haem top tier Flashcards
1
Q
anaemia epidemoiology
A
common
esp pre-menopausal
2
Q
different types of anaemia
A
microcytic = small rbc size
normocytic = normal
macrocytic = large
3
Q
microcytic anaemia causes
A
iron deficiency
– microcytic hypochromic (small with less colour) = iron def until proven otherwise
chronic illness
thalassemia
4
Q
normocytic anaemia causes
A
- chronic illness
- acute blood loss (trauma, periods, haemolysis, hypersplenism( increased rbc removal), rbc disorders)
- combined micro and macro (iron and b12 def - malabsorption)
- increase in volume (so relative low rbc conc) – pregnancy, overhydration
- bone marrow failure - aplastic
5
Q
name examples of haemolysis
A
sickle cell
malaria
chronic illness
6
Q
rbc disorders
for each:
- eg
- presentation
- epidemiology
A
membranopathies
- Eg spherocytosis, elliptocytosis
- Mild, benign, common
cause= decrease in red cell membrane proteins
- Presentation = neonatal jaundice, anaemia
enzymopathies
- Inherited enzyme deficiencies so less fuel for ebc
- Shortened rbc lifespan from oxidative damage
- Eg - glucose-6-phosphate dehydrogenase deficiency
- Epidemiology = men>women (x linked). African, Middle East, S Asia, mediteranian
- Often asymptomatic , usually self limiting. Exacerbated by broad beans, infections, drugs → brown urine (so avoid broad beans, occasionally need transfusion)
7
Q
what is another cause of normocytic anaemia (in which the causes are not actually normocytic!)
A
combined micro and macro cells - balance out
— iron and B12 def (think malabsorption
8
Q
what is the cause of bone marrow failure
how does it present
treatment
A
infection
genetic
drugs
more bleeding, more infection
remove causative agent
blood transfusion
9
Q
macrocytic anaemia causes
A
- b12 / folate
- alcohol /liver disease
- hypothyroidism
- haem causes (reticulocytes (immature rbc) increased)
10
Q
b12 deficiency
aka
appears as
why might there be b12 def
A
pernicious anaemia (gradually worse)
- macrocytic anaemia
- hyper-segmented neutrophil (more than 5 dark blue bits - normally 3-5)
b12 absorption requires intrinsic factor (made in gastric parietal cells) for terminal ileum absoprtion
- so issue is with intrinsic factor or terminal ileum
11
Q
differential diagnosis of anaemia
A
n third trimester of pregnancy, there is an increase in rbc number but also an increase in volume so appears anaemic
12
Q
what is anaemia
what is the affect
pathological consequences
A
reduced red cell mass OR increased plasma volume (dilutes rbc conc)
decrease in oxygen transport --> tissue hypoxia physiological compensation -- increased tissue perfusion ----- increased HR -- increased oxygen transfer to tissues ----- oxygen saturation curve ----- breathing rate increases?
