Path 3 Flashcards
(184 cards)
1
Q
What is the best measure of kidney function?
A
GFR
2
Q
Functions of the kidney
A
- waste excretion
- fluid regulation and acid-base balance and
- hormone secretion
3
Q
functional unit of kidney
A
nephron
4
Q
functional unit of kidney
A
nephron
5
Q
GFR (normal)
A
120ml/min (7.2L/h)
decreases with age, lower in males
6
Q
What is serum creatinine influenced by?
A
muscularity
age
sex
ethnicity (higher in afro-caribbean)
7
Q
ethylene glycol poisoning - sx, ix and mx
A
early sx:
- vomiting
- intoxication
- abdominal pain
late sx
- decreased level of consciousness
- headaches
- seizures
Ix ?
Mx ?
8
Q
red cell casts
A
cells embedded in ?proteinacious matrix
suggestive of glomerular dysfunction
9
Q
Renal imaging modalities
A
Plain KUB (x-ray
IVU (intravenous urogram)
CT KUB (e.g. for renal stones)
US KUB
MRI
Functional imaging (status and dynamic renograms)
10
Q
AKI stage 1-3 definitions
A
AKI Stage 1: Increase in sCr by ≥26 µmol/L, or by 1.5 to 1.9x the reference sCr
AKI Stage 2: Increase in sCr by 2.0 to 2.9x the reference sCr
AKI Stage 3: Increase in sCr by ≥3x the reference sCr, or increase by ≥354 µmol/L
11
Q
Causes of pre-renal AKI
A
True volume depletion
Hypotension
Oedematous states
Selective renal ischaemia (e.g. renal artery stenosis)
Drugs affecting glomerular blood flow
12
Q
How do different drugs affect pre-renal AKI risk?
A
NSAIDs - decrease afferent arteriolar dilatation
Calcineurin inhibitors - decrease afferent arteriolar dilatation
ACEi or ARBs - decrease efferent arteriolar constriction
Diuretics – affect tubular function, decrease preload
13
Q
ATN
A
- intrinsic AKI that follows a condition of severe and persistent hypoperfusion or toxic injury of epithelial cells causing detachment of the basement membrane and tubular dysfunction.
14
Q
What structures may be involved in intrinsic AKI?
A
Vascular Disease e.g. vasculitis
Glomerular Disease e.g. glomerulonephritis
Tubular Disease e.g. ATN
Interstitial Disease e.g. analgesic nephropathy
15
Q
Outcomes of AKI
A
40% full recovery
20% death
15
Q
Outcomes of AKI
A
40% full recovery
20% death
16
Q
How many stages to define CKD?
A
5
17
Q
Stages of CKD
A
1.
2. mild
3. moderate
4. severe
5. end stage
18
Q
Stages of CKD
A
1.
2. mild
3. moderate
4, severe
5. end stage
19
Q
Causes of CKD
A
Diabetes!!! (mainly T2DM driving CKD here)
Atherosclerotic renal disease
Hypertension
Chronic Glomerulonephritis
Infective or obstructive uropathy
Polycystic kidney disease
20
Q
Functions of the kidney
A
Excretion of water-soluble waste
Water balance
Electrolyte balance
Acid-base homeostasis
Endocrine functions
EPO, RAS, Vit D
21
Q
Consequences of CKD
A
1]Progressive failure of homeostatic function
-Acidosis
-Hyperkalaemia
2]Progressive failure of hormonal function
-Anaemia
-Renal Bone Disease
3]Cardiovascular disease
-Vascular calcification
-Uraemic cardiomyopathy
4]Uraemia and Death
22
Q
Renal acidosis
A
Metabolic acidosis
Failure of renal excretion of protons
Results in:
- Muscle and protein degradation
- Osteopenia due to mobilization of bone calcium
- Cardiac dysfunction
Treated with oral sodium bicarbonate
23
Q
Hyperkalaemia ECG changes
A
- tall tented t-waves
- flattened p-waves
- wider QRS complex
can lead to VT and VF
24
NSAIDs and potassium levels
NSAIDs increase potassium levels
25
erythropoietin stimulating agents
25
erythropoietin stimulating agents
26
Renal bone disease
Complex entity resulting in reduced bone density, bone pain and fractures:
-Osteitis fibrosa
-Osteomalacia
-Adynamic bone disease
-Mixed osteodystrophy
27
Renal bone disease
Complex entity resulting in reduced bone density, bone pain and fractures:
-Osteitis fibrosa
-Osteomalacia
-Adynamic bone disease
-Mixed osteodystrophy
28
Mx of renal bone disease
Phosphate control
- Dietary
- Phosphate binders
Vit D receptor activators
- 1-alpha calcidol
- Paricalcitol
Direct PTH suppression
Cinacalcet
28
Mx of renal bone disease
Phosphate control
- Dietary
- Phosphate binders
Vit D receptor activators
- 1-alpha calcidol
- Paricalcitol
Direct PTH suppression
Cinacalcet
29
What is cinacalcet
29
Is HIV a CI for renal transplant?
