Flashcards in Haematology Deck (446)
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1
What is polycythaemia (erythrocytosis)?
an increase in Hb, PCV and RBC
2
What is absolute polycythaemia?
true increase in red cell volume, primary or secondary
3
What is relative or stress/spurious polycythaemia?
normal red cell volume, decreased plasma volume, can occur in dehydration and burns
4
Is Hb or PCV a better indicator for polycythaemia?
PCV, as Hb could be low during iron deficiency
5
What is a normal PCV in the blood?
45%
6
Primary causes of polycythaemia?
polycythaemia rubra vera, epo receptor mutations, high oxygen affinity Hb
7
Secondary causes of polycythaemia?
increase in epo from hypoxia, smoking, high altitude, chronic lung disease, anoxia and tumour
8
What is polycythaemia rubra vera?
stem cell disorder with an alteration in the pluripotent progenitor cell, >95% in JAK2 mutations
9
What is the JAK2 gene?
a signal transducer, especially those triggered by haemopoetic growth factors
10
Symptoms of polycythaemia rubra vera?
tiredness, depression, vertigo, tinnitus, hypertension, angina, intermittent claudication, severe itching after hot bath, gout and peptic ulcer, plethora, deep dusky cyanosis, splenohepatomegaly, easy bleeding
11
What complications can polycythaemia lead to?
thrombosis
12
Treatment of polycythaemia?
venesection, chemo (IFN and hydroxyurea), low dose aspirin for thrombosis prophylaxis, anagrelide, radioactive 32P, surgery to prevent leukaemia (splenectomy), keep PCV and platelet count low, cytotoxic myelosuppresion hydroxycarbamide, regular removal of blood, phlebotomy to keep haematocrit
13
How many polycythaemia cases develop into myelofibrosis or AML?
myelofibrosis in 30%
AML in 5%
14
What will investigations show in polycythaemia?
raised haematocrit, Hb, RCC, MCV, raised WCC and platelets, neutrophil leucocytosis, o2 sat >92%, thrombocytosis, splenomegaly,
15
What will bone marrow show in polycythaemia?
bone marrow hypercellular with prominent megakaryocutes, low epo
16
What is the WHO diagnostic criteria for polycythaemia?
2 major and 1 minor or main major and 2 minor
17
What are the major criteria for polycythaemia?
Hb>16.5g/dL in women and 18.5d/dL in men
red cell mass >25% above normal
JAK2 617V F mutation
18
What are the minor criteria for polycythaemia?
BM biopsy showing hypercellularity
low serum epo
endogenous erythroid colony in vitro
increased serum uric acid and vit b12 and vit b12 binding protein
19
What is the prognosis of polycythaemia without treatment?
6-18 months
20
Why is uric acid increased in polycythaemia?
increased RBC breakdown, increases uric acid
21
Treatment of secondary polycythaemia?
phlebotomy to maintain circulation and reduce viscosity
treat underlying condition
o2 for hypoxia, weight loss, smoking cessation, surgery to correct AV shunts
hydroxyurea
22
What is disseminated intravascular coagulation?
widespread inappropriate fibrin deposition within the vasculature from increased tissue factor
23
What are the causes of DIC?
infection - meningococcaemia, septicaemia, malaria, varicella, CMV, HIV
malignancy - AML, mucin secreting adenocarcinoma
obstetric complications - amniotic fluid embolus, retained placenta, septic abortion
anaphylaxis
trauma, burns
liver failure
pancreatitis
heat stroke, acute hypoxia, blood loss, snake venom
24
Pathophysiology behind DIC?
activation of the coagulation pathway in response to infection, this uses up platelets and coagulation factors so secondary activation of fibrinolysis leading to fibrin degradation products which inhibit fibrin polymerisation, and no platelets left for other clotting
25
Clinical features of DIC?
acutely ill, shock, can be no bleeding or widespread haemorrhage, bleeding from mouth, nose, venepuncture
26
Where in the body is mainly affected by DIC?
skin, brain and kidneys
27
What will investigations show in severe DIC?
prolonged PT, APPT, TT
low fibrinogen level
high FDPs and D dimer due to intense fibrinolytic activity, stimulated by the prescence of fibrin
severe thrombocytopaenia
blood film shows fragmented RBC
28
What will investigations show in mild DIC?
without bleeding
raised FDPs
increased synthesis of coagulation factors and platelets
normal PT, APTT, TT and platelets
29
What is the treatment of DIC?
transfusion of platelet concentrates, FFP, cryoprecipitate and RBCs if bleeding
activated protein c concentrates
NO inhibitors of fibrinolysis as may cause fibrin deposition
30
Complications of DIC?
gangrene from thrombosis
31
Are PT and APTT intrinsic or extrinsic?
PT - extrinsic
APTT - intrinsic
32
What makes up cryprecipitate?
fibrinogen, factor VIII
33
What are the 2 main platelet disorders?
idiopathic thrombocytopenic purpura
thrombotic thrombocytopenic purpura
34
What is a petechia?
individual purple spots in a purpuric rash
35
What is thrombocytopenia?
a reduced platelet production in the bone marrow, excessive peripheral destruction of platelets or sequestrian in an enlarged spleen
36
What causes immune/idiopathic thrombocytopenia purpura (ITP)?
immune destruction of platelets after binding to Fc receptors on macrophages - caused by congenital thrombocytopenia (absent or malfunctioning MK in BM), infiltration of bone marrow (lymphoma, leukiemia, myeloma), reduced TPO production (liver disease), low platelet production (low B12/folate, low TPO, toxins), dysfunctional production of platelets (myelodysplasia)
37
What is the onset like for children and adults in immune/idiopathic thrombocytopenia purpura (ITP)?
acute in children
chronic in adults
38
At what age is immune/idiopathic thrombocytopenia purpura (ITP) most common in children?
2-6years
39
What are the symptoms of children immune/idiopathic thrombocytopenia purpura (ITP)?
mucocutaneous bleeding, severe bleeding (recent viral infection)
40
Is immune/idiopathic thrombocytopenia purpura (ITP) more common in males or females?
females
41
What other diseases is immune/idiopathic thrombocytopenia purpura (ITP) associated with?
autoimmune illnesses, CLL, solid tumours, HIV
42
Clinical features of immune/idiopathic thrombocytopenia purpura (ITP)?
rare major haemorrhage if severe, easy brusing, purpura, epistaxis, menorhagia, bleeding, splenomegaly
43
What will investigations show in immune/idiopathic thrombocytopenia purpura (ITP)?
isolated thrombocytopenia, bone marrow examination, platelet autoantibodies, increased or normal megakaryocytes in bone marrow, FBC, peripheral blood smear
44
Treatment of immune/idiopathic thrombocytopenia purpura (ITP) in children?
no treatment unless serious bleeding
45
Treatment of immune/idiopathic thrombocytopenia purpura (ITP) in adults?
