Loading presentation...

Present Remotely

Send the link below via email or IM

Copy

Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.

DeleteCancel

Make your likes visible on Facebook?

Connect your Facebook account to Prezi and let your likes appear on your timeline.
You can change this under Settings & Account at any time.

No, thanks

Haematology Phase 2 Revision

No description
by

Nina De Flora

on 10 January 2014

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of Haematology Phase 2 Revision

Haematology
RED
WHITE
CLOT
Normal Function
RBC Properties
packed with haemoglobin
no nucleus
no DNA/RNA
no cell division
lifespan of 120 days
SA:V ratio is high
biconcave disc
D: 8um, W: 2um @ edge, 1um @ centre
number measured with haematocrit
Erythropoiesis
RBCs produced in bone marrow
from pluripotent stem cells
regulated by EPO hormone (from kidney)
more EPO at high altitude/athlete
can become anaemic with renal failure
nucleus darkens and shrinks with maturation
mature RBC smaller than predecessor
Metabolic Pathways
RBC ion balance + cell volume regulated by Na+/K+ pump dependent on ATP
RBC does not have mitochondria
ATP is thus produced anaerobically
glucose is the key fuel
NADH from glycolysis keeps Iron as Fe2+
(HbFe3+ cannot bind oxygen)
some glucose is metabolised to produce NADPH
NADPH maintains glutathione levels
23BPG, (biproduct of glycolysis) releases O2 from Hb when pp is low
Glutathione
a tripeptide
made of glutamine, cysteine and glycine
reduced glutathione combats oxidative stress
maintains a reduced state in cells
excess free radicals cause oxidative stress
glutathione protects against these
lack of glutathione leads to cell wall damage
NADPH is needed to reduce glutathione
Carbon Dioxide
CO2 carried to heart by venous system
CO2 to lungs via pulmonary artery
carried 3 ways:
dissolved in solution (10%)
bound to Hb -globin part (30%)
as bicarbonate ion (60%)
carbonic anhydrase needed to make bicarbonate from CO2 and H2O
chlorine enters cells as bicarbonate leaves
Haemoglobin
Production
has 4 protein subunits
each subunit has a haem group
each haem group has a Fe2+ ion
when saturated 1g Hb binds 1.34 ml O2
haem group made of pophyrin ring
porphyrin ring synthesised in mitochondrion
Regulation
binding is allosteric
does not follow Michaelis-Menten
sigmoidal curve shape
Destruction
Liver and spleen remove old RBCs
Phagocytes engulf old RBCs
globular Hbs broken down to amino acids (enter blood stream)
haem group converted to bilirubin
bilirubin transported to liver and secreted to bile (into faeces)
iron binds to transferrin in blood
Disorders
too many?
POLYCYTHAEMIA RUBRA VERA
Description
clonal malignant disorder
overgrowth of red cell precursors
Symptoms
hepatomegaly
splenomegaly
acute gout
other myeloproliferative disorder (e.g. myelofibrosis)
acute leukaemia
increased risk of thrombosis
stroke, MI, DVT
headache
blurred vision
mental slowing
hypertension
itch (esp. after bath)
Complications
Aetiology
True polycythaemia:
myeloproliferative disorder
haematological malignancy
Low plasma vol polycythaemia
stress
excess smoking,
excess alcohol
Pseudopolycythaemia
hypoxia
EPO secreting tumour
Secondary polycythaemia
diuretics
dehydration
Investigations
red cell mass increase in bone marrow trephine
true polycythaemia:
normal plasma volume
high red cell mass
low plasma vol polycythaemia
low plasma volume
normal red cell count
Epidemiology
more common in middle age
low plasma volume polycythaemia is more common
90% with JAK2 mutation
aspirin
venesection
cytoreduction
Treatment
too few?
Male : <13g/dl
Female: <12g/dl
measure with Hb concentration
measure with haematocrit
measure MCV
decreased production?
not enough?
not mature?
deficiency?
deformity?
Iro
IRON DEFICIENCY ANAEMIA
Description
low body iron
not enough for erythropoiesis
not enough for electron transport
not enough for oxygen transport
iron is needed in the 2+ state, toxic in 3+ due to free radicals
found in erythroid marrow, liver stores, (as ferritin) red cell Hb, macrophages, in transferrin circulating
minimal loss and gain (so great loss with minimal gain is problem)
Aetiology
not enough in diet
relative in women of childbearing age
vegetarians
blood loss
