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Look over this nice picture of blood cells
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Define anaemia + the different types
Anaemia = Hb <125g/dL
Microcytic -> low MCV -> defective haemoglobinisation
Macrocytic -> MCV >100 -> Defective DNA synthesis
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What are the causes of Microcytic anaemia?
TAILS
- Thalassaemia
- Anaemia of Chronic disease
- IDA
- Lead Poisoning
- Sideroblastic anaemia
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For IDA give;
-3 CF
-2 causes
-Ix
-Mx
CF
Spooned nails, angular stomatitis, atrophic glossitis [pale & painless], Oesophageal web [Plummer-Vinson syndrome]
Causes;
- Blood loss -> GI until proven otherwise
- Malabsorption -> Gastric acid req for release, abs in small intestine [Coeliac]
- ^^Physiological demand -> pregnancy, infancy, puberty
Ix -> low Serum ferritin, TF saturation <16%
Mx -> Treat cause, Ferrous fumerate
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What are the investigation results of Anaemia of chronic disease?
- Film -> normocytic, normochromic, RBC rouleuax
- ^ESRN/^Serum ferritin
- Total iron binding capacity = low
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Breifly outline B-Thalassaemia
- AR inherited disorder of globin genes [missing one]
- CF -> dyserythropoeisis, hair on end skull XR, anaemia + spleenomegaly
- Mx -> Blood transfusion + chelation therapy
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Give 4 causes of Marocytic anaemia?
Defective DNA synthesis;
- B12 deficit
- Folate deficit
- Cytotoxic drugs
- Myelodysplasia
Other;
- Marked reticulocytosis
- Elevated plasma lipid -> alcohol, pregnancy, hypothyroidism
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Ix of Macrocytic anaemia?
- Hb = low
- MCV >120
- Blood film
- SF = elevated
- Plasma LDH = elevated
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Outline B12 deficiency and give 3 causes?
B12 [Cobalamin]
bound to intrinsic factor -> abs in terminal ileum
Causes:
- Diet deficit -> strict vegans, rare
- Gastric factors -> impaired acid secretion
- Pernicious anaemia -> autoimmune destruction of parietal cells [no intrinsic factor]
- small bowel -> ceoliac, IBD, tapeworms
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Outline folate deficiency and causes?
Required for DNA synthesis
Causes:
- diet -> poor green leafy vegetables
- Malabsorption -> Coeliac diasease
- ^^demand state -> pregnancy, cell proliferation
- Drugs -> phenytoin, OCP, MTX [only worsen existing deficit]
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Outline the congenital anc acquired causes of haemolytic anaemia. Give 2 for each.
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What are the FBC + U+E + urinary features of haemolysis?
- Low Hb
- ^bilirubin
- ^LDH
- ^reticulocytes
- ^Urinary bilinogen
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Outline the causes Ix + Mx of warm type AHA?
IgG, middle aged females
Causes -> Idiopathic, NHL, CLL, Methyldopa, pen
Ix -> features of haemolysis, Direct Coombs may NOT be +ve
Mx -> treat underlying disease
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Outline Cold AHA
IgM binds to RBC in cold condtitions
Causes: Idiopathic, old people w B cell lymphoma
Ix -> blood film, cold agglutinins
Mx -> Keep warm
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Outline the Direct coombs test [Direct Antiglobulin test] and its uses
DAT = Ab directly bound to RBC
ELISA -> Monoclonal Ab for Fc-R -> agglutination = positive
For;
- AHA
- HDN
- Transfusion reaction
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Outline indirect coombs test?
Ab in plasma -> crossmathing of blood
For;
- Pre-transfusion screening
- Pregnancy screening for risk of HDN
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Draw the clotting cascade;
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What are;
-APTT
-PT
-INR
APTT = Activated partial thromboplastin time = intrinsic + common
PT = extrinsic pathway = warfarin etc
INR = PT but standardised
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Define Leukaemia
Malignant disorder of haematopoetic stem cell compartment, clinical course varies on type
- ALL Children get leukaemia
- AML mor common in adults
- CLL
- CML = philidelphia [9:22]
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In general what are the risk factors for Leukaemia?
