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Phase 2a Sam > HAEMATOLOGY > Flashcards

HAEMATOLOGY Flashcards

1
Q

Define Anaemia

A

Anaemia is a decrease in haemoglobin below reference range due to a reduction in cell mass or increased plasma volume

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2
Q

What can anaemia be subdivided into? What are the names of the categories?

A

Anaemia can be classified based on the Mean Corpuscular Volume (MCV).
It is based on the size of the red blood cell (the MCV)

  • Microcytic anaemia(low MCV indicating small RBCs)
  • Normocytic anaemia(normal MCV indicating normal sized RBCs)
  • Macrocytic anaemia(large MCV indicating large RBCs)
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3
Q

Nearly all types of anaemia present with the same symptoms and signs - What are the general symptoms for anaemia?

A

Symptoms:
* Fatigue
* Lethargy
* Dyspnoea – difficulty or laboured breathing
* Palpitations
* Headache

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4
Q

Nearly all types of anaemia present with the same symptoms and signs - What are the general signs for anaemia?

A

Signs
* Pale skin
* Pale mucous membranes – nose and eyelids
* Systolic flow murmur
* Tachycardia (compensatory to meet demand)

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5
Q

What does MCV stand for?

A

MCV stands for Mean Corpuscular Volume, which is a measure of the average size of red blood cells.

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6
Q

What does MCHC stand for?

A

MCHC stands for Mean Corpuscular Hemoglobin Concentration, which is a measure of the average amount of hemoglobin in a red blood cell.

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7
Q

What are the general consequences of anaemia?

A

Consequences of anaemia:
* Reduced O2 transport
* Tissue hypoxia
Compensatory changes:
○ Increased tissue perfusion
○ Increased O2 transfer to tissues
○ Increased RBC production

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8
Q

What are the main causes of Microcytic anaemia?

A

TAILS

Thalassaemias
Anaemia of chronic disease
Iron deficiency
Lead poinsoing
Sideroblastic anaemia

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9
Q

Normal physiology - what are the two types of Iron you get in your diet?
How are they absorbed from the duodenum?

A

Heme Iron - found in the Fe2+ state - can be directly absorbed into the duodenal cells, where it is broken down to release Fe2+ molecules.

non-heme iron found in the Fe3+, state. - needs to be converted into heme iron first, by enzymes activated by the stomach acid before it can be absorbed into the duodenum.

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10
Q

Normal Physiology - what does iron do in the structure of haemoglobin?

A

Haemoglobin is made of four haem molecules which contain iron.

The iron in haem is what binds to Oxygen, Tso each haemoglobin molecule can bind four molecules of oxygen.

In addition, iron is also an important part of proteins like myoglobin, which delivers and stores oxygen in muscles; and mitochondrial enzymes like cytochrome oxidase, which help generate ATP

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11
Q

Normal Physiology - what to Fe2+ molecules bind to in
a) Cells
b) for transport in the blood?

A

a) Fe2+ molecules then bind to a protein in the duodenal cells called ferritin, which temporarily stores the iron. Fe2+ binding to ferritin is how iron is stored in body cells

b) When needed to be transported in the blood, Fe2+ molecules are converted into Fe3+ molecules and carried by Transferrin

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12
Q

Anaemia caused by iron deficiency is the most common cause of anaemia worldwide. - What are some causes of it?

A
  • Vegetarian/ vegan diet -
  • H.pylori infection causes gastric ulcers and bleeding, and takes iron for itself
  • Pregnancy
  • Young children and adolescents
  • Inflammatory bowel disease/Coeliac impairs iron absorption
  • Certain drugs e.g. PPIs inhibit gastric acid, so non haem cannot be absorbed as it is not converted into haem iron
    Heavy menstruation
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13
Q

What happens to RBC production as a result of iron deficiency?

A

Leads to impaired haemoglobin production.

Since there’s not enough haemoglobin for a normal sized RBC, the bone marrow starts pumping out microcytic RBCs. - these have less Haemoglobin so are called hypochromic, as appear pale

Microcytic RBCs can’t carry enough oxygen to the tissues - hypoxia.
Hypoxia signals the bone marrow to increase RBC production.
The bone marrow goes into overdrive and pumps out incompletely formed RBCs.