- Myocardial fatty charge
- Aggravate angina /claudication
- Fatty change in liver
- Skin and nail atrophic changes
- CNS cell death
13
Q
why does iron matter in terms of anaemia
A
Iron necessary for formation of haem on each strand in haemoglobin → ineffective haemoglobin
14
Q
surrogate marker for anaemia (low rbc) =
A
haemoglobin
15
Q
common anaemic symptoms
A
Fatigue, lethargy Dyspnoea Short of breath on exertion Faintness Palpitations Headache
16
Q
what additional anaemia symptoms would you have if you were
iron def
B12 def
folate def
haemolytic
A
Iron def
- Brittle nails, spooning. Brittle hair
- -Glossitis (tongue inflammation)
B12 def
– Neurological problems
Folate def
- -Glossitis
- -Slow development
Haemolytic
- -Jaundice
- -Gallstones
- -Leg ulcers
17
Q
how might B12 def (Anaemia ) be picked up
A
IF (intrinsic factor) antibodies (IF needed to absorb B12)
Schilling test - measures B12 intestinal absorption (radiolabelled B12 supplement)
coeliac antibodies (may affect terminal ileum)
B12 in blood
18
Q
anaemia investigations
A
bloods
- haemoglobin levels
- reticulocytes (immature rbc) rbc)
- B12, folate, ferritin levels
- U/E
- LFT
- TSH
blood film
- see type (size )
- colour
- eveness
- shape
19
Q
hypo/normo/hyperchromic
A
this refers to rbc colour (in aneamia)
rbc colour is given by haemoglobin so it indicates haem levels
20
Q
why are reticulocytes a useful tool for anaemia
A
Reticulocytes = immature rbcs
Marker of balance between rbc creation and removal (spleen, liver, bone marrow, blood loss)
– lots of reticulocytes = lots of creation eg short life span of sickle cells
21
Q
microcytic hypochromic
A
= iron deficiency anaemia (until proven otherwise)
22
Q
Hypersegmented neutrophil
A
(more than 5 dark blue clumps)
=B12 deficiency
23
Q
anaemia treatment
A
treat the cause
- dietary supplements (iron, B12, folate (folic acid))
- immunosuppression if autoimmune (eg B12, some genetic haemolytic ones)
- hypersplenism –> surgery
24
Q
anaemia complications
A
Worsens angina Worsens claudication Tissue ischaemia - pain, loss of sensation, loss of function Nails brittle, spoon shape Hair thin/receding/loss (?)
25
thalassemia and sickle cell anaemia in broad terms
thalassemia = decrease in QUANTITY of haemoglobin
sickle cell = decrease in QUALITY of haemoglobin
26
what is the cause of thalassaemia
different varieties=
Globin chain production switched off, so reduction in haemoglobin (genetic, heterogenous- carriers asymptomatic)
Varies in severity - major/intermedia/minor
alpha/beta (alpha rarer, more die)
27
where is thalassaemia most common
South asia, central africa, far east
28
symptoms of thalassaemia and when does it present
```
Presents 6-12 months
Failure to feed
Pale
Listless
crying
```
29
management of thalassaemia
- Transfusion regularly
- Iron chelation (to prevent iron overload that is caused by transfusion)
- Endocrine supplementation (hormones)
- Bone health
- psychological
- Fertility
- Monitor - ferritin, endocrine, function, heart and liver MRI, bone density
30
what is iron chelation and why is it needed
removal of iron in body via drugs
| to prevent iron overload that is caused by transfusion
31
what is normal adult and foetal haemoglobin
```
normal = 2 alpha, 2 beta, heme group on each.
Foetal = 2 alpha, 2 gamma
```
32
cause of sickle cell anaemia
genetic. Disease is homozygous (or heterozygous if with other haematological disorders eg thalassemia). HbS carrier symptom free + falciparum malarial protection. Spread from malarial regions to UK/USA via slave trade.
33
sickle cell anaemia symptoms
acute and chronic
affects multiple systems
Acute
- Pain - sickle cell crisis = blockage of vessels in bone so bone marrow swells
- Lungs- sickle chest syndrome = occlusion of micro-vessels --> chest pain, cough, fever, hypoxia
- Stroke
Chronic
- Poor circulation
- Renal impairment
- Joint impairment
- Pulmonary hypertension ( → heart failure)
many effects more
34
sickle cell anaemia management
Treat complications
Treat disease
- Blood transfusion
- Stem cell transplant
- Gene therapy (genetic information introduced to cells)
- Gene editing (DNA modified in someone)
- Hydroxycarbamide for sickle cell crises (suppresses bone marrow?)
