinary Outflow Obsrtuction Cilia defects = Kartagener's syndrome and smoking Burns/wounds Poor phlebotomy, catheterisation Indwelling lines ```
130
Reticular Dysgenesis
- severe combined immune deficiency - rare genetic syndrome - only red cells and platelets present in blood - few days of life before overwhelming infection - sterile isolation needed until bone marrow transplant
131
SCID
Severe combined immune deficiency - have phagocytes - no B or T lymph - 2 years of life with AB support in sterile isolation - need bone marrow transplant
132
Hyper IgM syndrome
- very rare - inherited defect - loss of signal from activated CD4 T helper cells to APCs - no B cell class switching - High IgM, low G and A - pneumocystis carinii - mutation of CD40 ligand on T lymph is commonest cause, X linked - CD40 lack on APC is rarer cause, aut recessive
133
Hyper |gE syndrome
Job's syndrome if STAT3 mutation - eosinophilia - facial and skeletal abnormalities - eczema, staph infec, candida, pneumonia
134
Wiskott-Aldrich syndrome
X linked - defective cytoskeletal protein found in haemoapoetic cells - thrombocytopenia = bleeding - affects B and T lymph & phagocytes - ear, sinuses infections, lymphomas
135
Chediak-Higashi syndrome
- defect moving material into lysosomes - phagocyte affected - affects production of cytolytic granules in T lymph and NK cells - neutropenia - peripheral neuropathy - bacterial infections and fungi
136
Ataxia telangectasia
``` aut recessive defect in ATM gene for DNA repair - whites of eyes = telangectasia - T & B lymph affected - infections, lymphoma, leukaemia ```
137
Secondary causes of combined defects
- common - gluco-corticosteroids - azathioprine mycophenolate MTX Ciclosporine Tacrolimus Inflixmab block TNF
138
Ix for immunodeficiency diseases
FBC ESR & CRP U&E, LFT, bone profile, TFT C3 & C4, C1q, C2, C1 esterase inhibitor Mannose binding ligand Immunoglobulins - IgG, A, M Specific AB to infections before and after immunisations, CD3,4,8,19,56 Measure T lymph proliferation response to stimulation Neutrophils number genetic tests Infections = cultures, swabs, HIV, Hep B and C, EBV, CMV, imaging
139
Define commensal organism
Micro-organism that derives benefit from another organism without causing damage
140
Define primary pathogen
Cause of disease in healthy hosts
141
Iatrogenic causes of immunodeficiency
2ry cause | Treatments - steroids, chemo
142
Non iatrogenic causes of immunodeficiency
2ry cause | due to disease process
143
Which organisms damage skin barrier and how?
Flora Perineal flora Bacillus fungi Via surgery, trauma, burns, cannula
144
Which organisms damage mucosa barrier and how?
``` Normal commensal flora translocate Gram negative Candida Aerobes Via chemo, broad spectrum AB ```
145
Which organisms damage resp tract barrier and how?
Intubation From GI and URT secretions Candida Gram -ve
146
Which organisms damage urinary tract barrier and how?
Catheter Perineal flora Gram -ve Candida
147
Which organisms damage vaginal barrier and how?
Broad spectrum AB | Candida
148
What diseases cause primary caused phagocyte defects?
Chronic granulomatous disease | Neutrophil migration defects
149
What diseases cause secondary cause phagocyte defects?
``` AML Aplastic anaemia Diabetes Chemo associated neutropenia Corticosteroids - impair neutrophil function ```
150
Which organisms usually cause disease in phagocyte defects?
``` S. aureus Pseudomonas Aspergillus Zygomycetes Normal commensals ```
151
Prevention of disease due to phagocyte defects
Prophlactic AB early = quinolones Antifungals IFNgamma Vaccinations
152
What things cause secondary complement defects?
