Path 4 Flashcards
1
Q
Common radiological findings in rickets
A
- bowed femurs
- epiphyseal plate widening
2
Q
URTI vs LRTI examples
A
URTI
sinusitis
tonsilitis
LRTI
bronchitis
pneumonia
empyema
bronchiectasis
lung abscess
3
Q
What is empyema?
A
pockets of pus that have collected inside a body cavity
Lungs: collection of pus in the pleural space.
Caused by an infection that spreads from the lung and leads to an accumulation of pus in the pleural space, the infected fluid can build up to a quantity of a pint or more, which puts pressure on the lungs, causing shortness of breath and pain.
Risk factors include recent lung conditions like bacterial pneumonia, lung abscess, thoracic surgery, trauma or injury to the chest.
4
Q
Examples of compromises to respiratory defenses
A
- poor swallow (CVA, muscle, alcohol)
- abnormal ciliary function (smoking, viral infection, Kartagener’s)
- abnormal mucous (CF)
- dilated airways (bronchiectasis)
- defects in host immunity (HIV, immunosuppression)
5
Q
What is a collapsed lung lobe
A
Lobar collapse refers to the collapse of an entire lobe of the lung
As such it is a subtype of atelectasis
6
Q
streptococcus on microscopy and sensitivity plates
A
gram +ve diplococci
alpha haemolytic on sensitivity plates
7
Q
What % of CAP is b/c of strep pneumoniae?
A
30-50%
8
Q
Presentation of strep pneumoniae pneumonia
A
acute onset
severe pneumonia
fever
rigors
lobar consolidation
almost always penicillin sensitive
9
Q
How do you manage strep pneumoniae pneumonia
A
penicillin sensitive
10
Q
What is pneumonia?
A
inflammation of the lung alveoli
11
Q
mortality of pneumonia
A
5-10%
20-40% are admitted to hospital
12
Q
Sx of penumonia
A
fever
cough
pleuritic chest pain
SOB
malasie, lethargy, n&v
abnormal CXR
13
Q
Underlying factors to consider in pneumonia
A
pre-existing lung disease
immunocompromise
geography
seasons
epidemics
travel
exposure to animals
14
Q
Main organisms causing CAP
A
in most cases, no microbiological ID made.
strep pneumoniae
haemophilus inluenzae
moraxella catarrhalis
staphylococcus aureus
klebsiella pneumoniae
so mainly g+ but can also be g-
15
Q
Pneumonia pathogens in children and young people - common pathogens
A
0-1 mths- E.coli, GBS, Listeria
1-6mths- Chlamydia trachomatis, S aureus, RSV
6mths-5yrs- Mycolpasma, Influenza
16-30yrs- M pneumoniae, S pneumoniae
16
Q
Typical and atypical causes of CAP
A
typical (85%)
- S. pneumonia
- H. influenza
Atypical (15%)
- Legionella
- mycoplasma (Epidemics 4-6 years)
- Coxiella burnetii (Q fever)-worldwide, farm animals, hepatitis
- Chlamydia psittaci (Psittacosis)-exposure to birds, splenomegaly, rash, haemolytic anaemia
17
Q
Ix in ?pneumonia
A
- FBC, U&E, CRP
- blood culture
- sputum MC&S
- ABGs
- CXR
Curb-65
18
Q
CURB-65 score - clinical decision
A
score 2 = ?admit
score 2-5 = manage as severe
19
Q
components of CURB-65
A
confusion
urea >7mmol/l
RR >30
BP <90 systolic or <50 diastolic
>65yo
20
Q
What is bronchitis?
A
inflammation of medium sized airways
21
Q
Main organisms causing bronchitis?
