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Haematology + Immunology > Pathophysiology > Flashcards

Pathophysiology Flashcards

1
Q

What is anaemia?

A

Reduction in RBC or their haemoglobin content due to blood loss, increased destruction, decreased production or defective production

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2
Q

Describe the pathophysiology of congenital anaemia

A

Genetic defect (usually autosomal recessive- asymptomatic in carrier state) + geographical variation in one of the erythrocytes components-
1. In membrane
2. In metabolic pathways (enzymes)
3. Haemoglobin
Abnormality of cell means it doesnt last the normal amount of time (120 days) in circulation- increased rate of haemolysis

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3
Q

Explain the defect in erythrocyte membrane which can lead to congenital anaemias. What is the common congenital condition that causes such a defect?

A

RBC membrane is composed of a lipid bilayer and skeletal proteins that maintain its shape. Mutation in any of these proteins (ankyrin, band 3, spectrin) results in change to RBC shape= increased haemolysis
Cause: Hereditary Spherocytosis

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4
Q

What is hereditary spherocytosis? Describe its pathophysiology, presentation and treatment.

A

Commonest congenital anaemia (autosomal dominant) which denature the main proteins of the erythrocyte membrane (ankyrin, band 3, alpha + beta spectrin, protein 4.2) resulting in spherical RBCs
S+S: Anaemia (inc haemolysis), Jaundice (inc bilirubin, esp in neonates), Splenomeagly (Inc work), Pigment Gallstones (due to inc bilirubin)
Treatment: Folic Acid (inc RBC turnover), transfusion (virus/ recurrence), splenectomy (recurrence)

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5
Q

What are the main congenital anaemic membrane disorders?

A
  1. Hereditary Spherocytosis (commonest)
  2. Hereditary Elliptoytosis
  3. Hereditary Pyropoikilocytosis
  4. South East Asian Ovalocytosis (asymptomatic)
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6
Q

Explain the defect in erythrocyte enzymes which can lead to congential anaemias. What is the common congential condition which causes this defect?

A

Glycolysis (provide energy) + Pentose Phosphate Shunt (protect from oxidative damage via G6PD enzyme- glutathione)
Cause: G6PD Deficency (reduced glutathione)

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7
Q

What is congenital G6DP Deficency? Describe its pathophysiology, presentation and treatment

A

X linked reduction (asymptomatic in females) in Glucose-6-phosphate dehydrogenase enzyme resulting in reduction of glutathione which protects RBCs from oxidative damage.
Results in blister + bite cells
S+S: Jaundice (neonatal), Splenomeagly (haemolysis in circulation + spleen), Pigment Gallstones (inc bilirubin), trigger (drug, broad bean/ infection) precipitated jaundice and anaemia
Treat: remove trigger and treat haemolytic anaemia if it occurs (02, transfusions)

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8
Q

Why is G6DP Deficency more common in areas with existing/ past malarial outbreaks?
What other triggers/ risk factors exist?

A

Confers protection against malaria
+ Infection (acute illness eg./ DKA), Broad Beans, Drugs (esp- anti-malarials, analgesics eg./ asprin, vit K analogues etc)
All trigger haemolysis in G6DP Deficency

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9
Q

What are the main congenital anaemic enzyme disorders?

A
  1. G6DP Deficency (commonest)

2. Pyruvate Kinase Deficency

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10
Q

Explain the defect in erythrocyte haemoglobin which can lead to congenital anaemias. What is the common congential condition that causes this affect?

A

Common in malaria endemic regions
Haemoglobin is made up of alpha and beta chains. You get 2 sets of alpha genes from each parent and 1 set of beta genes (1 from each parent). Therefore, abnormalities in B chains are of high incidence as can have a mutation in an alpha gene from each parent and still produce alpha chains/ if mutations in both copies from a parent then alpha gene can be replaced with gamma (foetal haem) or delta (HbA2)
NOTE: if lose both pairs of alpha genes- incompatible with life
Cause: Thalassaemia (absent chain), Sickle Cell (mutation)

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11
Q

What is sickle cell disease? Describe its pathophysiology, presentation and treatment

A

Point mutation in B chains (glutamine replaced by valine) creating a haemoglobin S. Under conditions of stress (hypoxia eg. renal bed) crystalises RBC changing its shape (irreversible)- unable to carry 02- haemolysis- endothelial activation, promotion of inflammation, coagulation activation, dysregulation of vasomotor tone (NO)= vaso-occlusion- multiorgan dysfunction
S+S= mental retardation/ dec concentration (brain infarcts), HYPOspelnic( atrophy due to infarcts)- immunocompromised, painful vaso-occlusions, chest crisis, stroke, chronic haemolytic anaemia, sequestion crisis
Management: Acute Events- hydration, 02, treat infection, analgesia (opiates + NSAIDS); blood transfusion, bone marrow transplant, hydroxycarbamide (inc foetal haem levels)

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12
Q

What is chest crisis? In what inherited condition is this commonly seen?

A

In Sickle Cell Anaemia
Sickling in lungs results in hypoxia- lack of oxgenation of arterial blood- more hypoxia etc
= Chest pain, fever, worsening hypoxia
Inv- See inflitrates on xray
Treat- Respiratory support, IV fluids, Antibiotics, Analgesia, Transfusion (exchange sickle blood for HbA) to get HbS <30%

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13
Q

What is painful crisis? In what hereditary condition is it commonly seen?

