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Phase 2A > Haematology > Flashcards

Haematology Flashcards

1
Q

Pathophysiology of Iron Deficiency Anaemia

A

Iron is needed for the formation of haem in RBC.

If you are iron deficient you have small, hypochromic red blood cells and there is a lack of effective erythrocytes leading to anaemia symptoms.

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2
Q

What type of anaemia is iron deficiency anaemia

A

microcytic

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3
Q

What is anaemia

A

low Hb concentration either due to a low red cell mass ( with or without a reduced haemoglobin concentration) or an increased plasma volume

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4
Q

what is an example of a patient who may have anaemia with reduced Hb but increased red cell mass

A

third trimester of pregnancy

body produces more blood to support fetal growth, however if you are not getting enough iron then Hb conc may decrease as red cell mass increases

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5
Q

what are the 2 consequences of anaemia

A

Reduced oxygen transport

Tissue hypoxia

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6
Q

how does the body try and counteract anaemia

A

increasing tissue perfusion
increasing O2 transfer to tissues
Increasing red cell production
Tachycardia

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7
Q

How do we keep red cell balance in the body

A

erythrocytes are produced then destroyed at the end of their life cycle of 120 days

reticulocytes are immature red blood cells and act as a marker of the balance between production and removal of red blood cells

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8
Q

what are the three categories of anaemia

A

microcytic
normocytic
macrocytic

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9
Q

what is microcytic anaemia

A

low MCV

presence of small, often hypochromic red blood cells in a peripheral blood smear

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10
Q

three causes of microcytic anaemia

A

iron deficiency
chronic disease
thalassaemia

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11
Q

what is normocytic anaemia

A

MCV within range

have normal sized red blood cells but you have a low number of them

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12
Q

three causes of normocytic anaemia

A

acute blood loss
anaemia of chronic disease
combine haematinic deficiency (iron deficiency + B12 deficiency (combined the deficiencies cancel each other out so appears in normal range)

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13
Q

what is macrocytic anaemia

A

high MCV

anaemia that causes unusually large red blood cells. RBC also have low Hb

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14
Q

3 causes of macrocytic anaemia

A

FAT RBC

Fetus (pregnancy) 
Alcohol excess
Thyroid disease (hypothyroidism)  
Reticulocytosis 
B12 deficiency/folate (main one) 
Cirrhosis and chronic liver disease
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15
Q

Aetiology of iron deficient anaemia

A

Blood loss

Cancer

Increased demands seen in growth (puberty) and
pregnancy.

Poor diet

Malabsorption

Hookworm

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16
Q

Symptoms of anaemia

A 
Fatigue 
Dyspnoea
Syncope
Palpitations 
Headache 
Pallor
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17
Q

Signs of chronic iron deficiency

A

Signs of chronic iron deficiency
Koilonychia (spoon nails)
Angular cheilosis (ulceration at the side of the mouth)
Atrophic glossitis

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18
Q

Investigations in iron deficient anaemia

A

Serum ferritin (storgate marker for iron). It is an acute phase reactant so may not be accurate (as it can be elevated in the presence of inflammation).

Serum iron (is low)

Blood film:
pencil shaped cells
Hypochromic microcytic erythrocytes (increased pallor in the centre of the cell)

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19
Q

Treatment for iron deficient anaemia

A

Treat the cause

Oral iron (ferrous sulfate) 
SE: nausea, black stools, diarrhoea or constipation 
Use IV iron if oral iron is contraindicated e.g in chronic renal failure
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20
Q

Pathophysiology of anaemia of chronic disease

A

Microcytic and normocytic anaemia

Poor use of iron in erythropoiesis

Cytokine-induced shortening of RBC survival (shortened RBC lifespan → due to direct cellular destruction via toxins from cancer cells, viruses or bacteria)

Decreased production of and response to erythropoietin

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21
Q

Aetiology of anaemia in chronic disease

A

Chronic infection

Vasculitis

Rheumatoid

Malignancy

Renal failure

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22
Q

Investigations in chronic disease anaemia

A

Serum ferritin is normal or increased in microcytic anaemia

Blood film
B12
Folate
TSH

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23
Q

Treatment of anaemia in chronic disease

A

Treat the underlying cause

Erythropoietin

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24
Q

Pathophysiology of macrocytic anaemia

A

High MCV

Inhibition of DNA synthesis during RBC production. Leads to cell growth without division.

Anaemia that causes unusually large red blood cells

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25
Q

Pathophysiology of B12 deficient anaemia

A

Absorption of vitamin B12 occurs in the terminal ileum.
Needs intrinsic factor (secreted by the gastric parietal cells) for transport across the intestinal mucosa.
Deficient intrinsic factor → reduced vitamin B12 absorption → anaemia

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26
Q

3 causes of B12 deficient anaemia

A

Poor diet

Malabsorption
Autoimmune condition in which atrophic gastritis leads to lack of intrinsic factor secretion from destruction of parietal cells in the stomach.
Crohn’s, coeliac

Other autoimmune conditions

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27
Q

Signs of B12 deficient anaemia

A 
B12 deficient signs 
Lemon tinge 
Glossitis (big beefy-red sore tongue) 
Angular cheilosis 
Neurological problems (irritability, depression, psychosis)
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28
Q

Investigations in B12 deficient anaemia

A

Schilling test for B12 deficiency

Bloods - FBC
Low Hb
Low WCC and platelets if severe

Serum B12 is decreased

Serum parietal cells autoantibodies

Blood film:
Macrocytic erythrocytes
Hypersegmented neutrophils

Bone Marrow investigation
Megaloblasts (developing red blood cells with delayed nuclear maturation relative to that of the cytoplasm) present

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29
Q

Treatment of B12 deficient anaemia

A

Hydroxocobalamin (vitamin B12) oral

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30
Q

Cause of folate deficient anaemia

A

Poor dietary intake

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31
Q

What is the difference in clinical presentation between B12 deficient anaemia and folate deficient anaemia?