no, not anymore
30
BMI >30 is a CI to renal transplant, T or F?
F
31
Active sepsis - CI for renal transplant?
YES
32
Types of diaysis
haemodialysis (more common, can be done at home)
peritoneal (10%)
32
Types of diaysis
haemodialysis (more common, can be done at home)
peritoneal (10%)
33
PUO definition
prescriptive set of mandatory investigations
3 days of hospital investigations
34
Durack and Street criteria for PUO - categories
classic
nosocomial
immune deficient (neutropenic)
HIV-associated
35
DUKE criteria
can come up in exams
36
RIPL
rare and imported pathogens laboratory
you send a sample with the story and then they do the appropriate tests.
37
Campylobacter vs Salmonella
Campylobacter
- diarrhoea
- cramps
- bloating
- no fever
- no manegemtn
Salmonella
- diarrhoea
- vomiting
- may have fever
- usually supportive management, in typhi and paratyphi might give AABx
38
Abx for salmonella
39
Causes of polycythaemia in foetuses
Twin-to-twin transfusion
Intrauterine hypoxia
Placental insufficiency
40
Causes of anaemia in foetuses
Twin-to-twin or Foetal-to-maternal (rare) transfusion
Parvovirus infection (virus not cleared by immature immune system)
Haemorrhage from cord or placenta
41
haem -> causes of damage to the foetus
Irradiation
Damage by something crossing the placenta (e.g. drugs, chemicals, antibodies)
Anticoagulants ( haemorrhage or foetal deformity (e.g. vitamin K if given in the first trimester))
Antibodies can destroy red cells, white cells or platelets
Substances in breast milk (e.g. G6PDD-baby may suffer from haemolysis if mother eats fava beans)
42
transient abnormal myelopoiesis / TAM
- remits spontaneously
- often transforms into a leukemia that does not remit
- occurs in trisomy 21
43
Splenic sequestration
in children
sickled cels move into spleen -> infarcts -> spleen enlarges -> can be very dangerous and cause
43
Splenic sequestration
in children
sickled cels move into spleen -> infarcts -> spleen enlarges -> can be very dangerous and cause
43
Splenic sequestration
in children
sickled cels move into spleen -> infarcts -> spleen enlarges -> can be very dangerous and cause
44
Stroke risk is higher in infants with SCD than in adults
45
Inherited haemolytic anaemias n children - where can the defects be?
Red cell membrane
Haemoglobin molecule
Red cell enzymes—glycolytic pathway
Red cell enzymes—pentose shunt
Not to mention other rare conditions that you really don’t want to hear about
45
Inherited haemolytic anaemias n children - where can the defects be?