A
- mainly viruses
S. penumoniae
H. influenza
M. catarrhalis
22
Q
Physiotherapy in bronchitis
A
- to remove the secretions
23
Q
Haemophilus influenzae - microscopy morphology
A
gram -ve coccobacilli
24
Q
What % of CAP is by H. influenzae
A
15-35%
25
H influenza is more common with pre-existing lung diseasse
may produce beta-lactamase
26
Legionella pneumophilia - route of transmission and key risk
- inhalation of infected water droplets (aerosol exposure)
- can result in MOF
27
What is atypical pneumonia?
pneumonia caused by organisms without a cell wall
(mycoplasma, legionella, chlamydia, coxiella)
-> cell wall active abx (e.g. penicillins do not work)
extra-pulmonary complications e.g. low sodium
flu-like prodrome before fever and pneumonia
20% of CAP
28
When to suspect atypical pneumonia?
extra pulmonary features
e.g. hepatitis, low sodium
29
Abx for atypical pneumonia
macrolides (clarithromycin, erythromycin)
tetracyclines (doxycycline)
-> antibiotics that are aimed at the cell wall (e.g. penicillins will not work)
30
legionella penumophilia
aerosol sperad
environmental outbreaks, can be associated with air conditioning
associated with confusion, abdo pain, diarrhoea
lymphopaenia, hyponatraemia
Dx by antigen in serum/urine
sensitive to macrolides
31
Coxiella burnelli (pneumonia)
common in domestic/farm animals
transmitted by aerosol or milk
dx by serology
sensitive to macrolides
32
Chlamydia psittaci (pneumonia)
Spread from birds by inhalation
Dx by serology
Sensitive to macrolides
33
classical CXR finding in TB
upper lobe cavitation
but can vary considerably, can be anything really
34
Test for TB
auramine stain and ziehl nielsen stain
35
Definition of HAP
>48h in hospital
36
organisms causing HAP
often gram -ve
enterobacteriaciae 31%
staph aureus 19%
pseudomonas spp 17%
fungo (candida sp.) 7%
acinetobacter baumanii 6%
37
Pneumocystis jirovecii
protozoan
ubiquitous in environment, many will have been exposed
insidious onset
dry cough, weight loss, SOB, malaise
CXR 'bat's wing'
Dx immunofluorescence on BAL
Rx Septrin (co-trimoxazole)
prophylaxis septrin (e.g. in people with cancer)
test: measure sats at rest and after walking a few steps, they will desaturate
38
What medication do you treat PCP with?
septrin (co-trimoxazole)
38
What medication do you treat PCP with?
septrin (co-trimoxazole)
39
Different types of aspergillus fumigatus lung infection
- allergic bronchopulmnary aspergillosis
- aspergilloma
- invasive aspergillosis
40
Aspergillus on microscopy
flowering spores
41
Immunosuppression and LRTI - what occurs with what?
HIV: PCP, TB, atypical mycobacteria
Neutropenia: fungi e.g. Aspergillus spp
BM transplant: CMV
splenectomy: encapsulated organisms (S. pneumonia, H. influenzae, one more) ?neiseria
42
microbio lab dx of LRTI
sputum/induced sputum *
blood cultures *
BAL
pleural fluid
Ag tests
Ab test
immunofluorescence
PCR
*send pre abx
43
urine antigen tests for pneumonia
S. pneumoniae
legionella pneumophillia
Send in severe community-acquired pneumonia
44
factors helping pick abx in treatment of RTI
community vs hospital
severity of illness
?ventilator
45
Mx of CAP
Follow local guidelines
Mild/moderate: Amoxicillin or erythromycin/clarithromycin
Moderate/severe: hospital admission
- augmentin (co-amoxiclav) and clarithromycin
- if allergic: cefuroxime and clarithromycin
46
Mx of HAP
1st line: Ceftazidime/Ciprofloxacin +/- vancomycin
2nd/ITU: Piperacillin/tazobactam AND vancomycin
Specific therapy:
MRSA: Vancomycin.
Pseudomonas: Piperacillin/tazobactam or Ciprofloxacin +/- gentamicin.