Eculizumab | Myeloma auto antibodies
153
Impact of complement defects
Increased risk of neisseria meningitis Meningococcal meningitis Menigococcal sepsis
154
Prevention of disease due to complement defects
Proph AB | Vaccinations
155
Causes of primary humoral immune defects
IgA defciiency | Hyper IgM
156
Causes of secondary humoral immune defects
CLL Splenectomy Corticosteroids Rituximab
157
Impact of humoral immune defects
Strep pneumoniae H. influenzae Neisseria meningitis (encapsulated organisms if IgG deficiency) GI pathogens (protozoa) if IgA deficiency
158
Prevention of disease in humoral immune defects
Proph AB | AB replacement = immunoglobulins from blood
159
Splenectomy infection prevention
Vaccination - before splenectomy better | Prop AB = pen V
160
Causes of primary cell mediated immune defects
Combined Di-George Hyper IgM
161
Causes of secondary cell mediated immune defects
``` HIV Malignancy Anti-rejection therapy Steroids Anti-TNF Stem cell transplant Radiotherapy Malnutrition ```
162
Impact of cell mediated immune defects
``` HIV targets CD4 cells = T helper response poor Mycobacteria, salmonella, listeria Cryptococcus, PCP, histoplasma CMV Toxoplasma ```
163
Prevention of disease in cell mediated immune defects
Aciclovir for viral Cotrimoxazole for fungal and latent TB Immunisations Avoid live vaccines!
164
When to suspect primary immunodeficiency
- infectiosn requiring IV AB - FH of it - 4 or more new ear infections in 1 year - 2 or more new sinus infections in 1 year - 2 or more months on at least 2 AB - 2 or more pneumonias within 3 yrs - frequent deep skin abscesses - thrush/skin fungal infection >6m - 2 or > deep infections within 3 yrs
165
Chronic persistent infection define
Infection maintained by continuous replication of a virus
166
Chronic latent infection define
Persistent or life long infection maintained by pool of latently infected cells (non replicating)
167
Viral infections in cell mediated immune deficiency
``` Herpes = Simplex, Varicella zoster, CMV, EBV Paramyxoviruses = RSV, measles, parainfluenza Papillomarviruses = HPV Polyomaviruses = BK, JK ```
168
HSV
Herpes Simplex Virus - nearly always HSV-1 - genital herpes HSV-2 - direct contact spread with lesions - swab lesion PCR - Tx = aciclovir
169
HSV Primary infection
asymptomatic | Maybe = fever, pharyngitis, ulceration and lymphadenopathy
170
HSV Secondary recurrence
Very common Prodromal tingling Localised painful blisters Resolve 5-7 days
171
Varicella Zoster
Most have had exposure | Diagnosis = swab area
172
Varicella Zoster Primary Infection
``` Chickenpox Fever + generalised rash Sporadic Spring-summer peak Highly infectious via resp droplets and lesion shedding - most infectious 1-2 days before rash ```
173
Varicella Zoster Reactivation
``` Shingles In immunosuppressed May be multidermatomal Encephalitis Infectious until all lesions crusted Uncomplicated in healthy Severe with pneumonitis otherwise ```
174
Treatment of HSV and VZV
Treat immunocompromised always Antivirals = reduce symp, duration, shedding, complications If VZV have pneumonitis, encephalitis, eye disease = IV treatment
175
ACE Viruses
Adenovirus, CMV, EBV - major hazard for allogeneic HSCT - primary infection and reactivation - transmitted from donor
176
CMV
- virus in saliva, urine, breast milk - common in childhood - usually minimal symptoms and self limiting - mononucleosis like - remains latent in blood and bone marrow cells and can reactivate when suppressed - important causes of congenital abnormalities - pathogen of solid organ and bone marrow transplant patients
177
CMV diagnosis
Pre transplant serology | Post transplant monitoring for viraemia/infection
178
CMV infection vs. disease
``` Infection - lab evidence of virus activity - primary and re-infection Disease - clinical evidence of disease - syndrome - organ specific ```
179
CMV management
PROPH - anti-viral after transplant regardless Pre-emptive = start antiviral therapy at first indication of active CMV replication after transplant (if bone marrow and SCT)
180
EBV
- herpes virus establishes latency - most of pop have past infection - in immunosuppressed = lymphoma (transplant and HIV patients) and post transplant lymphoproliferative disorder (first year)
181
Risk Factors of PTLD
``` <5 yrs Antirejection Therapy Tacrolimus >ciclosporin CMV seromismatch Small bowel/heart/lung/liver/renal/BM/pancreas transplants EBV seronegative prior to transplant ```
182
PTLD Symptoms
``` Fever unexplained GI upset Lymphadenopathy Tonsillar hypertrophy IM Hepatic/splenic enlargement Anaemia Graft dysfunction ```
183
Adenovirus
3 main syndrome - resp (mild, self limiting), keratoconjunctivitis, gastroenteritis - immunosuppressed - transplant (RF = child, severe GvH disease, cord blood transplant, liver, heart)
184
Adenovirus in immunosuppressed
Asymptomatic viral shedding/ end organ disease/ disseminated more than 2 sites
185
Management of adenovirus in immunosuppressed
Screening via blood = urine PCR | Reduction of immune suppressed
186
Polyomarviruses
JC and BK Early life acquired Initial viraemia = kidney seeding = latency Reactivation due to viruria = viraemia = end organ disease Asymptomatic
187
3 syndromes of polomarviruses
BK virus associated haemorrhagic cystitis BK virus associated nephropathy JC-PML
188
Define confidentiality
Agreement that gives the confider the right to expect discretion from the confidant as well as guardianship of the information received
189
Define confidential information
Info disclosed to the professional about the patient before or after death which has a nature of confidence or seen by the patient as having such a nature Patient identifiable data
190
When does confidentiality cease to exist
Only when no representatives can give consent or refuse disclosure
191
How long should health records be retained for?
