Path 3 Flashcards
Risk factors for SSI
- age (>45)
- ASA 3 or more
- diabetes
- malnutrition
- low serum albumin
- DMARDs
- obesity (adipose tissue is poorly vascularised)
- smoking
Main pathogens causing SSI
FC levels of SSI deep superficial etc
Measures to decrease number of surgical site infections
PRE-OP
- pre-op showering
- nasal décolonisation (for some surgeries, e.g. cardiac)
- antibiotic prophylaxis (at induction of anaesthesia, need to achieve bactericidal levels at the time the incision is made; in prolonged OP or lots of blood loss,
- hair removal not with razor but electrical clippers because prevent micro abrasions
OP
- reduce number of poeple in theatre
- ventilation (+ve pressure, direction of air flow is from theatre to rest of the hospital; 20 air changes/h, all air coming in is filtered, keep theatre doors closed; orthodoxy surgeries in laminar flow theatres)
- sterilised instruments
- skin prep (chlorhexidine in 70% EtOH)
- asepsis and surgical technique
- normothermia
- O2 sats >95%
Incidence of SA
Incidence of SA
mortality and morbidity in SA
RFs for SA
- prosthesis
- immunosuppression
- underlying joint disease
- IVDU
Pathophysiology of SA
see screenshot
includes bacterial and host factors
Pathophysiology of SA
see screenshot
includes bacterial and host factors
Host factors for SA pathophysiology
- genetic variation in cytokine expression
- more
bacterial factors in SA pathophysiology
Commonest pathogens
- staph aureus
- streptococci
- gram -ve organisms
Presentation of SA
- ## 1 red, hot, swollen joint
Ix for SA
- blood cultures
- synovial aspiration
- bloods
USS to guide needle aspiration
MRI scan to look at damage and
Abx for SA
flucloxacillin
cephalosporin
may need to add vancomycin if MRSA
review after 2 weeks -> switch to oral for 4w if good response, if not good continue for 4 weeks IV
Vertebral osteomyelitis
- acute haematogenous
- add
Commonest organisms in vertebral osteomyelitis
- staphylococcus
- streptococci
commonest location of
lumbar spin
- cervical spine
PC in VOM
- back pain
- fever
- may have neurological sx
Ix in VOM
MRI?
add mroe
Mx of VOM
- 6w Abx
- may need longer course if untrained abscess, foreign material
- may need surgery if there are neurological issues/compression
commonest organisms causing prosthetic joint infection
- coagulase -ve staphylococci
- staph aureus
- g-ve less common
what dies the presence of alpha-defensin indicate?
infection (in the bone)
what dies the presence of alpha-defensin indicate?
infection (in the bone)
What haematological changes are normal in pregnancy?
- mild anaemia (physiological) - plasma volume rises 150%, red cell mass rises 120-130%)
- macrocytosis (normal - physiological, but does not exclude folate or b12 deficiency)
- neutrophlia
- thrombocytopenia (and increased platelet size)
iron deficiency in pregnancy - consequences
IUGR
prematurity
PP haemorrhage
Dose of folate pre conception and in first trimester
400 ug/day
What happens to platelets in pregnancy?
count decreases (15% women will have below 150)
size increases
there may also be some clumping
Causes of thrombocytopenia in pregnancy
- physiological
- pre-ecclampsia
- ITP
- microangiopathic syndromes
- other (e.g. DIC, leukemia, …)
thrombocytopenia number
<140 x 10^8 /L
double check this
IgG autoantibodies from ITP can cross the placenta so the baby may be affected
significantly low platelets (<20) in 5% of the babies
How do you manage ITP in pregnancy?
- steroids
?check IViG?
HUS and I think there is a lot more to say here and I think there is so much more to say here
What medication can be given to women to increase uterine contraction?
syntosin
(synthetic oxytocin)
What medication can be given to women to increase uterine contraction?
syntosin
(synthetic oxytocin)
When around pregnancy is the risk of VTE highest?
6 weeks following delivery
VTE risk assessment done before, throughout and after pregnancy
good hydration is important during pregnancy
Causes of DIC
- infections
- obstetric causes
fill out this list
Scan to check for metabolically active metastases?
FDG-PET
Scan to check for bone metastases?