A

In sickle cell anaemia
Severe pain due to vaso-occlusions
Give analgesics, 02, hydration, antibiotics

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14
Q

What is the prophylactic management of sickle cell disease?

A

Vaccination
Penecillin (malarial) to avoid stress
Folic Acid

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15
Q

What is Thalassaemia? Explain its pathophysiology and the types that exist

A

Hereditary absence of globin chains- chain imbalance- chronic haemolysis + anaemia

  1. Homozygous alpha zero thalassaemia- no alpha genes (mutations in all 4 sets)= hydrops foetus (incompatible with life)
  2. Homozygous Beta Thalassaemia- Beta Thalassaemia Major, no beta chains (mutations from mum + dad), transfusion dependent
  3. Non- transfusion dependent thalassaemia (intermedia)- mixed, small mutations on either chain
  4. Thalassemia Minor- carrier state, mild anaemia but asymptomatic
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16
Q

What is Beta Thalassemia Major? Describe its pathophysiology, presentation and treatment

A

Hereditary loss of beta chains (via mutations from mum + dad). Can make foetal + HbA2 but these will fail to rise with maturity- transfusion dependent
S+S: severe anaemia presentation at 3-6 months; bone deformities (expansion of ineffective bone marrow); splenomeagly; growth retardation; expansion or cranial vault, maxillary sinuses + mandible.
Treat: 4-6 weekly, chronic transfusions + must give iron chelation therapy eg./ desferrioxamine to prevent iron loading (organ failure + severe diabetes), bone marrow transplant is curative

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17
Q

What is Sideroblastic Anaemia?

A

Hereditary dysfunction in mitochondrial aspect of haem synthesis

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18
Q

What are defects in cytoplasmic steps of haem synthesis called?

A

Porphyrias

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19
Q

What is the general presentation of a patient with anaemia?

A 
Can't get 02 to tissues-
Pallor/ Tiredness
Dizziness
Breathlessness/ chest pain
Ankle Swelling
\+ Cause:
1. Bleeding- menorrhagia, dyspepsia, PR bleeding
2. Malabsorption- Diarrhoea, weight loss
3. Jaundice
4. Splenomegaly/ Lymphadenopathy
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20
Q

Describe what tests can be used to measure red cell size and haemoglobin count

A
  1. Mean Cell Volume (MCV)

2. Mean Cell Haemoglobin (MCH)

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21
Q

What is Hypochromic Microcytic Anaemia? What is the most common cause of this? Therefore, what test is most appropriate?

A

Hypochromic- pale (less haem)
Microcytic (small cells)
Usually a result of an iron deficiency (less haem produced) so check serum ferritin.
NOTE: in young women/ menorrhagia then no need for serum ferritin
If low= iron deficiency
If normal/ inc= Thalassaemia, Secondary Anaemia, Hereditary Sideroblastic Anaemia

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22
Q

A pt present to surgery with tiredness and breathlessness. On examination they had an atrophic tongue, angular cheilitis and koilonychia. Their tests show Iron Deficiency Anaemia. What test was carried out? What are the main causes of this disease? How will you treat them?

A
  1. MCV + MCH- Hypochromic Microcytic Anaemia- Serum Ferritin
  2. Hx of bleeding (GI-Dyspepsia, Menorrhagia etc); Diet; Malabsorption (Coeliac, gastrectomy, colon carcinoma, gastritis); Pregnancy
  3. Correct deficiency (oral/IV iron)
    Correct Cause- diet, ulcer therapy, gynae interventions, surgery
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23
Q

What is Normochromic Normocytic Anaemia? What tests would you then carry out? What are the likely diagnoses’?

A

Right size and shape but not enough RBCs (MCV, MCH)
Check Reticulocyte Count (Marrow production)
If Normal/ Low (no compensation)= Secondary Anaemia, Hypoplasia, Marrow Infiltration (malignancy?)
If Increased (marrow compensating)= Acute Blood Loss/ Haemolysis, IV haemolysis (mechanical, severe infection, PET, HUS, TTP)

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24
Q

Why can there be a normal haemoglobin level in haemolytic anaemia?

A

Normal size and shape but not enough
There is accelerated haemolysis decreasing Hb levels + a compensation by bone marrow (in high Reticulocyte Count)
Hb levels don’t change due to balance between production and destruction of RBCs

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25
Q

List the main types of haemolytic anaemia. Are they extra or intra vascular?

A
  1. Congenital- hereditary spherocytosis; enzyme deficiency (G6PD/ Pyruvate); haemoglobinopathy
  2. Acquired, Extravascular, immune- Auto-immune haemolytic anaemia
  3. Acquired, Intravascular- Mechanical (eg./ heart valve), severe infection, PET, HUS, TTP
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26
Q

How can you tell the difference between immune mediated and non-immune mediated haemolytic anaemia? Why is this relevant? How do you further differentiate between different types of immune haemolysis?

A

Direct Antibody Test (DAGT)
Positive= Immune Mediated
Negative= non-immune mediated
If warm auto-antibody (only bind at warm temperatures)- autoimmune, drugs, virus’
If Cold Auto-antibody- Infections, lymphoma, CHAD
If alloantibody bound- transfusion reaction
Important as Immune causes tend to undergo extravascular haemolysis (RES) where’s non immune tend to be intravascular (in circulation)

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27
Q

What is an allo-antibody?