47
Diabetes definition
Fasting plasma glucose over 7.0mM
HbA1c >6.5% (48mmol/mol)
OGTT of > 11.0mM
48
causes of metabolicc alkalosis
H+ loss e.g. vomiting
hypokalaemia
ingestion of bicarbonate
49
Formula for osmolality
2 (Na+K) + urea + glucose
50
Anion gap formula
Na + K - Cl - bicarb
51
Causes of hypokalaemia
1. intestinal loss (diarrhoea, vomiting, fistula)
2. renal loss (mineralocorticoid excess, diuretics, renal tubular disease)
3. redistribution (insulin, alkalosis)
4. decreased intake (rare!!)
52
Cushing's with severe hypokalaemia
ectopic ACTH production likely
there are no RCTs proving this but Karim Meeran said this
How? high levels of glucocorticoid bind to aldosterone receptor causing hypokalaemia
53
Causes of ectopic ACTH
lung cancer
other cancers
54
How do you manage ATN?
dialysis for 3 weeks
the patient should then recover
55
What % of population have kidney disease?
11%
56
main barrier in transplantation
HLA/MHC
minor histocompatibility complex and ABO blood groups are less important
57
Chromosome of HLA genes
6
58
HLA class 1 and class 2 letters
1: A, B, C
2: DP, DQ, DR
59
peptide binding groove present to T-cells
60
are HLA antigens highly polymorphic?
yes, there are many variants one might have
61
Most antigenic HLAs
A B and DR
Over the last years we have also learned that DQ mismatches are also quite antigenic
62
What do HLA mismatches refer to? e.g. 0:0:0 or 1:1:0
HLA-A
HLA-B
HLA-DR
63
probability of HLA matching with sibling
6 MM - 25%
3 MM - 50%
0 MM - 25%
64
tissue typing - what is it?
determining the donor and recipient HLA type
via PCR based DNA sequence analysis for HLA alleles to determine the individuals genotype
65
How does HLA disparity cause rejection?
T-cell mediated rejection
- phase 1: presentation of donor HLA by APC in the context of recipient HLA
- phase 2: T-cell activation, IL-2 and IL-15 production, help for Ab production by B-cells
- phase 3: effecter phase: graft damage by immune cells (cytotoxic T-cells, monocytes/macrophages)
66
Biopsy of immune T-cell mediated rejection
Lymphocytes and macrophages infiltration ( in tubules in renal transplant, this makes the kidneys not filter as well as they should and this makes their creatinine rise; when the patient comes for check ups and Cr is raised you do a real biopsy and may find T-cell rejection)
67
T-cell rejection can occur in any solid organ transplant
pancreas - acini
heart - interstitial infiltration in between myocytes
68
Drugs used in T-cell mediated transplant rejection
- calcineurin inhibitors (e.g. tacrolimus)
- MTOR inhibitors
- anti proliferative drug like azothiaprine, myciophenolate motefil
- corticosteroids
etc.
69
Ab- mediated transplant rejection
Phase 1: B-cells recognise foreign HLA
Phase 2: proliferation and maturation of B-cells with anti-HLA Ab production
Phase 3: effector phase; antibodies bind to graft endothelium
70
antibodies in infection - box divided in whether they need complement activation or not
complement dependant and complement independent damage to the graft
???
71
microscope of Ab mediated rejection
- capillaries filled with inflammatory cells
- swollen endothelial cells
in T-cells it is in the interstituum and tubules; in Ab mediated
72
What is worse, T-cell or Ab mediated rejection?
acutely they both present the same
T-cell mediated responds well to treatment
Ab mediated is very difficult to treat.
73
are anti-HLA antibodies naturally occurring?
No
pre-foremed: transplantation, pregnancy, transfision
post-formed: arise after transplantation
other
74
ABOq
glycoproteins on
75
screening for HLA antibodies
before transplant
at time of transplant
post transplant
76
types of assay for anti-HLA antibodies
cytotoxicity assay (does the recipient serum kill the donor's lymphocytes in the presence of complement
Flow cytometry: does recipient serum bind to donor lymphocytes
Solid phase assay (more recent): synthetic beads coated with different HLA epitope; if recipient has antibodies they will stick to the bead. Then your run this through flow cytometry
77
Treatment of antibody mediated rejection
plasma exchange to remove antibodies
rituximab to deplete B-cells
proteasome inhibition (Velcade)
complement inhibitors (e.f. eculizumab)
IVIg to reduce the production of immunoglobulins globally
78
How do we prevent organ rejection?