35
what viral infection worsens sickle cell and why
treatment
if have parvovirus too, a common infection that reduces RBC production, there is a dramatic drop in Hb as short life span of sickle cells. Associated with death, need asap blood transfusion
36
deep vein thrombosis risk factors
triggers
older
surgery/hospital
thrombophilia
malignancy
```
Contraceptive pill (oes )
Pregnancy (oes)
Surgery >30min
fracture/ immobility
Long haul flights
```
37
deep vein thrombosis pathophysiology
Clot in a deep vein in leg
Disrupts circulation
Can embolise
38
signs and symptoms of DVT
normally unilateral
```
SIGNS
Tenderness
Swelling
Warmth
Discolouration
```
```
SYMPTOMS
Pain / cramping esp walking
Throbbing
Swelling
red/darkened skin
Warm skin
Swollen veins -hard/sore
```
39
well's score (DVT)
Short survey - no= 0, yes =1. Score of 2+ means likely DVT
Questions = cancer, paralysis, recent surgery/bedridden 3+ days, swollen leg, calf 3cm+ other calf, large veins, previous DVT, pitting oedema (thumb mark compression when prodded)
40
DVT investigations
well's score
D dimer
= fibrin degradation product (blood test.)
Positive does not confirm (not specific) but negative (normal result) does rule it out
So if +ve then do ultrasound
ultrasound
Looks at proximal veins for DVT : popliteal fossa to groin
With probe, if can squash flat, it is fine. If not-clot
41
DVT management
LMW (low molecular weight) Heparin injection = immediate anti-coag
Oral warfarin - longer term but takes a while to act (so hep first)
DOAC (direct oral anticoagulants)
Oral, 2xday, longterm
Compression stockings
Treat/seek underlying cause
Malignancy
Thrombophilia (genetic predisposition)
42
DVT prevention
need to prevent around surgery/immpbility
Compression stockings (pre and post surgery)
Early mobilisation after op
Hydration
Foot pumps during theatre if high risk/ long surgery
LMW heparin for many inpatients
43
PE small vs big clot effects
Small clot = more common
- Chest pain, pleuritic
- Sob
- DVT symptoms
- Tachycardia
- Tachypnoea
Big clot = emergency /death
- Hypotension
- R sided heart strain/heart failure
- Dyspnoea
- Cyanosis = bluish skin
- Hemoptysis = coughing up blood
44
PE investigations
wells score
CXR- usually normal
ECG - sinus tachycardia (and excludes dif diagnosis
blood gases - type 1 resp failure
45
well's score (PE)
2-6 is medium probability, 6+high probability. (all d dimer, 2-6 consider CTPA and high sensitivity d dimer, 6 def ctpa (dont bother d dimer)
Questions : DVT symptoms, immobilisation 3d/ surgery in the last month, previous DVT/PE, tachycardia 100+, hemoptysis, cancer
46
PE treatment
Same as DVT (LMW Heparin, Oral warfarin DOAC )
Plus IV heparin (needs monitoring)
Plus aspirin - irreversible inhibitor
47
who gets leukaemia most commonly- age
v old or v young
48
leukaemia pathophysiology and cause
Cancer of Blood cells residing mainly in bone marrow / blood
Due to an undetected , undestroyed mutation. then more likely for further generations to have further abnormal mutations
49
leukaemia vs lymphoma
both cancer of blood cells (too many produced)
leukaemia - too many wbc residing mainly in bone marrow/ blood
lymphoma = too many lymphocytes residing mainly in lymph nodes
50
types of leukaemia
ALL
CLL
AML
CML
ALL : acute lymphoblastic leukaemia
CLL : chronic lymphoblastic leukaemia
AML: acute myeloid leukaemia
CML: chronic myeloid leukaemia
51
risk factor for ALL (acute lymphoblastic leukaemia)
Down’s syndrome
radiation
benzene
52
CML (chronic myeloid leukaemia) cause
Philadelphia chromosome- genetic swap between chromosome 9 and 22 . makes new protein: active tyrosine kinase
also can cause AML, ALL
53
CML (chronic myeloid leukaemia) treatment
Treatment = imatinib. Blocks tyrosine kinase activity (specific). Mutations in cancer can stop from working.
