Haematology Flashcards
1
Q
Where is erythropoietin made, what does it do and what is it stimulated by?
A
- Kidney.
- Stimulates precursor cells to proliferate + differentiate into erythrocytes.
- Stimulated by tissue hypoxia.
2
Q
Explain the configuration of erythrocytes.
A
- Lifespan of 120 days.
- Contain haemoglobin, a tetrameric protein (2 alpha, 2 beta proteins) + this carries + delivers oxygen to tissues as oxygen reversibly binds with Fe2+ (the haem group) in aq environment.
3
Q
What constituents make up foetal + adult haemoglobin?
A
- Foetal is 2x alpha, 2x gamma sub-units.
- Adult is 2x alpha, 2x beta sub-units.
4
Q
What attributes to the removal of erythrocytes?
A
- Spleen, liver, bone marrow + blood loss.
5
Q
What is the purpose of vitamin B12 and folate and what can a deficiency cause?
A
- Needed for DNA synthesis + so a deficiency means RBCs cannot be made in the bone marrow + so less are released leading to anaemia.
6
Q
What is needed for B12 absorption?
A
- Intrinsic factor produced by gastric parietal cells, B12 absorption occurs in the terminal ileum.
7
Q
Where is folate absorbed and what can cause folate deficiency?
A
- Duodenum/jejunum.
- Malabsorption, poor diet, increased haemolysis or methotrexate.
8
Q
What does the common lymphoid progenitor stem cell line give rise to?
A
- Natural killer cells + lymphocytes.
9
Q
What does the common myeloid progenitor stem cell line give rise to?
A
- All cells apart from natural killer cells + lymphocytes.
- Erythrocytes, mast cells, basophils etc.
10
Q
Explain the function of neutrophils.
A
- Multi-lobar nucleus.
- Phagocytic, role in inflammation, infection + myeloid leukaemia.
11
Q
Explain the function of eosinophils
A
- Tri-lobed nucleus.
- Show diurnal variation (more common in morning), often raised in parasitic infections.
12
Q
Explain the function of basophils.
A
- Similar role to mast cells, stimulated to secrete histamine + associated with hypersensitivity reactions.
13
Q
Explain the function of monocytes.
A
Immature cells that differentiate into macrophages when they leave bloodstream, phagocytic.
14
Q
Explain the function of lymphocytes.
A
- T cells, mediators in cellular immunity (CD8+, CD4+).
- B cells, mediators in humoral immunity (antibody mediated responses).
15
Q
Explain the function of platelets.
A
- Involved in primary haemostasis as they adhere to damaged endothelium to form a platelet plug, this determines bleeding time (prothrombin time, extrinsic pathway).
16
Q
What does the activated partial thromboplastin time (APPT) measure?
A
- Bleeding time (intrinsic pathway).
17
Q
What is the fibrinolytic system?
A
- Plasminogen>plasmin which cuts fibrin into fragments + prevents blood clots from growing + becoming problematic.
18
Q
What factor is required to convert prothrombin into thrombin?
A
- Xa.
19
Q
IRON DEFICIENCY ANAEMIA
What is the pathophysiology of iron deficiency anaemia?
A
- Iron is necessary for the formation of haem meaning that when there is insufficient iron there is a lack of effective erythrocytes leading to anaemic symptoms.
- Iron elimination fixed at 1mg/day.
20
Q
IRON DEFICIENCY ANAEMIA
What is the aetiology of iron deficiency anaemia?
A
- Blood loss (most common).
- Increased demands in growth (puberty) + pregnancy.
- Decreased absorption (small bowel disease).
- Poor intake.
- Pre-menopausal women at higher risk due to menses.
21
Q
IRON DEFICIENCY ANAEMIA
What is the clinical presentation of anaemia?
A
Anaemia... - Fatigue. - Lethargy. - Syncope. - Headache. - Pallor. Iron deficiency... - Brittle hair + nails. - Atrophic glossitis. - Angular stomatitis.
22
Q
IRON DEFICIENCY ANAEMIA
What are the differentials for iron deficiency anaemia?
A
Other causes of microcytic anaemia…
- Thalassaemia.
- Sideroblastic anaemia.
- Anaemia of chronic disease.
23
Q
IRON DEFICIENCY ANAEMIA
What investigations would you do in someone with iron deficiency anaemia?
A
FBC…
- Serum ferritin will be low (acute phase reactant so might not be accurate, also low in infection).
- Serum iron is low, total iron-binding capacity is high.
Blood film…
- Hypochromic microcytic erythrocytes.
24
Q
IRON DEFICIENCY ANAEMIA
What is the treatment for iron deficiency anaemia? What are some side effects from this treatment?
A
- Oral iron salts like ferrous sulfate.