1 - oral corticosteroids
IV IgG to raise platelet count
2 - splenectomy
3 - high dose corticosteroids, IV IgG, chemo
anti D immunoglobulin, immunosuppressants, platelet transfusion
46
When would you not have to treat immune/idiopathic thrombocytopenia purpura (ITP) in adults?
when platelets are >30x90^9/L unless they are having surgery
47
What can cause immune thrombocytopenia?
heparin induced, neonatal induced, post transfusion purpura
48
How do neonates cause immune thrombocytopaenia?
due to fetamaternal incompatibility for platelet specific antigens
49
How does blood transfusion cause thrombocytopaenia?
rare, but also occurs in patients previously immunised by blood transfusion of pregnancy
50
Where are platelets destroyed in immune/idiopathic thrombocytopenia purpura (ITP)?
in the spleen
51
What is thrombotic thrombocytopenia purpura (TTP)?
platelet consumption leads to profound thrombocytopenia
52
Causes of thrombotic thrombocytopenia purpura (TTP)?
familial or acquired
secondary to cancer, HIV, pregnancy, certain drugs, idiopathic
53
Treatment of thrombotic thrombocytopenia purpura (TTP)?
plasma exchange to increase ADAMTS-13, plasmapheresis, corticosteroids, rituximab
54
How can you monitor treatment in thrombotic thrombocytopenia purpura (TTP)?
platelet count and serum LDH
55
Where do micro thrombi from thrombotic thrombocytopenia purpura (TTP) usually affect?
kidneys, heart, brain
56
Neurological symptoms caused by thrombotic thrombocytopenia purpura (TTP)?
stroke, headaches, delirium, bizarre behaviour, hallucination
57
What anaemia occurs in thrombotic thrombocytopenia purpura (TTP)?
microangiopathic haemolytic anaemia - small blood clots damage RBC causing intravascular haemolysis
58
pathology behind thrombotic thrombocytopenia purpura (TTP)?
reduced ADAMTS-13 so reduced break down of ultralarge von willebrand factor multimers (ULVWM), so it accumulates, with platelet aggregation and clots in multiple organs
59
What conditions have microangiopathic haemolytic anaemia?
thrombotic thrombocytopenia purpura (TTP), DIC and HUS
60
complication of thrombotic thrombocytopenia purpura (TTP)?
AKI
61
clinical features of thrombotic thrombocytopenia purpura (TTP)?
fiond purpura, fever, fluctuating cerebral dysfunction, microangiopathic haemolytic anaemia, red cell fragmentation, AKI
62
How does thrombotic thrombocytopenia purpura (TTP) affect lactic dehydrogenase levels?
raises them due to haemolysis
63
What can cause over anticoagulation?
warfarin, heparin, rivaroxaban, dabigatran
64
What converts fibrinogen to fibrin?
thrombin
65
Anitdote of rivaroxaban and dabigatran?
none
66
antidote of heparin over anticoagulation?
protamin
67
What is thrombocytosis?
platelet count above 400x10^9/L leading to thrombosis
68
Causes of thrombocytosis?
splenectomy, malignant disease, inflammatory disorders, major surgery, post haemorrhagic, myeloproliferative disorders, iron deficiency
69
Treatment of thrombocytosis?
treat underlying cause, aspirin, hydroxycarbamide to reduce platelet count, dialysis
70
What does the liver produce to stimulate platelet production form magakaryocytes by binding to platelet and MK receptors
thrombopoietin
71
What is the charge on an activated platelets phospholipid surface
negative - to allow coagulation factors to blind
72
What produces thromboxane A2?
arachidonic acid in platelets via COX-1
73
function of thromboxane A2?
induces aggregation and vasoconstriction
74
What conditions consume platelets?
DIC, TTP, HUS, HELELP, major haemorrhage
75
What is heparin induced thrombocytopenia?
development of an IgG antibody against the complex form between platelets and heparin and instead binds to and activates platelets forming thrombosis and platelet consumption, most at risk after unfractioned heparin treatment or cardiac bypass surgery
76
What is Von Willebrand Disease?
deficiency of von villebrand factor leading to impaired platelet adhesions and aggregation
77
Treatment of heparin induced thrombocytopaenia?
alternative anticoagulation, never reexpose to heparin
78
How does heparin induced thrombocytopaenia present?
sharp fall in platelets 5-10 days after starting heparin treatment
79
What are the 2 types of P2Y12 receptor inhibitors?
thienopyridines and non thienopyridines
80
Types of thienopyridines?
clopidogrel - hepatic CYP2c19 conversion into active metabolite 2 step process
prasugrel - single CYP step therefore faster transformation into active metabolite, rapid action but greater risk of bleeding
81
Types on non theinopyridines?
ticagrelor - reversibly binding oral P2Y12 anatgonist, does not require metabolic conversion to an active form, so faster onset of action
82
Example of GP IIbIIIa inhibitors?
tirofiban - non peptide tyrosine derivative, rapid onset, rapid reversibility of anti platelet effect
83
Life span on platelets?
7-10 days
84
shape of platelets?
disc shape to allow them to flow close to endothelium
85
How are old platelets removed?
phagocytosed by splenic macrophages in red pulp
86
Function of thrombopoietin?
decrease in platelets, cause increase in TPO to increase binding to MK and platelet receptors to increase platelet production
87
Platelet physiology?
platelets adhere to damaged endothelium via collagen and vWF. Binding of collagen stimulates cytoskeleton shape change for increase in SA, releases ADP, fibrinogen, thrombin and Ca2+ from platelet granules. Aggregation of platelets by fibrin, coagulation factors bind.
88
What chromosome if vWF gene on?
12
89
What are the 4 types of vWF disease?
1 - poor quantitative deficiency (autosomal dominant)
2 - qualitative abnormality (autosomal dominant)
3 - near complete deficiency (autosomal recessive)
4 - type normandy
90
Clinical features of type 1 and 2 vWF disease?
bleeding post trauma or surgery, epistaxis and menorrhagia
91
Clinical features of type 3 vWF disease?
severe bleeding but rare joint and muscle bleed
92
Treatment of vWF disease?
desmopressin, plasma derived factor VIII concentration that contain vWF treat bleeding and surgery, cryoprecipitate
93
function of vWF?
binds to GpIb receptor on platelets to subendothelial collagen and transport of factor VIII
94
Causes of vit K insufficiency?
warfarin, malabsorption, alcholism, CF, CKI, cholestatic disease
95
Symptoms of vit K insufficiency?
inrease PT and PTT, bruising, haematuria, GI bleeding
96
Treatment of vit K insufficiency?
IV phylomenadione, vit supplements, vit k rich foods
97
What is haemophilia?
X linked recessive bleeding and bruising disorder
98
What is haemophilia A?
factor VIII deficiency, normal vWF
99
Clinical features of haemophilia A?
mild - bleeding after injury or surgery later in life
moderate - severe bleeding post injury, occasional spontaneous bleeds
severe - frequent spontaneous bleeding into joints and muscles lead to deformity
100
What are the factor VIII levels in haemophilia A?
normal = 50-150iu/dL
mild = >5
moderate = 1-5
severe =
101
What will investigations show in haemophilia A?
low factor VIII, coagulation factor assay, increased PTT, normal PT, increased APPT
102
Treatment of haemophilia A?
educate, counselling, testing, avoid anticoagulants
mild - desmopressin
severe - require IV replacement with plasma concentration factor VIII
103
What is the half life for factor VIII and therefore how many time is replacement necessary?
12 hours, twice a day
104
What complications can haemophilia A lead to?
patients immune system may start to reject the IV plasma factor VIII
joint destruction by recurrent bleeding
105
Which is more common haemophilia A or B?