A

symptoms of anaemia with no neuropathy signs like in B12 deficient anaemia

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32
Q

Investigations in folate deficient anaemia

A

Bloods
Red cell folate is low
Serum folate is low

Blood film
Macrocytic erythrocytes

Bone Marrow examination
Megaloblasts erythrocytes

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33
Q

Treatment for folate deficient anaemia

A

Treat the underlying cause

Oral folic acid for 4 months

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34
Q

Pathophysiology of haemolytic anaemias

A

Results from an increased destruction of erythrocytes with a reduction of the circulating lifespan.

There is a compensatory increase in bone marrow activity with premature release of reticulocytes

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35
Q

Aetiology of haemolytic anaemias

Name 1 inherited cause and 1 acquired cause

A 
Inherited 
Red cell membrane defect 
Hb abnormalities (thalassaemia, sickle cell) 
Metabolic defects

Acquired
Autoimmune
Mechanical destruction
Infections (malaria)

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36
Q

Clinical presentation of haemolytic anaemia

A

Symptoms of anaemia

Haemolytic signs include: jaundice, gallstones and leg ulcers

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37
Q

Pathophysiology of sickle cell anaemia

A

Amino acid substitution in the gene coding for the beta globin chain.

Leads to the production of HbS rather than HbA

Homozygous individuals (SS) have sickle cell anaemia. 
HbS polymerizes when deoxygenated causing erythrocytes to deform, producing sickle cells which are fragile and haemolyse, occluding small vessels and can result in a vaso-occlusive crisis.
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38
Q

investigation of haemolytic anaemia

A 
Thorough history 
FBC and blood film
Reticulocyte count 
U&Es, LFTs, TSH
B12, folate, ferritin (checking for malabsorption)
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39
Q

what is the lifespan of a sickle cell

A

5-10 days

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40
Q

what feature do heterozygotes HbAS have

A

sickle cell trait which causes no disability and protects against P.falciparum malaria

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41
Q

when does sickle cell anaemia present and why

A

Production of foetal Hb is normal, disease doesn’t manifest until 6 months

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42
Q

Clinical presentation of sickle cell anaemia

A

Acute pain in hands and feet in early childhood (vaso-occlusion of small vessels + avascular necrosis of bone marrow)

Adults, affects the long bones, ribs, spine and pelvis

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43
Q

what 3 acute complications can arise in sickle cell anaemia and present

A

Painful crisis (blockage of blood vessels inside the bone)
Parvovirus infection in children (can be v dangerous as it leads decreased erythrocyte production (slapped cheek syndrome)
Stroke
Cognitive impairment

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44
Q

3 chronic complications in sickle cell anaemia

A

Renal impairment
Priapism in males
Splenic/hepatic sequestration (organs become engorged with erythrocytes leading to an acute fall in Hb and rapid organ enlargement)

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45
Q

Investigations for sickle cell anaemia

A

Bloods
FBC : low Hb with a high reticulocyte count
Blood film : sickled erythrocytes

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46
Q

How is sickle cell anaemia picked up in neonates

A

Identified in neonatal screening via a heel prick test. The diagnosis is made with Hb electrophoresis showing 80-95% HbSS and absent HbA `

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47
Q

what is painful crisis in sickle cell anaemia

A

blockage of blood vessels in bone causing pain as the bone marrow swells up

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48
Q

Treatment of sickle cell anaemia

A

Hydroxycarbamide prevents painful crises
Folic acid
Pain relief
Bone marrow transplant can be curative

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49
Q

Pathophysiology of thalassaemia

A

Diminished synthesis of one or more globin chains leading to a reduction in haemoglobin.

Imbalanced globin chain production leads to precipitation of globin chains within red cells or precursors resulting in cell damage, ineffective erythropoiesis and haemolysis)

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50
Q

difference between alpha and beta thalassaemia

A

alpha: reduced alpha chain synthesis from gene deletion. usually leads to death in utero.
beta: reduced beta chain synthesis from a point mutation.

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51
Q

presentation of beta thalassaemia major

A

6-12 months at age of presentation
severe anaemia causes : failure to feed, listless, crying, pale
- skull bossing and hepatosplenomegaly

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52
Q

Investigations in beta thalassaemia major

A

FBC
low Hb
low MCV
normal ferritin

Hb electrophoresis is diagnostic

Blood film
Large and small (irregular pale cells)
Nucleated red blood cells in the peripheral circulation

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53
Q

Treatment of beta thalassaemia major

A

Promote fitness and healthy diet

Regular life long transfusions

Iron chelation therapy

Endocrine supplementation and testing. Patients have an increased risk of diabetes due to pancreatic iron overload

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54
Q

what do you need to look out for when giving regular tranfusions to thalassaemia patients

A

need to monitor iron levels as consequence can be a progressive increase in body iron load leading to liver fibrosis and cirrhosis. Can also lead to cardiac hemosiderosis

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55
Q

what are membranopathies

A

Structural protein losses leading to an unstable erythrocyte cell membrane

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56
Q

name 2 membranopathoes

A

spherocytosis

elliptocytosis

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57
Q

pathophysiology of elliptocytosis

A

RBC are elliptical in shape

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58
Q

pathophysiology of spherocytosis

A

spherical RBC that are less capable of being reshaped and can become trapped in the spleen

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59
Q

aetiology of membranopathies

A

autosomal dominant condition

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60
Q

clinical presentation of membranopathies

A

Can be asymptomatic and are generally mild conditions.