- Black stool, constipation/diarrhoea, nausea.
25
PERNICIOUS ANAEMIA
| What is the pathophysiology of pernicious anaemia?
- Absorption of vitamin B12 in the terminal ileum is intrinsic factor dependent for transport across the intestinal mucosa + so deficient intrinsic factor will lead to reduced vitamin B12 absorption + so pernicious anaemia.
26
PERNICIOUS ANAEMIA
| What is the aetiology of pernicious anaemia?
- Autoimmune condition in which atrophic gastritis leads to lack of intrinsic factor secretion from destruction of parietal cells.
- Malabsorption from Crohn's, coeliac disease.
- Dietary (vegans).
27
PERNICIOUS ANAEMIA
| What can pernicious anaemia be associated with?
- Other autoimmune diseases.
| - Thyroid diseases.
28
PERNICIOUS ANAEMIA
| What is the clinical presentation of pernicious anaemia?
```
Anaemia...
- Fatigue.
- Lethargy.
- Syncope.
- Headache.
- Pallor.
B12 deficiency...
- Neurological problems (irritability, depression, psychosis).
- Glossitis (beefy-red sore tongue).
```
29
PERNICIOUS ANAEMIA
| What are the differentials for pernicious anaemia?
Other causes of macrocytic anaemia...
- Alcohol.
- Folate-deficiency anaemia.
30
PERNICIOUS ANAEMIA
| What are the investigations for pernicious anaemia?
```
Bloods...
- Low Hb, low WCC (+ platelets if severe).
- Serum B12 decreased.
Serum parietal cells autoantibodies.
Blood film...
- Macrocytic erythrocytes.
- Hypersegmented neutrophil nuclei.
Bone marrow examination...
- Megaloblasts (Developing RBCs with delayed nuclear maturation relative to that of the cytoplasm).
```
31
PERNICIOUS ANAEMIA
| What is the treatment for pernicious anaemia?
- Hydroxocobalamin (vitamin B12).
| - Do NOT give folic acid as this can aggravate neuropathy.
32
FOLATE-DEF ANAEMIA
| What is the pathophysiology of folate-deficiency anaemia?
- Folate deficiency can develop over 4 months of deficiency due to bodily reserves but eventually the insufficient folate causes macrocytic, megaloblastic anaemia.
33
FOLATE-DEF ANAEMIA
| What is the aetiology of folate-deficiency anaemia?
- Poor dietary intake – can be in combination with excessive utilisation/malabsorption of folate.
34
FOLATE-DEF ANAEMIA
| What is the clinical presentation of folate-deficiency anaemia?
```
Anaemia...
- Fatigue.
- Lethargy.
- Syncope.
- Headache.
- Pallor.
Folate deficiency...
- No neuropathy (differentiates from pernicious anaemia).
```
35
FOLATE-DEF ANAEMIA
| What are the investigations for folate-deficiency anaemia?
```
Bloods...
- FBC = red cell folate low, serum folate low.
Blood film...
- Macrocytic erythrocytes.
Bone marrow examination...
- Megaloblasts present.
```
36
FOLATE-DEF ANAEMIA
| What is the treatment for folate-deficiency anaemia?
- Treat underlying cause, oral folic acid.
37
HAEMOLYTIC ANAEMIA
| What is the pathophysiology of haemolytic anaemia?
- Results from increased destruction of erythrocytes with a reduction of the circulating lifespan.
- There is compensatory increase in bone marrow activity with premature release of immature red cells (reticuloctytes).
38
HAEMOLYTIC ANAEMIA
| What is the aetiology of haemolytic anaemia?
Inherited...
- Red cell membrane defect (spherocytosis).
- Hb abnormalities (thalassaemia, sickle cell disease).
- Metabolic defects (G6PD, pyruvate kinase deficiency).
Acquired...
- Autoimmune.
- Mechanical destruction.
- Infections (malaria).
39
HAEMOLYTIC ANAEMIA
| What is the clinical presentation of haemolytic anaemia?
```
Anaemia...
- Fatigue.
- Lethargy.
- Syncope.
- Headache.
- Pallor.
Haemolytic...
- Jaundice.
- Gallstones.
- Leg ulcers.
```
40
SICKLE CELL ANAEMIA
| What is sickle cell anaemia and who is it most commonly seen in?
- AR disorder in which production of abnormal Hb results in vaso-occlusive crisis.
- People of African origin.
41
SICKLE CELL ANAEMIA
| How does sickle cell anaemia come about and what is the impact of this?
- Arises from an amino acid substitution (glutamine>valine) which leads to production of HbS rather than HbA.
42
SICKLE CELL ANAEMIA
| What is the pathophysiology of sickle cell anaemia?