GI tumours
mennhoragia
haematuria
absorption problem
coelic diseae
achlorohydria
Symptoms
skin changes
koilonychia
angular stomatitis
pallour (skin, eyes)
Iro
ANAEMIA OF CHRONIC DISEASE
Description
malutilisation of iron
red cells broken down by macrophages
iron builds up inside cell
not enough per red cell
Investigation
increased ferritin (increased transcription of ferritin mRNA)
increased hepcidin (blocks iron movement)
Symptoms
skin changes
koilonychia
pallour
Aetiology
chronic inflammation
malignancy
Iro
PORYPHYRIN SYNTHESIS PROBLEM
Symptoms
skin changes
koilonychia
pallour
Aetiology
pyridoxine response
lead poisoning
CONGENITAL SIDEROBLASTIC ANAEMIA
THALASSAEMIA
3 forms of Hb:
HbA (in 97%) - 2 alpha, 2 beta
HbA2 (in 2.5%) - 2 alpha, 2 delta
HbF (in 0.5% of adults- foetal Hb) - 2 alpha, 2 gamma
2 alpha genes, 1 beta gene
alpha on choromose 16
beta on chromosome 11
gene expresison changes through life
haemoglobinopathies are hereditary
ALPHA THALASSAEMIA
BETA THALASSAEMIA
reduced or absent alpha chains
affects all Hb types as alpha chains found in all
if there is one deleted -> a+
if both are deleted -> a0
not usually point mutations
patterns
silent alpha thalassaemia trait (-a/aa)
alpha thalassaemia trait (--/aa) or (-a/-a)
HbH disease (--/-a)
Hb Barts Hydrops Fetalis (--/--)
HbH disease
Description
a severe form
alpha chain less than 30% of normal
Investigation
low MCV
low MCH
excess beta chain tertramers (called HbH) cannot carry oxygen
Symptoms
Splenomegaly (due to haemolysis)
Jaundice (due to haemolysis)
Can be asymptomatic when treated
Epidemiology
south east asia
middle east
mediterranean
Treatment
transfusion
folic acid supplement
splenectomy
Hb Barts Hydrops Fetalis
Description
most severe forml
Investigation
excess beta chain tetramers and gamma chain tetramers (called HbH and Hb Barts) cannot carry oxygen
small amounts of Hb Portland
HPLC
electrophoresis
PCR
Symptoms
pallor
oedema
cardiac failure
hepatosplenomegaly
skeletal abnormality
cardiovascular abnormality
Epidemiology
few survive birth
Treatment
transfusion
folic acid supplement
splenectomy
Disorder of Beta chain synthesis
reduced B+ or absent B0
caused by point mutations
deletions are rare
autosomal recessive
classified on severity
Beta thalassaemia trait (B+/B) or (B0/B)- aysymptomatic
Beta thalassaemia intermedia (B+/B+) or (B0/B+) - occasional transfusion
Beta thalassaemia major (B0/B0)
BETA THAL. MAJOR
Symptoms
presents at 6-24 months
fail to thrive
pallor
extramedullatory haemotopoiesis
hepatosplenomegaly
skeletal changes
organ damage
iron overload
Investigations
low MCH
low MCV
reticulocytosis
HbF mainly
little HbA
HbA2 high
Treatment
lifelong transfusions
SICKLE CELL ANAEMIA
Description
Autosomal recessive
point mutation in codon for beta globin
HbS formed (2 alpha, 2 beta)
HbS polymerises with low oxygen
can be sickle trait (asymptomatic (B/Bs))
Symptoms
vascular occlusion
tissue infarction
leg ulcers
severe pain
chronic haemolysis
poor growth
infection
organ damage
Complications
Crises due to:
hypoxia
dehydration
infection
cold exposure
treat with
opiate analgesia
hydration
rest
oxygen
antibiotics if infection
Treatment
hydroxycarbamide
increased destruction?
Normal Function
Disorders
too few?
POLYCYTHAEMIA RUBRA VERA
Description
clonal malignant disorder
overgrowth of red cell precursors
Symptoms
hepatomegaly
splenomegaly
acute gout
other myeloproliferative disorder (e.g. myelofibrosis)
acute leukaemia
increased risk of thrombosis
stroke, MI, DVT
headache
blurred vision
mental slowing
hypertension
itch (esp. after bath)
Complications
Aetiology
True polycythaemia:
myeloproliferative disorder
haematological malignancy
Low plasma vol polycythaemia
stress
excess smoking,
excess alcohol
Pseudopolycythaemia
hypoxia
EPO secreting tumour
Secondary polycythaemia
diuretics
dehydration
Investigations
red cell mass increase in bone marrow trephine
true polycythaemia:
normal plasma volume
high red cell mass
low plasma vol polycythaemia
low plasma volume
normal red cell count
Epidemiology
more common in middle age
low plasma volume polycythaemia is more common
90% with JAK2 mutation
aspirin
venesection
cytoreduction
Treatment
too many?
reactive?
malignancy?
NEUTROPHILIA