79
How ado we treat graft rejection?
80
What must we balance when treating organ transplant rejection/prphylaxis?
need for immunosuppression
vs
risk of infection/malignancy/drug toxicity
81
Tx of post transplant lymphoproliferative disease
malignant transformation f B-cells
associated with EBV infection
reduce IS drugs
sometimes give chemotherapy
82
Which cells cause damage in T-cell mediated rejection effector phase?
T-cells and macrophages/monocytes
83
What does TRH stimulate?
TSH and prolactin
84
If PRL is >6000 and the patient is not pregnant it is always a prolactinoma
85
DA agonists
cabergoline and bromocriptine
86
dynamic test for acromegaly
OGTT
87
best treatment for acromegaly
surgery
if suitable for the patient, surgery is 1st line
radiotherapy, cabergoline and octreotide are also options
88
What is the mechanism for spherocyte production in autoimmune haemolytic anaemia?
partial membrane loss due to spleen taking bits off?? relsiten to this part or read
89
What is the mechanism for spherocyte production in hereditary spherocytosis?
inability to assemble membrane correctly due to genetic mutation
90
In what conditions do you get DAT+ve acquired haemolytic anaemia?
CLL
lymphoma
SLE
rheumatoid
myeloid d/o don't have association with acquired haemolytic anaemic; not all because the patient would be dead from sepsis or on treatment before this could develop
patients with any disease of the immune system, e.g. malignant (CLL, Lymphoma) or non-malignant e.g. SLE or rheumatoid
91
causes of mediastinal masss
teratoma
thymoma
terrible lymphoma
3 Ts
occasionally B cell lymphomas
92
why do teratomas cause widening of the mediastinum?
?
93
What are the major pathogens in surgical site infections?
MSSA
MRSA
E coli
Pseudomonas aeruginosa
94
What type of bacteria is pseudomonas?
gram -ve gammaproteobacteria
rod shaped
polar flagellated
it is a MDR organism
95
what dose of bacteria in surgical site increases risk of SSI?
If surgical site is contaminated with
> 10^5 microorganisms per gram of tissue, risk of SSI is increased.
dose of bacteria needed is much lower if there is foreign material present (e.g. silk suture)
96
Levels of SSI
Superficial incisional- affect skin and subcutaneous tissue
Deep incisional- affect fascial and muscle layers
Organ/space infection- any part of anatomy other than incision
97
Neisseria meningitidis - what type of bacteria
gram -ve meningococcus
98
RFs for SSI
older age (>75)
obesity
underlying illness (ASA >=3; diabetes;l malnutrition; low serum albumin; radiotherapy; steroid use; rheumatoid arthritis;
Smoking
99
Why is smoking associated with an increased risk of SSI?
- Nicotine delays primary wound healing
- Peripheral vascular disease
- Vasocontrictive effect of reduced oxygen-carrying capacity of blood
-> Encourage tobacco cessation
-> Smoking duration and number of cigarettes smoked relevant
100
RA - how to manage DMARDs to reduce the risk of SSI
Stop disease modifying agents for 4 weeks before and 8 weeks post-op.
101
How much does diabetes increase risk of SSI? How should you control glucose?
2-3x increased risk
Association with post-op hyperglycaemia
-> Control blood glucose. HbA1C < 7
102
measures to decrease risk of post op infections
- pre-surgery skin decontamination - no difference if chlorhexidine or soap/bar is used; shower the day of or before surgery
- hair removal - do not shave because micro-abrasions can increase risk of infection; DO NOT remove hair unless it will interfere with surgery
- nasal decontamination (important RF for SSI following cardiothoracic surgery)
- prophylactic antibiotics
103
ABx prophylaxis in surgery - when should bactericidal concentration be achieved?
at incision
give abx at induction of anaesthesia
104
What to do intra-op to reduce the risk of SSI?