If severe (usually spherocytosis) :
Splenomegaly is detected in childhood
Predisposition to gallstones
Neonatal jaundice

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61
Q

Investigations in membranopathies

A

FBC - raised reticulocytes and reduced Hb

Blood film: spherocytes and reticulocytes

Serum bilirubin and urinary urobilinogen raised from haemolysis

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62
Q

Treatment for membranopathoes

A

Folic acid

Splenectomy if severe

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63
Q

two types of enzymopathies

A

glucose-6-phosphate dehydrogenase deficiency

pyruvate kinase deficiency

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64
Q

pathophysiology of G6PD deficiency

A

shortened erythrocyte lifespan as G6PD protects cells against oxidative damage

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65
Q

pathophysiology of pyruvate kinase deficiency

A

reduced ATP production causes reduced erythrocyte survival

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66
Q

aetiology of G6PD deficiency

A

X linked inheritance

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67
Q

what factors precipitate G6PD deficiency

A

broad beans, infection, henna and drugs

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68
Q

aetiology of PKD

A

autosomal recessive inheritance

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69
Q

clinical presentation of enzymopathies

A

Most are asymptomatic but may get oxidative crises due to decreased glutathione production, precipitated by other factors

G6PD: haemolysis, jaundice

PKD: homozygotes have neonatal jaundice. Later have haemolysis with splenomegaly +/- jaundice

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70
Q

Investigation of enzymopathies

A

Measurement of enzyme levels in the erythrocyte (enzyme assay)

Diagnosed by a screening test for NADPH

G6PD blood film
Bite and blister cells

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71
Q

Treatment of enzymopathies

A

Avoid precipitating factors

Folic acid

Transfusion if necessary

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72
Q

Pathophysiology of aplastic anaemia

A

Deficiency of all cell elements of the blood (pancytopenia) with hypocellularity (state of having abnormally few cells) of the bone marrow
Reduction in the number of pluripotent stem cells together with a fault in those remaining or an immune reaction against them so that they are unable to repopulate the bone marrow.

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73
Q

aetiology of aplastic anaemia

A

congenital
idiopathic
cytotoxic drugs
EBV, HIV, TB

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74
Q

clinical presentation of aplastic anaemia

A

anaemia symptoms
bone marrow failure signs:
increased susceptibility to infection, bruising and bleeding, bleeding gums, epistaxis

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75
Q

investigations in aplastic anaemia

what do they show?

A

FBC
Pancytopenia with low/absent reticulocytes

Bone marrow biopsy
Hypocellular marrow with increased fat spaces

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76
Q

Treatment for aplastic anaemia

A

Removal of causative agent

Bone marrow transplant care

Immunosuppressive therapy
Reduce the number of lymphocytes circulating in the bloodstream which stimulates the bone marrow to restart blood cell production

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77
Q

What is deep vein thrombosis

A

Formation of a thrombus in a deep vein which has the potential of embolising

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78
Q

pathophysiology of DVT (where do most venous thrombi begin?)

A

Most venous thrombi seem to begin at the valves.
Valves naturally produce a degree of turbulence because they protrude into the vessel lumen and may be damaged by trauma, stasis and occlusion. Thrombi grow. If blood pressure is allowed to fall it makes thrombosis more likely

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79
Q

aetiology of DVT

A

Disease or injury to the leg

Immobility

Broken bone

Obesity

Inherited disorders

Autoimmune disorders that increase the likelihood of blood clotting

Medicines that increase your risk of clotting (e.g the oral contraceptive pill)

Antiphospholipid syndrome

Lupus anticoagulant

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80
Q

symptoms of DVT

A

Non-specific
Pain on walking
Swelling of the calf or thigh - usually asymmetrical

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81
Q

signs of DVT

A 
Tenderness
Swelling
Warmth 
Discolouration 
Pitting oedema
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82
Q

what investigations would you perform to diagnose DVT

A

Calculate Well’s score
D-dimer
Ultrasound compression test in the proximal veins (diagnostic)

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83
Q

where in the lower limb would you get a sizeable clot formation

A

clot between the popliteal fossa and groin

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84
Q

what is Well’s score

A

calculates the likelihood that a patient has a DVT.
2 or more = DVT likely
Less than 2 = DVT unlikely
Takes into account the history of the patient as well as clinical findings

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85
Q

why is a d-dimer test used and what are the limitations of its use

A

Normal test excludes diagnosis of DVT. Positive test does not confirm it.
Used after clinical assessment to determine who needs to go on to have an ultrasound
Only helpful in outpatients

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86
Q

what does an ultrasound compression test of the proximal veins show us

A

If cannot compress the vein with the probe then there is likely to be a clot
Diagnostic test

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87
Q

Prevention of DVT

A

Mechanical
Hydration
Early mobilisation
Compression stockings

Chemical
Low molecular weight heparin - once daily injection

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88
Q

What is the treatment plan for DVT

A

Initial treatment: Low molecular weight heparin s/c injection

Then: Oral warfarin for 6 months with an INR 2-3

OR Direct Oral AntiCoagulant (DOAC) oral medication e.g Rivaroxaban from onset

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89
Q

what is a pulmonary embolism

A

clot that has started in the leg, detached, gone through the heart and become lodged in the pulmonary arteries

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90
Q

symptoms of a pulmonary embolism

A

Breathlessness
Pleuritic chest pain
May have signs/symptoms of DVT

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91
Q

signs of a pulmonary embolism

A 
Tachycardia 
Tachypnoea 
Pleural rub 
Cyanosis 
Severe dyspnoea 
Hypotension
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92
Q

investigations for pulmonary embolism

A

Chest X-ray - usually normal. Done to look for signs of pneumonia

ECG : sinus tachycardia, done to exclude a cardiac cause

ABG: Type 1 resp failure

D-dimer

Ventilation/perfusion scan to show mismatch defects

CT pulmonary angiogram : diagnostic

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93
Q

Treatment of pulmonary embolism

A

Clot lysis

Low molecular weight heparin s/c injection once daily

Oral warfarin or a DOAC

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94
Q

define thrombosis

A

blood coagulation inside a vessel

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95
Q

what is the precursor for an acute arterial thrombotic event

A
  • atherosclerosis
96
Q

symptoms of arterial thrombosis

A

intermittent claudication - muscle pain in the lower limbs on exercise
walking impairment - fatigue, aching, cramping or pain in lower limb
relieved by rest
male impotence
ischaemic rest pain - severe unremitting pain in the foot esp at night - partially relieved by hanging the foot out of the bed

97
Q

signs of peripheral arterial disease

A 
6Ps
Pallor
Perishingly cold
Pulseless
Pain
Parasthesia
Paralysis
98
Q

risk factors for venous thrombosis

A 
previous history 
family history 
cancer
increasing age 
immobilisation 
smoking 
BMI over 30 
male 
hypertension
99
Q

why does immobilisation increase a persons risk for DVT

A

stasis of blood

100
Q

why does smoking increase a persons risk of thrombosis

A

associated with a higher level of NO and free radicals and can damage the blood vessel, changing the intimal surface.