A

Antibodies made in response to pregnancy, transfusion, or transplantation targeted against a blood group antigen that is not present on the person’s red blood cells.

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28
Q

How can you determine is a pt is haemolysing?

A

FBC
Reticulocyte Count
Blood Film
Serum Bilirubin
Serum Haptoglobin (mops up prehaemoglobin, if working then low levels)
Urine (excess iron)
Direct Antiglobulin Test (Coombs) will tell mechanism

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29
Q

How do you treat haemolytic anaemia?

A

Support Marrow Function- folic acid
Determine + Correct cause- Autoimmune (immunosuppression via steroids); Stop Haemolysis (splenectomy); Non-Immune (IV) treat sepsis, leaky prosthetic valve, malignancy etc

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30
Q

What is macrocytic anaemia? What tests would you do to reach a diagnosis?

A

Large Cells
B12/Folate assay required
1. Deficiency- Megaloblastic eg./ pernicious anaemia, gastro/ileal disease, alcohol, drugs, hypothyroidism, myelodysplasia
2. Normal- Non-Megaloblastic eg./ Myelodysplasia, marrow infiltration, drugs

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31
Q

What is the cause of megaloblastic anaemia? What test proves this? Describe the symptomatology, causes and available treatment

A

B12/ folate deficiency, do B12/ folate assay.
Causes: Pernicous Anaemia (autoimmune, antibodies against intrinsic factor and parietal cells causing malabsorption of dietary B12, takes 1-2 years to develop symptoms can cause subacute degradation of cord); Gastric/ illegal disease; dietary; haemolysis; GI pathology (eg./ coeliac
Clinically: lemon yellow tinge
Treat: Replace Vit B12 (IM loading dose then 3 monthly), Oral folate

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32
Q

What is the difference between a thrombus and thromboembolism?

A

Thrombus- clot arising in the wrong place (arterial, venous, microvascular)
Thromboembolism- movement of clot along vessel eg./ DVT-PE

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33
Q

Depict Virkows triad and what is predisposes to

A

Factors increasing the risk of thrombus formation-

  1. Stasis eg./ bed rest, travel
  2. Hypercoaguability eg./ pregnancy, trauma
  3. Vessel Damage eg./ atherosclerosis
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34
Q

Describe the pathophysiology, risk factors, common sites and management of an ARTERIAL thrombus

A

Is a white clot (platelets + fibrin) resulting in ischaemia and infarction commonly in Coronary (MI, unstable angina), Cerebro(stroke, transient ischaemia), Peripheral (limb ischaemia) areas, secondary to atherosclerosis
RF: Increasing Age, Smoking, Sedentary Lifestyle, Hypertension, DM, Obesity, Hypercholestrolaemia.
Manage: Prophylaxis (lifestyle, treat risk factors); Acute Presentation (thrombolysis, antiplatet/sometimes anticoags)

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35
Q

Describe the pathophysiology, risk factors, common sites and management of an VENOUS thrombus

A

Is a red clot (red cells + fibrin) vascular occlusion due to stasis and hypercoagulability leading to venous back pressure and gradual onset of symptoms eg./ DVT, PE, Visceral, Intracranial, Superficial Thombophlebitis
RF: Increasing age, Immobility, Obesity, Pregnancy, FH, Surgery, Systemic Disease, Hormonal Therapy (COCP/HRT), Tissue Trauma
Investigations:D- Dimer, CT Pulmoary Angioram, V/Q Scan, Doppler US
Treat: Anticoags (LMWH, Warfrin, DOACs), Thrombolysis (if massive PE)

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36
Q

What systemic diseases can cause venous thromboembolisms?

A
  1. Cancer (+ treatment)
  2. Myeloproliferative Neiplasm
  3. Autoimmune Disease- IBD, Connective Tissue eg./ SLE, Antiphospholipid Syndrome (arterial + venous)
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37
Q

What systemic disease can cause arterial and venous thrombus?

A

Antiphospholipid Syndrome

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38
Q

What is heritable thrombophila? What are the common and rarer classifications? What is used to differentiate between these classifications? Screening?

A

Inherited predisposition to VENOUS thrombosis
All reduce naturally occurring anti-coagulants
Common: Factor V Leiden, Prothrombin G20210A
Rare: Antithrombin Deficiency, Protein C + S deficiencies
Genetic Testing used to differentiate
Screening limited to high risk hereditary thrombophilia as screening doesn’t change long term management

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39
Q

Describe the pathophysiology, risk factors, common sites and management of an VENOUS thrombus

A

Produced by platelets +/- fibrin and results in diffuse ischaemia (extremeties)
Critically unwell pts

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40
Q

What is DIC? When and why does it occur?

A

Diffuse Systemic Coagulation Activation
Activation of coagulation cascade- drive towards clotting + activation of fibrinolytic pathways producing increased breakdown and an aquired bleeding disorder
Occurs in septicaemia, malignancy and eclampsia (pregnancy) causing gangrene and organ failure (children lose fingers and toes)

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41
Q

Physiologically, what does wrong to result in a bleeding disorder? What is this called? How can you characterise the 3 pathological mechanisms in terms of where the bleeding occurs?