Red cell membrane
Haemoglobin molecule
Red cell enzymes—glycolytic pathway
Red cell enzymes—pentose shunt
Not to mention other rare conditions that you really don’t want to hear about
46
Haemolytic anaemias in chldern
Red cell membrane defects
Hereditary spherocytosis
Hereditary elliptocytosis
Haemoglobin defects
Sickle cell anaemia
Glycolytic pathway defects
Pyruvate kinase deficiency
Pentose shunt defects
G6PD deficiency
47
spherocytes on film
reduced central pallor
48
Heinz body
48
Heinz body
49
What can precipitate haemolytic in G6PD deficency?
- Infections
- Drugs
- Naphthalene
- Fava beans
falafel now sometimes made with a mixture of chickpeas and broad beans
50
Defects of coagulation in children
Haemophilia
vWD
?
51
When do you see Auer rods?
52
mutation in polycythaemia vera
JAK2 V617F
53
What does roleaux on blood film indicate?
53
What does roleaux on blood film indicate?
54
thrombotic thrombocytopaenic purpura
The underlying defect in thrombotic thrombocytopenic purpura is a deficiency of a plasma protein called von Willebrand factor cleaving protease (or ADAMTS13)
55
Presentation of FMF
- episodic fevers for 48-96 hours
associated with:
- Abdominal pain due to peritonitis
- Chest pain due to pleurisy and pericarditis
- Arthritis
- Rash
56
Complication of FMF
Complication - AA amyloidosis
Liver produces serum amyloid A as acute phase protein
Serum amyloid A deposits in kidneys, liver, spleen
57
Dx of FMF
High CRP, high SAA
Blood sample to specialist genetics laboratory to identify MEFV mutation
58
Management of FMF
Colchicine 500mcg bd - binds to tubulin in neutrophils and disrupts neutrophil functions including migration and chemokine secretion
IL-1 blocker (anakinra, canukinumab)
TNF alpha blocker
59
What is IPEX?
Immune dysregulation, polyendocrinopathy, enteropathy, X- linked syndrome IPEX
mutations in FoxP3 cause it -> failure to negatively regulate Tregs
60
What is ALPS?
Auto-immune lymphoproliferative syndrome
Mutations within FAS pathway
61
ALPS symptoms
High lymphocyte numbers with large spleen and lymph nodes
Auto-immune disease
commonly auto-immune cytopenias
Lymphoma
62
Why do we worry about infections in pregnancy?
Maternal complications (Influenza, VZV, Hep E)
Miscarriage / stillbirth (rubella, measles, Hep E)
Teratogenicity (VZV, Zika)
IUGR / prematurity (rubella / CMV)
Congenital disease (CMV, HSV)
Persistent infection (HIV, Hep B/C)
63
pregnant woman with rash - which viruses?
Varicella Zoster virus (chickenpox/ shingles)
Epstein barr virus
Herpes simplex virus
Cytomegalovirus
Parvovirus B19
Enterovirus
Measles
Rubella
64
HSV details
- transmission vii close contact
- incubation: oropharyngeal/oro-facial 2-12 days; genetical infection 4-7 days
- Sx: Asymptomatic
Painful vesicular rash
Lymphadenopathy
Fever
- latency: established in nerve cells
- lesion swab for viral PCR
65
Foetal HSV infection
- very uncommon
- foetal infection ascending in PROM
66
Neonatal HSV infection
- can be very dangerous
Routes of infection:
- Direct contact with infected maternal secretions during delivery
- Oral herpes : kissing baby
- Non familial transmission: other relatives, hospital staff etc
67
HSV vertical transmission in pregnancy
VERTICAL TRANSMISSION
Greatest risk of transmission is primary genital infection in the 3rd trimester
- If active HSV in final 6 weeks before delivery then C-section is recommended
68
What do you do with a woman that has active HSV in pregnancy>
- GUM clinic referral
- aciclovir in primary infection
- HSV Ab testing
- consider planned C-section
69
mortality in neonatal HSV f untreated
80%
70
Why is HSV under diagnosed in babies?
