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Year 5 -krish finess > HAEM: Systemic disease > Flashcards

HAEM: Systemic disease Flashcards

1
Q

What does a deficiency of FVIII cause?

A

Haemophilia A –> bleeding disorder

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2
Q

What does a deficiency of protein C cause?

A

Pro-thrombosis

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3
Q

What is the types of primary haematological disorders. Give examples of each.

A

1.Germline mutation/inherited

  • FIX e.g. FIX deficiency = haemophilia B
  • Erythrocytes e.g. beta globin chain deficiency causes beta-thalassaemia

2.Somatic/acquired

  • Erythrocytes - JAK2 V617F mutation in polycythaemia vera
  • Myeloid/granulocyte - BCR-ABL1 mutation in CML
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4
Q

What is the difference between a primary and secondary haematological disorder?

A

Secondary are changes in haematological parameters secondary to a non-haematological disease e.g. cyanotic heart disease causing polycythaemia or excess FVIII in inflammatory responses

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5
Q

What does VHL gene mutation cause?

A

Chuvash polycythaemia causing excess erythrocytes

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6
Q

When are soluble haematological components increased?

A

in inflammation - this increases thrombosis

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7
Q

When are erythrocytes raised/reduced?

A

Raised:

  • EPO secreting tumour
  • Altitude
  • Hypoxia

Reduced:

  • BM infiltration
  • Deficiency disease e.g. B12 or Fe
  • Shortened survival in haemolytic anaemia
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8
Q

When are platelets raised/reduced?

A

Raised:

  • bleeding
  • inflammation
  • splenectomy

Reduced:

  • BM infiltration
  • Deficiency disease e.g. B12
  • Shortened survival e.g. ITP, TTP
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9
Q

When are leukocytes raised/reduced?

A

Raised:

  • Inflammation
  • Infection
  • Corticosteroids

Reduced:

  • BM infiltration
  • Deficiency disease e.g. B12
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10
Q

List 4 types of anaemia.

A
  1. Iron deficiency
  2. Autoimmune haemolytic
  3. Microangiopathic
  4. Leucoerythroblastic
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11
Q

What are the laboratory findings in Fe deficiency anaemia?

A
  1. Microcytic
  2. hypochronic
  3. Reduced ferritin
  4. Reduced TF saturation
  5. Raised TIBC
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12
Q

Which cancers can cause occult blood loss causing Fe deficiency anaemia?

A
  1. GI cancers - gastric, colorectal
  2. Urinary tract cancers (less common - renal cell carcinoma, bladder

NB: Fe deficiency is bleeding until proven otherwise

  • Menorrhagia in pre-menopausal women
  • GI blood loss in men and post-menopausal women
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13
Q

What is leucoerythroblastic anaemia? Why is it important?

A
  • Red and white cell precursor anaemia of variable degree
  • Usually the first manifestation of a bone marrow malignancy – breakdown in barrier from immature cells leaving the bone marrow
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14
Q

What is the morphology of a leucoerythroblastic anaemia on peripheral blood film?

A
  • Teardrop RBCs – aniso and poikilocytosis
  • Nucleated (normal in BM but should lose nucleus before they leave) RBCs (left purple cell)
  • Immature myeloid cells (right purple cell)
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15
Q

What are 3 causes of a leucoerythroblastic film?

A
  1. Malignant – haematological (leukaemia/lymphoma/myeloma) or non-haematological (metastatic/breast/bronchus/prostate)
  2. Severe infection e.g. miliary TB or severe fungal infection
  3. Myelofibrosis
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16
Q

Define haemolytic anaemia.

A

Shortened RBC survival

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17
Q

What are the common lab features of all haemolytic anaemias? Which liver associated proteins are raised?

A
  • Anaemia – may be compensated
  • Reticulocytosis – immature red cell production in an attempt to compensate for some short cell survival
  • Unconjugated bilirubin raised i.e. pre-hepatic
  • LDH raised – intracellular enzyme released as a result of cell content release due to lysis
  • Haptoglobins reduced
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18
Q

How are haemolytic anaemias classified?

A
  1. Inherited
  2. Acquired
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19
Q

Give 3 examples of inherited haemolytic anaemias.

A

Inherited = defects of the red cell /germline DNA mutation

  • Membrane e.g. hereditary spherocytosis
  • Cytoplasm/enzyme e.g. G6PD deficiency
  • Haemoglobin e.g. SCD (structural) or thalassemia (quantitative)
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20
Q

Give 2 types of acquired haemolytic anaemias.

A

Acquired = RBC is healthy but is due to defects in the environment where the RBC finds itself

  • (1) Immune-mediated (DAT aka Coombs positive)
  • (2) Non-immune mediated (DAT -ve)
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21
Q

What are the two types of immune-mediated haemolytic anaemia?