Tc bisphosphoante scan
What happens to the apex beat in LV hypertrophy?
the apex beat is normal
LV hypertrophy does not cause apex displacement.
tall R waves and deep s-waves because the muscle is huge.
you only see displacement if there is also heart failure
do not confuse a dilated heart with a hypertrophic heart
commonest cause of LV hypertrophy
untreated HTN
What type of bacteria are neisseria gonorrhoeae?
gram -ve diplococci
What type of bacteria are neisseria gonorrhoeae?
gram -ve diplococci
What can cause gram -ve meningitis in children? (rods)
g-ve diplococci on LP in meningitis Sx
Neisseria meningitidis
g-ve rods causing meningitis Sx in a 6yo child - organism?
Haemophilus influenzae
less common in vaccinated kids but in the unvaxxed
E coli is also a gram -ve rod and causes meningitis in neonates and premies
gram +ve diplococci causing sepsis that we are worries about
strep pneumoniae
19 yo with PUO cultures -ve for 2 months but cold agglutinins are positive - organism?
mycoplasma
- gives you cold agglutinins
?also takes long to culture?
gram+ve cocci in clusters from pus of a boil
staph aureus
the clusters make it likely to be staph aureus
it is the aggressive organism that attacks joints, foreign material etc.
staph epidermidis
found on skin
can also cross the skin and cause sx
much less aggressive than staph aureus
Strep viridans
gram +ve cocci
can cause strep viridans endocarditis
PUO
slowly can damage the endocardium
Which organism are you more likely to get endocarditis/sepsis from?
strep pyogenes and strep viridans
strep pyogenes kills you by sepsis before it can settle on valves
strep viridans can cause PUO and endocarditis because it is less virulent and can settle on the valve
more virulent bugs may be less likely to cause endocarditis thereby
Signs of subacute endocarditis
- splenomegaly
- haematuria
- splinter haemorrhages
- heart murmurs
Where does strep viridans come from
teeth
What is the commonest cause of meningitis
viral
e.g. coxsackie B virus
what is aseptic meningitis?
viral meningitis
how do you manage viral meningitis?
?supportive management
LP result in SAH
- red cells
- yellow colour
Stain in TB
Ziehl nielsen
LP result in TB meningitis
normal LP but culturign shows TB
Commonest cause of secondary immunodeficiency worldwide
malnutrition
especially protein loss malnutrition
measles induced immunodeficiency
- lasts months to years
- implicated in increased morbidity and mortality
How does TB lead to immunodeficiency?
???
TB IRIS
TB immune reconstitution syndrome
Drugs as a cause of immunodefiocicnet
- small molecules (steroids, cytotoxic agents, calcineurin inhibitors, anti epileptic drugs, DMARDs)
- Jak inhibitors
- biologics and cellular therapies
- haematological cancers (B-cell and plasma cell cancers; chemotherapy; Goods’ syndrome)
Goods’ syndrome
- thymoma associated with Ab deficiency
- combined T- and B-cell problem
- absent B cells, no antibodies
- increased risk of PJP, CMV, fungal and AI disease
Ix for ?secondary ID
FISH
FBC
Immunglobulins
S??
HIV test
Ix for ?secondary ID
FISH
FBC
Immunglobulins
S??
HIV test
How many people are living with HIV?
37 million
How many of the people living with HIV are taking ART
21 million of 47 million
How many poeple in the UK are living with HIV?
101 200
approx 100 000
virus family of HIV
lentivirus family
what kind of virus is HIV?
double stranded RNA virus
structural, replicative and accessory proteins
retrovirus
What does HIV bind to?
CD4
CCR5
CXCR4
How does HIV replicate?
via DNA intermediate
integrates into host genome
HIV DNA transcribed to viral mRNA
viral RNA translated to viral proteins
packaging and release of mature virus
Origin of HIV
4 distinct linneages
MNOP
commonest variant of HIV worldwide
Group M
natural history of HIV infection
- acute (flu-like illness in 70% people)
- asymptomatic but progressive for 8-10 years
- AIDS
what is the risk of HIV transmission related to?
viral load
therefore risk of transmission is highest in the acute phase
driving force for viral diversity in HIV
error prone nature of HIV RT
short generation time of viral cycle and length of infection
Characteristic features of untreated HIV imunlogy
insert
loss of tetanus vaccine responses in HIV
ART in UK
-reverse transcriptase inhibitor (NRTI, NNRTI)
- boosted protease inhibitors (ritonavir + PI)
- integrates inhibitor (
……..
who is typically affected by MDS?
elderly
signs and sx of myelodysplasia
of general BM failure
Issues in MDS
- cytopenias
- quality decline of the cells
- increased risk of AML
Pelger Heut abnormallity
bi-lobed neutrophils
seen in MDS
Blood and BM morphological features of MDS
- Pelger Huet abnomrality
- dysgrabnulopoiesis of neutrophils
- dyseryhtropoiesis of erythrocytes
- myelokathexis
- ringed sideroblasts
- myeloblasts with Auer rods (seen in AML)
….. more
what do Auer rods indicate?