- HbS polymerises when deoxygenated causing erythrocytes to deform, producing sickle cells which are fragile, haemolyse + occlude small vessels.
- Sickle cells lifespan is 5–10 days.
43
SICKLE CELL ANAEMIA
| What can be said about homozygotes and heterozygotes in sickle cell anaemia?
- Homozygotes have sickle-cell anaemia (HbSS).
- Heterozygotes have sickle-cell trait (HbAS) which causes no disability but may still experience symptomatic sickling in hypoxia (e.g. unpressurised aircraft, anaesthesia).
44
SICKLE CELL ANAEMIA
| What unique protective factor does sickle cell anaemia give?
- Protection from Falciparum malaria.
45
SICKLE CELL ANAEMIA
| What are the acute complications of sickle cell anaemia?
- Infections like parvovirus in children leads to decrease erythrocyte production + can cause dramatic drop in Hb.
- Strokes.
- Painful crisis.
46
SICKLE CELL ANAEMIA
| What are the chronic complications of sickle cell anaemia?
- Priapism in males.
- Splenic/hepatic sequestration (organs become engorged with erythrocytes leading to acute fall in Hb + rapid organ enlargement).
- Pain, swollen joints.
47
SICKLE CELL ANAEMIA
| When does sickle cell anaemia tend to manifest and why?
- 6 months of age.
| - Production of foetal Hb (Hb F) is normal + so the disease doesn't manifest until Hb F decreases to adult levels.
48
SICKLE CELL ANAEMIA
| What is the clinical presentation of sickle cell anaemia?
Vaso-occlusion...
- Early childhood = acute pain in hands + feet.
- Avascular necrosis of bone marrow.
- Adults = affects long bones, ribs, spine + pelvis.
- Avascular necrosis = shortened bone in children.
49
SICKLE CELL ANAEMIA
| Why don't patients with sickle cell anaemia tend to get anaemic symptoms?
Chronic haemolysis produces stable Hb level.
50
SICKLE CELL ANAEMIA
| What are the investigations for sickle cell anaemia?
Bloods...
- FBC shows low Hb, high reticulocyte count.
- Blood film shows sickled erythrocytes.
- Neonatal screening via heel prick test.
Diagnosis with Hb electrophoresis showing HbSS present + HbA absent.
51
SICKLE CELL ANAEMIA
| What is the treatment for sickle cell anaemia?
- Hydroxycarbamide prevents painful crises.
- Folic acid, fluids.
- Bone marrow transplant can be curative.
52
THALASSAEMIA
| What are the thalassaemia's and where are they most common?
- Group of disorders arising from one or multiple gene defects, resulting in a reduced rate of production of ≥1 globin chains.
- Mediterranean, middle east.
53
THALASSAEMIA
| What is the difference between alpha + beta thalassaemia?
- Alpha = reduced alpha chain synthesis.
| - Beta = reduced beta chain synthesis.
54
THALASSAEMIA
| What is the pathophysiology of thalassaemia?
- Imbalanced glibin chain production leads to precipitation of globin chains within precursors (ineffective erythropoeisis) + erythrocytes (haemolysis).
- Get faulty production + immature destruction.
55
THALASSAEMIA
| What is the different classifications of beta-thalassaemia?
- Thalassaemia major.
- Thalassaemia intermedia.
- Thalassaemia carrier/heterozygote.
56
THALASSAEMIA
| What is the clinical presentation of beta-thalassaemia heterozygote and intermedia?
Thalassaemia heterozygote...
- Mild/absent anaemia, iron stores + ferritin normal.
Thalassaemia intermedia...
- Moderate anaemia
- Might be splenomegaly, bone abnormalities + gallstones.
57
THALASSAEMIA
| What is the clinical presentation of beta-thalassaemia major?
- 6–12m at presentation.
- Severe symptoms = failure to feed/thrive, crying, pale.
- Skull bossing + hepatosplenomegaly.
58
THALASSAEMIA
| What are the investigations for thalassaemia?
Bloods...
- FBC = low Hb, raised reticulocyte count.
- Blood film = hypochromic, microcytic anaemia, nucleated erythrocytes.
Diagnosis with Hb electrophoresis showing increase in Hb F + absent/reduced Hb A.
59
THALASSAEMIA
| What is the treatment for beta-thalassaemia major?
- Regular transfusion dependent.
- Splenectomy if hypersplenism persists.
- Folic acid supplements.
- Promote fitness + healthy diet.
60
THALASSAEMIA
| What is important in regards to the treatment of beta-thalassaemia major? How can this be addressed?
- Monitor iron levels as risk of iron overload from regular transfusions which can be deposited in organs like liver + spleen causing fibrosis.
- Iron chelation (desferrioxamine).