nicotine causes vasoconstriction of blood vessels

101
Q

why is obesity a risk factor for thrombosis

A

state on chronic inflammation, changes blood constituents

hyperlipidemia

102
Q

why is hypertension a risk factor for thrombosis

A

change in the pattern of blood flow and damage to endothelium

103
Q

describe the pharmacological mechanism of heparin

A

heparin binds to endogenous antithrombin and increases its activity.
This then inhibits thrombin action (IIa) and Xa clotting factor.
Coagulation cascade is inhibited

104
Q

describe the pharmacological mechanism of aspirin

A

inhibits cyclo-oxygenase irreversibly

inhibits thromboxane formation and therefore platelet aggregation

105
Q

describe the pharmacological mechanism of warfarin

A

warfarin is a vitamin K reductase inhibitor
Reduced vitamin K isn’t produced
gamma-carboxyglutamic acid cannot be produced
clotting factors II, VII, IX and X (1972) are not produced.
Inhibits and stops coagulation cascade

106
Q

Pharmacological action of DOACs

A

directly act on clotting factor II or X to stop the coagulation cascade

107
Q

Basic principles of the pathophysiology of leukaemia`

A

presence of rapidly proliferating immature blast blood cells (can be precursors of RBCs, platelets or white cells)
Cells divide rapidly but are non-functional so the body wastes energy making the cells. Less energy available to make useful cells.
Take up a lot of space in bone marrow

108
Q

what is the commonest malignancy of childhood

A

acute lymphoblastic leukaemia

109
Q

what are the peak ages for acute lymphoblastic leukaemia

A

0-4
15-25
over 70

110
Q

pathophysiology of acute lymphoblastic leukaemia

A

Malignancy of the immature lymphoid cells.

Mutation causes the B or T lymphocyte cell lines to stop maturation and promote the uncontrolled proliferation of immature blast cells (myeloblasts and lymphoblasts)

Blast cells take up a lot of space in the bone marrow and so other cells get crowded out and causes : anaemia, thrombocytopenia, leukopenia.

Blast cells eventually spill out into the circulation, some settle in liver and spleen.

111
Q

Aetiology of acute lymphoblastic leukaemia

A

Mutation - chromosomal translocation or abnormal chromosome number

112
Q

Risk factors for acute lymphoblastic leukaemia

A

Down’s Syndrome
Ionising radiation
Exposure to alkylating chemotherapy

113
Q

what is different in the cells affected in adults and children with acute lymphoblastic leukaemia

A

B cells = children

T cells = adults

114
Q

Clinical presentation of acute lymphoblastic leukaemia

A

Marrow Failure
- Anaemia due to decreased Hb : shortness of breath, tiredness, lightheadedness, palpitations
- Infection (decreased WCC) esp chest, mouth, perianal and skin
- Bleeding due to thrombocytopenia
Easy bruising and bleeding. Usually mucosal bleeding. Rash

Infiltration of leukemic cells into organs

  • hepatosplenomegaly → abdominal fullness
  • bone pain
  • lymphadenopathy
  • headache and cranial nerve palsies
  • mediastinal masses with SVC obstruction
115
Q

Diagnosis and investigations in acute lymphoblastic leukaemia

A

FBC : WCC high (increased circulating lymphocytes and lymphoblasts). Decreased circulating RBCs, platelets, mature neutrophils.

In acute leukaemia FBC changes quite rapidly

Blood film: characteristic blast cells on blood film and bone marrow (they have very little cytoplasm and areas that look slightly lighter in the nucleus)

Lymphoblasts are smaller cells with little cytoplasm and coarse chromatin.

Bone Marrow biopsy: blast cells

Chest XR and CT to look for mediastinal and abdominal lymphadenopathy

Lumbar puncture to look for CNS involvement

Check B12, folate and iron

116
Q

what is characteristic for diagnosis for acute lymphoblastic leukaemia

A

blast cells on blood film and bone marrow

117
Q

characteristics of lymphoblasts

A

smaller cells
coarse chromatin
little cytoplasm

118
Q

Treatment of acute lymphoblastic leukaemia

A

Educate and motivate patient

Supportive
Blood/platelet transfusion
IV fluids
Allopurinol

If have an infection → give immediate IV antibiotics

Chemotherapy

Matched related allogeneic marrow transplantations

119
Q

Pathophysiology of acute myeloid leukaemia

A

Neoplastic proliferation of blast cells derived from marrow myeloid elements (gives rise to basophils, eosinophils and neutrophils)

120
Q

aetiology of acute myeloid leukaemia

A

Associated with radiation and Down’s syndrome

121
Q

signs and symptoms of acute myeloid leukaemia

A

Bone marrow failure :
Anaemia
Infection
Bleeding (usually mucosal)

Infiltration :
Hepatomegaly 
Splenomegaly 
Gum hypertrophy 
Skin involvement

Disseminated Intravascular Coagulation can occur in a subtype of AML where there is a release of thromboplastin

122
Q

Diagnosis and tests used to investigate acute myeloid leukaemia

A

FBC: WCC is increased

Blood film :
Myeloblasts (large cells, fine chromatin, prominent nucleoli)

Bone marrow biopsy:
Myeloblast cells with Auer rods in the cytoplasm (crystals of coalesced granules)

Immunophenotyping : CC10

123
Q

what differentiates AML from ALL

A

Auer rods in cytoplasm

124
Q

complications of AML

A

infection - give prophylaxis!

be alert to sepsis

125
Q

Treatment of AML

A

Chemotherapy
Very intensive
Daunorubicin and cytarabine

Bone marrow transplant

Infection is a major issue so give prophylaxis

126
Q

pathophysiology of chronic lymphocytic leukaemia

A

Neoplastic monoclonal proliferation of mature functionally abnormal B lymphocytes in the bone marrow and blood.