Causes:
infection
especially bacterial- pneumonia, UTI
inflammation
rheumatoid arthritis
tissue damage
trauma, surgery
malignancy
pregnancy
myeloproliferative disorder (rare)
EOSINOPHILIA
Causes:
infection
epecially parastitic
allergies
asthma, dermatitis
Churg-Strauss syndrome
bone marrow disorder
BASOPHILIA
Causes:
stimulated by eosinophils
very rare
seen occasionally in CML
MONOCYTOSIS
Causes:
infection
especially bacterial- pneumonia, UTI
inflammation
rheumatoid arthritis
tissue damage
trauma, surgery
malignancy
pregnancy
CML(rare)
LYMPHOCYTOSIS
few in blood
most in lymph nodes
lymph nodes enlarge
Causes:
infection:
especially viral and atypical organisms, fungal and protozoal
myeloid?
lymphoid?
marrow?
nodes?
mature?
immature?
immature?
mature?
ACUTE LYMPHOBLASTIC LEUKAEMIA
Description
malignancy of lymphoid cells
affects either B lymphocyte or T lymphocyte lineages
uncontrolled proliferation of immature blast cells
leads to bone marrow failure and tissue infiltration
childhood ALL and adult ALL are distinct
Risk Factors
genetic susceptibility
translocations, gains and losses of whole chromosomes
Down's syndrome
environmental triggers
ionizing radioation
X-rays during pregnancy
Classification
morphological
FAB system- L1, L2, L3
immunological
surface markers used- precursore B, T, B
cytogenic
chromosomal analysis
Presentation
marrow failure:
anaemia (due to decreased RBC)
infection (due to decreased WBC)
chest, mouth, skin, perianal
bacterial septicaemia
zoster
CMV
measles
candidiasis
pneumocystis pneumonia
bleeding (due to decreased platelets)
infiltration:
hepato-splenomegaly
lymphadenopathy
supeficial
mediastinal
orchidomegaly
CNS involvement
cranial nerve palsies
meningism
Management
supportive
blood/platelet transfusion
IV fluids
allopurinol
Hickman line for IV access
infections
prophylactic antibiotics, antivirals, antifungals
chemotherapy (multiagent)
bone marrow transplant
70-90% cure rate in children, lower in adults
Testing
blood film
shows characteristic blast cells
high WBC count
CXR and CT scan to look for mediastinal and abdominal lymphadenopathy
lumbar puncture to see CNS involvement
CHRONIC LYMPHOCYTIC LEUKAEMIA
Description
accumulation of mature B cells
they escape programmed cell death
most common form of leukaemia
Risk Factors
genetic susceptibility
mutations
trisomies
deletions
environmental triggers
pneumonias
Staging
Rai staging
0, I, II, III, IV
Symptoms
often asymptomatic
may be finding on routie FBC
may be anaemia
may be increased infections
may be weight loss, night sweats and anorexia
Complications
autoimmune haemolysis
increased infections due to decreased IgG
bacterial
viral
herpes zoster
marrow failure
Testing
increased lymphocytes
autoimmune haemolysis may occur resulting in decreased Hb, neutrophils and platelets
Signs
enlarged, rubbery, non-tender nodes
splenomegaly
hepatomegaly
Management
needed if symptomatic
chemotherapy
steroids
radiotherpy
supportive care:
transfusions
IV human immunoglobin
stem cell transplants
1/3 never progress, 1/3 progress in time, 1/3 progressing
ACUTE MYELOID LEUKAEMIA
Description
neoplastic proliferation of blast cells
progresses rapidly
can be a long term complication of chemotherapy
associated with myelodysplastic states
Aetiology
disease of the elderly
can occur de novo or secondary (e.g. to chemotherapy)
Presentation
marrow failure:
anaemia (due to decreased RBC)
infection (due to decreased WBC)
chest, mouth, skin, perianal
bacterial septicaemia
zoster
CMV
measles
candidiasis
pneumocystis pneumonia
bleeding (due to decreased platelets)
infiltration:
hepato-splenomegaly
lymphadenopathy
supeficial
mediastinal
orchidomegaly
gum hypertrophy
DIC
Management
supportive
blood/platelet transfusion
IV fluids
allopurinol
Hickman line for IV access
chemotherapy (multiagent)
intensive, with marrow suppression
bone marrow transplant
allogenic marrow transplant (siblings/unrelated)
can result in graft versus host
autologous marrow transplant (from selves)
70-90% cure rate in children, lower in adults
Testing
FBC
increased WBCs
coagulation screen
marrow aspirate
bone marrow trephine
cytogenetics
immunopheotype
indicated cell lineage
blood film
showing blasts
Auer Rods - diagnostic