61
MEMBRANOPATHIES
| What is the pathophysiology of hereditary spherocytosis? How does this differ to elliptocytosis?
- There are structural protein losses leading to an unstable erythrocyte cell membrane.
- In elliptocytosis, the erythrocytes are elliptical in shape.
62
MEMBRANOPATHIES
| What inheritance pattern do membranopathies follow?
- AD.
63
MEMBRANOPATHIES
| What is the clinical presentation of membranopathies?
- Gallstones (excess bilirubin).
- Jaundice.
- Splenomegaly in childhood if severe.
64
MEMBRANOPATHIES
| What are the investigations of membranopathies?
```
FBC...
- Raised reticulocytes, low Hb.
Blood film...
- Spherocytes + reticulocytes.
- Serum bilirubin + urinary urobilinogen raised from haemolysis.
```
65
MEMBRANOPATHIES
| What is the treatment of membranopathies?
- Folic acid.
| - Splenectomy if severe.
66
ENZYMOPATHIES
| What are enzymopathies?
- Occur when there are enzyme deficiencies/mutations leading to shortened erythrocyte lifespan.
67
ENZYMOPATHIES
| Name 2 enzymopathies.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
| - Pyruvate kinase (PK) deficiency.
68
ENZYMOPATHIES
| What is the pathophysiology of G6PD deficiency?
- Shortened erythrocyte lifespan as G6PD protects cells against oxidative damage.
- X-linked inheritance.
- Precipitated by broad beans, infection + henna.
69
ENZYMOPATHIES
| What is the pathophysiology of PK deficiency?
- Reduced ATP causes reduced erythrocyte survival.
| - AR inheritance.
70
ENZYMOPATHIES
| What is the clinical presentation of enzymopathies?
- Haemolysis (± splenomegaly).
| - Jaundice (neonatal in PK deficiency).
71
ENZYMOPATHIES
| What are the investigations and treatments for enzymopathies?
- Enzyme assay.
- Blood film shows 'Bite + Blister' cells in G6PD deficiency.
- Folic acid, transfuse if necessary, avoid precipitants.
72
APLASTIC ANAEMIA
| What is the pathophysiology of aplastic anaemia?
- Pancytopenia (deficiency of all cell elements of blood) with hypocellularity of bone marrow – bone marrow failure.
- There is reduction in number of pluripotent stem cells together with a fault in those remaining/immune reaction against them so they are unable to repopulate the bone marrow.
73
APLASTIC ANAEMIA
| What is the aetiology of aplastic anaemia?
- Congenital.
- Idiopathic acquired.
- Cytotoxic drugs.
- Infections (EBV, HIV, TB).
74
APLASTIC ANAEMIA
| What is the clinical presentation of aplastic anaemia?
Bone marrow failure...
- Increased susceptibility to infection.
- Bruising + bleeding.
- Bleeding gums + epistaxis.
75
APLASTIC ANAEMIA
| What are the investigations for aplastic anaemia?
FBC...
- Pancytopenia with low/absent reticulocytes.
Bone marrow biopsy (from posterior iliac crest)...
- Hypocellular marrow with increased fat spaces.
76
APLASTIC ANAEMIA
| What are the treatments for aplastic anaemia?
- Remove causative agent.
- Bone marrow transplant.
- Blood/platelet transfusion.
- Immunosuppressive therapy.
77
DEEP VEIN THROMBOSIS
| What is the pathophysiology of DVT?
- Thrombus formation in a deep vein which has the potential of embolising + often flows up into the pulmonary circulation as a pulmonary embolism (major complication).
78
DEEP VEIN THROMBOSIS
| What are the risk factors for DVT?
- Surgery, immobility, leg fracture.
- Oral contraceptive pill, HRT, pregnancy.
- Genetic predisposition (inherited thrombophilia).
- Long haul flights/travel (rare).
79
DEEP VEIN THROMBOSIS
| What preventative measures can be taken to prevent DVTs in at risk individuals?
```
Mechanical...
- Hydration + early mobilisation.
- Compression stockings + foot pumps.
Medical...
- Low molecular weight heparin (LMWH).
```
80
DEEP VEIN THROMBOSIS
| What are the symptoms of DVT?
- Pain.
| - Swelling of legs.
81
DEEP VEIN THROMBOSIS
| What are the signs of DVT?
- Pitting oedema.
| - Calf warmth/tenderness/swelling/erythema.
82
DEEP VEIN THROMBOSIS
| What are the investigations for DVT?
- Well's score ≤ 1 = DVT unlikely.
- D-dimer used for negative exclusion value as if normal then DVT excluded, abnormal D-dimer ≠ diagnosis.
- Coagulation screen.