A
  1. Warm AIHA - IgG , extravascular haemolysis
  2. Cold AIHA - IgM (or IgG), intravascular haemolysis
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22
Q

List some causes of warm and cold AIHA.

A
  • Warm - lymphoma, CLL, drug allergy, SLE, idiopathic
  • Cold - M. pneumoniae, EBV, CMV
23
Q

What are the laboratory findings in immune mediated haemolytic anaemia?

A
  1. DAT positive (direct antglobulin/Coomb’s test)
  2. Spherocytes (but not hereditary spherocytosis)
  3. Agglutination
24
Q

Which conditions are associated with immune-mediated haemolytic anaemia?

A
  1. Malignancy e.g. lymphoma or CLL
  2. Auto immune e.g. SLE
  3. Infection e.g. mycoplasma
  4. Idiopathic
25
Q

Describe the principles of the Coomb’s test.

A

Two types:

  1. Direct - tests for antibodies or complement on the surface of RBC e.g. in AIHA
  2. Indirect - tests for antibodies in the serum e.g. in pre-natal antibody screen

Positive test = agglutination

26
Q

Give 3 examples of non-immune mediated haemolytic anaemias.

A
  1. Malaria (and other infections)
  2. Micro-angiopathic haemolytic anaemia (MAHA) e.g. due to HUS or underlying adenocarcinoma
  3. Paroxysmal nocturnal haemoglobinuria (Ham’s test +ve)
27
Q

What are the laboratory features of non-immune mediated acquired haemolytic anaemia?

A
  • DAT negative
  • RBC fragments (schistocytes)
  • thrombocytopenia
  • hereditary spherocytosis (spherocytes with a negative Coomb’s test)
28
Q

Why does malaria cause acquired haemolytic anaemia?

A

Parasite enters RBC and shortens RBC survival

29
Q

List 3 causes of MAHA.

A
  1. Adenocarcinoma
  2. HUS e.g. E coli 0157
  3. TPP
30
Q

How does adenocarcinoma cause MAHA?

A
  • Underlying adenocarcinoma releases granules into circulation
  • These are pro-coagulant and activate the coagulation cascade
  • Platelet activation, fibrin deposition, degradation
  • Red cell fragmentation due to low-grade DIC
  • Bleeding (low platelet and coagulation factor deficiency)
31
Q

What is the triad of haemolytic uraemic syndrome?

A
  • MAHA
  • thrombocytopenia
  • AKI
32
Q

What is the pentad of thrombotic thrombocytopenia purpura? (TTP) What is the treatment?

A
  1. MAHA
  2. Thrombocytopenia
  3. AKI
  4. Neurological impairment
  5. Fever

Tx: plasma exchange

  • Autoimmune; ADAMTS13 mutation –> deficiency in VWF cleaving protease
  • High VWF acts like cheese wire in blood vessels
33
Q

What % myeloblasts is abnormal in BM?

A

>5% myeloblasts is abnormal in BM

34
Q

List 5 causes of neutrophilia.

A
  • Corticosteroids
  • Underlying neoplasia
  • Tissue inflammation à colitis or pancreatitis
  • Myeloproliferative or leukemic disorders
  • PYOGENIC INFECTION (most likely)
35
Q

List 3 infections that do not produce a neutrophilia.

A
  • Brucella
  • Typhoid
  • Viral infections
36
Q

What are the causes of abnormalities in neutrophils? Describe the profiles of how to differentiate these.

A

Reactive /infection - neutrophilia, toxic granulation +no immature cells

Malignant (massively raised neutrophils)

  • CML - neutrophilia/basophilia + immature cells (myelocytes) + splenomegaly
  • AML - neutropenia + myeloblasts
37
Q

What are the causes of eosinophilia? Describe these.

A

Reactive

  1. Parasitic infection
  2. Allergic diseases –> asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
  3. Underlying neoplasms esp. Hodgkin’s, T-cell NHL
  4. Drugs e.g. reaction erythema multiform

Chronic eosinophilic leukaemia

  1. Eosinophils part of “clone”
  2. FIP1L1-PDGFRa fusion gene
38
Q

What are the causes of monocytosis?

A

(rare, seen in some chronic infections and primary haematological disorders)

  • Bacterial: TB, brucella, typhoid
  • Viral: CMV, varicella zoster
  • Sarcoidosis
  • Chronic myelomonocytic leukaemia (CMML, myelodysplastic syndrome)
39
Q

List some causes of reactive lymphocytosis.

A
  • EBV, CMV, Toxoplasma
  • Infectious hepatitis, rubella, herpes infections
  • Autoimmune disorder
  • Sarcoidosis

High WCC

40
Q

List some causes of reactive lymphopenia.