- keep number of people in theatre to a minimum
- ventilation
- sterilisation of surgical instruments
- antiseptic skin prep
- asepsis and surgical technique
- normothermia
- oxygenation
105
SA stats
Incidence is 2-10 cases per 100,000
In patients with RA incidence is 28-38 per 100,000 population.
Mortality is 7-15%
Morbidity is 50%
106
RFs for SA
Rheumatoid arthritis , osteoarthritis, crystal induced arthritis
Joint prosthesis
Intravenous drug abuse
Diabetes, chronic renal disease, chronic liver disease
Immunosuppression- steroids
Trauma- intra-articular injection, penetrating injury
107
SA pathophys
Organisms adhere to the synovial membrane, bacterial proliferation in the synovial fluid with generation of host inflammatory response.
Joint damage leads to exposure of host derived proteins such as fibronectin to which bacteria adhere
108
Bacterial factors in SA
S.aureus has receptors such as fibronectin binding protein that recognise selected host proteins.
Kingella kingae synovial adherence is via bacterial pili
Some strains produce the cytotoxin PVL ( Panton-Valentine Leucocidin) which have been associated with fulminant infections.
109
Host factors in SA
Leucocyte derived proteases and cytokines can lead to cartilage degradation and bone loss.
Raised intra-articular pressure can hamper capillary blood flow and lead to cartilage and bone ischaemia and necrosis.
Genetic variation in expression of cytokines may lead to differential susceptibility to septic arthritis.
110
Causative organisms in SA
Staph. aureus 46%
- Coagulase negative staphylococci 4%
Streptococci 22%
Streptococcus pyogenes
Streptococcus pneumoniae
Streptococcus agalactiae
Gram negative organisms
-E.coli
- Haemophilus influezae
- Neisseria gonorrhoeae
- Salmonella
Rare- Lyme, brucellosis, mycobacteria, fungi
111
Ix for SA
Blood culture before antibiotics are given
Synovial fluid aspiration for microscopy and culture
ESR,CRP
-Traditionally a synovial count> 50,000 cells/mm3 used to suggest septic arthritis
(Negative culture result does not exclude septic arthritis)
112
Imaging in SA
US- confirm effusion and guide needle aspiration
MRI- joint effusion, articular cartilage destruction, abscess, contiguous osteomyelitis
113
locaalisation of vertebral osteomyelitis
cervical- 10.6%
cervico-thoraco- 0.4%
lumbar 43.1%
114
Sx of vertebral osteomylitis
Back pain- 86%
Fever- 60%
Neurological impairment 34%
115
Commonest causative organisms in vertebral osteomyelitis
S.aureus- 48.3%
CNS- 6.7%
GNR- 23.1%
Strep- 43.1%
116
How can you get vertebral osteomyelitis?
Acute haematogenous
Exogenous
- after disc surgery
- implant associated
117
Ix for vertebral osteomyelitis
MRI: 90% sensitive
Blood cultures
CT/ open biopsy
118
Mx of vertebral osteomyelitis
- Six weeks treatment
- Longer treatment if undrained abscesses/implant associated
- Surgery if there is spinal cord compression
119
chronic osteomyelitis Sx
Pain
Brodies abscess
Sinus tract
120
Ix for chronic osteomyeltitis
MRI
Bone biopsy for culture and histology
121
Masquelet technique
used for chronic osteomyelitis
Radical sequestrectomy
Removal of foreign bodies; filling the defect with antibiotic loaded cement spacer and external fixation
In 6-8 weeks , remove the cement spacer, and fill the defect with autologous bone graft
122
Sx of prosthetic joint infection
Pain
Patient complains that the joint was ‘never right’
Early failure
Sinus tract
123
Causative organisms of prosthetic joint failure
Gram positive cocci
-coagulase negative staphylococci
-staphylococus aureus
Streptococci sp
Enterococci sp
Aerobic gram negative bacilli
Enterobacteriaceae
Pseudomonas aeruginosa
Anaerobes
Polymicrobial
Culture negative
Fungi
124
Traffic light system for risk of Prosthetic joint infection
Fig 1
https://online.boneandjoint.org.uk/doi/full/10.1302/0301-620X.103B1.BJJ-2020-1381.R1#F1
1. PJI unlikely
2. Infection likely
3. PJI confirmed
125
Intraoperative Microbiological sampling
Tissue specimens from at least 5 sites around the implant
Histopathology – infection defined as >5 neutrophils per high power field.