127
Q

what is the hallmark sign of chronic lymphocytic leukaemia

A

progressive accumulation of a malignant clone of functionally incompetent B cells

128
Q

aetiology of chronic lymphocytic leukaemia

A

mutations in cells chromosomes

129
Q

symptoms of chronic lymphocytic leukaemia

A

often none and usually presents as a surprise finding on a routine FBC

Anaemia
Thrombocytopenia : bleeding and bruising
Neutropenia: more frequent bacterial infections, fever, pneumonia, sepsis

Severe: weight loss, sweats, anorexia

130
Q

signs of chronic lymphocytic leukaemia

A

Enlarged rubbery non-tender nodes
Splenomegaly
Hepatomegaly

131
Q

Complications of chronic lymphocytic leukaemia

A

Autoimmune haemolysis (leading to anaemia)
Increased infection risk due to hypogammaglobulinemia (low IgG)
Marrow failure

132
Q

Tests for chronic lymphocytic leukaemia

A

FBC

  • Low Hb
  • Raised WCC with very high lymphocytes
  • Low RBCs, platelets, neutrophils

Blood film
Smudge cells in peripheral smear (immature B cells) → DIAGNOSTIC

Immunophenotyping: looking for premature cells that express these proteins on their cell membrane :CD5, CD19, CD23

133
Q

what is diagnostic on a blood film to diagnose chronic lymphocytic leukaemia

A

smudge cells in a peripheral smear (immature B cells)

134
Q

Treatment of chronic lymphocytic leukaemia

A

Supportive

  • Transfusions
  • IV human immunoglobulin

Chemotherapy
Rituximab

Radiotherapy

Stem cell transplant

Bone marrow transplant

135
Q

what ages are most likely diagnosed with chronic myeloid leukaemia

A

40-60 years

136
Q

risk factors for chronic myeloid leukaemia

A

benzene and radiation exposure

137
Q

pathophysiology of chronic myeloid leukaemia

A

Uncontrollable clonal proliferation of myeloid cells leading to premature cells.
Caused by the activated of tyrosine kinase activity from a genetic mutation leading to a fusion gene of BCR and ABL genes.
Premature leukocytes accumulate in the bone marrow until they spill out and enter the bloodstream.Some cells deposit in organs and some stay in circulation

138
Q

aetiology of chronic myeloid leukaemia

A

t(9;22) Philadelphia chromosome translocation is diagnostic

139
Q

symptoms of chronic myeloid leukaemia

A
  • weight loss
  • tiredness
  • fever
  • sweats
  • bleeding
  • abdominal discomfort

accelerated phase

  • recurrent infections
  • anaemia
  • lymphadenopathy
  • bleeding
140
Q

signs of chronic myeloid leukaemia

A

splenomegaly
hepatomegaly
anaemia
bruising

141
Q

investigations in chronic myeloid leukaemia

A 
FBC 
-very high WCC
- decreased Hb
- increased folate 
Bone marrow aspirate 
- hypercellular 
- pseudo gaucher cells in bone marrow
142
Q

what cell is found in the bone marrow of chronic myeloid leukaemia patients?

A

pseudo gaucher cells

143
Q

what is the treatment for chronic myeloid leukaemia?

A

ORAL IMATINIB

144
Q

what is the mechanism of action for the drug used to treat chronic myeloid leukaemia?
name 3 side effects?

A

specific BCR-ABL tyrosine kinase inhibitor

nausea, cramps, oedema, rash

145
Q

what are lymphomas?

A

disorders caused by the malignant proliferation of lymphocytes

146
Q

what is the normal physiology in B cell development?

A
  1. starts in bone marrow (primary lymphoid organ)
    precursor B cell –> naive B cell –> blood –> lymph nodes
  2. B cells differentiate into plasma cells which are found in the medulla of the lymph nodes
147
Q

what is the incidence of Hodgkin’s Lymphoma?

A

It has a bimodal incidence

  • Young adults (15-24)
  • Elderly
148
Q

what are the risk factors for developing Hodgkin’s lympgoma

A

An affected sibling
EBV
Lupus
Post-transplantation

149
Q

what is the aetiology of Hodgkin’s lymphoma

A

Genetic mutation in the B-cell causes uncontrollable division and proliferation becoming a neoplastic cell

150
Q

pathophysiology of Hodgkin’s lymphoma?

A

An abnormal B-cell escapes regulation and starts to divide uncontrollably to become a neoplastic cell.

Neoplastic cells spread to nearby lymph nodes.

Neoplastic cells are surrounded by inflammatory cells and activate fibroblasts and eosinophils.

151
Q

what differentiates Hodgkin’s lymphoma from non-Hodgkin’s lymphoma?

A

Hodgkin’s has characteristic REED STERNBERG CELLS

- have a mirror image nuclei

152
Q

symptoms of Hodgkin’s lymphoma

A

Enlarged, non-tender, rubbery superficial lymph nodes. Usually cervical.

Can have systemic syndromes as well (known as B symptoms) : fever, weight loss (unintentional loss of 10% of body weight over the last 6 months), night sweats, anorexia.

Pruritus
Lethargy
Compression syndromes (eg present with swollen leg as the glands can grow to compress lymphatics)

153
Q

signs of Hodgkin’s lymphoma

A 
Lymphadenopathy 
Cachexia (weakness and wasting of the body due to severe chronic illness) 
Anaemia 
Splenomegaly 
Hepatomegaly
154
Q

Investigations in Hodgkin’s lymphoma?

A
  1. Blood film and bone marrow aspirate
    - REED-STERNBERG CELLS ARE DIAGNOSTIC
  2. Lymph node biopsy
  3. Imaging
    -CXR
    -CT scan of thorax, abdomen or pelvis - looking for other enlarged lymph nodes
  4. Immunophenotyping
    CD20 found on the surface of B lymphocytes only
155
Q

why is immunophenotyping important in Hodgkin’s lymphoma?

A
  • diagnostic tool

- gives indication about treatment as there is a targeted monoclonal antibody for CD20

156
Q

Outline the staging of Hodgkin’s lymphoma

A

I : single lymph node region

II : 2 or more nodal areas on same side of the diaphragm

III : involvement of nodes on both sides of the diaphragm

IV : spread beyond the lymph nodes (liver or bone marrow)

A: no systemic symptoms
B: presence of B symptoms (worse disease)

157
Q

why is staging important?

A

influences treatment and prognosis

158
Q

what is the treatment for a stage 1-2A Hodgkin’s lymphoma?