A
106
What is haemophilia B?
factor IX deficiency (xmas disease)
107
Treatment of haemophilia B?
educate, counselling, testing, avoid anticoagulants, desmopressin, IV infusion of factor IX, gene therapy
108
What is the half life of factor IX and how often is a given in haemophilia B?
18 hours, twice a week
109
Complications of haemophilia B?
joint destruction by recurrent bleeding
110
What is malaria?
an infectious disease caused by parasitic Plasmodium, spread by the female Anopheles mosquito
111
What are the 4 species of the plasmodium infection?
plasmodium falciparum, plasmodium virax, plasmodium ovale, plasmodium malariae
112
Which plasmodium species causes a more severe illness?
plasmodium falciparum
113
Which plasmodium species is most likely to relapse after many years?
plasmodium virax and plasmodium ovale
114
Symptoms of malaria?
fatigue, night sweats, flu like symptoms, fever of 41, diarrhea, nausea, vmiting, anaemia, splenomegaly, siezures
115
Complications of malaria?
cerebral malaria, anaemia, DIC, blackwater fever, jaundice, splenic rupture, tertian fever, quartan fever
116
What is Tertian fever?
fever that recurs every second day for 48 hours
117
What is Quartan fever?
fever that recurs every fourth day
118
What does cerebral malaria cause?
decreased consciousness, confusion, convulsions, coma
119
What is blackwater fever?
widespread intravascular haemolysis causing dark urine
120
If a patient presents with fever and foreign travel, what should you think of?
malaria
121
When does mortality increase with malaria?
if less than 3 years or pregnant
122
When do malaria symptoms usually present?
within a month of bite
123
What is used for malaria diagnosis?
thick and thin blood films - look at the number of infected cells to detect level of parasitaemia
124
What medications are given for malaria prophylaxis?
atovaquone with proguanil or quinine with doxycycline
125
What does the treatment of malaria depend on?
type of malaria, severity and where is was caught
126
What medications are used to treat malaria?
atovaquone with proguanil or quinine with doxycycline
127
contraindications for atovaquone-proguanil?
pregnant/breast feeding, severe kidney problems
128
Side effects of atovaquone-proguanil?
stomach upset, headaches, skin rash, mouth ulcers, expensive
129
Why are Chloroquine and proguanil not prescribed for malaria as much now?
largely ineffective against plasmodium falciparum, but good in places where that species is less common
130
Investigations for malaria?
bloods
blood film - parasites on Giemsa stained thick/thin film
renal time PER
antigen detection kits
lumbar puncture to exclude bacterial infection
131
What disease protects against malaria?
sickle cell disease (and lacking the Duffy antigen)
132
What malaria species causes anaemia and hepatosplenomegaly?
p.vivax, p.ovale
133
How does a mosquito infect a human with malaria?
female mosquito is infected after taking a blood meal containing gametocytes and the protozoa develop in the mosquito and the sporozoites migrate to the salivary glands so inoculate a human when biten
134
Where do sporozoites migrate to in the mosquito in malaria?
salivary glands
135
What happens to sporozoites once inoculated in a new human host?
travel to liver, infect hepatocyts, and multiply then from schizonts and then merozoites, the hepatocytes then rupture so merozoites released into the blood stream, continue to replicate until RBC ruptures which can then be transferred to feeding mosquito
136
How could vaccines prevent malaria?
maintain high antibody levels to prevent infection
can prevent transfer
can prevent progression of disease
137
What drug inhibits haem metabolism?
lumfantrine
138
What drug inhibits falciporum sarcoplasmic?
endoplasmic reticulum calcium ATPase
139
What drug inhibits haem polymerase?
chloroquine, and quinine
140
What drug inhibits plasmodial protein synthesis?
doxycycline
141
What measure help prevent malaria?
mosquito eradication, bed nets, insect repellent, antimalarial prophylaxis
142
Management of uncomplicated malaria?
chloroquine
artemisnin based drug
primaquine to eradicate hepatic hyponozoiles to prevent relapse
artemisinin based combination therapy
143
Management of severe malaria?
IV artesunate, ICU for ventilation, blood tranfusion, monitor fluid balance, treat complications e.g. hypoglycaemia
144
What is hyperreactive malarial splenomegaly?
exaggerated immune response to repeated infections causing anaemia, massive splenomegaly, elevated IgM levels
145
What is anaemia?
reduced red cell mass w/wo reduced Hb concentration
146
What is the normal Hb conc for male and female?
male = 13.1-16.6g/dL
female = 11-14.7d/dL
147
What is a normal MCV?
82-96fl
148
Life span of RBC?
120 days
149
Where are RBC produced and removed?
produced in bone marrow, removed in spleen, liver, bone marrow and blood loss
150
What are the 3 sizes of RBC?
microcytic
normocytic
macrocytic
151
What does anaemia cause?
reduced O2 transport, tissue hyposxia, increase tissue perfusion, increase O2 transfer to tissues
152
What investigations show be done for anaemia?
WBC. platelet, reticulocute, blirubin, blood film, ferritin, transferritin
153
Anaemia symptoms?
tired, malaise, reduced exercise tolerance, SOB, angina, claudication, symptoms of underlying cause, palpitations
154
Signs of anaemia?
pallow, pale mucous membranes and palmar creases, glossitis, angular stomatitis, kylonichia
155
What is the most common form of anaemia?
microcytic
156
what causes microcytic anaemia?
iron deficiency, chronic disease, sideroblastic anemia, thalassaemia
157
What foods have iron in?
vegetables and grains
158
Where is haem iron absorbed?
proximal intestine via the intestinal haem transporter HCP1 in the duodenum (upregulated in iron deficiency and pregnancy)
159
Is haem iron or non haem iron more rapidly absorbed?
haem
160
What is haem used for?
Hb production
161
What causes lack of iron?
use more, lose more, lack of it in diet, bleeding
162
What is the usual serum iron level?
13-32umol/L
163
How is iron transported in the body?
2 ferric ions bound to transferrin, normally only 1/3 saturated, iron then binds to erythoblasts and reticulocytes in marrow and removed
164
How much iron is stored in the HB?
2/3rds
165
When is other iron stored?
reticuloendothelial cells, hepatocytes and skeletal muscle cells and plasma
166
How is iron lost?
faeces, urine, sweat, menstruation
167
What conditions cause an increase in iron?
hereditary haemochromatosis (mutation in HFE gene) and secondary haemochromatosis (iron overload from blood transfusion)
168
What causes iron deficiency?
blood loss from GI or uterus, hookworm, poor diet
169
Clinical features of iron deficiency?
brittle nails, spoon shaped nails, atrophy of papillae of tongue, angular stomatitis, brittle hair, dysphagia and glossitis
170
What will investigations show in iron deficiency anaemia?
microcytic hypochromic RBC, decreased iron, increase binding sites, decreased serum ferritin, increased serum soluble transferrin receptors
171
What is the treatment of iron deficient anaemia?
treat the cause, ferrous sulphate 200mg, treat for 3 months post resolving
172
Side effects of ferrous sulphate medication?
constipation
173
What chronic diseases cause anaemia?