A

Haemorrhgaic Diathesis (quantitative/ qualitative abnormality resulting in an inhibition of function concerning platelets/ vWF/ Coagulation Factors results in a bleeding disorder

  1. Platelet and vWF abnormalities result in bleeds to surfaces- skin eg./ petechiae, bruising, mucosal, post surgical, epistaxis, purport, menorrhagia, GI etc)
  2. Coagulation Factor abnormality results in bleeds into muscles (haemotoma), joints (articular), head, CNS, peritoneum
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42
Q

Briefly outline the important questions to ask a patient presenting with a possible bleeding disorder

A
  1. Hx of bleeding- bruising, epistaxis, post surgical eg./ dental, circumcision, tonsillectomy, appendectomy, menorrhagia, PPH, post-trauma
  2. Severity- appropriate/inappropriate/ unprovoked response to bleeding
  3. Pattern- platelet + vWF or CF abnormality
  4. Congenital/ Acquired
  5. Mode of inheritance
43
Q

Describe the mode of inheritance of Haemophilia A + B, how it clinically presents, diagnosis and treatment

A

X Linked deficiency of F8 (A) + F9 (B) resulting in abnormal bleeding. Classified by level of CF activity-
<1%- severe
1-5%- moderate
5-30%- mild
Clinically presents with bleeding into weight bearing joints eg./ hyinge joints- knees + ankles (haemarthrosis); muscle haemotomas (calf + bicepts), CNS bleeding, retroperitoneal bleeding, post- surgical bleeding + muscle wasting/ atrophy distal to sites
Diagnosis: Clinical, Prolonged APTT, Normal PT, Reduced F8/9, Genetic analysis
Treat: Coagulation Factor replacement (8/9); Mild/ Moderate- DDAVP Injection (prophylactic); transexamic Acid.
In severe haemophilia emphasis on prophylaxis (DDAVP injection) to bring CF levels from <1% to moderate (1-5%) + splints, physiotherapy, analgesia, synovectomy, joint replacement

44
Q

A pt presents with a PMHx of inaporopriate bleeding post surgery and swelling of knees and ankles. What is their most likely diagnosis? What clinical complications can also occur in this disease?

A

Haemophilia A/B due to inapropriate bleeding post surgery and into hyginge joints. Check for +ve family Hx (X linked)
Test: Clotting Factor (<50%)
Complications can include- MSK- synovitis, chronic haemophilic arthropathy-chronic inflammation of joints requires replacement, Neurovascular Compression (compartment syndromes), other sequelae of bleeding eg./ stroke

45
Q

A 6 month old child presents to A+E with bleeding into joints, pain and inability to walk. What inherited condition must you rule out and how would you do this?

A

Haemophilia A/B

Clinically- bleeding into joint spaces, FH, Prolonged APTT, Normal PT, Reduced F8/9, Genetic Analysis

46
Q

DDAVP is use in the prophylactic treatment of haemophilia. When is it contraindicated?

A

In elderly due to MI risk and in children due to hyponatraemia (fits)

47
Q

Outline the 3 different types of von Willebrand Disease and what treatment is available

A

vWD is platelet type bleeding
Type 1- Quantitative deficency
T2- qualitative deficiency determined by the site of mutation in relation to vWF function
T3- Severe (complete) deficiency
Treat: vWF concentrate/ DDAVP; Tranexamic Acid, OCP

48
Q

Briefly list the acquired bleeding disorders

A
  1. Thrombocytopenia
  2. Liver Failure
  3. Renal Failure
  4. DIC
  5. Drugs- warfarin, Heparin, Asprin, Clopidogrel, Rivaroxiban etc etc
49
Q

Describe the pathology, presentation of a pt with thrombocytopenia

A

Either
1. Decreased Production (not making enough platelts)- marrow failure, aplasia, infiltration
2. Increased Consumption- Immune ITP, Non-Immune DIC (abnormal activation of coagulation), Hypersplenism (platelets stuck in big spleen)
S+S: Petechia, Ecchymosis (bleeding), mucosal bleeding, CNS bleeding (rare)

50
Q

What is Immune Thrombocytopenic Purpura (ITP)? What can cause it, how it is diagnosed and treated?

A

Acquired bleeding disorder when platelets are destroyed by an exaggerated immune response (decrease in normal clotting)
Associated with Infection (EBV, HIV), Lymphoma, Drug induced eg./ quinine
Normal WBC + RBC but low platelets (blood film)
Treat: Raise platelet count via Steriods + IV Immunoglobulin.
If develop chronic leave unless very low PC then give thrombopoietin analogues

51
Q

Briefly describe the livers role in promotion of bleeding and thrombus and what happens to tip this process causing an acquired bleeding disorder

A

Liver produces a variety of proteins- anti-coagulants + pro- coagulants at a balance. In liver disease this homeostatic balance is shifted (more likely to shift to bleeding or thrombosis)

52
Q

How can haemorrhagic diseases occur in newborns?

A

Immature coagulating systems in newborns + Vit K deficient diet resulting in fatal and incapacitating haemorrhage
Prevented by IM VIt K injection at birth

53
Q

What percent of human cancers have haematological origins? What sex is more commonly affected?