8 years min. | 25 for maternity/obstetric
192
Why do we have duty of confidentialtiy?
- no trust otherwise = no info. = no care = no business - unpleasant legal/professional consequences - precondition of autonomy
193
When can confidentiality be relaxed?
- patient gives explicit consent to disclose for purposes of epidemiology/research/education, to relatives - must be informed of purpose and consequences and whom - may refuse - if in patient's best interest = young patient abuse tell guardians - in society's best interest = dangerous drivers, harm to individuals - professional has dual responsibility = member of armed forces, prison worker - in case of serious crime/assault = disclose to police - court of law - tax inspectors for financial info
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What is not a notifiable disease?
AIDS | Notifiable to PH Act
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Statutory Duties
``` Abortions Drug Addicts Births Deaths Certain infections ```
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Fitness to drive
- depends on vehicle - up to age of 70 years then renews every 3 years, automatically done unless driver reports problem - must inform DVLA of potential medical disability
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Doctor concerns with patient informing DVLA
- inform patient they have legal duty to - if refuse = suggest second opinion of diagnosis and risks and advice not to drive until obtained - if continue to drive = persuade not to, involve next of kin - if still drives = tell them that DVLA will be informed - discuss matter with patient's defence organisation - give medical info to medical adviser at DVLA - write to patient informing you have done
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Prescribed drugs affecting fitness to drive
``` Transquillisers Antiepileptics Antidepressants Antipyschotics Antihistamines Analgesics Anaesthetics Opoiates, cannabis, LSD, alcohol ```
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When is it justified to withhold truth from patient?
- if will cause real predictable harm =make them suicidal | - if patient states informed preference not to be told the truth
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Helsinki Principles
1 - must conform to accepeted scientific principles and based on adequate lab and animal experiments 2 - Independent committee which conform with local laws should be able to guide/comment 3 - conducted by scientifically qualified people and under supervision of clinically competent medical people 4 - importance of research objective must be in proportion to inherent subject risk 5 - Assessment of risk and benefits must be done & concern for interests of subject must outweight interest of science and society 6 - respect subject's autonomy and privacy, minimise harm 7 - docotrs cease investigation if hazards outweight risks 8 - physician obliged to preserve accuracy, reports should concord with principles laid down otherwise not published 9 - subject correctly informed and can withdraw at any time, consent needed in writing 10 - consent to be free from coercion 11 - informed consent obtained from legal guardian in case of incompetence
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Who should patient sue in what scenario?