- can be small lesions
- can be mistaken for other things
71
types of neonatal HSV
- SEM (skin, eye, mouth)
- CNS involvement (+/- SEM)
- disseminated
-> prevent HSV! Swab them, if concerned, treat with acyclovir)
72
Why are we worried about VZV in pregnancy>
MATERNAL VARICELLA
- 10-20% of women in childbearing age susceptible
- 10-20%
- of pregnant women with varicella will have varicella pneumonia.
Encephalitis is rare but mortality is 5-10%
CONGENITAL VARICELLA SYNDROME
- 0.4% if maternal infection weeks 0-12
- 2% if weeks12-20
- skin scarring and limb abnormalities
Find out if this woman has had a varicella infection/vaccination or not? or check IgG
73
PEP for maternal VZV
- consult guidance
- within 7d of exposure (Oral aciclovir 800mg
OR
Oral Valaciclovir 1000mg TDS
from day 7-14 after exposure)
- present after 7d of exposure (Oral aciclovir 800mg QDS
OR
Oral Valaciclovir 1000mg TDS
up until day 14 post exposure)
74
How do you treat maternal VZV?
Aciclovir
75
How common is CMV in pregnancy>
76
How does foetal CMV infection present?
77
How do we manage CMV infection in pregnancy?
- check serology and compare to booking serology
- refer to foetal medicine team, regaular USS perhaps amniocentesis
- no treatment
78
Rubella presentation
- Starts on face and spreads to trunk/limbs within hours
- lymphadenopathy
- most people in the UK are vaccinated so not that big of an issue at the moment
79
When in pregnancy is Rubella a problem?
Greatest risk is in the 1st trimester
- If infection before 8 weeks -> 20% spont abortion
- If infection before 10 weeks 90% incidence of fetal defects
- If infection after 18-18 weeks -> hearing defects and retinopathy
- If infection after 20 weeks risk is much lower
80
CRS
congenital rubella syndrome
Sx:
- bone lesions
- microcephalau
81
What may you be able to see in the mouth in rubella infection?
Froschheimer spots
82
How does measles spread?
Measles starts behind the hairline, around the ears, spreads cephaocaudally over a few days (~3d)
83
Measles - complications for mother
- secondary bacterial infection
- otitis media
- pneumonia (10% mortality)
- gastointestinal
- encephalitis
84
Risk of measles infection in pregnancy
- foetal loss
- preterm delivery
- SSPE
- no congenital abnormalities
85
Risks of parvovirus B19 in pregnancy
- before 20w transmission 33%
- 9% risk of infection in trransmission
- 3% hydros foetalis f infection
- 1% foetal anomalies
- 7% foetal loss
- no risk documented after 20w
86
What is hydros foetal is aand what can cause it?
- cytotoxic to foetal red bood precurrsos cels -> anemie aanaard accumulaton of fluid in soft tissues and serous cavities, and can
86
Refer to fetal medicine for monitoring
May require intrauterine transfusion
87
Questions to ask a pregnant woman presenting with rash?
- Gestation of pregnancy (date of last menstrual period/Due date by scan)
- Date of onset, clinical features, type and distribution of rash, associated features
- Past relevant history of infection
- Past relevant history of antibody testing
- Past immunisation history (and dates/places)
- Any known contacts with rash illness (dates)
- Travel history
88
Investigations for pregnant woman with rash
Antenatal booking bloods
Antibody test to determine immunity/susceptibility
Swab/scrape from rash (if vesicular)
Blood sample
Antibody
+/- PCR
Postpartum vaccination if not had
89
Complications of PID
peritonitis
bacteraemia
infertility
intestinaal....?
90
Meaan age for cervical cancer
45-50 years
91
High risk HPVs for cancer
16 and 18
92
When does dysplasia/carcinoma in situ change to invasive cervical cancer?
When the basement membrane is crossed?
92
When does dysplasia/carcinoma in situ change to invasive cervical cancer?
When the basement membrane is crossed?