A

10% of all cancers are haematological malignancies

Commoner in males

54
Q

What is the most common childhood cancer?

A

Acute Lymphoblastic Leukemia

55
Q

Name the 2 different bone marrow malignancies that categorise each cell type

A

Myeloid Malignancies- Red Cells, Platelets, Granulocytes, Monocytes
Lymphoid- B + T Cell

56
Q

Describe the process’ in which a hematopoetic stem cells alters in terms of myeloid and lymphoid pathways producing malignancies

A
  1. Proliferation BUT blocked differentiation of myeloid cells resulting in accumulation of early myeloid progenitors (can’t mature)= Acute Myeloid Leukaemia with bone marrow full of useless blast cells and no end cells in blood.
  2. Profliferation PLUS differentiation of myeloid cells accumulating myeloid cells= myeloproliferative disease (like bone marrow in blood)
  3. Mutation drives disease phenotypes along lymphoid pathways. Proliferation BUT blocked differentiation= Acute Lymphoblastic Leukemia (commonest malignancy in childhood)
  4. Mutations occur in differentiated cells in secondary lymphoid organs- germinal centre of lymph nodes (Bcells), paracortec (Tcells)= mature lymphoid malignancies eg./ Multiple Myeloma, Lymphomas, Chronic Lymphocytic Leukemia
57
Q

Describe the difference between leukaemia and lymphoma

A

Describe situation of disease not pathology
In Blood + Bone Marrow= Leukemia
In Lymph/ solid tissue= Lymphoma eg./ commonest form of leukaemia is Chronic Lymphocytic Leukaemia but if presents in lymph then called small cell lymphatic lymphoma

58
Q

Briefly, describe the main difference between acute and chronic leukaemia with regards to-
Cell differentiation
State of Bone Marrow
Survival

A

In acute cells don’t differentiate/ are uniform under the microscope. They do in chronic.
In acute, the bone marrow fails. In chronic there is proliferation without bone marrow failure.
Acute is rapidly fatal if untreated whereas chronic are well for a long time.
Both are potentially curable

59
Q

What is the triad of bone marrow failure? Where is it seen?

A
  1. Anaemia
  2. Thrombocytopenic Bleeding (purport and mucosal membrane bleeding)
  3. Infection due to neutropenia (bacterial eg./ staph aureus cellulitis/fungal- chest x-ray, aspergillus can cause abscess’ in lungs and brain- CT)
    Seen in acute leukaemia (rapid onset- death)
60
Q

Where about is the rearrangement process for B cells? What pathology can occur here?

A

Naive B cell (in blood) encounters antigen, in germinal centre of lymph node B cell there is a rearrangement process to produce a memory cell.
Lymphoma can occur due to B cell mutations here can cannot be destroyed

61
Q

What are the clinical signs of a lymphoma? What are your next steps in a patient presenting with these?

A
  1. Nodal Disease- lymphadenopathy (swollen lymph nodes)
  2. Extranodal Disease +/- nodal involvement
  3. Systemic Symptoms (B)- fever, night sweats, wight loss, parities, fatigue
    Investigations: Biopsy (lymph node/ bone marrow), CT (tells where it is not what it is eg./ lymphoma vs leukaemia)
62
Q

A pt presents with a localised and painful lymphadenopathy. What is the most likely diagnosis?

A

Bacterial infection of draining site eg./ tender submandibular in tonsilitis

63
Q

A pt presents with a localised and painless lymphadenopathy. What is the most likely diagnosis?

A
  1. Rare infection eg./ TB
  2. Metastatic carcinoma from draining site- hard
  3. Lymphoma- rubbery
  4. Reactive no cause identified.
    Get biopsy to tell between mets and lymphoma
64
Q

A pt presents with a generalised, painful/ tender lymphadenopathy. What is the most likely diagnosis?

A

Viral Infection- EBV, CMV, Hep, HIV

65
Q

A pt presents with a generalised and painless lymphadenopathy. What is the most likely diagnosis?

A
  1. Lymphoma
  2. leukemia
  3. Connective Tissue Disease eg./ Sarcodosis
  4. Drugs
66
Q

What are the 2 subgroups of Acute leukaemia? What is the pathology of these 2 conditions? What defines an acute leukaemia?

A
  1. Acute myeloblastic leukaemia (AML)- is proliferation but not differentiation of myeloid cells.
  2. Acute lymphoblastic leukaemia (ALL)- is proliferation but not differentiation of lymphoid cells
    Both sets of cells don’t differentiate and fill bone marrow, pushing out normal cells, rendering it ineffective
67
Q

Describe the key clinical features in Acute Myeloid Leukaemia

A

Triad of bone marrow failure

  1. Anaemia (lack of RBC production as marrow populated by abnormal cells)
  2. Thrombocytopenic bleeding (purport and mucosal membrane bleeding) eg./ ecchymosis (confluent bruise)
  3. Infection due to low neutrophil count (bacterial/fungal)
68
Q

Briefly outline the pathology, presentation, essential investigations and treatment in Acute Myeloid Leukaemia