TB, Crohn's, RA (inflammatory disease)
174
How does chronic disease cause anaemia?
high levels of hepadin, lack of erythropoetin and renal disease cause decrease of iron from bone marrow to erythroblasts, inadequate erythropietin response to the anaemia and decreased RBC survuval
175
What is normocytic anaemia?
seen in anaemia of chronic disease, endocrine disorders and some haemotological disorders
176
What are the two types of macrocytic anaemias?
megaloblastic and non megaloblastic depending on bone marrow findings
177
What is a megaloblastic anaemia?
presence of erythroblasts with delayed maturation due to defective DNA synthesis in bone marrow
178
What causes folate deficiency?
poor intake, excessive utilization, malabsorption
179
What are the clinical findings of folate deficiency?
asymptomatic, anaemia symptoms, symptoms of underlying cause, glossitis
180
What investigations are done for folate deficiency?
serum and red cell folate
181
What is the treatment of folate deficiency?
5mg of folic acid/day to replace body stores
prophylactic folic acid if planning pregnancy
182
What is the treatment of B12 deficiency?
hydroxocobalamin 1000ug IM, oral B12 mg/day
183
What are B12 and folate used for?
DNA synthesis
184
What does B12 and folate deficiency cause?
pancytopenia
185
Where is folic acid broken down?
upper GI
186
What is the form of folic acid in the body?
methyl THF monoglutamate in the serum
187
In what foods in folate found?
green vegetables
188
In what foods in B12 found?
meat, eggs, fish
189
Where is B12 stored?
liver
190
Where does macrocytic anaemia manifest first?
bone marrow
191
Causes of macrocytic anaemia?
liver disease, alcohol, hypothyroid, B12 and folate deficiency
192
Where is B12 absorbed?
terminal ileum
193
What is the most common cause of B12 deficient anaemia?
pernicious anameia
194
What is pernicious anaemia?
an autoimmune disorder where there is atrophic gastritis with loss of parietal cells, causing decreases intrinsic factor and B12
195
In who is pernicious anaemia most common in?
fair haired, blue eyes, type a blood, females, over 60 (rarely congenital in children with early onset)
196
what two antibodies are seen in pernicious anaemia?
parietal cell antibodies and intrinsic factor antibodies
197
What are the 2 types of intrinsic antibodies?
inhibits intrinsic factor binding to B12
inhibits B12 intinsic factor complex to receptor site on ileum
198
What are the parietal cells and chief cells replaced with in pernicious anaemia?
mucin secreting cells
199
Treatment of pernicious anaemia?
corticosteroid therapy
IM hydroxycobalamin
200
Clinical features of pernicious anaemia?
lemon/yellow colouring, glossitis, red tongue, angular stomatitis, nerulogical changes
201
Clinical features of pernicious anaemia in serious cases?
symmetrical paraethesiae in fingers and toes, early loss of vibration sense and proprioception, progressive weakness and ataxia
202
What do investigations show in pernicious anaemia?
megablastomic, increased serum bilirubin, increased LDH, serum methylmalonic acid, homocysterine, decreased serum vit b12, increased serum folate levels, megaloblasts in bone marrow, low Hb, wcc and platelets
203
What is the absorption test called to find the cause of pernicious anaemia and what does it involve?
Schilling test - oral radioactive B12 and IM non radio-active IM
normal = >10% of oral dose in urine
abnormal if not - so redo with intrinsic factor capsules, if it is normalised, then it is pernicious anaemia
if still abnormal then lesion in terminal ileum or bacterial overgrowth
204
What is macrocytosis without megablastic change?
raised MCV with normoblastic
205
What is the cause of macrocytosis without megablastic change?
pregnancy, alcohol, liver disease, drugs, reticulocytosis, hyperthyroidism, some haemotological disorders, cold agglutinin due to autoagglutinations of red cells
206
What will investigations show in macrocytosis without megablastic change?
normal B12 and folate
increased lipid deposition in red cell membrane and increased in reticulocytes leading to increased MCV
207
What is aplastic anaemia?
pancytopenia with hypocellularity (aplasia) of the bone marrow
208
Cause of aplastic anaemia?
immune mechanisms, activated cytotoxic T cells in bone marrow and blood, cytotoxic drugs, NSAIDs, inherited fancous anaemia, aplastic anaemia, transient eythroblastopenia, parvovirus B19 infection, malignancy
209
Why can't bone marrow repopulate in aplastic anaemia?
reduction in pluripotential stem cells and a fault in the remaining ones
210
What can aplastic anaemia lead to?
myelodysplasia, paroxysmal nocturnal haemoglobinuria, AML
211
Clinical features of aplastic anaemia?
anemia, bleeding, infection
212
What will investigations show in aplastic anaemia?
pancytopenia, virtual abscence of reticulocytes, hypocellular bone marrow with increased fat spaces, negative coombs and normal bilirubin, absent red cell precusors on bone marrow examination
213
Treatment of aplastic anaemia?
steroids, supportive care and treatment to accelerate bone marrow recovery, transfusions, prevent infection, bone marrow transplantation, immunosuppressive therapy
214
What is haemolytic anaemia?
caused by increased destruction of RBCs in the macrophages of the bone marrow, liver and spleen, normal or increased RBC production
215
Is haemolytic anaemia more common in intra or extravascular?
extravascular
216
What is the difference between intra and extravascular haemolytic anaemia?
e - RBCs are emoved from circulation by macrophages
i - RBCs destroyed in circulation and haemoglobin is liberated to be reabsorbed by renal tubules and broken down and deposited as haemosiderin
217
What can be used to estimate RBC survival?
IV 51Cr labelled red cells
218
What does pernicious anaemia lead to?
achlorydia and b12 malabsorption
219
Congenital causes of haemolytic anaemia?
heriditary spherocytosis, sickle cell disease, thalassaemia, sideroblastic anaemia, enzyme disorders
220
Acquired causes of haemolytic anaemia?
immune autoantibodies against RBC, mechanical
221
What is hereditary spherocytosis?
RBC are sphere shaped, varies from mild-severe
222
Symptoms of hereditary spherocytosis?
anaemia, jaundice, enlarged spleen, gall stones, leg ulcers
223
Treatment of hereditary spehrocytosis?
folic acid and spelnectomy
transfusion or steroids in aplastic crisis
224
What is sideroblastic anaemia?
a ringed sideroblast, caused by congenital of leukaemias due to not being able to incorporate iron into Hb
225
What is the treatment of sideroblastic anaemia?
treat if symptomatic, RBC transfusion with iron chelation therapy, avoid alcohol, reduce vit C intake as it can increase iron absorption
226
What do investigations show in sideroblastic anaemia?
high serum iron and transferritin saturation
227
What are the 4 types of normocytic anaemia?
acute haemorrhage, anaemia of chronic disease, aplastic anaemia, haemolytic anaemia
228
What do investigations show in acute haemorrhage anaemia?
normocytic normochromic anaemia, increased reticulocytes, normal bilirubin
229
pathophysiology of anaemia of chronic disease?