93
CIN -> squamous carcinoma
CGIN -> cervical adenocarcinoma
94
Adenomyosis
endometrium is present in areas within the muscle wall
95
Staging for endometrial Ca
FIGO
includes
- depth of invasion
- local and/or regional spreads the tumour
- metastases
- lymph nodes
96
Serous carcinoma of ovary - origin is often the Fallopian tube
97
Which cancer is associated with endometriosis?
Clear cell carcinoma
98
Normal K+ levels
3.5-5.0 mol/L
99
What is the main Xcellular ion?
potassium
100
Hormones in the regulation of potassium?
angiotensin II
aldosterone
101
stimuli for aldosterone release
Angiotensin 2
potassium
102
Main causes of hyperkalaemiaa
1. decreased GFR (renal failure,
2. decreased renin (type 4 renal tubular acidosis - rare (diabetic nephropathy), NSAIDs)
3. ACE1
4. ARBs (e.g. losartan)
5. Addison's disease
6. Aldosterone antagonists (e.g. spironolactone)
7. rhabdomyolysis (K+ leaks from cells)
8. acidosis (K+ is lost to maintain electroneutrality)
103
where is renin produced/relased?
juxtaglomerular apparatus
104
Which drugs reduce renin?
NSAIDs
105
Mian ca
renal impairment
drugs (ACEi, ARBs,spironolactone, NSAIDs)
low aldosterone
release from cels
106
ECG finding with hyperkalaemia
- peaked T-waves
107
Management of patients with hyperrkalaemia
- 10ml 10% calcium gluconate
- 100ml of 20% dextrose + 10 units of insulin
- nebulised salbutamol
- treat the underlying cause
108
- loop diuretics
- batter syndrome
- thiazide diuretics
- gitelman syndrome
more sodium to distal tubules or excess aldosterone
109
Causes of hypokalaemiia
- GI loss (vomiting)
- Renal loss (hyperaldosteronism, excess cortisol); increased sodium delivery to distil nephron; osmotic dieresis)
- redistribution into cells (insulin, beta-agonists, alkalosis)
- rare causes: renal ......
110
Clinical features of hypokalaemia
- muscle weakness
- cardiac arrythmia
- polyuria and polydipsia (nephrogenic DI)
111
aldosterone renin ratio
112
What diuretic causes hypokalaemia?
Furosemide
113
Why does cutanoues exposure to allergens promote allergy and oral exposure promote tolerance?
oral -> IgG responses and promotion of tolerance via Treg cells
cutaneous and resp -> IgE response, promotion of Th2 responses
114
Results of skin prick test do not correlate to severity of reaction
115
Advantages and disadvantages of skin prick tests
116
skin prick vs intradermal test for allergy
117
What tests can you do for allergy>
- Skin prick
- intradermal tests
- sensitisation (IgE antibody) blood tests
- component resolved diagnostics
117
What tests can you do for allergy>
- Skin prick
- intradermal tests
- sensitisation (IgE antibody) blood tests
- component resolved diagnostics
118
Detection of IgE is necessary but not sufficient to make a diagnosis of allergic disease
allergy is a clinical diagnosis
119
Biomarkers for anaphylaxis
mast cell tryptase (pre-formed protein in mast cell granules; systemic degranulation of mast cells during anaphylaxis results in increase in serum tryptase)
120
Biomarkers for anaphylaxis
mast cell tryptase (pre-formed protein in mast cell granules; systemic degranulation of mast cells during anaphylaxis results in increase in serum tryptase)
anaphylaxis not allergy
serial measurements at 30 minutes and 2h and then at least 24h
121
Management of anaphylaxis
- correct positioning (supine, legs up)
- IM adrenaline
- ABCDE
- antihistamines only one ABC have been corrected
- if no response to IM adrenaline, repeat and give IV crystalloid fluids
-> refer to allergy/immunology clinic and give IM epipen; liaise with school/nursery in children.
121
Management of anaphylaxis
- correct positioning (supine, legs up)
- IM adrenaline
- ABCDE
- antihistamines only one ABC have been corrected
- if no response to IM adrenaline, repeat and give IV crystalloid fluids
-> refer to allergy/immunology clinic and give IM epipen; liaise with school/nursery in children.