If 3 or more specimens yield identical organisms, this is highly predictive of infection (sensitivity 65%, specificity 99%)
126
Single Stage Revision (surgery)
Remove all foreign material and dead bone
Change gloves, drapes etc
Re-implant new prosthesis with antibiotic impregnated cement and give iv antibiotics .
127
Endo Klinik single stage revision
Aspirate joint to identify pathogen
Excision of infected tissue , synovectomy
Add antibiotics to bone cement according to culture results
Implantation of a cemented hip or knee prosthesis using antibiotic loaded cement
Give 7-10 days of iv antibiotics
Culture drain tips
Success rate is 89% in 2002
128
Two stage revision (surgery)
for prosthetic joint infection
Remove prosthesis
Take samples for microbiology and histology
Period of iv antibiotics (6weeks). Stop antibiotics for 2 weeks
Re-debride and sample at second stage
Re-implantation with antibiotic impregnated cement
No further antibiotics if samples clear
OPAT
129
DAIR (surgery)
( debridement, antibiotics and implant retention)
for prosthetic joint infection
Within 3 weeks of operation
Tissue sampling
Radical debridement
Exchange of modular components
Antibiotics
130
Causes of abnormal colliery function?
smoking
viral infection
Kartagener's syndrome
131
Kartageners syndrome
- rare
- autosomal recessive
- triad of: situs inversus, chronic sinusitis, bronchiectasis
- larger group of ciliary motility disorders called primary ciliary dyskinesias
132
Mx of Bronchitis
bronchodilation
physiotherapy
+/- abx
133
features of H influenza pneumonia
15-35% of CAP
more common in pre-existing lung disease
may produce beta-lactamase
more commonly presents as bronchopneumonia
134
Moraxella catarrhalis gram stain
g-
135
klebsiella pneumoniae gram stain
g-
136
What is the difference between bronchopneumonia and segmental pneumonia
?
137
How do you culture legionella pneumophilia?
buffered charcoal yeast extract
138
What causes bat wing on CXR?
Pneumocystis jirovecii
139
Pneumocystis jirovecii CXR finding
bat wing
140
Mx of Pneumocystis jirovecii pneumonia
Rx Septrin (Co-trimoxazole)
prophylaxis: septrin
141
Management of invasive aspergillosis
Amphotericin B
142
Who gets invasive aspergillosis?
immunocompromised poeple
143
Sx of Allergic bronchopulmonary aspergillosis
Chronic wheeze, eosinophilia
Bronchiectasis
144
Sx of Allergic bronchopulmonary aspergillosis
Chronic wheeze, eosinophilia
Bronchiectasis
145
Aspergilloma
Fungal ball often in pre-existing cavity
May cause haemoptysis
146
abx for MRSA HAP
Vancomycin.
147
abx for pseudomonas HAP
Piperacillin/tazobactam or Ciprofloxacin +/- gentamicin.
148
Ab tests in pneumonia
Only useful on paired serum samples
Usually collected on presentation and 10-14 days later
Look for rise in antibody level over time
Most useful for organisms that are difficult to culture eg:
- Chlamydia
- Legionella
149
Which pathogen (causing pneumonia) can immunofluorescence be used for dx?
- PCP – Pneumocystis carinii (now renamed P. jiroveci) immunofluorescence is the only common IF test used in microbiology laboratories
- Antibody labelled with fluorescent dye
- Technique often used in Virology
- May also be detected by Silver stain in cytology lab