Complications
infection
septicaemia
bacterial
viral
fungal
candida
aspergillus
CHRONIC MYELOID LEUKAEMIA
Description
chronic proliferation of myeloid cells
actually a myeloproliferative disorder
granulocytes as well as other lineages
Risk Factors
male predominance
40-60 years old (rare in childhood)
Philadelphia chromosome
translocation between 9 and 22
worse prognosis without this
Symptoms
Management
chemotherapy
target therapy
imatinib
stem cell transplantation
allogenic from donor or sibling
Testing
FBC
increased WBCs
neutrophils
myelocytes
basophils
eosinophils
low/normal Hb
decreased platelets
hypercellular bone marrow
Philadelphia chromosome on cytogenic analysis
Progression
chronic phase
accelerated phase
blast crisis
chronic and insidious
weight loss
tiredness
fever sweats
gout
bleeding
abdominal discomfort
Signs
splenomegaly (often massive)
hepatomegaly
anaemia
bruising
HODGKIN'S LYMPHOMA
Description
caused by malignant proliferation of lymphocytes that accumulate in the lymph nodes
leads to lymphadenopathy
characteristic Reed-Steinberg cells with mirror like nuclei
Epidemiology
2 peaks of incidence:
young adults (peak age at 30)
elderly
twice as common in males
increased risk with affected sibling
EBV / glandular fever
SLE
post-transplant
Symptoms
enlarged lymph nodes
painless/non-tender
rubbery
superficial
often cervical, also axillary and inguinal
fever
weight loss
night sweats
pruritis
lethargy
may be alcohol induced lymph node pain
Signs
lymph node enlargement
cachexia
anaemia
splenomegaly
hepatomegaly
Tests
tissue diagnosis
lymph node excision biopsy (image guided)
FBC
blood film
ESR
LFT
urates
calcium levels
Staging
influences treatment and prognosis
CXR
CT thorax, abdomen, pelvis
bone marrow biopsy
Ann Arbor system
stages I to IV depending on number of nodes
substages A/B depending on systemic symptoms
50% survival with stage IV, 90% survival with stage I
Treatment
chemotherapy
SEs:
myelosuppression
alopecia
nausea
infection
CHOP, ABVD
radiotherapy
can result in secondary malignancies
single treatment in early stages
can cause pulmonary fibrosis
ABVD
adriamycin
bleomycin
vinblastine
dacarbazine
PET scanning to check if effective
NON-HODGKIN'S LYMPHOMA
Description
all lymphomas withouet Reed-Steinberg cells
caused by malignant proliferation of lymphocytes that accumulate in the lymph nodes, although also other extranodal tissues
mostly from B lymphocyte cell lines
Presentation
nodal disease
superficial lymphadenopathy
oro-pharyngeal lymphoid tissue (Waldeyer's ring) disease
extranodal disease
systemic symptoms
fever
night sweats
weight loss (less common than Hodgkin's)
pancytopoenia
anamia
neutropenia/infection
thrombocytopoenia/bleeding
Testing
Ann Arbor System
stages I-IV
substages A/B
using CT/MRI of chest, abdomen and pelvis and marrow aspiration
Diagnosis with lymph node biopsy
Bloods
FBC
U+E
LFT
LDH
Histology
low grade lymphomas
indolent (i.e. little or no pain)
often incurable
widely disseminated at presentation
due to failure of apoptosis
e.g. follicular, marginal zone, lymphocytic,
high grade lymphomas
more aggressive
long term cure may be achievable