IL-6 are increasing hepcidin, causing a decreased response to EPO and decreased production over time
230
What are the 4 types of haemolytic anaemia?
membrane defect - hereditary spherocytosis
enzyme defect - G6PD deficiency
haemoglobinopathy - sickle cell disease, thalassaemia
immune haemolytic anaemia
231
Features of haemolytic anaemia?
increased serum unconjugated bilirubin, increased urinary urobilinogen, increased faecal stercobilinogen, spelomegaly, reticulocytosis, expansion of bone marrow
232
What is the consequence of sphere shaped RBC in hereditary spherocytosis?
they are more rigid and less deformable so unable to pass through the splenic microcirculation so have a shortened lifespan
233
What do investigations show in hereditary spherocytosis?
anaemia, spherocytes on blood film, eviden haemolysis, increased lysisity, negative antiglobulin test
234
What is hereditary elliptocytosis?
red cells are elliptical from protein deficiency leading to weakness of horizontal protein interaction and membrane defect
235
What is hereditary stomaocytosis?
When RBC have pale central area appearing slit like, due to membrane defect or excess alcohol
236
What is thalassaemia?
autosomal inherited recessive condition producing microcytic aaemia due to problem in globin chain production which alters Hb synthesis
237
What is B thalassaemia?
mutation in b globin chain on chromosome 11 which causes an increase in globin production
238
What are the 3 types of b thalassaemia?
minor (heterozygous)
intermediate (homozygous b and a)
major (cooleys anaemia)
239
Symptoms of B thalassaemia minor?
asymptomatic, mild/absent anaemia, increase in HbA2 and HbF, Carner state
240
Symptoms of B thalassaemia intermediate?
moderate anaemia, no transfusions, splenomegaly and bone deformities, recurrent leg ulcers, gallstones and infections
241
Symptoms of B thalassaemia major?
severe anaemia, cranial bossing due to extra medullary haematopoiesis, bone marrow expansion in hand, failure to thrive and recurrent bacterial infection
242
Is B thalassaemia mutation or deletion?
point mutation
243
What is A thalassaemia?
an a globin gene mutattion causing gene deletion and a globin synthesis, results in excess B globin production
244
On what chromosome is the mutation in A thalassaemia?
chromosome 16
245
Is A thalassaemia mutation of deletion?
deletion
246
What is the effect of each deletion in A thalassaemia?
1 - no significant anaemia
2 - microcytosis w/wo mild anaemia
3 - HbH disease - it does not carry O2 and precipitate everything in erythroblasts leading to moderate anaemia and splenomegaly
4 - has no a chain and only y4 so leads to still born (Barts hydrops fetalis)
247
What will investigations show in A thalassaemia?
A thalassaemia on blood film, microcytic, hypochromic anaemia, decrease MCV and MCH, iron and ferritin normal, Hb electrophoresis shows increases HbA2 and increased HbF, high performance liquid chromatography, x ray show bone abnormalities
248
Complications of A thalassaemia?
galls stones, iron overload, splenomegaly, increased risk of infection, HF, arrhythmias, bone abnormalities (cranial bossing)
249
What is HbH?
4 B chains, low HbA and Y4 and reduced HbA2
250
Treatment of thalassaemia?
education, genetic counselling, based on symtpoms, transfusions if Hb
251
pathophysiology of B thalassaemia?
homozygous state, point mutation in B glbin gene, decrease in B globin chain production, excess of a chains, causing decrease in HbA and increase in HbA2 and HbF, leading to haemolysis
heterozygous state (carrier) is asymptomatic or mild anaemia, increases HbA2
252
What is G6PD deficiency?
a decrease in G6PD, causing reduced glutathione and acute oxidant induced haemolysis from drugs, surgery and infection, broad beans
253
What do investigations show in G6PD deficiency?
decreased G6PD enzyme assay levels, increased bite cells, blister cells and heinz bodies on blood film, reticulocytes, evident haemolysis, G6PD normal immediately after attck
254
Treatment of G6PD deficiency?
avoid precipitants, blood transfusion, treat underlying cause
255
Symptoms of G6PD deficiency?
acute drug induced haemolysis, favism, chronic haemolytic anaemia, neonatal jaundic, infections and acute illness caused by rapid intravascular haemolysis
256
What is sickle cell anaemia?
HbS is caused by mutations of adenine to thymine, changing a B globin chain, in sickle cell anaemia, both b genes are abnormal, trait is just one chain abnormal
257
At what age does sickle cell anaemia develop?
6 months old
258
pathology behind sickle cell anaemia?
deoxygenated HbS molecules are insoluble, polymerizable under deoxygenated conditions and eventually become sickle like in appearance becoming irreversible due to dehydration from K+ leaving the RBC, decreased RBC survival and impairs passage through vessels leading to blockage
259
Cause of sickle cell anaemia?
infection, dehydration, cold, acidosis, hypoxia
260
What are the 3 types of sickle cell anaemia?
homozygous HbSS (most severe)
combined heterozygosity HbSC (intermediate)
heterozygous HbAS (no symptoms)
261
Symptoms of sickle cell anaemia?
acute pain in hand and feet from small vessel vaso occlusion, severe pain in bones, fever, pulmonary hypertension, anaemia, bone marrow aplasia, acute chest syndrome, splenic sequestrain and painful enlargement, splenic pooling of RBC and hypovalaemia, liver sequestrain
(heterozygous individuals have no symtpoms except for when in hypoxic enviroment)
262
What do investigations show in sickle cell anaemia?
increased reticulocytes, hyposplenism, turbid appearance due to HbS, No HbA, parents have sickle cell trait, electrophoresis identifies individuals wthether HbAS or HbSS
263
Treatment of sickle cell anaemia?
avoid/treat precipitating factors, supportive therapy with IV fluids and analgesia, o2 and antibiotics, folic acid, penicillin, blood transfusions, splenectomy, stem cell transplantation, hydroxycarbamide to increase HbF concentrations and reduces pain acute chest syndrome, counselling, prognosis varies
264
Long term problems of sickle cell anaemia?
delayed growth, development and menstruation, infections in tissues, leg ulcers, cardiomegaly, arrhythmias, cardiomyopathy, pigment stones, chronic tubulointerstitial nephritis, background retinopathy, impaired placental blood flow causing abortion and intrauterine growth retardation, priapism (painful erection), transient ischaemic attack, stroke, fits
265
What is sickle cell trait?
one abnormal b globin chain
266
symptoms of sickle cell trait?
no symptoms, extreme cases cause anorexia
267
Investigations of sickle cell trait?
60% HbA, 40%HbS, blood count, film nromal, positive sickle test, Hb electrophoresis
268
Which is more serious, sickle cell trait or sickle cell aneamia?
sickle cell anaemia
269
What does a combination of TB and sickle cell trait resemble?
sickle cell anaemia
270
symptoms of HbE heterozygotes?
asymptomatic, normal Hb, microcytic red cells causing mild microcytic anaemia
271
Symptoms of HbE and B thalassaemia?
causes variable anaemia, can be severe as B thalassaemia major
272
Who would be offered prenatal screening?
for offspring of patients who have both B thalassaemia or sickle cell trait as 25% will have either of these, involves counselling, pregnent women screened for anaemia, partners should be tested, foetal DNA
273
What kind of inheritance is sickle cell anaemia?
autosomal recessive
274
What is vaso occlusive crisis?
triggered by hypoxia, infection, dehydration
coagulation in the microvasculature lead to CNS infarction, breathing difficulties, bone pain
275
Treatment of vaso occlusive crisis from sickle cell anaemia?
hydroxycarbamide - breaks down cells that are prone to sickle and therefore reduced the frequency of vasoocclusive attacks
276
What are the 4 types of leukaemia?