A

short course chemotherapy + radiotherapy

159
Q

what is the treatment for stage 2B-4 Hodgkin’s lymphoma?

A

combination chemotherapy

160
Q

what is the combination chemotherapy used in Hodgkin’s lymphoma?

A 
ABVD
Adriamycin
Bleomycin
Vinblastine 
Dacarbazine
161
Q

what is the pathology of Non-Hodgkin’s Lymphoma (NHL)

A

Malignant proliferation of lymphocytes without Reed Sternberg cells
Most are derived from B cell lines

162
Q

what are the two subtypes of NHL

A 
Indolent/low grade NHL lymphoma 
Follicular 
Slow growing
Incurable 
Neoplastic B cells 	 
High grade/aggressive NH lymphoma 
Diffuse Large B Cell Lymphoma is the most common  
Often curable
often a short history 
1/3 of cases have extranodal involvement
163
Q

clinical presentation of NHL ?

A

Painless lymphadenopathy

B symptoms : fever, night sweats, weight loss

Pancytopenia from marrow involvement (anaemia, infection, bleeding)

Extranodal disease
Bowel obstruction (GI tract)
Fatigue, easy bruising, recurrent infections (bone marrow)
motor/sensory deficits (spinal cord)

164
Q

investigations in NHL

A

Bloods

  • FBC (may show anaemia, high WCC and low platelets)
  • LFTs can show liver involvement
  • U&Es

Bone marrow/lymph node biopsy
- NO Reed Sternberg Cells

165
Q

what is the treatment for indolent NHL

A

If symptomless - do nothing and monitor

Combination chemotherapy

Monoclonal antibodies: rituximab maintains remission. Kills CD20 positive cells.

Radiotherapy may be curative in localised disease

166
Q

what is the treatment for aggressive NHL

A

R-CHOP regimen chemotherapy

early - R-CHOP + radiotherapy
late - R-CHOP + monoclonal antibodies

167
Q

what is myeloma?

A

neoplasm of plasma cells in the bone marrow

168
Q

what is the aetiology of myeloma?

A

Abnormal proliferation of a single clone of plasma or lymphoplasmacytic cells leading to secretion of Ig or an Ig fragment causing the dysfunction of many organs.

169
Q

what are the clinical features of myeloma?

A 
CRAB
Calcium high (hypercalcaemia)
Renal impairment 
Anaemia (tiredness and malaise)
Bone pain (osteolytic bone lesions +/- fractures)
170
Q

investigations in myeloma?

A 
1. Bloods 
FBC
- normocytic normochromic anaemia 
Blood film
- U&Es: Hypercalcaemia, high urea and creatinine 
- Raised ESR
- Rouleaux cells
  1. Bone marrow biopsy: myeloma bone marrow, many plasma cells with abnormal forms
  2. Imaging: X-ray of spine, chest and pelvis may show punched out lesions, vertebral collapse and fractures
  3. Electrophoresis : Ig paraprotein monoclonal bands in serum or urine
171
Q

what are the key features in order to make a diagnosis of myeloma?

A

need to have a high index of suspicion!

  • monoclonal paraprotein band in serum or urine electrophoresis
  • increased plasma cells on bone marrow biopsy
  • evidence of end organ damage from myeloma (hypercalcaemia, anaemia)
  • bone lesions
172
Q

What is the treatment for myeloma?

A 
Supportive: 
Analgesia for bone pain
Bisphosphonate
Transfusion and erythropoietin (anaemia)
Hydrate (renal insufficiency) 
Isolation and handwashing (better hygiene to reduce infection risk)

Chemotherapy

Stem Cell Transplant if suitable

173
Q

what is the most prevalent malaria parasite?

A

Plasmodium falciparum

174
Q

in what two species of malaria parasite is there a dormant stage? what is a dormant stage?

A

Plasmodium ovale and Plasmodium vivax

Dormant stage means that if the infection is inadequately treated the merozoites can be released from the liver weeks or years later after the initial infection causing recurrent disease

175
Q

where in the world has the majority of cases of malaria?

A

Sub-Saharan Africa

176
Q

what is the vector for malaria parasites?

A

female anopheles mosquito

177
Q

name two other routes of transmission of malaria (rare with no mosquito involvement)

A

transfusion
needle sharing
organ transplantation

178
Q

pathophysiology of malaria and the life cycle ?

A
  1. Infected female mosquito bites human and injects sporozoite into the blood which travels to the liver.
  2. Sporozoite enters hepatocytes and replicates : sporozoite → merozoites → schizont.
  3. Hepatocyte ruptures releasing the merozoites into the blood.
  4. Merozoites invade RBC and multiply until the cell bursts releasing the merozoites into the blood.
  5. Merozoite forms a trophozoite in a RBC which replicates to form many more merozoites.
  6. RBC bursts releasing into the blood. This repeats.
  7. after several asexual cycles merozoites can invade RBC and develop into plasmodium gametocytes
  8. if an unaffected mosquito then bites the infected human it ingests the male and female gametocytes and they develop into mature gametes in the vector stage.
179
Q

what gives rise to the clinical symptoms of malaria and why?

A

the blood stage
when the parasite is developing in the RBC it produces waste products and toxic factors. when the infected cells lyse they release these toxic factors into the blood
this stimulates the macrophages to produce pro inflammatory cytokines which causes symptoms

180
Q

what are the signs and symptoms of malaria?

A 
Fever and chills 
Headache
Myalgia
Fatigue
Diarrhoea 
Cough

If diagnosis is delayed or it is severe disease, then patients may present with haematological changes.

Haemolysis: haemolytic anaemia (breathless, fatigue, pre-hepatic jaundice, haemoglobinuria)

Monocytosis and lymphopenia : loss of WBC → infection

Triggering of the coagulation cascade : thrombocytopenia

181
Q

what is cytoadherance?
when is it observed?
what complications can it cause?

A
  • infected RBCs display specific membrane proteins on their surface which adhere to microvascular endothelium
  • characteristic of P. falciparum malaria
  • accumulate in capillaries, block blood flow and can get cerebral malaria due to haemorrhage
182
Q

what is rosetting in malaria?