A

Pathology: multiplication not differentitation of myeloid cells in bone marrow
Presentation: Triad of bone marrow failure
Investigations: Blood count, blood film, bone marrow aspirate, cytogenetics from leukaemia blasts (diagnosis is >20%), Immunophenotyping of blasts, CSF (if symptoms eg./ CN palsy), targeted molecular genetics for associated acquired gene mutations (FLT3, NPM1, IDH)
Treatment: Supportive, Anti-Leukaemia Chemotherapy- Daunorubicin + Cytosine Arabinosdie results in aplastic bone marrow so give pluripotent stem cells/ allogenic (siblings/ donors) to repopulate marrow OR All-trans retinoic acid(ATRA) + arsenic trioxide (ATO) in low risk, is chemo free
NEW: targeted antibodies eg./ Gemtuzumab Ozogamicin + new delivery systems eg./ CPX- 351

69
Q

Briefly outline the pathology, presentation, investigations and treated of Chronic Myeloid Leukaemia

A

Multiplication and differentiation of myeloid cells due to Philadelphial chromosome- WCC Increases.
S+S: Anaemia (BMF- INC WCC + Viscosity- protective), Splenomegaly, Hypercatabolic- weight loss, Fundal Haemorrhage, Venous Congestion, Altered Consciousness, Respiratory Failure, Gout (high cell turnover)
Investigations: Blood Count (High WCC, High Platelets, High Myeloid, Anaemia (low Hb), Blood film shows differentiation and proliferation
Treat: Tyrosine Kinase Inhibitors (TKI) eg./ Imatinib if doesn’t work Dasatinib. Allogenic Transplantation (in younger pts/ TKI Failure)

70
Q

Explain why Fundal Haemorrhage and venous congestion are seen in chronic myeloid leukaemia

A

Failure of bone marrow and increase in differentiation and proliferation of myeloid cells results + supression of erythropoesis (protective anaemia against high WCC)- chemo;lytic/ spontatneous hyperleukostasis (tumour lysis syndrome) results of bursting of cells in the circulation (see inc in plasma urate)
Can result in altered conciousness and respiratory failure

71
Q

What chromosome is commonly seen in Chronic Myeloid Leukaemia? Where can it be picked up?

A

Philadelphia Chromosome t(9;22) see in bone marrow and blood cells
Also seen in Acute Lymphoblastic Leukaemia
Is a marker of poor prognosis

72
Q

Briefly, describe the features of a myelodysplastic syndrome and how it arises. Additionally., list the 3 classifications and common mutations involved

A

Acquired clonal disorder of bone marrow- Failure of bone marrow and increase in differentiation and proliferation of myeloid cells results resulting in bone marrow failure or AML
Commonly seen in old age
S+S: macrocytic anaemia + pancytopenia (like acute leukaemia)
Treat: Supportive/ stem cell transplantation
Types:
1. Polycythaemia Vera-JAK2V617F
2. Essential Thrombocythaemia- JAK + CALR
3. Idiopathic Myelofibrosis- JAK

73
Q

An elderly pt presents with plethoric faeces, splenomegaly and a history of stroke, venous and arterial thromboses.
On investigation they have a raised haemoglobin, haematocrit, WCC, Platelets, Uric Acid and a true increase in red cell mass when BV measured.
What kind of myelodysplastic syndrome are they most likely to have? How is this treated? And why is treatment urgent?

A

Polycythaemia due to JAK2V617F mutation- acquired proliferation and differentiation of myeloid cells.
Treat via venesection- aim to keep haematocrit <0.45 men, <0.43 women + aspirin, hydroxycarbamide may be used if phelobotomy doesn’t help or switch to Ruxolitinib (Jak2 inhibitor) if this fails and systemic symptoms (Itch, Headache, TIA etc)
If untreated scaring of the bone marrow (secondary myelofibrosis) thus producing Acute Myeloid Leukaemia

74
Q

What is a raised uric acid indicative of?

A

An increased cell turnover

75
Q

What is the haematocrit?

A

the ratio of the volume of red blood cells to the total volume of blood

76
Q

An elderly pt presents with a Hx of arterial and venous thrombosis, digital ischaemia, gout and headache with mild splenomegaly. On investigation, their blood count shows high levels of platelets. What myeloproliferative disease is this most likely? How would you treat it? What conditions can occur if the disease if allowed to progress?

A

Essential Thrombocytopenia (JAK2V617F/ CALR)
Treat with aspirin + hydroxycarbamide or anagrelide.
Can progress to myelofibrosis or AML

77
Q

Describe the pathology behind myeloma, its common clinical presentation, diagnosis + treatment

A

Abnormal neoplastic proliferation of a single clone of plasma/ lymphoplasmic cells leading to an increased production in a single type of immunoglobulin (paraprotein)
Peaks in the 7th decade
Commoner in black pop
S+S: Bone Disease (lytic lesions eg./ PPS, pathological fractures, cord compression, hypercalcaemia)- Bone pain that is not improving
Bone Marrow Failure- anaemia
Infections (hypogammaglobulinaemia)
Renal Failure (Ig blocks renal tubules)
Bleeding (hyperviscosity) + Cardiac Failure, Pulmonary Congestion, Confusion
Amyloidosis
Diagnosis: finding excess plasma in bone marrow (>10% bone marrow pop); type of paraprotein via monoclonal protein band in serum / urine electrophoresis (most commonly IgG); staging via albumin and beta-1-microglobulin; X-Ray of test, skull, pelvis
Treat: Chemo ( Proteasome Inhibitors, IMiDs, Monoclonal antibodies), Bisphophonate Therapy eg./ zoledronic acid (inhibit bone breakdown), Radiotherapy, Steroids, Surgery (decompress spinal chord, pin long bones), Autologous stem cell transplant

78
Q

What sign on X-ray is commonly associated with multiple myeloma?