AML
Scoring system for MDS
IPSS-R
revised international prognostic scoring system
the higher the score the higher the lower the survival and time to progress to AML
Scoring system for MDS
IPSS-R
revised international prognostic scoring system
the higher the score the higher the lower the survival and time to progress to AML
MDS genetic abnormalities
- driver mutations in MDS (carry prognostic significance)
add more info
Myelodysplasia - Evolution
- deterioration of blood counts (worsening consequences of marrow failure)
- development of AML (in 5-50% <1 year, some cases of MDS are much slower to evolve, AML from MDS has an extremely poor prognosis and is usually not curable
- 1/3 will die of infection
1/3 will die of bleeding
1/3 will die of acute leukaemia
Treatment of MDs
- allogenic SCT
- intensive chemotherapy
only a minority of MDS patents can really benefit from this
Supportive care in MDS
- Supportive care
- blood transfusion
- antimicrobial therapy
growth factors (Epo, G-CSF, TPO-receptor agonist) - Biological modifiers
- immunosuppressive therapy
- azacytidine
- decitabine
- lenalidomide - oral chemotherapy
hydroxyurea/ hydroxycarbamide - low dose chemotherapy )s.c. low dose cytarabine)
- intensive chemo/sct
in a minority of patients
when do you use lenalidomide
MM
5qdel variant of MDS
Primary causes of BM failure
Secondary causes of BM failure
What is more common - primary or secondary BM failure?
secondary is much more common
Drugs and BM failure
- predictable (dose dependat, common) - cytotoxic drugs
- idiosyncratic (NOT dose dependant, rare
- Antibiotics
etc/
What is chloramphenicol used for?
it is used as an antibiotic in eye drops
used to be a systemic medication; can cause BM failure
incidence of aplastic anaemia?
2-5 cases/million/year
slightly more common in Asian pop
Which age groups are affected by aplastic anaemia
all age groups can be affceted
bimodal incidence in 20s and 60s
Causes of aplastic anaemia
70-80% are idiopathic
inherited: dyskeratosis congenita, Fanconi anaemia, Schwachmann-diamond syndrome
secondary anaemia: radiation, drugs, viruses, immune e.g. SLE
miscellaneous: PNH (paroxysmal nocturnal haemoglobinuria), thymoma
idiopathic aplastic anaemia
failure of BM to produce blood cells
stem cell problem (CD34, LTC-IC
immune attack
triad of BM failure
- anaemia (fatigue, breathlessness)
- leucopenia (infections)
- thrombocytopenia (bruising)
diagnosis of MDS
- blood (cytopenia)
- marrow (hyopcellular)
Ddx of pancytopenia and hypo cellular marrow
- hypoplastic MDS / AML
- hypocellular ALL
- hairy cell leukemia
- mycobacterial (usually atypical infection)
- anorexia nervosa
- idiopathic thrombocytopenic purpura (BM tap will be normal)
Camitta criteria
low reticulocyte count
low neutrophils
low platelets
BM <25% cellularity`
Mx of BM failure
- seek and remove cause (detailed drug and occupational hx)
- supportive (blood transfusion, abx, iron chelation therapy)
- Immunosuppressive therapy (anti-thymocyte globulin, steroids, CyA)
- drugs to promote marrow recovery (G-CSF, TPO R agonists, oxymethome)
- SCT
- other treatments in refractory cases e.g. aletuzumab (anti-CD52, high dose cyclophosphamide)
Specific treatment of idiopathic aplastic anaemia is based on…
- illness severity
- age of patient
- potential stem cell donor
Specific treatment of idiopathic aplastic anaemia
insert
late complications following immunosuppressive therapy for AA
- relapse of AA (35% over 3 years)
etc
small risk fo solid tumours
cure rate of young patients with AA treated with SCT
80%
cure rate of young patients with AA treated with SCT
80%
Fanconi anaemia
most common form of inherited AA
AR x-linked inheritace
etc
Fanconi anaemia
most common form of inherited AA
AR x-linked inheritace
etc
What is the most common cause of inheritedAA?