A

infected RBCs can adhere to other non-infected RBCs in rosettes

183
Q

what is complicated malaria?

what complications can arise?

A

infections are complicated by serious organ failures

Cerebral malaria 
Renal failure 
Acute respiratory distress syndrome (rapid widespread inflammation across the lungs)
Bleeding 
Shock
184
Q

investigations in malaria

A

Immediate blood test

Microscopy of thick and thin blood smear.

Thick: looking for number of little black dots per 100 RBCs (severity)

Thin: looking morphologically at the shape of the RBCs to decide which species of plasmodium it is. 3 in 24 hrs.

Rapid diagnostic test of the parasite antigen

FBC (anaemia and thrombocytopenia) 
U&Es (AKI) 
Clotting (DIC)  
Glucose 
ABG (acidosis) 
Urinalysis (haemoglobinuria)
185
Q

what is the treatment for complicated malaria?

A

IV artesunate

186
Q

what is the treatment for uncomplicated malaria?

A

artemisinin combination therapies

187
Q

what drug would you use to eliminate hypnozoites in the liver stage for dormant stage P.ovale and P.vivax

A

Primaquine

188
Q

what treatments would you use to treat complications arising due to malaria?

A

Cerebral = anti-epileptics

ARDS = ventilation support, oxygen

Renal failure = hydration (dialysis if severe)

Sepsis = broad spectrum antibiotics

Bleeding/anaemia = blood products

189
Q

name some prevention methods used to stop the spread of malaria?

A

Vector control

  • destruction of mosquito breeding sites
  • long-lasting insecticidal nets
  • sterile male mosquito release

Chemoprophylaxis
- antimalarial drugs to prevent clinical disease

190
Q

what is polycythaemia?

A

disease state in which the haematocrit is raised

191
Q

how is polycythaemia divided?

A

Relative Polycythaemia: decreased plasma volume and normal RBC mass

Absolute Polycythaemia:
Increased RBC mass

192
Q

aetiology of acute and chronic relative polycythaemia?

A

acute : dehydration

chronic : associated with obesity, hypertension and a high alcohol and tobacco intake

193
Q

aetiology of primary and secondary absolute polycythaemia?

A

Primary
Polycythaemia vera

Secondary

  • due to hypoxia
  • High altitude
  • Chronic lung disease
  • Cyanotic congenital heart disease
  • Heavy smoking
  • Inappropriately increased erythopoietin secretion (renal carcinoma)
194
Q

what is polycythaemia vera?

A

malignant proliferation of a clone derived from one pluripotent stem cell causing an excess proliferation of RBCs, WBCs and platelets leading to hyperviscosity and thrombosis

195
Q

presentation of polycythaemia vera?

A

May be asymptomatic and only detected on FBC.

May present with vague symptoms due to hyperviscosity: headache, dizziness, tinnitus, visual disturbance

Characteristic:
Itching after a hot bath
Erythromelalgia (burning sensation in fingers and toes)

196
Q

signs of polycythaemia vera

A

Facial plethora
Splenomegaly
Gout may occur due to increased urate from RBC turnover

197
Q

investigations in polycythaemia vera

A

FBC

  • Increased red cell count
  • Increased haemoglobin
  • Increased hematocrit
  • Increased packed cell volume

Increased B12

Marrow shows hypercellularity with erythroid hyperplasia

Decreased serum erythropoietin

Raised red cell mass

198
Q

what is the treatment for polycythaemia vera?

A

Aim is to keep haematocrit < 0.45 to decrease the risk of thrombosis

Younger patients: venesection (remove blood from circulatory system)

Higher risk (over 60 and previous thrombosis) - hydroxycarbamide

Aspirin 75mg given daily

199
Q

outline the normal physiology of platelets?

A
  • produced in bone marrow
  • arise from megakaryocytes
  • regulated by thrombopoietin (produced by the liver)
  • play an important role in primary homeostasis
  • annulcleate cell fragment with lifespan of 7-10 days
  • old platelets are removed by the spleen
200
Q

what is the normal platelet count ?

A

150-400 x 10^9/L

201
Q

what is thrombocytopenia

A

deficiency of platelets in the blood

202
Q

what is the pathophysiology of immune thrombocytopenia purpura ?

A

IgG antibodies form against platelet and megakaryocyte surface glycoproteins

increased destruction of platelets

203
Q

aetiology of immune thrombocytopenia purpura ?

A

Thrombocytopenia caused by antiplatelet autoantibodies

Primary : may follow viral infection/immunisation in children

Secondary: occurs in association with some malignancies (CLL) and infections (HIV, Hep C)

204
Q

presentation of primary immune thrombocytopenia purpura?

A

Acute onset with sudden self limiting purpura (purple spots on the skin caused by bleeding underneath the skin)
Muco-cutaneous bleeding

205
Q

presentation of secondary immune thrombocytopenia purpura ?

A 
chronic presentation 
fluctuating course of :
- bleeding
- purpura 
- epistaxis 
- menorrhagia
206
Q

investigations in suspected immune thrombocytopenia purpura

A

Bone marrow biopsy shows increased megakaryocytes

Antiplatelet autoantibodies often present but are not needed for diagnosis

207
Q

what is the treatment for immune thrombocytopenia purpura ?

A

None if mild

Symptomatic :
Prednisolone
IV immunoglobulin may raise platelet count temporarily

If relapse:
Splenectomy
B cell depletion with rituximab

208
Q

what is the pathology of thrombotic thrombocytopenia purpura?

A

Large multimers of vWF form resulting in platelet aggregation and fibrin deposits in small vessels leading to microthrombi.
Large consumption of platelets leads to profound thrombocytopenia

209
Q

aetiology of thrombotic thrombocytopenic purpura

A

occurs due to a reduction in the protease enzyme

Idiopathic
Autoimmune
Cancer 
Pregnancy
Drug association
210
Q

clinical presentation of TTP

A

Purpura
Fever
Fluctuating cerebral dysfunction
Haemolytic anaemia with red cell fragmentation often accompanied by AKI

211
Q

Investigations for diagnosis of thrombotic thrombocytopenia purpura

A

Normal coagulation screen

Lactate dehydrogenase is raised

Blood film: Schistocytes

212
Q

treatment for TTP

A

Urgent plasma exchange to remove antibody and replace ADAMST-13

IV methylprednisolone

IV rituximab

213
Q

pathology of disseminated intravascular coagulation

A

Cytokine release in response to systemic inflammatory response syndrome

Widespread systemic generation of fibrin within blood vessels caused by the initiation of the coagulation pathway (MASSIVE ACTIVATION OF COAGULATION CASCADE)

Will either cause microvascular thrombosis and organ failure OR the consumption of platelets and coagulation factors leading to bleeding

214
Q

aetiology of disseminated intravascular coagulation

- include initiating factors

A

Never occurs in isolation

Severe infection activates the clotting cascade and consumes platelets.