A

Lymphopenia [LOW WCC]

  • HIV
  • Auto immune disorders
  • Inherited immune deficiency syndromes
  • Drugs (chemotherapy)
41
Q

How can you evaluate whether the lymphocytosis is normal or abnormal using a blood film?

A

Look at morphology:

Mature lymphocytes (PB)

  • Reactive/atypical lymphocytes (IM)
  • Small lymphocytes and smear cells (CLL/NHL)

Immature lymphoid cells in PB

  • Lymphoblasts (ALL)
42
Q

How do you determine clonality in B-cell lymphocytosis? What is the difference between reactive and malignant lymphocytosis?

A

Use light chain restriction

Reactive = POLYCLONAL - kappa:lambda 60:40

Malignant = MONOCLONAL - kappa only or lambda only e.g. 99:1

43
Q

What are the 4 stages that a tissue biopsy undergoes to establish a diagnosis?

A

See image.

Morphology - assess if mature/immature, small or large, if invasive or not.

Immunophenotype - assess if myeloid or lymphoid and if T or B cells, including stage of maturation.

Cytogenetics - check for philadelphia chromosome, prognostic info (e.g. 17p in CLL), translocations (e.g. t(8;14) in Burkitt’s)

Molecular genetics - check for JAK2 mutation in PV, BCR-ABL cDNA deetction and quantification

44
Q

Where would you see:

  1. Primitive lymphoid blast cells expressing B cell marker?
  2. Mature lymphoid cells expressing T cell antigens and involving skin?
  3. Mature erythrocytes with JAK2 mutation?
A
  1. Primitive lymphoid blast cells expressing B cell marker = B cell Acute lymphoid leukaemia
  2. Mature lymphoid cells expressing T cell antigens and involving skin = cutaneous T cell lymphoma
  3. Mature erythrocytes with JAK2 mutation = polycythaemia vera
45
Q

What are the 3 types of mutations causing leukaemia and lymphoma?

A
46
Q

Give an example of conditions caused by the 3 types of mutations in leukaemias and lymphomas.

A
  1. Cellular proliferation (type 1) - BCR-ABL CML, JAK2 in MPD
  2. Impair/block cellular differentiation (type 2) - PML PARA in acute promyelocytic leukaemia
  3. Prolong cell survival (anti-apoptosis) - BCL2 and follicular lymphoma
47
Q

Compare the morphology seen in myeloproliferative neoplasm (chronic) to acute myeloid leukaemia (acute).

A

Chronic - normal differentiation, just a lot of cells

Acute - not differentiated i.e. many blasts

48
Q

What is the morphology and immunophenotype of B-cell lymphoblastic lymphoma? (3)

A
  • TdT +ve (indicates immature** cells; used in **VDJ rearrangement)
  • CD19 +ve (indicates B-cell lineage)
  • Surface Ig -ve (abnormal)
49
Q

What is the morphology and immunophenotype seen in multiple myeloma? (3)

A
  • TdT -ve (normal)
  • Surface Ig +ve (normal)
  • CD138 +ve (abnormal)
50
Q

What is the precise classification of haematological cancers used for generally?

A
  1. Predict likely course
  2. Choose appropriate treatment
51
Q

What do the complications of leukaemias and lymphomas generally relate to?

A
  • Lympho-haemopoietic failure (a dispersed organ)
    • Bone marrow: anaemia, infection (neutrophils) bleeding (platelets)
    • Immune system: recurrent infection
  • Excess of malignant cells
    • Erythrocytes (polycythaemia): impair blood flow to lead to stroke or TIA
    • Enlarged lymph nodes (lymphoma) compress structures, bowel, vena cava, ureters, bronchus
  • Impaired organ function
    • CNS lymphoma
    • Skin lymphoma
  • Other
52
Q

What is the explanation for this anaemia?

  1. IDA
  2. Anaemia of chronic disease
  3. BM mets from breast Ca
  4. MAHA
  5. AIHA
A

BM mets from breast Ca

  1. IDA
    • would not expect jaundice
    • would not give nucleated red cells in PB
  2. Anaemia of chronic disease
  3. BM mets from breast Ca
  4. MAHA
    • Not get leucoerythroblastic problems in blood as BM is healthy
  5. AIHA
    • AIHA is DAT-positive
53
Q

What is the likely diagnosis?

  1. B-cell ALL
  2. Mature B cell lymphoproliferative disorder
  3. Infectious mononucleosis
  4. T-cell acute leukaemic lymphoma
A
  • B cell acute lymphoblastic leukaemia
  • Mature B cell lymphoproliferative disorder (e.g. CLL)
    • No abnormal cells in the blood (all mature cells)
  • Infectious mononucleosis (e.g. EBV)
    • IgG serology is historical (past infection), IgM is current
    • Would expect 60/40 proliferation of Kappa/Lambda
  • T cell acute leukemic lymphoma

Year 5 -krish finess (55 decks)

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