Fanconi anaemia
somatic/congential abnormalities in Fanconi anaemia
short stature
cafe au lait spots
abnormality of thumbs
developmental delay
hypo pigmented patches
skeletal abnormality
check and add details
complications of fanconis anaemia
AA (90%) median age 9
leukemia 10% - 14
liver disease
cancer\
????
dyskeratosis congenita
inherited d/o characterised by
- BM failure
- cancer predisposition
- somatic abnormalities
nail dystrophies
leukoplakia
white patches n skin
rare!!
add more details
dyskeratosis congenita
inherited d/o characterised by
- BM failure
- cancer predisposition
- somatic abnormalities
nail dystrophies
leukoplakia
white patches n skin
rare!!
add more details
DC genetic basis
telomere shortening
X-linked, AD or AR possible
DKC1 gene and TERC gene
which genes are implicated in DC (dyskeratosis congenita)?
telomere shortening is a feature of idiopathic aplastic anaemia and also of dyskeratosis congenital
mx options for hypoglycaemia
Alert and orientated
- juice/sweets
- sandwish
drowsy/confused but swallow intact
- buccal glucose
- hypostop/glucofgel
- start thinking about IV access
unconscious or concerned about swallow
-IV access
- 20% glucose
…
im iv etc
Sx of hypoglycaemia
- adrenergic
- tremor
- palpitations
- sweating
- hunger - neuroglycopaenic
- somnolescnece
- confusion
- incoordination
- seizures, coma - None = impaired awareness of hypoglycaemia (could be people that take insulin)
relief of sx with glucose administration
Sx of hypoglycaemia
- adrenergic
- tremor
- palpitations
- sweating
- hunger - neuroglycopaenic
- somnolescnece
- confusion
- incoordination
- seizures, coma - None = impaired awareness of hypoglycaemia (could be people that take insulin)
relief of sx with glucose administration
Counter-regulation in hypoglycaemia
low glucose -> decrease in insulin, increase in glucagon
- reduces peripheral uptake of glucose
- increases glycogenolysis
- increases gluconeogenesis
- increases lipolysis
increased lipolysis increases FFAs -> become ATP via beta oxidation; a by-product of this is ketone body production
the minute you have insulin you will have no lipolysis
Low neuronal glucose is sensed in the hypothalamus and leads to
1. sympathetic activation - catecholamines
2. ACTH, cortisol, GH
Ix in hypoglycaemia
- confirm that there is hypoglycaemia with glucometer
- may be more difficult in person that is otherwise healthy because it might be difficult to get a sample at the time they are hypo whereas people with diabetes monitor their blood glucose regularly
venous vs capillary BG measurement
capillary - poor precision and low levels of glucose
if you think there is hypoglycaemia the gold standard is lab measured venous glucose
Reasons why people without diabetes develop hypoglycaemia
- post gastric bypass
- organs failure
- extreme weight loss
- factitious
- hyperinsulinism
- critically unwell
fasting or active
paediatric vs adult
What to consider in hypoglycaemia in people with diabetes?
medications
inadequate CHO intake / missed meals
impaired awareness
excessive alcohol
strenuous exercise
co-existing AI conditions (e.g. exclude Addisons)
Which meds can cause hypglyxameia
glucose lowering drugs (sulphonylureas, meglitinides, GLP-1 agents)
Insulin (rapid acting with meals, inadequate meal. long acting at nighty or in between meals)
Other drugs (b-blockers, salicylates…) add
Impaired awareness of hypoglycaemia
insert
Ix for hypoglycaemia in someone w/o diabetes?
- thorough hx and examination
biochemical tests (do them at the right time)
- insulin levels *
- c-peptide*
- drug screen* (e.g. sulfonylurea)
- auto-antibodies
- cortisol/GH
- FFA/blood ketones*
- lactate
- indicates the most basic tests. you would not do an autoantibody screen on everyone
Why do we measure both insulin and c-peptide in hypoglycaemia
because c-peptide is a marker for endogenous insulin.
endogenous and exogenous insulin contribute to the insulin level but only endogenous contributes to c-peptide level
hypoglycaemia with high insulin, low c-peptide - what could this be?
hypoglycaemia in a diabetic
factitious disaese
someone has injected the insulin.
Hypoinsulinaemic hypoglycaemia
- fasting/starvation
- exercuse
etc
neonatal hypoglycaemia
hypoinsulinaemic hypoglycaemia
go over slide
could also be due to inborn error of metabolism e.g. in FA oxidation pathway, would not have ketones
neonatal hypoglycaemia
hypoinsulinaemic hypoglycaemia
go over slide
could also be due to inborn error of metabolism e.g. in FA oxidation pathway, would not have ketones
What is the appropriate / inappropriate response in hypoglycaemia?