AML, ALL, CML, CLL
277
In who is ALL most common?
children
278
In who is CML most common?
elderly
279
What is the general treatment of leukaemia?
chemotherapy (induction, consolidation and maintenance), bone marrow transplant for poor prognosis or relapse
280
What is leukaemia?
rare neoplasm of blood or bone marrow, occuring at any age
281
What are the complications of leukaemia?
death, increased infection risk, haemorrhage, pulmonary intracranial, depression
282
Symptoms of anaemia?
breathlessness, fatigue, angina, claudication, pallow, cardiac flow murmur
283
Symptoms of neutropenia?
infections, fever, mouth ulcers
284
Symptoms of thrombocytopenia?
bleeding, bruising, petechiae, gum bleeding, fundal haemorrhage
285
What are blast cells?
immature precursor cells
286
What are myeloblasts?
immature precursor of myeloid cells
287
What are lymphoblasts?
immature precursors of lymphoblasts
288
In who are blast cells seen?
not in normal individuals, they are suggestive of chronic disease or leukaemia beginning to transform into an acute disease
289
What is diagnostic for AML on microscopy?
Auer rods
290
What are smudge cells?
lymphocytes that lack an identifiable cytoplasmic membrane and nucleus
291
When do smudge cells develop?
develop due to fragile lymphocytes in CLL
292
On what chromosome is the BCR gene?
22
293
On what chromosome is the ABL gene?
9
294
What is the Philadelphia chromosome?
contains ABL and BCR gene, it is 22- chromosome
295
What causes ALL?
lymphoblasts are over produced in the marrow, immature lymohocytes are produced and inhibition of other white blood cells due to lack of space and nutrients so there are less of them in the blood, and lymphoblasts infiltrate other tissues
296
Risk factors for ALL?
downs syndrome, ionising radiation, pregnancy, benzenes, environmental triggers, with genetic susceptibility
297
symptoms of ALL?
reflect the underproduction of healthy RBCs, platelet and WBCs
general fatigue, weakness, dizziness, frequent fever, injection, weight loss, bruising, bone pain, SOB, purpura, night sweats
298
How is ALL diagnosed?
exclude other causes e.g. coagulation to exclude DIC
blood smears show blasts in peripheral blood
csf sample shows if there has been invasion into brain and CNS
medical imaging shows invasion into other tissues
cardiac function for planning therapy
299
How is ALL classified?
B or T cell lineage, association with philadelphia chromosome
300
Treatment of ALL?
induce remission with dexamthasone, vincristine, anthracycline antibiotics and cyclophosphamide
maintain with methotrexte, mercaptopurine, cytarabine, hydrocortisone
continued oral/IV chemo at less frequent rate
immunotherapy/marrow transplant
301
What is the survival and prognosis for ALL?
5yr survival is 85%, prognosis based on age, race, gender, genotype
302
What is leukaemia chemotherapy treatment stages based on?
remission induction, consolidation/intensification and maintenance therapy
303
What is the function of the remission stage in ALL chemo?
acheieves absence of blasts in peripheral blood and
304
What is the function of consolidation in ALL chemo?
further reduction of cancerous cells
305
What is the function of maintenance therapy in ALL chemo?
killing any residual cells not killed by previous therapy, lasts years
306
Where about on your body can radiotherapy be used?
painful bony areas
307
In who is CLL mainly seen?
>60
308
Cause of CLL?
gradual accumulation of B lymphocytes from blood/bone marrow and lymph glands
309
What are the symptoms of CLL?
asymptomatic, bone marrow failure, non tender lymphadenopathy, malaise, weight loss, night sweats, anaemia, fever, recurrent infection
310
How do lymph nodes appear in CLL?
enlarged, rubbery, soft tender lymph nodes, slowly enlarge over time
311
How do ALL and CLL symptoms differ?
similar but CLL may be asymptomatic and diagnosis can be by chance
312
What is CLL prognosis like?
1/3 progress slowly, 1/3 progress rapidly, 1/3 never progress
313
What will investigations show in CLL?
positive ZAP-70 marker (worse prognosis), decreased Hb and plateletsm increased WBC, lymphocytosis, small lymphocytes, lymphocyte infiltration
314
Treatment of CLL?
chlorambucil, fludarabine, rituximab, prednisolone, cyclophosphamide, monoclonal antibodies, transplant, targeted therapy, transfusion
315
What is the most common leukaemia in adults?
AML
316
Symptoms of AML?
same as ALL, with hepatosplenomegaly and gum hypertrophy, bone marrow failure, malaise, weight loss, night sweats
317
What is the diagnosis for AML?
auer rods, blood film, bone marrow and lymph node biopsy, immunotyping, genetic, FAB classification
318
Risk factors of AML?
myeloproliferative disease, alkylating agents, ionising radiation exposure, downs syndrome
319
What is AML treatment if younger than 60?
chemo w/anthracycline and cytarabine or methotraxate - given 5 cycles of 1 week blcoks
prophylatic cover for bacteria, viruses and fungi as infection is a major risk
320
What is AML treatment if older than 60?
palliative anthracycline, cytarabine or mitoxantrone
bone marrow transplant if poor prognosis
321
Which leukemia has the strongest association with the philadelphia chromosome?
CML
322
clinical features of CML?
bone marrow failure, gout, bruising, hepatosplenomegaly, malaise, weight loss, night sweats, pallor, extramoddallar, soft tissue leukaemic diposit chlooma
323
What is the Philadelphia chromosome?
t(9;22) (in 80% of CML cases) forms bcr-abl fusion gene
324
What do investigations show in CML?
neutrophilia, mature myeloid precursors, increased basophils and eosinophils, decreased Hb, increased WBC
bone marrow aspiration shows increased cellularity, and increased myeloid precursors
325
Risk factors of CML?
ionising radiation exposure
326
What is the main treatment for CML?
imatinib
327
Treatment of CML?
imatinub
328
What is the difference between leukaemia and lymphoma?
leukaemia - bone marrow proliferative disorder (myeloid of lymphoid lineage)
lymphoma - neoplastic disease of mature lymphocyes in lymphoid tissue - solid tumour
329
What happens in cells in acute and chronic stages?
acute - excess of blast cells, multipotent cells, rapidly dividing causing acute onset
chronic - cells tend to be more mature and have a more functional role, less rapidly dividing, so less acute onset of disease
330
Which leukaemia is associated with downs syndrome?
ALL
331
Why does hepatomegaly and splenomegaly occur in ALL?
higher basal metabolism so hep
excess defective cells have to go to spleen to be destroyed so sple
332
What causes marrow failure in ALL?
replacement of marrow cells with blast cells
333
What are the 3 stages of CML?
chronic (asymptomatic), accelerated (bleeding and splenomegaly) and blast phase (bone pain and AL signs)
334
What are the two types of lymphoma?
Hodgkin's and non-Hodgkin's
335
What are B symptoms?
temperature of >38, weight loss >10% of body weight in last 6 months, symptoms due to enlarge mass e.g. cough
336
What is Non Hodgkin's Lymphoma?
malignancies of B cell or T cell origin, and it is classified by the stage or maturation
337
What 2 things can lymphoid progenitor cells become in the bone marrow?