- Ionising radiation -> radiotherapy, foetal XR
- Cytotoxic drugs -> Alkylating agents, Benzene
- Retrovirus -> rare T cell cause
- Genetic -> Philidelphia [9:22] Trisomy 21
- Immune -> hypogammaglobulinaemia
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Define acute leukaemia. Give 4 CF and 2 Ix
Acute Leukaemia -> proliferation of primitive stem cells [blasts]. BM infiltration + leak into circulation
CF
BM failure -> anaemia, bruising/bleeding, infection- Also;
- rapid onset, lethargy, bone pain, gum hyperplasia
Ix
- Bloods -> normocytic anaemia, severe thrombocytopaenia, neutropenia
- Film -> blasts -> ^^=worse prognosis
- BM trephine -> Hypercellular, ^^blasts [>20%], AML -> Auer rods
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What is the Mx of acute leukaemia? Include supportive Mx
Sepcific therapy -> chemo trial ASAP
- Aim -> eradicate abn clone + induce remission
- ^^morbidity -> bleeing, infections, hair loss, sterility
- AML -> ?BM transplant
- ALL -> beware CNS invasion -> vincristine [neuropathy]
Suppportive
- Anaemia -> BTx
- Bleeding -> PLTs + FFP
- Infection -> treat rapid, ?Granulocyte TFx
- Metabolic Problems -> monitor fluids + electrolytes
- Tumour lysis syndrome -> allopurinol stop hyperuricaemia
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Define CML, outline its natural history + give 3 CF
CML = chronic myeloid leukamia = Philadelphia [9:22]
Peak ~55yo
NH
- Chronic phase -> Tx responsive [imatinib] last ~5years
- Accelerated phase -> Mx = more dificult
- Blast crisis -> transforms into AML -> refractory
CF
- Symp -> vague, TATT, weight loss, SoB, abdo discomfort, lethargy, anorexia, sweating, bruising
- Sign -> Spleenomegaly, hepatomegaly
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Outline the Mx of CML
Chronic phase -> Imatinib
MoA = inhibit Tyrosine Kinase BCR ABL - reduces uncontrolled proliferation
Accelerated + blast crisis = dificult = ?hydroxycarbamide?
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Define CLL
Most common Leukaemia, M:F 2:1
- Incidentaloma
- anaemia, infections, painless lymphaedonpathy, systemic symptoms
Mx -> treat only if BM failure
Caveat;
- 11q22 deletion -> younger + more aggressive
- Richter transformation -> high grade B cell lymphoma [loss of p53]
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Define Lymphoma
Lymphoma = lymphoid neoplasm -> mainly of B-cells
2 types;
HL = Hodgkins Lymphoma -> reed-sternberg cell
- NHL -> Non-hodgkins -> High v low grade
- High = rapid division, over weeks, life threatening
- Low = Slow, present for months, indolent
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Define HL + give 3 CF
Hodgkins lymphoma
Characteristic Reed-Sterberg cell -> large bi-nucleate B-cell, sorrounded by reactive cells
CF
- Painless tubbery lymphadenopathy, generalised itch, ?alcohol induced LN pain
- B symptoms -> weight loss, drenching night sweats
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Outline the staging of HL
Ann-Arbor staging
- 1 - single LN site/ extranodal site
- 2 - 2/>2 LN - same side of diaphragm
- 3 - both sides of diaphragm +/- spleen +/- extralymphatic tissues
- 4 - diffuse involvement of lymphatic tissues
can be A or B [B if night sweats, weight loss]
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Outline the Ix and Tx of HL?
Ix
- Excision Biopsy = gold, but scarring + slow
- Core biopsy = little scar, easier
- FBC - ?anaemia -> BM invasion
- U+E -> eGFR
- LFT -> hepatic infiltration
- CXR -> Mediastinal Mass
- CT CAP -> TNM staging
Mx
- 1 or 2A = single node Rt
- Chemo = good 90% remission
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for NHL give CF + Mx
NHL = monoclonal expansion of B or T cells, Grading = most important
CF
- Widely disseminated at Pc
- Lymphadenopathy
- Weight loss, fever, night sweats, itching
- BM failure in Low grade
- Compression syndromes -> obstruction, Ascites, SVC obstruction MCSC
Mx
- Low grade -> symptomatic -> BM failure, compression syndromes
- Rituximab [Anti CD20 may be useful]
High grade -> Tx at Pc -> R-CHOP
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Give 3 causes of secondary BM failure [Aplastic anaemia]
Primary = rare
Secondary;
- Drugs -> cytotoxics, azathioprine, ABx
- Chemicals -> benzene, insecticides
- Viral hepatitis
- Pregnancy
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Define Myeloma and give 4CF
- malignant proliferation of plasma cells in marrow
- producing proteins -> Paraprotein [Ig of single heavy + light chains] Bence-Jones [Light chain only -> urine]
CF
- Lytic lesions of bone
- Bone pain
- Patho #
- Hypercalcaemia -> confusion, constipation, abdopain [stones, groans + psychiatric overtones]
- BM failure
- renal failure
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Mx of Myeloma
Immediate
- ^^fluids -> renal impairment + ^^Ca
- Analgesia
- Bisphosphonates
- Allopurinol -> urate neuropathy
- Plasmaphoresis
- Oncological Mx
- Chemo -> Thalidomide
- Rt -> bone pain
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