If GP = direct claim | If hospital doctor = against health authority and doctor
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Define negligence
- duty of care - breach of that duty - person claiming suffered harm/damage - damage caused by breach
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Duty of care
Good Samaritans - ethical duty not a legal one
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breach of duty of care
Failure to reach level of proficiency of peers
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Bolitho Modification
- ignorance is not a defence - genuine errors of clinical judgement not negligence if based on reasonable skill - breach done (commission) or not done (ommission - failure to attend to a patient) - misdiagnosis if history taking was poor, investigation poor, compared to reasonable doctor, not referred to specialist if doubt
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Actionable Harm or Damage
Disability Injury Loss of earnings Reduced quality of life
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Legal Process
Letter of claim - must be acknowledged within 14 days and copies of requested notes within 40d - letter of response within 3m - claim form by civil court - denial by defendant - proofing - assessment of quantum, settlement reached by trust leaving doctors to feel that justice was not done - 5% go to court, decision based on expert opinion
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Examples of neonatal single gene disorders
``` Sickle Cell Cystic fibrosis Hypothyroidism Phenylketonuria Medium chain Acyl CoA dehydrogenase deficiency Maple Syrup Urine Diseasse Isovaleric Acidaemia Glutaric aciduria type 1 Homocystinuria ```
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Define single gene disease
Genetic disorder caused by a change affecting only 1 gene
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Inheritance pattern of single gene diseases
``` Simple Mendelian patterns Auto dominant, recessive etc. X linked recessive X linked dominant Y linked dominant Imprinting Mitochondrial ```
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Define epigenetics
Study of changes in organisms caused by modification of gene expression rather than alteration of genetic code itself
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Type of DNA mutations
Missense Nonsense (stop codons) Fram Shift
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Transcriptional control
Mutations in regulatory elements | Epigenetics = DNA methylation/chromatin modification, deletions, insertions, inversions, translocations
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X linked recessive disorders
Haemophilia A X linked severe combined immune disorder Duchenne muscular dystrophy Becker muscular dystrophy
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X linked recessive inheritance mechanism
Males born to carrier mothers 1/2 sons affected Daughters of affected fathers are carriers Never father to son
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Duchenne muscular dystrophy
Dystrophin mutation Dystrophin - stabilises sarcolemma, protects muscle fibres from LT damage, links microfilament network of actin to proteins Stem cells regenerate muscle to some extent but eventually die and get replaced by fat and CT
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DMD vs Backer Muscular Dystrophy
DMD = dystrophin gene absent or non functional vs. partially functional in Becker DMD greater incidence Becker later onset 12 yrs vs. 3-5 yrs in DMD Longer LE in Becker = 40s vs. 20s in DMD Cardiomyopathy may present before skeletal symptoms in Becker vs. after in DMD
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X linked dominant disorders
Some forms of retinitis pigmentosa Chorndrodysplasia Punctata (cartilage and bone dev.) Hypophosphatemic rickets
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Mechanism of X linked dominant inheritance
Both sexes More females Affected sons have affeted mother All daughters from affected father are affected
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Autosomal recessive diseases
Pheylketonuria Tay-Sachs Hemochromatosis Cystic Fibrosis
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Autosomal Dominant Diseases
Huntingtons Achondroplasia Polycystic Kidney Disease Werner mesomelic syndrome
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Werner mesomelic syndrome
- hypo or aplasia of the tibiae - preaxial polydactyly of hands and feet - five fingered hand with absence of thumbs - overexpression of SHH
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Y linked dominant diseases
Retinitis pigmentosa
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Y linked dominant inheritance mechanism
Only males | From father to all sons
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Examples of imprinting conditions
Beckwith-Wiedemann syndrome Prader-Willi Angelman syndrome
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Imprinting inheritance mechanism
Certain genes expressed in a parent of origin specific manner If allele inherited from father is imprinted it is silenced and only the allele from the mother is expressed
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Angelman syndrome
Neuro-genetic Severe intellectual and developmental disability Sleep disturbance Seizures Both sexes - only when mutated chromosome is maternally inherited If mother is carrier = chance is 50%
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Examples of mitochondrial conditions
Mitochondral myopathy DM and deafness Leber's hereditary optic neuropathy Leigh syndrome, subacute sclerosing encephalopathy
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What can gene therapy help with?
Recessive disorders Loss of function mutations Small gene Tissue is accessible = skin/blood
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Treatment options
Gene therapy Genome Engineering = CRISPR-Cas9 technique Gene repair of double strand breaks
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Complex disease = multi gene diseases
- common - polygenic - high frequencies of variants in pop - variants have small affects on gene function - unclear modes of inheritance
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How to determine if genes are important?
Familial aggregation Twin studies Adoption studies
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Examples of complex diseases
Essential HTN CHD Diabetes Asthma, epilepsy, cancer
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Genetic causes of HTN
- rare inherited syndromes of HTN - majority of cases = polygenic complex - 30-50% genes, 50-70% lifestyle factors
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miR-425
Present in atria and ventricles - expressed at levels similar to miR-208a which is known to have significant biological functions in the heart - inhibiting it could enhance atrial ANP release in response to salt excess and HF

CSP1 (20 decks)

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