Precursor T cell of precursor B cell
338
In Non Hodgkin's Lymphoma, are maligancies of B cell or T cell more common?
B cell (80%)
339
Where do precursor T cells mature to become thymocytes?
In the thymus
340
Why are T cells double negative?
Because they can become CD8+ or CD4+
341
Where do naive T cells become activated?
In the lymph node
342
What enzymes help precursor B cells undergo VDJ recombination of light and heavy chains to become naive B cell?
RAG1/RAG2
343
What do naive B cells have?
IgM
344
Where do naive B cells travel to?
lymph node
345
What happens when a B cell comes across an antigen?
Phagocytoses the antigen and presents it on its surface until it comes across a T cell
346
What happens in co stimulation of T and B cells?
naive CD4 T cell stimulates the B cell and vice versa to produce activated T cell and B cell
347
What do T cell cytokines cause the B cell to do?
proliferate into centroblasts, undergo somatic hyper mutation by the AID enzyme, allowing point mutation so there are many centroblast with different IgM antibodies as their variable regions have slightly changed, so there can be increased or decreased affinity to that antigen
348
Where do centroblasts move through after somatic hyper mutation?
through the germinal center to where there are many follicular dendritic cells which are presenting many antigens on its surface, also T helper cells there, they become centrocytes
349
What do centrocytes need to survive and mature and how do they get this?
cytokines - so they sample the antigens from the dendritic cells using their specific IgM antibodies to then present to the T helper follicular cell to proliferate and differentiate
350
What happens to centrocytes that have a decreased affinity for the antigens?
they will die through apoptosis
351
What can centrocytes proliferate into?
memory B cell or undergo class switching plasmoblast which can become plasma cells that secrete antibodies
352
What is the process called that allows B cells to change IgM into IgE, IgG etc/?
class switching
353
What are thymic B cells?
B cells that reside in the thymus
354
What is lymphoma?
tumour of the lymph from B and T cell development - heterogenous, with proliferation of lymph tissue
355
How do lymphomas differ?
different cellular origin, morphology, immunophenotype, cytogenic and molecular abnormalities and response to treatment and prognosis
356
How common is Non Hodgkin's Lymphoma?
6th most common cancer, increasing prevalence
357
Risk factors for Non Hodgkin's Lymphoma?
family history, genetic polymorphism (SCID), immunological autoimmune disease, virus, HTLV-1, H.pylori, HHV-8, HBV+EBV, HIV, peticides, herbicides and smoking
358
What lymphomas can T cells in the thymus give rise to?
precursor T cell neoplasm
359
What lymphoma can T cells in lymph node give rise to?
peripheral T cell neoplasm
360
When can T cell lymphomas arise?
during genetic rearrangement of the T cell lymphoma and during positive and negative selection in the thymus which can then lead to precursor of peripheral T cell neoplasms
361
Why are B cell lymphomas more common then T cell?
as they go through more genetic changes
362
What lymphomas can B cells give rise to?
mantle cell lymphomas, chronic lymphocytic leukemia and small lymphocystic lymphoma, Burkitt's lymphoma, Germinal centre B like lymphoma (DLBCL), follicular lymphoma, activated B cell like DLBCL, primary mediastinal DLBCL
363
What is the prognosis like for germinal center DLBCL?
60% 5yr survival
364
What is the prognosis like for activated DLBCL?
35% %yr survival
365
What are the most common Non Hodgkin's Lymphoma?
DLBCL and follicular
366
What neoplasms can plasma cells give rise to?
multiple myeloma - caused by too many plasma cells being produce
367
How do lymphomas arise?
translocation of chromosomes and genetic mutations during rearrangement
368
What chromosomes are translocated in lymphoma?
Bcl-2 and Bcl-6 genes
369
What mutations and amplifications occur in lymphoma?
p53, Bcl-2, Bcl-6, MYC
370
How do Non Hodgkin's Lymphoma present?
painless lymphadenopathy, unintentional weight loss, fever, dyspnoea, hepatosplenomegaly, lymph node mass
371
What is the Ann Arbor classification?
for lymphoma classification from lymph node biopsy
1-single lymph node region, lymphoid structure or extranodal site
2-two or more lymph node regions one side of diaphragm
3-two or more lymph node regions both side of diaphragm
4-diffuse or disseminated involvement of on of more extralymphatic organs
372
What is the main diagnostic difference seen in Non Hodgkin's Lymphoma and Hodgkin's Lymphoma?
Hodgkin's Lymphoma has Reed Sternberd cells
373
What is the treatment of Non Hodgkin's Lymphoma?
R-CHOP regimin
cisplarn, etoposide, methotrexate
374
What does R-CHOP stand for?
rituximab
cyclophosphamide
hydroxydaunomycin
oncovin
prednisolone
375
What is the second most common Non Hodgkin's Lymphoma and when does it mainly occur?
follicular lymphoma - in mid-late life - has bone marrow infiltration
376
Treatment of follicular lymphoma?
field megavoltage irradiation, chemotherapy, R-CHOP, radioimmunotherapy, myeloblative consolidation in younger patients, HSCT
377
Which is the most common Non Hodgkin's Lymphoma in children?
Burkitt's
378
What are the 3 types of Burkitt's?
endemic (EBV associated), sporadic (30% EBV related), AIDs related
379
Which is the most rapidly proliferative lymphoma?
Burkitt's
380
How does Burkitt's lymphoma present?
rapidly gorwing jaw tumour, abdominal mass with bone marrow involvement, mass in CNS, kidney, testis
381
In who is DLBCL most common?
adults, male >female
382
What prognostic index fatcors decrease prognosis in DLBCL?
>60, stage 3/4, high serum lactate dehydrogenase level, performance status 2, 1 or more extended site
383
Treatment of DLBCL?
allopurinol, RCHOP, chemoimmunotherapy, interum PET scanning, intrathecal methotrexate, palliative chemo and radiation, peripheral blood stem cell harvest and autograft
384
In who is mantle cell lymphoma most common?
late life, male >female
385
Treatment of lymphoblastic lymphoma?
plasmapheresis to reduce paraprotein, blood transfusions and if young bone marrow transplant
386
What is primary extranodal lymphoma?
lesion or mass at site, normally in CNS, stomach and skin
387
What is primary CNS lymphoma usually seen?
DLBCL in immuno-competent and immuno-suppressed
388
What is primary gastric lymphoma?
extanodal marginal zone lymphoma of mucosa associated tissue or DLBCL on a background of MALT lymphoma
389
symptoms of primary gastric lymphoma?
gastric ulceration, mass, indigestion, bleeding, endoscopic biopsy
390
Treatment of primary gastric lymphoma?
regular endoscopys, heliobactor eradication therapy, irradiation to gastric bed, chemoimmunotherapy
391
What lymphoma can be T or B cell?
primary cutaneous lymphoma, both arise singly and multiply in the skin and persue a very long natural history
392
Complications of lymphoma?
increased infection risk, recurrence and metastases, chemo complications, neuro complications
393
How do Reed Steinburg cells appear and what causes them in Hodgkin's Lymphoma?
giant cells, owl appearance
due to eosinophilic inclusions in the nuclei
394
What are popcorn cells?
small cell with hyperlobulated nuclues and small nucleoli, a variant of reed steinberg cells
395
When does Hodgkin's Lymphoma usually occur?
young adults and elderly
396
Symptoms of Hodgkin's Lymphoma?