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14
Q

What are some signs of iron deficiency anaemia?

A

○ Pallor
○ Conjunctival pallor
○ Glossitis inflammation of the tongue
○ Koilonychia (spoon-shaped nails)
○ Angular stomatitis sored on the corners of the mouth

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15
Q

What are some symptoms of iron deficiency anaemia?

A
  • Symptoms
    ○ Fatigue
    ○ Dyspnoea
    ○ Dizziness
    ○ Headache
    ○ Nausea
    ○ Bowel disturbance
    ○ Hairloss
    ○ Pica (abnormal cravings)
    ○ Possible exacerbation of cardiovascular co-morbidities causing angina, palpitations, and intermittent claudication.
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16
Q

What investigations would you do in suspected iron deficiency anaemia?

A

FBC blood count - look for low Hb, Low MCV, Low MCHC

Iron Studies - looking at:

  • serum iron,
  • serum ferritin,
  • total iron binding capacity,
  • transferrin saturation
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17
Q

What would someone with iron deficiency anaemia’s iron studies (serum iron, serum ferritin, total iron binding capacity, and transferrin saturation) look like?

A

○ Serum iron - low
○ Serum ferritin: low in anaemia
○ Total iron binding capacity: can be used as a marker for how much transferrin is in the blood. Increased in anaemia
○ Transferrin saturation: gives a good indication of the total iron in the body. Decreased in anaemia

Note - ferritin is an acute phase protein, so can also increase with inflammation (i.e. due to infection/malignancy)

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18
Q

What are the management options of iron deficiency anaemia?

A
  • Treat the underlying cause
  • Oral iron supplements: ferrous sulphate or ferrous fumarate
    ○ Side effects: constipation and black coloured stools, diarrhoea, nausea and dyspepsia/epigastric discomfort.
  • Iron infusion e.g. cosmofer
  • Blood transfusions may be needed in severe cases
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19
Q

What are some chronic disease that can lead to anaemia?
What type of anaemia?

A

Microcytic anaemia

Causes:
Crohn’s
Rheumatoid arthritis
TB
Systemic lupus erythematosus
Malignant disease
CKD

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20
Q

What is
a) Alpha Thalassaemia?
b) Beta Thalassaemia?

What is it’s genetic pattern, autosomal or sex linked, dominant or recessive?

A

Alpha Thalassaemia - genetic disorder where there’s a deficiency in production of the alpha globin chains of haemoglobin

Beta thalassaemia - is a genetic disorder where there’s a deficiency in the production of the β-globin chains of haemoglobin.

BOTH AUTOSOMAL RECESSIVE

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21
Q

Where is thalassaemia most present, and why?

Where is
a) Alpha Thalassaemia most present
b) Beta Thalassaemia most present

A
  • Thalassaemia is prevalent in areas with malaria as there is evidence to suggest that thalassaemic red cells provide immunity against the parasite.
  • Alpha thalassaemia: Asian and African descent
  • Beta thalassaemia: South-East Asian, Mediterranean, and Middle Eastern descent
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22
Q

Alpha thalassaemia - How many alleles, are responsible for alpha chain synthesis?
What does someone with one gene deletion experience?
What would someone with 2 gene deletions experience?

A

4 alleles, on chromosome 16

One gene deletion does not cause symptoms of alpha thalassaemia.
2 gene deletion - mildly anaemic with near-normal haemoglobin electrophoresis.

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23
Q

Alpha thalassaemia -
What would someone with 3 gene deletions experience, what do the beta chains form?

A

3 gene deletions are unable to form alpha chains. The beta chains form tetramers (HbH), which damage erythrocytes causing moderate to severe disease

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24
Q

Alpha thalassaemia -
What would someone with 4 gene deletions experience, what do the beta chains form?

A

4 gene deletions die in utero because the gamma chains form tetramers (Hb Barts), which cannot carry oxygen efficiently

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25
Q

What are some signs of alpha thalassaemia?