122
What are the types of adverse reactions to food
1) Food intolerance Food poisoning (bacterial, scromboid toxin)
Enzyme deficiencies (lactase)
Pharmacological (caffeine, tyramine )
2) Food aversion Fads, eating disorders
3) Food allergy
- IgE mediated reactions (anaphylaxis, OAS)
- Mixed IgE and cell mediated (atopic dermatitis)
- Non IgE mediated (coeliac disease)
Cell mediated (contact dermatitis)
123
90% of food allergies are caused by 8 foods (peanuts, milk, egg, shellfish, tree nut, fish)
124
Important risk factors for food allergy
Moderate/severe atopic dermatitis is an important risk factor for food allergy (indication for allergy testing even in absence of clinical history)
125
skin prick in food allergies
positive skin prick is good at a confirming the diagnosis
negative is good at excluding disease
126
Food associated exercise induced anaphylaxis
- ask in history if they exercised within 4-6 h of ingestion
- Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion
- Common food triggers are wheat, shellfish, celery
127
Delayed food-induced anaphylaxis to beef, pork, lamb
- Symptoms occur 3-6 hours after eating red meat and gelatin
- IgE antibody to oligosaccharide alpha-gal (α1, 3-galactose) found in gut bacteria (lipid from meat is released, you are exposed to alpha-gal)
0 Induced by tick bites
128
Coroner's toxicology reasons (deaths reported to coroner)
o Violent
o Unnatural or sudden
o Cause of death is unknown
129
What is the only specimen that can give a chronic drug history
Hair
130
Timeframe of drug use based on PM samples
- In Blood/serum, drugs typically can be detected for <12 hours
- In Urine, drugs typically can be detected for 2-3 days
- Hair: detects long term drug use (months/years e.g. 6months ago -> 6th centimetre)
131
How do you calculate osmolality
2(Na+K)+urea+gulcose
132
anion gap forula
Na+K-Cl-bicarb
133
nomal anion gap
18-20 mM
134
High anion gap causes
- ketones
- methanol
- ethanol
- lactate (rare)
135
Mx of HHC
gradual IV saline on ICU
136
How can metformin cause acidosis?
if you OD it increases lactate -> lactic acidosis
137
Definition of type 2 diabetes
FG >7.0 mM
GTT >11.1 mM at 2h
138
What is smouldering myeloma? (general)
- a stage between MGUS and MM
- premalignant condition
- there are no CRABs Sx but some of the lab values are 'worse' than with MGUS classification
139
What condition precedes MM?
MGUS (monoclonal gammopathy of unknown significance)
140
Incidence of MGUS in the elderly?
1-3.5%
141
What is the risk of progression with MGUS?
1% annual risk
(IgA and IgG progress to MM; IgM progress to lymphoma)
142
What are some primary and secondary events that lead to MM?
PRIMARY
a. Hyperdiploidy (odd number of chromosomes) - occurs in 60%
b. IGH rearrangements (Chr 14q32)
- t(11;14) IGH/CCND1
- t(4;14) IGH/GFR3
- t(14;16) IGH/MAF
SECONDARY
* KRAS, NRAS
* t(8;14) IGH/MYC
* 1q gain / 1p del
* del 17p (TP53)
* 13-/ del 13q
143
What are some primary events that lead to MM?
a. Hyperdiploidy (odd number of chromosomes) - occurs in 60%
b. IGH rearrangements (Chr 14q32)
- t(11;14) IGH/CCND1
- t(4;14) IGH/GFR3
- t(14;16) IGH/MAF
144
What are some secondary events that lead to MM?
* KRAS, NRAS
* t(8;14) IGH/MYC
* 1q gain / 1p del
* del 17p (TP53)
* 13-/ del 13q
145
In what ways do MM cells interact with the bone marrow microenvironment? What effects to they have?