A

Pepper Pot Skull

Also seen in hyperparathyroidism and hyperthyroidism

79
Q

Are paraproteins common?

A

Yes, especially in the elderly population.

Usually release to no disease pathology- Monoclonal Gammopathy of uncertain significance (MGUS)

80
Q

Describe the difference between an autologous and allogenic stem cell transplant and the reasons for their use

A

OWN stem cells- autologous
Donor stem cells- allogenic collected
High dose of chemotherapy (melphalan) to kill myeloma. Also kills healthy stem cells so give them back after chemo.
If autologous may have to give normal chemo (as transplanted cells rein fusing cancer).

81
Q

How are IgM paraproteins different in terms of clinical and disease presentation?

A

IgM cannot cause a myeloma but instead a low grade lymphoma is seen
Clinically- Bone Marrow Failure (anaemia, thrombocytopenia), lymphadenopathy, hepatosplenomeagly, B symptoms
Bone disease is rare

82
Q

What is amyloidosis? When does in commonly occur?

A 
Deposition of fibrillar protein. 
When caused by paraprotein/ light chain= AL Amyloid
Results In-
Nephrotic Syndrome
Cardiac Failure
Carpal Tunnel
Autonomic Neuropathy 
Cutaneous Infiltration
Treat via chemo
Seen in: Myeloma, Alzheimers, T2DM, Haemodialysis
83
Q

Describe the classification of lymphomas

A

Hodgkin (specific)
Non-Hodgkin (broad)- High Grade (most common, diffuse, large B cell, fast growing and aggressive) or Low grade (follicular, marginal zone, slow growing)
+ Acute and Chronic Lymphoblastic Leukaemia (rarely need treatment, asymptomatic)

84
Q

Describe the pathology, presentation, investigations and treatment concerting Acute Lymphoblastic Leukaemia (ALL)?

A

Neoplastic disorder of lymphoid cells (T+B)- uncontrolled proliferation of immature blast cells + environmental trigger (eg/ X-rays) which decreases RBC and platelet levels- Diagnosis made by >20% lymphoblasts in bone marrow
B cell lineage, Commoner in Kids (better prognosis)- 2/3w Hx of BMF/bone + joint pain
S+S: Anaemic (Breathless,pale) unusual bleeding eg./ retinal haemorrhages, night sweats, fever, easy bruising, infections if CNS- headaches, seizures etc
Treat: Standard- multiagent Chemotherapy- remission, consolidation-CNS prophylaxis (intrathecal)- 18mnth maintenance treatment
Stem cell transplant if high risk/ toxicity
Newer- Bispecific T cell engagers (BiTE Molecules), Chimeric Antigen Receptor T Cells (CAR) via healthy own/third party T cell harvesting and train up to kill leukaemia can cause cytokine release syndrome (fever, hypotension, dyspnoea) and neurotoxicity (confusion, headache, focal neurology, coma)

85
Q

Outline the type of blood count and fim you would expect to see in CML? What does the bone marrow itself look like?

A 
Count:
WBC- Very High
Hb- Low (protective anaemia)
MCV- Low
Platelets- Very High
Lymphocytes- Normal
Myeloid Cells- Very High
Like the bone marrow has moved into the blood
Film: Differentiation (lots of different types) but exaggerated (high number) 
BM: Hypercellular
86
Q

Describe the pathology, presentation, investigations and treatment of Chronic Lymphoblastic Leukaemia

A

Accumulation of mature B cells that have evaded programmed cell death -
Blood >5x109 lymphocytes
Bone Marrow >30% lymphocytes
Commonest Leukaemia
Often asymptomatic- BMF ( haemolytic anaemia, thrombocytopenia, hypogammaglobunaemia), lymphadenopathy, splenomegaly, fever, sweats
Treatment: only consider if symptomatic, progressive BMF, massive lymphadenopathy, systemic symptoms)
Cytotoxic Therapy eg./ Fludarabine, Monoclonal Antibodies eg./ Rituximab

87
Q

What scale is used to stage CLL? What other markers provide a poor prognosis?

A

SA- <3 lymph node areas= no life expectancy change
SB- 3+= 8 year survival
SC- 3+ + anaemia/ thrombocytopenia= 6 year survival
Other indicators of poor prognosis include-
Loss/ mutation of P53 (tumour suppressor)
Rapid lymphocyte doubling time (<12m)
Atypical lymphocyte morphology
CD 38+ expression

88
Q

Briefly describe the presentation, investigations and staging of lymphoma

A

Presents with lymphadenopathy (nodal, extranodal, systemic (B), bone marrow involvement
Assessment- staging via lymph node biopsy/CT Scan/ Bone marrow aspirate/ Trephine
S1- Localised to single node/ organ
S2- 2 or more regions on same side of diaphragm
S3- 2 or more regions above and below diaphragm
S4- Widespread, multiple organs +/- nodes

89
Q

What is Hodgkins Lymphoma? How is it different from Non-Hodgkins and how does it occur? How is it treated?