A

Patients with alpha thalassaemia trait are usually asymptomatic. Clinical features of HbH disease are highly variable and generally develop in the first years of life

  • Signs
    • Pallor: due to anaemia
    • Jaundice: due to unconjugated bilirubin
    • Chipmunk facies: compensatory extramedullary hematopoiesis in the skull causes marrow expansion
    • Hepatosplenomegaly
    • Failure to thrive
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26
Q

What are some symptoms of alpha thalassaemia?

A
  • Shortness of breath: due to anaemia
  • Palpitations: due to anaemia
  • Fatigue: due to anaemia
  • Swollen abdomen: due to hepatosplenomegaly
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27
Q

Beta Thalassaemia - what kind of mutations leads to it? How many alleles are involved?

A

2 alleles (on chromosome 11) are responsible for chain synthesis.

due to a point mutation in the beta globin gene present on chromosome 11

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28
Q

What are the three types of beta thalassaemia?

A

The genes defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta-globin protein at all. Based on this, beta-thalassaemia can be split into three types:

Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major

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29
Q

Beta Thalassaemia - what is seen in Thalassaemia minor - what would a patient with this experience?

A

Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.

Thalassaemia minor causes a mild microcytic anaemia and usually patients only require monitoring and no active treatment.

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30
Q

Beta Thalassaemia - what is seen in Thalassaemia intermeida - what would a patient with this experience?

A

Patients with beta thalassaemia intermedia have two abnormal copies of the beta-globin gene. This can be either two defective genes or one defective gene and one deletion gene.

Thalassaemia intermedica causes a more significant microcytic anaemia

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31
Q

Beta Thalassaemia - what is seen in Thalassaemia major - what would a patient with this experience?

A

Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta-globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.

Thalassaemia major causes:

Severe microcytic anaemia
Splenomegaly
Bone deformities

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32
Q

What are the investigations for suspected Alpha and Beta Thalassaemia?

A

Blood film – will show hypochromic and microcytic anaemia, target cells visible on film Irregular and pale RBCs

FBC - Increased reticulocytes and nucleated RBCs in peripheral circulation - known as reticulocytosis

Lab work may also show high serum iron, high ferritin, and a high transferrin saturation level.

Hb electrophoresis –
Skull XR – hair on end sign, enlarged maxilla

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33
Q

Investigations for thalassaemia - What is Hb electrophoresis?
What would you see on it for
a) Alpha thalassaemia
b) Beta Thalassaemia?

A

It is a test applies an electric current to a blood sample. This separates normal and abnormal types of haemoglobin - abnormal types can be indicative of diseases such as thalassaemia

HbH present in alpha thalassaemia,

Elevated HbA2 + HbF but low HbA seen in beta thalassaemia

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34
Q

What is the management for thalassaemia?

A

Depends on severity of the symptoms!!

  • Regular blood transfusions: may be required and will be guided by the Hb level.
  • Iron chelation:desferrioxamine acts as an iron chelator and can be given to treat or prevent iron overload in patients with regular transfusions
  • Folate supplementation:haemolysis leads to increased cell turnover and a state of folate deficiency
  • Splenectomy:
  • Stem cell transplantation:the onlycurativeoption recommended in those with severe disease
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35
Q

Management of Thalassaemia - what is iron chelation? Why would patients with thalassaemia may need a splenectomy?

A

Iron chelation DEFEREOXAMINE

  • (used to remove iron in the body) - It’s used to treat thalassemia because people with the disorder tend to accumulate excess iron in their bodies. The iron can build up in vital organs and lead to organ damage.

Because thalassaemia can lead to **splenomeglay due to extramedullary erythropoiesis. Can lead to Hypersplenism

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36
Q

What are some complications for thalassaemia?

A
  • Heart failure: severe anaemia can lead to high output cardiac failure
  • Hypersplenism:
  • Iron overload due to regular transfusions:excess iron leads to secondary haemochromatosis which can affect the liver, heart, pancreas, skin, and joints
    • Complications due to haemochromatosis: arrhythmias, pericarditis, cirrhosis, hypothyroidism and diabetes mellitus
  • Gallstones:haemolysis results in haemoglobin being broken down to bilirubin and forming pigmented gallstones
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37
Q

What happens in Sideroblastic anaemia?