- Ultrasound compression scan as cannot compress vein = thrombus.
83
DEEP VEIN THROMBOSIS
| What is the treatment for DVT?
- LMWH.
- Oral warfarin with INR 2–3.
- DOAC like rivaroxaban.
84
ALL
| What is the pathophysiology of acute lymphoblastic leukaemia (ALL)?
- Malignancy of lympoid cells, affecting B- or T-lymphocyte cell lineages, arresting maturation + promoting uncontrolled proliferation of immature blast cells (myeloblasts + lymphoblasts).
85
ALL
| What is the aetiology of ALL? What is it associated with?
- Combination of genetic susceptibility + environmental trigger (chemicals like benzene compounds + alkylating agents).
- Ionising radiation during pregnancy, trisomy 21.
86
ALL
| What age group is most affected by ALL?
- 0–4y/o, most common childhood cancer, CNS involvement is common.
87
ALL
| What is the clinical presentation of ALL?
Bone marrow failure...
- Anaemia (low Hb) = dyspnoea, fatigue, pallor.
- Infection (low WCC) = fever + mouth ulcers.
- Bleeding (low platelets) = bleeding + bruising.
Tissue infiltration...
- Hepatosplenomegaly.
88
ALL
| What are the investigations for ALL?
FBC + blood film...
- Characteristic blast cells on blood film + bone marrow.
- WCC high, low platelets.
CXR + CT scan...
- Look for mediastinal + abdominal lymphadenopathy.
Lumbar puncture...
- Assess CNS involvement.
89
ALL
| What is the treatment for ALL?
Supportive...
- Blood/platelets transfusions, IV fluids (Hickman line), allopurinol to prevent tumour lysis syndrome, antibiotics.
Chemotherapy + bone marrow transplantation (induce remission + replace).
90
ALL
| What is tumour lysis syndrome?
Where vast amounts of cancer cells lysed at once leading to their products being released into the blood causing electrolyte disturbances.
- Give allopurinol.
91
CLL
| What is the pathophysiology of chronic lymphocytic leukaemia?
- Uncontrolled proliferation + progressive accumulation of a malignant clone of functionally incompetent mature B cells.
92
CLL
| What rule can be said about the progression of CLL?
1/3rd...
- Never progress (or regress).
- Slowly progress.
- Actively progress.
93
CLL
| What is the aetiology + epidemiology of CLL?
- Genetic, family Hx ALL/CLL.
| - Usually older presentation, M:F = 2:1
94
CLL
| What are the complications with CLL?
- Autoimmune haemolysis (can lead to anaemia).
- Infection due to hypogammaglobulinaemia (reduced IgG).
- Marrow failure.
- Death (incurable).
95
CLL
| What are the symptoms of CLL?
- Often asymptomatic presenting as a surprise finding on a routine FBC.
- When symptomatic 'B' symptoms... weight loss, sweats, anorexia.
96
CLL
| What are the signs of CLL?
- Enlarged, rubbery, non-tender lymph nodes.
| - Hepatosplenomegaly
97
CLL
| What are the investigations for CLL?
FBC + blood film...
- Anaemia from autoimmune haemolysis.
- Marrow infiltration showing reduced Hb, neutrophils + platelets.
- Lymphocytes increased.
- Smear cells (fragile cell damaged in preparation).
98
CLL
| What is the treatment for CLL?
- Watchful waiting.
- Supportive = blood/platelet transfusions, IV human Ig.
- Chemotherapy.
- Radiotherapy (helps lymphadenopathy + splenomegaly).
99
AML
| What is the pathophysiology of acute myeloid leukaemia (AML)?
- Neoplastic proliferation of blast cells derived from bone marrow myeloid (basophils, neutrophils + eosinophils) elements.
100
AML
| What are the associations + epidemiology with AML?
- Radiation + syndrome like trisomy 21, prior chemotherapy.
- Can transform from myelodysplasia (preceding haematological disorder).
- Most common acute leukaemia of adults, middle-age ish.
101
AML
| What is the clinical presentation of AML?
Bone marrow failure...
- Anaemia (low Hb) = dyspnoea, fatigue, pallor.
- Infection (low WCC) = fever + mouth ulcers.
- Bleeding (low platelets) = bleeding + bruising.
Tissue infiltration...
- Hepatosplenomegaly.
- Gum hyerptrophy.
102
AML
| What are the investigations for AML?
```
FBC...
- Low Hb, variable WCC, low platelets.
Peripheral blood film...
- Monoblasts + myeloblasts.
- Auer rods (crystals of coalesced granules).
- Occasional blast cells.
Bone marrow biopsy.
```
103
AML
| What is the treatment of AML?