A

Reed- Sternberg Cells (mirror image nuclei) found- is a hodgkin cell surrounded by non- cancerous material
2 peaks of incidence- (15-35) + later life
Associated with EBV, familial, geographical
Treatment: Combination chemotherapy + Radiotherapy, monoclonal antibodies, immunotherapy, PET can be used to asses treatment response

90
Q

Briefly, describe non-hodgkins lymphoma, the 2 classes and how they are treated

A

All lymphomas without Reed- Stenberg Cells
Low Grade- Asymptomatic, responds to chemo, incurable
eg./ Follicular Lymphoma-
High Grade- Aggressive, fast growing, require combination chemo, can be cured
eg./ diffuse large B-cell lymphoma
Treat: Combination Chemo- anti-CD20 monoclonal antibody + chemo

91
Q

What supportive measures are in place to reduce the risk of sepsis in haematology?

A
  1. Prophylaxis- Antibiotics (ciprofloxacin), Antifungals (fluconazole), Antiviral (acyclovir), PJP (co-trimoxazole)
  2. Growth Factors eg./ G-CSF
  3. Stem Cell rescue/ transplant
  4. Protective Environment eg./ laminar flow rooms
  5. IV Ig Replacement eg./ retiximab
  6. Vaccine (NEVER live)
92
Q

How does neutropenia occur and why must it be treated?

A

Cause- marrow failure, immune destruction
Degree
<0.5 x109/L- significant risk
<0.2 x109/L- high risk

93
Q

What are the most common fugal infections in an immunocompromised pt? How are they treated?

A

Candida- thrush
Aspergillus- lung, liver, sinuses, brain (life threatening)
Treat via Fluconazole

94
Q

A pt presents with a fever (no localising signs), Rigors, pneumonia, cellulitis, UTI. What kind of sepsis do you think they have? Describe the treatment with specific reference to the antibiotic therapy

A

Neutropenic Sepsis

Single reading of >38.5 or 2 readings 1 hour apart of 38 + any localised symptoms eg./ Pneumonia, UTI, Cellulitis, Rigors
Sepsis 6
Antibiotics
1. Broad Spec- Tazocin + Gentamicin
Gram +ve= + vancomycin/ teicoplanin
If at 72hrs no response- Add antifungal eg./ Caspofungin

95
Q

What can cause an increase and decrease in neutrophil levels?

A

Neutrophilia- INC- Bacterial Infection, inflammation, myeloproliferative disorders, steroids, stress (trauma, surgery, burns etc)
Neutropenia- DEC- Viral Infection, Post- Chemo, Severe Sepsis, hypersplenism

96
Q

What can cause an increase and decrease in levels of lymphocytes?

A

Lymphoctosis- INC- Acute Viral Infections, Chronic Infection eg./Hep, syphilis, Leukaemias + lymphomas, EBV
Lymphopenia- DEC- steroid therapy, HIV, marrow infiltration, post chemo/ radiotherapy

97
Q

What can cause an increase in levels of eosinophils?

A

Drug reactions, allergies eg./ asthma, atopy, eczema parasitic infection

98
Q

When are monocyte levels commonly increased?

A

Chronic infection eg./ TB, malaria, protozoa

Acute Myeloid Leukaemia, Hodgkins Leukaemia

99
Q

When are basophil levels commonly increased?

A

myeloproliferative disease, IgE mediated hypersensitivity, inflammatory disorders eg./ rheumatoid arthritis

100
Q

What is the pathophysiology behind herediatary angioedema? How does it clinically present? In what cases is it an emergency and how is it treated?

A

C1- Inhibitor Deficiency (primary immunodeficiency)
Results in recurrent painless, non-pitting, non-purpuric, non-erythematous swellings of subcutaneous tissues, intestines and oropharynx
Emergency if swelling of pharynx/larynx/ acute abdopain
Treat: C1 inhibitor infusion/ FFP

101
Q

What is the pathophysiology behind 22q11 deletion (DiGeorge) syndrome? Describe how is present

A

Primary Immunodeficency (de novo mutation)
Causes developmental delay- learning difficulties, disability, behavioural, characteristic facial features (short forehead, Malaria flatness, protuberant ears, hooded eyes), hypoplasia of thymus- hypocalcaemia, psychiatric illness, structural abnormalities (eye, renal, skeletal, brain, GI), haematological disorders
1. Complete anomaly- DiGeroge + thymus aplasia (fatal <2yrs)
2. Atypical complete anomaly- Oligoclonal T cells, rash, lymphadenopathy
3. Typical complete DiGeorge anomaly- Low T-cell, no rash

102
Q

Premature Neonates have an immature immune system. What invasive fungal infection does this expose them to?

A

Invasive candidiasis

103
Q

Give 2 examples of primary immunodeficiencies and give the common treatment

A
  1. Symptomatic- treat infection

2 Treat cause- Ig substitution, Gene Therapy, Stem Cell Transplant, Thymus Transplant (DiGeorge)

104
Q

Broadly speaking, what are the 4 groups of primary immunodeficiencies?

A
  1. Phagocytic Disorders
  2. B-Cell Disorders
  3. T-Cell Disorders
  4. Combined Immunodeficiencies

Haematology + Immunology (2 decks)

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