A

Sideroblastic anaemia, , is a form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes), so body can’t carry enough O2.

This is because it cannot incorporate iron into the haemoglobin

due to vitamin B6 deficiency

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38
Q

What classifications of anaemia is sideroblastic anaemia under?

A

Microcytic.
Think of sideroblastic anaemia whenever microcytic anaemia is not responding to iron

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39
Q

What are the causes of Sideroblastic anaemia?

A

Congenital, genetic

Or idiopathic, can follow chemotherapy, irradiation

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40
Q

What are the 4 causes of normocytic anaemia

A

○ A – Acute blood loss
○ A – Aplastic Anaemia e.g. bone marrow suppression or chronic kidney disease (lack of EPO)
H – Haemolytic Anaemia
H - Hypothyroidism

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41
Q

What are the two types of Normocytic anaemia diseases?

A

Haemolytic and Non Haemolytic

Haemolytic anaemia occurs when RBCs are destroyed before 120 days (lifespan dependent on cause of haemolysis)

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42
Q

Define what sickle cell anaemia is

A

Sickle cell anaemia is an autosomal recessive mutation in the beta chain of haemoglobin, resulting in sickling of red blood cells (RBCs) and haemolysis.

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43
Q

Where is sickle cell anaemia most prevelant?

A

The prevalence of sickle cell trait in sub-Saharan Africa is the highest in the world. This may be because it is protective against malaria.

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44
Q

What are some risk factors for sickle cell anaemia?

A
  • African: 8% of black people carry the sickle cell gene
  • Family history: autosomal recessive pattern
  • Triggers of sickling: dehydration, acidosis, infection, and hypoxia
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45
Q

Outline the pathophysiology behind sickle cell anaemia - what leads to the change in structure to one of the beta chains?

A

Sickle cell disease is caused by defective haemoglobin.

The β-globin chains end up misshapen due to a point mutation in the beta globin gene, or HBB gene.

This point mutation leads to hydrophilic glutamic acid being substituted for a hydrophobic valine changing the structure of the beta chain.

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46
Q

Outline the pathophysiology behind sickle cell anaemia - what type of haemoglobin do sickle cell patients have instead?

A

Sickle cell trait patient will have reduced levels of HbA,
Sickle cell disease patients have no HbA, and instead have abnormal HbS, which is made of 2 alpha chains and 2 abnormal beta chains.

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47
Q

Outline the pathophysiology behind sickle cell anaemia - name some of the characteristics of HbS

A
  • HbS is prone tosicklingand haemolysis.
  • HbS carries oxygen well
    But when deoxygenated, HbS changes its shape, and clumps with other HbS proteins, causing the RBC to turn into a crescent shape
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48
Q

Outline the pathophysiology behind sickle cell anaemia - what happens to repeated sickling of RBCs in sickle cell anaemia, and what does this lead to?

A
  • Repeated sickling of red blood cells damages their cell membranes and promotes premature destruction - haemolysis

This destruction of red blood cells leads to anaemia and more free haemoglobin in the blood.

Free haemoglobin in the blood in the plasma is bound by haptoglobin and gets recycled; ==> a low haptoglobin level is a sign of intravascular haemolysis.

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49
Q

The pathophysiology behind sickle cell anaemia - what happens to the Haem group?

A

The Haem group that has come from the destruction of faulty RBCs in Sickle Cell Disease is turned into unconjugated Billirubin ==> so lots of it can lead to jaundice and gall stones

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50
Q

In order to counteract anaemia, in sickle cell disease, what does the bone marrow do?

A

To counteract the anaemia of sickle cell disease, the bone marrow makes increased numbers of reticulocytes. This can cause the bones to enlarge.

Extramedullary hematopoiesis can also happen - leading to splenomegaly.

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51
Q

What is more likely to happen with Sickled blood cells compared to normal? What will this lead to?