54
myeloid vs lymphoid
both progenitor cells
they are more differentiated than hematopoietic progenitor cell
myeloid cell can differentiate into eosinophils, basophils, monocytes (macrophage), rbc, neutrophil, megakaryocytes (platelets)
lymphoid cell can differentiate into B, T lymphocytes and natural killer cells
55
mast cell vs basophil
similar cells
NOT one is a mature version of the other as u once thought
they are different
basophil leaves bone marrow already mature
mast cell matures once it reaches tissue
56
leukaemia signs and symptoms
```
Due to anaemia
- Fatigue
- Sob on exertion
- Light headed
Due to thrombocytopenia
- Bruising
- Bleeding
Bone pain
Palpitations
```
57
low wbc =
high wbc=
symptoms-wise
If low wbc- recurrent, non-resolving infections
If high wbc- renal impairment, sob, hyperkalemia
58
leukaemia investigations
bloods
- FBC
- -- 20%+ blast cells (big cells, large nucleus with lots of patched nucleoli. usually less than 5%)
for acute:
- -- low platelets
- -- anaemia( low haemoglobin /rbc)
- -- WCC variable
for chronic
- -- anaemia
- -- raised WBC (if myeloid - raised non-lymphocyte wbc,if lymphoid- raised wbc)
- blood film
- haemolysis screen and biochem profile
- karyotype (looking for philadelphia chromosome for chronic myeloid leukaemia - switch between 9 and 22)
bone marrow biopsy
hepatosplenomegaly
59
blast cells and leukaemia
Blast cells = big cells with large nucleus and lots of patched nucleoli
normally make up <5% of bone marrow. In leukaemia, >20%
60
leukaemia treatment
watch and wait
chemo
supportive measures
- fertility cryopreservation
- rbc and platelet transfusion
- isolation (as they are immunosuppressed)
stem cell transplant (steroids and HRT alongside)
monoclonal antibodies
- end in 'mab' (rituximab)
- Sole target (“mono”) = CD20 protein on only B lymphocytes (so side effects low)
61
monoclonal antibodies
- called?
- action?
- what are they?
- conjugates
-"mab" (rituximab)
Sole target (“mono”) = CD20 protein on only B lymphocytes (so side effects low)
Chimeric- mouse and human (hot/cold, allergic side effects)
immuno/radio -conjugates = stick poison (chemo) or gamma-emitting radiation on end of monoclonal antibody- extra effect
62
lymphoma causes
Immunodeficiency
- -Primary
- - Secondary (HIV, transplant)
Autoimmune
Infection (EBV)- commonly virus- infect B cells, proliferate autonomously
63
hodgkins lymphoma
- age
- stage one, two, three, four
- prognosis
- two peaks! : teenagers/young adults and old 70+
1- one place
2- multiple places
3- nodes either side of diaphragm
4- disseminated to extra-lymphatic tissue
stages 1-2 = good prognosis: cure even if relapse (dont know about 3-4!)
64
indolent means?
not aggressive, causes little pain
| lymphoma can be indolent or aggressive
65
non-hodgkins lymphoma
- age
- how does it vary from hodgkins lymphome
- grades
- rare under 40y
- more variation in presentation, treatment and outcome
- more extra-nodal presentation than in Hodgkins
- low grade= slow growing, incurable, relapse, presents advanced
- high grade= nodal presentation with poorly patient, short hisrory
66
cure for follicular lymphoma
no cure. manageable though
67
neck lump differential diagnosis
Infection, inflammation
- - Reactive lymph node growth
- - Tender
- - Transient - <6w
Neck lump from other - thyroid enlargement
Embryological remnant
Metastatic cancer
lymphoma
68
symptoms and signs of lymphoma
Night sweats (distinguish from menopause)
Fatigue
Anaemic - breathless
Neck lump (lump in abdomen has to be really large to notice it)