- Bone destruction
- anaemia
- angiogenesis
- immunosuppression and inflammation
146
What is cast nephropathy in the context of MM?
formation of plugs (=urinary casts) in renal tubules from the free Ig light chains leading to renal failure
146
What is cast nephropathy in the context of MM?
formation of plugs (=urinary casts) in renal tubules from the free Ig light chains leading to renal failure
147
What is the 2nd commonest blood cancer?
multiple myeloma
(prevalence is increasing)
147
What is the 2nd commonest blood cancer?
multiple myeloma
(prevalence is increasing)
148
Bence Jones protein
urine monoclonal free light chains
indicates MM
149
What does 'M-spike' refer to?
it is a pattern on electrophoresis indicative of MM
150
RFs for MM
- m>f
- obesity/overweight
- genetics (sometimes there is familial MM)
- older age
- black > caucasian/asian
151
What is Waldenstrom's lymphoplasmacytic lymphoma
- low grade lymphoma
- B-cells (have features of lymphocytes and of plasma cells hence the name)
- IgM monoclonal gammopathy seen
152
CRAB features
-> mm
C - calcium > 2.75 mmol/L
R - renal disease (Creatinine >177umol/ or eGFR <40ml/L
A - anaemia (Hb <100g/L or drop of 20g/L)
B - bone disease (one or more bone lytic lesions on imaging)
152
CRAB features
-> mm
C - calcium > 2.75 mmol/L
R - renal disease (Creatinine >177umol/ or eGFR <40ml/L
A - anaemia (Hb <100g/L or drop of 20g/L)
B - bone disease (one or more bone lytic lesions on imaging)
153
What % pts with MM present with bone disease?
80%
154
What type of bone lesions do people with MM get?
- osteolytic, never osteoblastic
* Proximal skeleton
* Back (spine), chest wall and pelvic pain
* Osteolytic lesions, never osteoblastic
* Osteopenia
* Pathological fractures
* Hypercalcaemia
155
On which chromosome are HLA genes encoded?
Chromosome 6
155
On which chromosome are HLA genes encoded?
Chromosome 6
156
Which HLA are for MHC I and II?
MHC I: show antigen to CD8+ T-cells
HLA-A
HLA-B
HLA-C
MHC II: show antigen to CD4+ T-cells
HLA-DP
HLA-DQ
HLA-DR
157
Which HLAs are usually typed for compatibility purposes in SCT?
HLA-A
HLA-B
HLA-DR
158
What is GvHD?
What is affected in acute/chronic GvHD?
An immune response when donor cells recognise the patient as ‘foreign’
Acute GvHD affects skin, gastrointestinal tract and liver
Chronic GvHD affects skin, mucosal membranes, lungs, liver, eyes, joints
158
What is GvHD?
What is affected in acute/chronic GvHD?
An immune response when donor cells recognise the patient as ‘foreign’
Acute GvHD affects skin, gastrointestinal tract and liver
Chronic GvHD affects skin, mucosal membranes, lungs, liver, eyes, joints
159
RFs for GvHD
Degree of HLA disparity
Recipient age
Conditioning regimen
R/D gender combination
Stem cell source
Disease phase
Viral infections
160
Treatment of acute GvHD
Corticosteroids
Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
Mycophenylate mofetil
Monoclonal antibodies
Photopheresis
Total lymphoid irradiation
Mesenchymal stromal cells
161
Prevention of acute GvHD
Methotrexate
Corticosteroids
Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
CsA plus MTX
T-cell depletion
Post-transplant cyclophosphamide
162
How is neutropenic sepsis defined?
- temperature >38 sustained for one hour or single fever >39
- in a patient with neutrophils <1.0 x 10^9/L
163
How do you manage neutropenic sepsis?
Defined as temperature >38 sustained for one hour, or single fever >39, in a patient with neutrophils <1.0 x 10^9/L
164
Manifestations of CMV disease
- Pneumonitis
- Retinitis
- Gastritis – colitis
- Encephalitis
165
What is PTLD?
- post transplant lymphoproliferative disease
- life threatening
- associated with EBV