- Supportive (blood/platelet transfusions, IV fluids, allopurinol to prevent tumour lysis syndrome, fertility cryopreservation).
- Low risk of failure = chemotherapy in intervals, intermediate = chemotherapy w/ bone marrow transplant, high = bone marrow transplant.
104
CML
| What is the pathophysiology of CML?
Uncontrolled clonal proliferation of myeloid cells, myeloproliferative disorder.
105
CML
| What is the epidemiology of CML?
- Middle ages, associated to exposure to ionising radiation.
106
CML
| What are the symptoms of CML?
- Weight loss.
- Tiredness.
- Fever + sweats.
- Abdominal discomfort (from splenomegaly).
107
CML
| What are the signs of CML?
- Massive splenomegaly.
- Hepatomegaly.
- Anaemia, bruising.
108
CML
| What are the investigations for CML?
- FBC = high WCC.
| - Cytogenetic analysis of blood or bone marrow = presence of Philadelphia chromosome.
109
CML
| What is the Philadelphia chromosome?
- Present in >80% cases, if not then worse prognosis.
- Reciprocal translocation between long arms of chromosomes 9 + 22, forming a fusion gene BCR-ABL with tyrosine kinase activity which alters cell growth.
110
CML
| What is the treatment for CML?
- Tyrosine kinase inhibitor = imatinib.
| - Stem cell transplantation can be curative.
111
HODGKIN'S LYMPHOMA
| What are lymphomas? How are they histologically divided?
- Disorders caused by malignant proliferations of lymphocytes which accumulate in the lymph nodes causing lymphadenopathy but may also be found in peripheral blood or infiltrate organs (blood, liver, spleen + bone marrow).
- Hodgkin's + Non-Hodgkin's.
112
HODGKIN'S LYMPHOMA
| What are the risk factors associated with Hodgkin's lymphoma?
- Affected sibling.
- Primary + secondary immunodeficiency.
- Infection (EBV).
- Autoimmune disorders like SLE.
113
HODGKIN'S LYMPHOMA
| What is the epidemiology of Hodgkin's lymphoma?
- M:F = 2:1
| - Bimodal distribution – peaks in young adults + then elderly.
114
HODGKIN'S LYMPHOMA
| What are the complications with Hodgkin's lymphoma?
- Infertility.
- Secondary malignancies.
- Psychological issues.
- Cardiomyopathy.
115
HODGKIN'S LYMPHOMA
| What are the symptoms of Hodgkin's lymphoma?
- Enlarged, non-tender, rubbery superficial lymph nodes (cervical mostly).
- Alcohol induced lymph node pain.
- Systemic B symptoms (weight loss, fever, night sweats).
- Compression syndromes.
116
HODGKIN'S LYMPHOMA
| What are the signs of Hodgkin's lymphoma?
- Painless lymphadenopathy.
- Hepato or splenomegaly.
- Anaemia.
117
HODGKIN'S LYMPHOMA
| What are the investigations for Hodgkin's lymphoma?
Bloods...
FBC, ESR, lactate dehydrogenase.
Bone marrow/lymph node biopsy...
- Reed-Sternberg cells (mirror-image nuclei, often bi/multinucleate).
CT/PET thorax, abdomen + pelvis for staging.
118
HODGKIN'S LYMPHOMA
| What is the staging system for Hodgkin's lymphoma?
Ann Arbor system...
I = confined to single lymph node region.
II = involvement of ≥2 nodal areas on same side of diaphragm.
III = involvement of nodal areas on both sides of diaphragm.
IV = spread beyond lymph nodes (bone marrow).
- Each stage either A (no systemic symptoms) or B (systemic symptoms).
119
HODGKIN'S LYMPHOMA
What is the treatment for...
i) Stage 1–2A
ii) Stage 2B–4
Hodgkin's lymphoma?
i) Short course combination chemotherapy followed by radiotherapy.
ii) Combination chemotherapy.
120
NON-HODGKIN'S LYMPHOMA
| What is the pathophysiology of non-Hodgkin's lymphoma? What are some types?
- Includes all lymphomas without Reed-Sternberg cells where around 80% is B-cell origin.
- Low grade = follicular lymphoma, high grade = diffuse large B-cell lymphoma, very high grade = Burkitt's lymphoma.
121
NON-HODGKIN'S LYMPHOMA
| What is the aetiology of non-Hodgkin's lymphoma?
- Immunodeficiency.
- Strong link with AIDS, EBV, autoimmune conditions like SLE, RA.
- H. pylori in MALT lymphoma
122
NON-HODGKIN'S LYMPHOMA
| What is the clinical presentation of non-Hodgkin's lymphoma?
- Systemic B symptoms (weight loss, fever, night sweats).
- Superficial lymphadenopathy.