Loss of appetite/ weight
Oedema
69
lymphoma investigation
```
1 Do they have it ?
Needle biopsy
Blood test and blood film
Bone marrow biopsy
PCR
Immunophenotyping
Cytogenetic- karyotype analysis
```
```
2 if Yes
CT, PETscan, CXR, echo ,lung function tests PFT
--- How fit they are
--- How extensive is it- how many places
History
bloods
```
70
lymphoma treatments
chemotherapy
radiotherapy
monoclonal antibodies
- --“Mab” eg rituximab
- -- Targets CD20 - only on B lymphocytes- minimal side effects
- -- Chimeric- mouse and human - so allergy side effects
- -- immuno/radio -conjugates = stick poison (chemo) or gamma-emitting radiation on end of monoclonal antibody- extra effect
bone marrow treatment
watch and wait
71
"late effect" of lymphoma
= long term side effects of treatment
```
Infertility
Cardiomyopathy
Second cancers
Psychological issues
Peripheral neuropathy
Lung damage
```
72
what is ITP immune thrombocytopenia
- cause
- pathophys
- symptoms
- treatment
a complication of lymphoma
lymphocytes attack platelets
- bleeding
- tired
treatment= steroid + rituximab (monoclonal antibody)
73
lymphoma complications
bowel cancer
aneurysm
thyroid nodule
ITP immune thrombocytopenia
74
myeloma =
pathophysiology
cancer of plasma cells in the bone marrow
Clonal proliferation→ extra plasma cells → normally <5%, myeloma >10%
More plasma cells produce more antibodies. More of these are abnormal. They also produce paraproteins (light chain only of antibodies)
Paraproteins aggregate - increase blood viscosity
75
myeloma age
old , 60+
76
myeloma cause
mutation
77
myeloma vs multiple myeloma
same thang
78
mgus (monoclonal gammopathy of uncertain significance )
benign condition
abnormal protein in the blood
paraprotein
some will go on to develop myeloma
79
what is the most common type of antibodies produced in myeloma
IgG
| then IgA
80
myeloma investigations
blood
- hypercalcaemia
- raised globulins
- serum paraprotein - seen as a band on electrophoresis
- decrease in normal antibodies, increase in abnormal
- FBC - high wbc, low rbc and platelet
urine
- proteinuria (paraprotein)
- bence jones protein
Xray/ CT/MRI : lytic bone lesions (breakdown)
bone marrow biopsy
- aspirate and see percentage of plasma cells (normally less than 5, here more than 10)
81
myeloma affect on organs
kidney - deposition of light chains and amyloid in the distal tubule causes AKI and obstruction
bone- destruction as plasma cells cause an increase in osteoclastic activity and reduce osteoblast activity . this causes pain and osteocytic lesions. and hypercalcaemia
bone marrow - is infiltrated so there is reduced function
blood : paraproteins aggregate to greatly increase viscosity
eyes : protein aggregates --> blurred vision
82
myeloma presentation
quite silent , presents late
CRAB
calcium : hyper
renal failure (due to paraprotein deposition)
anaemia (shift toward stem cells making plasma cells)
bone - pain and resorption
```
tiredness and malaise (anaemia)
back/bone pain
fractures
infections - esp resp tract
bleeding
raynauds
purpura = red/purple dots from haemorrhage of small vessles
blurred vision (from paraprotein aggregates)
gangrene
dehydration (from hypercalcaemia)
```
83
diagnosis of myeloma
Plasma cells in bone marrow >10% (biopsy)
antibodies/paraproteins increase in serum/urine
1 or more of CRAB
84
myeloma management
Cytotoxic
- - Chemotherapy
- - Radiotherapy
Supportive
- - Given extra red cells, platelets - transfusion
- - stimulate stem cells
- - Isolation - stop getting bugs when immunosuppressed/ill
Bone marrow transplant?
Some respond well. ALL will eventually relapse
85
myeloma prognosis
Some respond well to treatment but ALL will eventually relapse
86
complications of myeloma
infection -- = major cause of death (lower normal immunoglobulins)
```
amyloidosis=
Amyloid is an abnormal protein produced from bone marrow. It builds up in tissues :(
Oedema in legs
Red marks on eyelids
Yellow on tongue
Organ failure
```
87
auer rods seen in?
AML
88
what can be seen in AML that distinguishes it
auer rods
89
reed sternburg cells seen in?
Hodgkins
90
hodgkins vs nonhodgkins neck lump
```
hodgkins = asymmetrical
non-hodg = symmetrical
```
91
painful drinking alcohol but painless lump =
hodgkins