short history of rapidly enlarging lymphadenopathy with systemic symptoms
due to increased mitotic rate
e.g. Burkitt's, lymphoblastic, diffuse large B cell
Treatment
depends on disease subtype
low grade:
no treatment if there are no symptoms
radiotherapy
chemotherapy
high grade:
chemotherapy
immunotherapy
Prognosis
worse with:
age >60
systemic symptoms
bulky disease- i.e. large abdominal mass
disseminated disease
survival at ~30% for high grade, and >50% for low grade
MYELOMA
Description
malignant proliferation of B-lymphocyte derived plasma cells
plasma cells are derived from B cells, which all begin by producing IgM
normally different plasma cells produce different Ig, however in myeloma identical Ig are produced
these are seen as a monoclonal band or paraprotein on serum or urine electrophoresis
Classification
based on the Ig product
2/3 IgG
1/3 IgA
small remainder IgD or IgM
Epidemiology
5/100000
peaks age 70
no more common in males or females
more common in those with afro-Caribbean heritage
Symptoms
osteolytic bone lesions
backache
pathological fractures
vertebral collapse
hypercalcaemia
marrow infiltration
anaemia
neutropoenia/infection
thrombocytopoenia/bleedings
recurrent bacterial infection
due to immunoparesis (i.e. a reduction in certain types of Ig)
also due to neutropenia
also due to chemotherapy
renal impairment
this is due to light chain deposition
hyperviscosity
amyloid deposits
Treatment
supportive:
bone pain should be treated with analgesia
bisphosphonate for osteoporosis
anaemia treated with transfusions/EPO
renal failure treated by increased fluid intake- may need dialysis
infections treated with broad spectrum antibiotics
may need regular immunoglobulin infusions
chemotherapy
steroids, alkylating agents, thalidomide
stem cell transplant can prolong survival
Testing
FBC: normocytic, normochromic anaemia
blood film: rouleaux formation (rows of cells)
elevated ESR, PV
serum and urine electrophoresis
beta 2 microglobulin
Bence Jones proteins dound in urine in 2/3 cases- free Ig light chains of kappa or lambda filtered by the kidney (can lead to reduced kidney function)
X rays show lytic lesions:
pepperpot skull
vertebral collapse
fractures
osteoporosis
CT or MRI
hypercalcaemia due to increased osteoclasts due to increased cytokines being produced - stones, bones, abdominal groans
Diagnosis
monoclonal protein band in serum or urine electrophoresis
increased plasma cells found on bone marrow biopsy
evidence of end organ damage from myeloma
hypercalcaemia
renal insufficiency
anaemia
bone lesions
Complications
hypercalcaemia
rehydrate and treat with salibe, bisphosphonates
spinal cord compression
need MRI if suspected, treat with dexamethasone and radiotherapy
hyperviscosity
reduced cognition, disturbed cision and bleeding- treat with plasmapharesis to remove light chains
acute renal failure
treat with rehydration, may need dialysis
Differential Diagnosis
for paraproteinaemia
multiple myeloma
Waldenstroms macroglobinaemia
primary amyloidosis
monoclonal gammopathy of uncertain significance
paraproteinaemia in lymphoma or leukaemia
heavy chain disease