Initiating factors:

1) Extensive damage to vascular endothelium exposing tissue factor e.g major trauma and tissue destruction
2) Enhanced expression of tissue factor by monocytes in response to cytokines

  • Sepsis
  • Advanced cancer
  • Obstetric complications
  • Major trauma
215
Q

clinical presentation of disseminated intravascular coagulation

A

Often acutely ill and shocked

Bleeding may occur from the mouth, nose and venepuncture sites.

Widespread bruising

Confusion

Thrombotic events may occur as a result of vessel occlusion by fibrin and platelets (skin, brain and kidneys are most affected)

216
Q

Investigation and diagnosis of disseminated intravascular coagulation

A

Diagnosis can be suggested from history from underlying cause (sepsis, malignancy or obstetric causes)

Decreased fibrinogen

Elevated fibrin degradation products (high D-dimer)

Blood film shows fragmented RBCs

Prolonged prothrombin time

217
Q

Treatment of disseminated intravascular coagulation

A

Treat the underlying condition - antibiotics

Replace platelets if very low via transfusion if patient is actively bleeding

Fresh frozen plasma to replace coagulation factors

Red cell transfusion in patients that are still bleeding

218
Q

epidemiology of HIV

A
  • 5000 new infections per day
  • majority in Sub-Saharan Africa
  • 50% of all new infections occur in 15-24 year olds
  • 1 in 4 people do not know they have HIV
219
Q

what are the modes of transmission of HIV?

A
  • sexual intercourse
  • sharing of contaminated needles
  • receipt of infected blood/blood products/donated organs
  • vertical transmission (mother to baby during labour and breast feeding)
220
Q

what does U= U mean?

A

undetectable = untransmittable

having an undetectable viral load when taking HIV treatment also stops transmission

221
Q

name 5 risk factors that increase your likelihood of getting HIV

A
  • sexual contact with people with high prevalence groups (MSM)
  • having multiple sexual partners
  • IVDU
  • Commercial sex workers
  • Vertical transmission (baby more likely to contract if mum has HIV)
222
Q

what type of virus is HIV?

What does this mean?

A

retrovirus

genetic material is RNA so has to undergo reverse transcription into DNA to be incorporated into the host cell

223
Q

what immune cell is HIV trophic to?

A

CD4+ T cells

224
Q

how does HIV infect a CD4+ T cell ?

A
  1. HIV free in plasma
  2. HIV recognises and fuses to CD4 and CCR5 receptors on the the CD4+ T cell
  3. virus fuses to the cell membrane and enters the cell
  4. caspid enters the cell
  5. enzymes reverse transcriptase and integrase enzyme both enable viral DNA to be integrated into the host cells DNA
  6. when the host cell replicates the viral DNA also replicates
  7. Viral proteins made
  8. Virus matures and buds out of the host cell
225
Q

what is the natural history of HIV

A
  1. initially get an acute primary infection when first acquire HIV
    - huge spike in viral replication
    - transient immunosuppression and fall in CD4 count
    - abrupt onset of non-specific viral/flu symptoms (can be severe) significant weight loss, fever, rash
  2. Body develops antibodies to HIV and is able to partially control the infection leading to a period of CLINICAL LATENCY (approx 7 years)
  3. Progresses to AIDS and get signs and symptoms
226
Q

What potential findings are there in the asymptomatic phase of HIV?

A
  • persistent generalised lymphadenopathy
  • shingles
  • cervical abnormalities
  • may be a high protein count on blood test (high immunoglobulins and normal albumin)
227
Q

what cells serve as a marker for HIV infection?

A

CD4 T cells

228
Q

what are 2 important prognostic factors for progression to AIDS?

A
  • conc of HIV RNA in the blood (viral load) at the time of diagnosis
  • CD4+ helper T cell count
229
Q

symptoms of early symptomatic HIV (AIDS related complex)

A
  • RECURRENT SHINGLES
  • Candidiasis
  • Diarrhoea
  • Night sweats
  • Weight loss
230
Q

symptoms of AIDS

A

the dominant clinical manifestations of AIDS are opportunistic infections and tumours.
Typical infections :
- Oesophageal candida
- Pneumocystis jirovecii pneumonia
- TB
- Chronic Herpes Simplex Virus Infection

AIDS defining conditions

  • Oesophageal candida
  • Pneumocystis jirovecii pneumonia
  • Kaposi’s carcinoma
  • Non-Hodgkin’s Lymphoma (caused by EBV)

Direct HIV effect :

  • HIV dementia
  • HIV wasting
231
Q

3 factors that the development of AIDS depends on

A
  • genetic background
  • repeated immune stimulation
    pregnancy
232
Q

at what CD4 T cell level do opportunistic infections occur?

A

less than 200

233
Q

What test to do in suspected HIV?

A

Blood test

tests for HIV antibody and antigen

234
Q

What is the treatment for HIV?

A

Antiretroviral treatment (HAART)

  • entry inhibitor drugs
  • fusion inhibitors
  • inhibition of viral replication
  • protease inhibitors
235
Q

Prevention of HIV spread

A
  1. PreP - take tablets before sex to protect
  2. Circumcision reduces risk of transmission
  3. PEP - take drugs after sex
  4. STI control - condoms!
236
Q

what is UNAIDS 90/90/90

A

to be achieved by 2020

  • 90% of people living with HIV are diagnosed
  • 90% of those diagnosed to be on ART therapy
  • 90% of those on ART to have viral suppression

Phase 2A (11 decks)

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