- Extranodal disease (gut, skin).
123
NON-HODGKIN'S LYMPHOMA
| What are the investigations for non-Hodgkin's lymphoma?
```
Bloods...
- FBC, liver function tests, U+E.
Bone marrow/lymph node biopsy...
- No Reed-Sternberg cells.
CT/PET thorax, abdomen + pelvis for staging.
```
124
NON-HODGKIN'S LYMPHOMA
What is the treatment for...
i) low grade
ii) high grade
non-Hodgkin's lymphoma?
i) Asymptomatic = watchful waiting, symptomatic = radiotherapy, combination chemotherapy + monocloncal antibody.
ii) Early = short course chemotherapy + radiotherapy, advanced = combination chemotherapy + monoclonal antibodies.
- R-CHOP regimen used.
125
MYELOMA
| What is the pathophysiology of myeloma?
- Neoplastic proliferation of bone marrow plasma cells where the malignant plasma cells produce an excess of one type of Ig known as monoclonal paraprotein.
126
MYELOMA
| What is monoclonality and the consequence of this?
- Abnormal proliferation of a single clone of plasma cell leading to Ig secretion + causing organ dysfunctoin (esp. to kidney).
- IgG in 2/3rds, IgA in 1/3rds.
- Other Ig levels low resulting in immunoparesis = increased susceptibility to infections.
127
MYELOMA
| What is the aetiology of myeloma?
- Peak presentation 60y/o.
| - Often preceded by monoclonal gammopathy of undetermined significance (MGUS).
128
MYELOMA
| What is the clinical presentation of myeloma?
OLD CRAB.
- Old.
- Calcium elevated.
- Renal failure.
- Anaemia.
- Bone lytic lesions, back pain.
129
MYELOMA
| Why do you get renal failure in myeloma?
- Nephrotic syndrome due to raised Igs which precipitate + deposit in organs (esp. kidneys) resulting in thirst due to lack of water retention.
- Bence jones protein in urine.
130
MYELOMA
| Why do you get anaemia in myeloma?
- Plasma cell infiltration of bone marrow.
131
MYELOMA
| Why do you get bone lytic lesions in myeloma?
- Malignant plasma cells releasing factors which activate osteoclasts, inhibit osteoblasts.
132
MYELOMA
| What are the investigations for myeloma?
Bloods...
- FBC = normocytic normochromic anaemia.
- Films show Rouleaux formation (aggregations of erythrocytes).
X-ray, CT + MRI...
- Lytic 'punched-out' lesions = pepper-pot skukk, vertebral collapse, fractures/osteoporosis.
Urine electrophoresis...
- Monoclonal protein band.
133
MYELOMA
| What is the diagnostic criteria for myeloma?
- Monoclonal protein band in serum or urine.
- Increased plasma cells on bone marrow biopsy.
- Hypercalcaemia/renal failure/anaemia.
- Bone lesions on skeletal survery.
134
MYELOMA
| What is the treatment for myeloma?
- Watchful waiting.
- Supportive (blood transfusions, plasmapheresis), Abx.
- Analgesia + bisphosphonates for bone-related.
- Chemotherapy, radiotherapy.
135
MALARIA
| What is malaria and how is it spread?
- Infection by plasmodium transmitted by a mosquito.
- Bite by an infective mosquito causes sporozoites in the saliva to travel to the liver to mature, rupture + release merozoites into blood + invade erythrocytes.
- They undergo asexual reproduction to create sporozoites that a new mosquito can pick up + cycle.
136
MALARIA
| What is the aetiology of malaria and who are at risk?
- Plasmodium falciparum, can be vivax, malariae.
| - Poor, young, pregnant, recently travelled abroad.
137
MALARIA
| What is the clinical presentation of malaria?
- Consider anyone w/ fever who has visited malarial area.
- Non-specific = fever, headache, diarrhoea, cough, myalgia.
- Hepato + splenomegaly.
138
MALARIA
| What are the investigations for malaria?
- Microscopy of thick + thin blood swear with Giemsa stain.
- Rapid diagnostic test to detect parasite antigens.
- Pregnancy test.
139
MALARIA
| What is the treatment for malaria?
- Quinine + doxycycline.
140
POLYCYTHAEMIA RUBRA VERA
| What is the pathophysiology of polycythaemia rubra vera?
Arises from clonal expansion of haematopoietic myeloid stem cells in bone marrow leading to excessive erythrocytes, variable increase in platelets + myeloid cells.
141
POLYCYTHAEMIA RUBRA VERA
| What is the aetiology of polycythaemia rubra vera?
- Primary = over-reactive bone marrow.
| - Secondary = heavy smoking, lung disease, high altitude.