POLYCYTHAEMIA
RUBRA VERA
Description
hyperproliferation of red blood cells- malignant proliferation of a clone derived from a pluripotent marrow cell
polycythaemia may be relative however (i.e. decreased plasma volume with normal RBC mass)
polycythaemia rubra vera is a primary cause of polycythaemia
secondary causes include:
hypoxia
high altitude
chronic lung disease
cyanotic congenital heart disease
heavy smoking
inappropriately high EPO secretion
there is excess proliferation of RBCs, WBCs and platelet
Risk Factors
mutation in JAK2
in >90%
more common if >60 years of age
Presentation
may be asymptomatic and detected on FBC
may present with vague signs of hyperviscosity
headaches
dizzinus
tinnitus
visual disturbance
characteristic itch after hot bath
erythromelalgia
vessels in the extremities become blocked, filled up with blood and inflamed
leading to burning pain and redness
facial plethora
splenomegaly (60%)
may be features of arterial or venous thrombosis

Investigations
FBC
increased RBCs
increased Hb
increased PCV
increased haematocrit
often increased WBC
often increased platelets
hypercellular marrow with erythroid hyperplasia seen
decreased serum EPO
examination for splenomegaly

Management
aim to keep haematocrit <0.45 to decrease risk of thrombosis
in younger patients
venesection
higher risk/patients >60 with previous thrombosis:
hydroxycarbamide
also given low dose aspirin daily
Prognosis
may remain well for years
thrombosis and haemorrhage (due to defective platelets) are the main complications
there is a transition to myelofibrosis in 30%
there is a transition to acute leukaemia in 5%
monitor FBC everyday for 6 months
ESSENTIAL THROMBOCYTHAEMIA

Description
clonal proliferation of megakaryocytes leading to persistently increased platelets
cause bleeding or arterial or venous thrombosis with microvascular occlusion
Presentation
bleeding
arterial thrombosis
venous thrombosis
microvascular occlusion
headache
atypical chest pain
light headedness
erythromyalgia

Management
low dose aspirin (75mg) daily
hydroxycarbamide to decrease platelets in those >60 or with previous thrombosis
Differential Diagnosis
increased platelets can be reactive
bleeding
infection
chronic inflammation (e.g. collagen disorders)
malignancy
trauma
post-surgery
iron deficiency

Description
hyperplasia of megakaryocytes which produce platelet derived growth factor
this leads to marrow fibrosis and myeloid metaplasia
there is haemopoiesis in the spleen and liver
Presentation
night sweats
fever
weight loss
abdominal discomfort
erythroblastic cells (nucleated red cells)
characteristic tear drop RBCs
massive hepatosplenomegaly

Management
marrow support
allogenic stem cell transplant in young people
high risk
MYELOFIBROSIS
Investigation
blood film
leukoerythroblastic cells (nucleated red cells)
characteristic teardrop red cells
bone marrow trephine for diagnosis

Prognosis
median survival of 4-5 years
Full transcript