What is the appropriate / inappropriate response in hypoglycaemia?
reactive/postprandial hypoglycaemia
main reason for hypoglycaemia in anorexia
not enough glycogen stored in liver
What is Km? (Michaelis menten constant)
subtrate concentration at which the reaction velocity is 50% of maximum
what do elevate serum enzymes point to?
disasesd organ
ALP
alkaline phosphatase
intra/extrahepatic bile ducts
bone
placenta (physiological increase in pregnancy)
intestine
there is also a physiological increase in childhood
what happens in ALP deficiency
osteomalacia
indicates that it is important for bones
What should you also check if there is a raised ALP?
hx
check LFTs (GGT and ALT) -> liver
check vitamin D -> bone
which organs do AST and ALT come from which one is more specific for the liver?
ALT is more specific for liver
both found in heart, liver muscle, kidney
Raised ALT - what could it be?
hepatocyte damage
(toxins, hepatitis, NAFLD, cancer, ischaemia e.g. post cardiac arrest)
not really used as a biomarker of kidney, heart or pancreas damage because we have better biomarkers
How can you detect intestinal ALP?
usually ALP should not be secreted when you are fasting
so get the person to fast and then measure ALP, it should be back to mnromal
is raised ALP in a pregnant person worrying
it is normal to have elevated ALP in pregnancy as it is secreted from the placenta
gamma-GT
released from liver and biliary system
if it is high the problem is in the RUQ
can also be increased in response to alcohol or certain drugs
LDH
lactate dehydrogenase
important for anaerobic metabolism
where is LDH found?
WBC
RBC
Placenta (germ-cell testicular cancer (seminoma))
skeletal muscle (myositis)
liver injury
cardiac (better biomarkers available)
where is LDH found?
WBC
RBC
Placenta (germ-cell testicular cancer (seminoma))
skeletal muscle (myositis)
liver injury
cardiac (better biomarkers available)
in what cancer is the LDH level proportional to tumour size
causes of increased amylase
acute pancreatitis
perf duodenal ulcer
bowel obstruction *and secondary disease to pancreas
salivary gland stones or infection (e.g. mumps)
macro-amylase (benign)
CK - where is it found?
skeletal muscle
cardiac muscle
Where is CK used as a biomarker?
rhabdomyolysis
myositis
polymyositis
dermatomyositis
severe exercise
……..
MI
add more
not used as a cardiac biomarker anymore because there are better markers (troponin)
Troponin I
we measure cardiac troponin
elevation indicates damage to cardiac myocytes
Reference range of troponin in men and women - same?
no, higher in men because they have bigger hearts
What regulates release of BNP?
stretch
hypoxia
cytokines
hormones
BNP
b-na… peptide
t1/2 18 minutes
difficult to measure in blood due to short half life
that is why we measure NT-proBNP because it is secreted in equimolar amounts to BNP
NT pro BNP is also a lot more stable
artiest - drug, what is it and what is it used for?
can cause false low levels of BNP so measure NT-pro-BNP
epitope for CAR T cells
CD19
epitope for CAR T cells
CD19
T-cell markers
CD3+ (all t-cells)
CD4
CD8
CD5
immature T cells can be 4+8+ but mature ones are wither 4+ or 8+
descrbe spherocytes
smaller than normal RBCs
loss of cerntal pallor
causes of spherovytosis
- AIHA
- hereditary spehrocytosis
causes of acquired non-immune haemolytic anaemia
malaria
HUS
drugs
MAHA
snake venom
drinking anti-freeze
Medication for CML
imatinib (Gleevec)
it is a tyrosine kinase inhibitor
(ABL kinase inhibitor)
Blast crisis
chronic leukemia progressing to an acute leukemia
transformed as it acquired new mutations
Test for polycythaemia vera
Jak2…17 mutation
check this!!!
which drug to treat CLL?
Ibrutinib
what is imatinib?
ABL kinase inhibitor
Ibrutinib
brutin tyrosine kinase inhibitor
Venetoclax - what is it?
BCL2 inhibito
Cause of renal failure in melanoma
cast nephropathy is most likely
AL amyloid, hypercalcaemia and ATN are also possible.
If there is a very high serum free light chain it is likely to be cast neohropathy, because they can pass through eh basement membrane and precipitate in the tubules
Cause of renal failure in melanoma
cast nephropathy is most likely
AL amyloid, hypercalcaemia and ATN are also possible.
If there is a very high serum free light chain it is likely to be cast neohropathy, because they can pass through eh basement membrane and precipitate in the tubules
what FFP do you give in an emergency
AB +/-
Who can you give 0+ blood too in emergencies
men and postmenopausal women
what would you give in bleeding with low fibrinogen and normal PT/APTT
cryoprecipitate