142
POLYCYTHAEMIA RUBRA VERA
| What mutation is seen in >95% of people with polycythaemia rubra vera and what does this cause?
- JAK2.
| - Erythroid progenitor offspring are unusual as do not need erythropoietin to avoid apoptosis.
143
POLYCYTHAEMIA RUBRA VERA
| What are the complications with polycythaemia rubra vera?
- Can transform into AML.
| - Thrombotic events.
144
POLYCYTHAEMIA RUBRA VERA
| What is the clinical presentation of polycythaemia rubra vera?
- Headaches, dizziness, visual disturbances (hyperviscosity).
- Splenomegaly.
145
POLYCYTHAEMIA RUBRA VERA
| What are the investigations for polycythaemia rubra vera?
- FBC = raised RCC, Hb, WBC, platelets + haematocrit.
- Reduced serum EPO.
- Genetic testing for JAK2.
146
POLYCYTHAEMIA RUBRA VERA
| What is the treatment for polycythaemia rubra vera?
- Keep haematocrit down via venesection, aspirin.
| - Treat underlying cause.
147
```
OVER-ANTICOAGULATION
What is the...
i) Pathophysiology.
ii) Aetiology.
iii) Clinical presentation.
iv) Treatment
```
for over-anticoagulation?
- Anticoagulation causes blood to inapproriately avoid clotting = bleeding, could bleed out to death.
- Iatrogenic (warfarin/heparin).
- Excessive bleeding.
- Warfarin = vitamin K (phytomenadione), heparin = protamine sulfate.
148
DIC
| What is the pathophysiology of disseminated intravascular coagulation (DIC)?
- Pathological activation of coagulation cascade which involves widespread generation of fibrin within blood vessel walls.
- Consumption of platelets + coagulation factors occur.
149
DIC
| What is the aetiology + clinical presentation of DIC?
- Sepsis, major trauma, malignancy.
| - Bleeding from unrelated sites (GI, resp, venepuncture), thrombotic events.
150
DIC
| What are the investigations + treatment for DIC?
```
Bloods...
- Elevated TT, PT + APTT.
- Decreased fibrinogen + platelets.
- Blood film = fragmented red cells.
Treatment...
- Underlying cause, platelet transfusion.
```
151
ITP
| What is the pathophysiology of immune thrombocytopenic purpura?
- Formation of antibodies against platelets, IgG, leading to thrombocytopenia.
- Spleen is site of autoantibody production + site of platelet phagocytosis.
152
ITP
| What is the aetiology + clinical presentation of ITP?
- Viral infection, malignancy, other autoimmune (SLE).
| - Rapid onset of purpura, easy bruising, epistaxis, menorrhagia.
153
ITP
| What are the investigations + treatment for ITP?
- Increased megakaryocytes in marrow, antiplatelet autoantibodies.
- FBC = isolated thrombocytopenia.
- Treatment = oral corticosteroids or last resort splenectomy.
154
TTP
| What is the pathophysiology of thrombotic thrombocytopenic purpura (TTP)?
Deficiency of ADAMTS13 protease which degrades vWF leading to large vWF multimers causing platelet aggregation + fibrin deposition in small vessels, autoantibody mediated against ADAMTS13.
155
TTP
| What is the clinical presentation of TTP?
- Florid purpura.
- AKI.
- Neurological symptoms (headache, seizure).
156
TTP
| What are the investigations and treatment for TTP?
- Raised lactate dehydrogenase levels (haemolysis).
| - Plasma exchange to remove autoantibodies, corticosteroids.
157
HEPARIN
| What is the mechanism and main clinical indications of heparin?
- Inhibits factor Xa + so thrombin formation in coagulation cascade by binding to anti-thrombin + increasing it's activity.
- DVT/PE treatment + prophylaxis, ACS.
158
HEPARIN
| What are the adverse effects + example of heparin?
- Bleeding.
| - Daltaparin.
159
WARFARIN
| What is the mechanism + main clinical indications of warfarin?
- Vitamin K antagonist, inhibits production of coagulation factors 2, 7, 9 + 10 and so prolongs PT.
- DVT/PE prophylaxis, embolic complications from AF/heart valve replacement.
160
WARFARIN
| What are the adverse effects + cautions with warfarin?
- Bleeding.
- Displaced in blood from carrier proteins by amiodarone which potentiates it = massive bleeding.
- INR (derived from PT) aim 2–3.
161
DOACS
| What are their mechanisms of action + main clinical indications? Give examples. What is the main adverse effects?
- Inhibits clotting factors 2 or 10, has a shorter half-life.
- Low-dose for extended thromboprophylaxis, treatment of AF + DVT/PE.
- Rivaroxaban, apixaban.
- Don't use in pregnancy as can anticoagulate foetus.