B symptoms, hepatosplenomegaly, alcohol induced pain, mediastinal lymphadenopathy, enlarged non tender rubbery nodal
397
Causes of Hodgkin's Lymphoma?
male, exotoxin exposure, infection with EBV, immunosuppresed, previous infection with mononucleosis HL
398
Do systemic symptoms suggest Hodgkin's or non Hodgkins Lymphoma?
Hodgkin's Lymphoma
399
What is the staging of Hodgkin's Lymphoma called?
Cotsworld staging
400
Treatment of Hodgkin's Lymphoma?
educate, macmillan, chemo (ABVD) following by radiotherapy
401
Who does G6PD deficiency mainly affect?
african, middle east, mediterranean, X linked so male, but women can also be affected
402
How is G6PD deficiency diagnosed?
by a screening test for NADPH
403
What is G6PD deficiency crisis characterised by?
haemolysis, jaundice and anaemia
404
Important drug interactions in G6PD deficiency?
primaquine, sulphonamides, nitrofurantoin, quinolones, dapsone
405
In who does parovirus occur in?
children in epidemics (also called slapped cheek syndrome)
406
What does the parovirus cause?
decreased RBC production, so dramatic Hb drop
407
Do elliptocytosis and spherocytosis have horizontal or vertical interactions?
e - horizontal
s - vertical
408
Function of G6PD?
protects from damage as it provides fuel for RBC and generates redox capacity to protect it, so without it leads to shortened RBC lifespan from oxidative damage
409
What is classed as febrile neutropenia?
temp >38 and neutrophil count
410
What is hyperviscosity?
increase in whole blood viscosity due to raise Ig from malignant clone of plasma cells
411
Effect of hyperviscosity?
sludging and lack of perfusion through the microvasculature leading to leukaemia, myeloma, polycythaemia, waldenstroms macroglobulinaemia
412
How does hyperviscosity present?
lethargy, headaches, confusion, visual disturbance, cranial nerve defects, ataxia, retinal haemorrhage, dyspnoea, cough
413
Treatment of hyperviscosity?
plasmapheresis, leucopheresis, stumbling blocks, avoid blood transfusions, chemo
414
What is tumour lysis syndrome?
life threatening matabolic derangement leading to renal, cardiac and neuro complications
415
When does tumour lysis syndrome occur?
in leukaemia and non hodgkins lymphoma
416
Treatment of tumour lysis syndrome?
aggressive IV hydration, cheo, prevent hyperuricaemia, allopurinol, treat hyperkalaemia, refer for dialysis, control electrolytes
417
Problems with blood provision?
donor population are mainly white british, sickle population is normally diverse background, often multiple transfusions needed, high risk of raising antibodies, may be difficult to provide large number of matched units quickly, infrom NBS early
418
What is acute sickle chest syndrome?
HbSS inheriting 2 cpies of beta chain mutation, polymerisation of Hb cascade of effects, reducing blood flow to tissue leading to infarction, causes hypoxia, raised RR, chest pain, fever
419
Treatment of acute sickle chest syndrome?
red cell exchange transfusion, cross match patient for 8 units of blood, usually require central access, liase with apheresis team, terminate the viscous cycle by reducing HbS, o2, opiates
420
What is myeloma?
malignant disease of plasma cells in the bone marrow
421
How common is multiple myeloma?
second most common haematological cancer
422
Who does multiple myeloma usually affect?
older people
423
Symptoms of multiple myeloma?
back pain, RTI, anaemia, tiredness, fatigue, renal failure, proteinuria, fractures, dehydration
424
What will investigations show in multiple myeloma?
proteinuria, lytic bone lesions
425
How is the vertebra affected in multiple myeloma?
undergoes lytic bone lesions and haematopoesis
426
pathophysiology of multiple myeloma?
increase in plama cell production so >10% plasma cells in bone marrow, so produce abnormal antibodies (IgG and IgA) in 75% of cases, and only produce only light chains (paraproteins)
427
What cells make and break down bone?
osteoblasts build
osteoclasts break down
428
What are bone marrow stromal cells?
regulates haematopoesis
429
What do osteoblasts secrete?
osteoids and minerals (calcium and phosphate) to form strong bones
430
What do osteoclasts secret?
HCl, causing release of calcium and phosphate form the bone to enter the blood
431
What activates osteoclasts?
osteoblasts that express RANKL which stimulates osteoclast activity and OPG decreases osteoclast activity
432
What happens to bone marrow stromal cells in multiple myeloma?
interact with cancerous cells through receptos and cytokines, resulting in cytokine mediated cell growth, survival, drug resistance and migration, allowing the multiple myeloma cells to survive, leading to increased osteoclast activity and reduced osteoblast activity
433
What do multiple myeloma cells secrete?
cytokines
e.g. IL-3 - inhibiting osteoblast activity
DKK1 - inhibitng OPG production so increases osteoclast activity
MIP1a - stimulates osteoclast activity
434
How can osteoclasts stimulate themselves?
through IL-6
435
What does an increase in osteoclatic activity lead to?
bone fractures and lesions and more calcium entering the body so hypercalcaemia, leading to dehydration and nerve proteins
436
What effect does paraproteins produced by multiple myeloma have?
leads to renal failure and light chains present in urine (Bencejones proteins)
437
How does multiple myeloma cause anaemia?
shift from myeloid progenitor to lymphoid progenitor, overproduction of plasma cells so lack of RBC production, kidney failure, so decrease erypotietin production
438
Investigations in multiple myeloma?
blood and urine
anaemia, paraproteinuria, hypercalcaemia, decrease normal antibodies, increased blood urea and nitrogen, increase in creatinine (renal incompentence), bence jones proteins, increased alkaline phosphatas
439
What will bone investigations show in multiple myeloma?
bone aspiration, bone marrow biopsy, >10% plasma proteins, osteoporosis, lytic lesions in bone and soft tissue, pepper pot skull, vertebral collapse, hyperviscosity is rare
440
Diagnosis of multiple myeloma?
prescence of monoclonal plasma cells in bone marrow >10%, monoclonal antibodies in serum or urine and one or more of the following: (CRAB)
hypercalcaemia
renal insuffieciency
anaemia
lytic bone lesions
441
Treatment of multiple myeloma?
chemotherapy and radiotherapy of vertebra etc
NSAIDs, bisphosphonates, EPO transfusion, IV Ig infusion, immunoparesis
442
What is virchows triad?
slowing of blood flow, hypercoagulability, vessel wall damage
443
At what age does multiple myeloma occur?
70 years
444
What is the main cause of death in multiple myeloma?
renal failure
445
What are the 4 classes of multiple myeloma?
symptomatic - significant paraproteinaemia or increase bone plasma cell, evidenceof organ damage
asymptomatic - significant paraproteinawmia, or increased bone plasma cells but no organ damage
monoclonal gammopathy of undetermined significance - monoclonal paraprotin in seum but not amm or smm
plasmacytoma - tumour of neoplastic plasma cells
446