A

Sickled RBCs can get stuck in capillaries, known as vaso-occlusion.

This can lead to vaso-occlusive crisis causing symptoms e.g. dactylitis (inflammation in finger or toe), priapism (long lasting painful erection), acute chest syndrome, stroke, depending on where the occlusion is.

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52
Q

Name some triggers that will cause sickling in Sickle disease/trait

A

dehydration, acidosis, infection, and hypoxia

sickle cell disease patients will sickle sooner than sickle cell trait patients!
HbAS(trait) patients sickle at PaO22.5 - 4 kPa, whilstHbSS(disease) patients at PaO25 - 6 kPa.

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53
Q

What are some chronic symptoms of sickle cell anaemia?

A
  • Chronic symptoms:
    • Pain
    • Related to anaemia: fatigue, dizziness, palpitations
    • Related to haemolysis: jaundice, and gallstones
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54
Q

Sickle cell crisis - What are some of the crisis’ that can happen, that will lead to acute symptoms?

A

Splenic Sequestration crisis - affects Spleen
Aplastic crisis - affects bone
Vaso-occlusive crisis - can affect bone, lungs, CNS, genitalia

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55
Q

What can these sickle cell crisis be brought on by?

A

They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.

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56
Q

Sickle Cell Vasoocclusive crisis - What happens in it, and what can it lead to?

In Bones, Lungs, CNS, Kidney, Genitalia

A

Painful, vaso-occlusive episodes occur as RBCs sickle in various organs - leading to Distal Ischaemia

In Bone - can lead to Dactylitis inflammation of digits, and Avascular Necrosis

In Lungs - can lead to Acute Chest syndrome - can see Chest pain, hypoxia, Pulmonary infiltrates on CxR

In CNS - can lead to stroke

Penis - Priapism

Kidney - Renal papillary necrosis

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57
Q

Sickle Cell Crisis - what is seen in a Aplastic crisis? What commonly causes the infection?

A

Severely reduced production of red blood cells due to bone marrow failure.

temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19, effecting the Bone marrow

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58
Q

Sickle Cell Crisis - What is seen in a Splenic sequestrain crisis?

A

Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen.

Leads to pooling of blood in the spleen, can lead to severe anaemia and hypovolaemia

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59
Q

What is the basic management seen in sickle cell crisis?

A

There is no specific treatment for sickle cell crises and they are managed supportively:

Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
Blood transfusion in anaemic cases
NIV/Breathing assistance in Acute Chest syndrome
Splenectomy in Splenic Sequestration Crisis

NSAIDs such as ibuprofen should be avoided where there is renal impairment.

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60
Q

What are the primary investigations to do for suspected sickle cell anaemia?

What confirms a diagnosis of sickle cell disease?

A

Screen neonates – blood/heel prick test
FBC: Low Hb, High reticulocyte count

Blood film – sickled erythrocytes
Hb electrophoresis for differential diagnosis – Hb SS present and absent Hb A confirms diagnosis of sickle cell disease

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61
Q

What is some of the ongoing management for sickle cell anaemia?

A

Supportive
Folic acid
Aggressive analgesia i.e. opiates
Treat underlying cause e.g. antibiotics

Fluids
Disease modifying
Hydroxycarbamide/hydroxyurea – increases HbF concentrations if frequent crises
Transfusion
Stem cell transplant

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62
Q

What is Hereditary Spherocytosis?

What is formed as a result, instead of normal RBCs?

A

Hereditary spherocytosis (HS) is an inherited haemolytic anaemia and is autosomal dominant in the majority of cases (75%), but can also be autosomal recessive.

Leads to the formation of spherocytes, - round mishaped RBCs

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63
Q

What are the risk factors for Hereditary spherocytosis?

A
  • Family history
  • Northern European descent

It is diagnosed in 1 in 2000 people, whilst a large proportion of these individuals are asymptomatic

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64
Q

What is the pathophysiology behind the Hereditary spherocytosis?

A
  • HS occurs due to a defect in red cell membrane proteins, such as ankyrin and spectrin.
    Leads to RBCs being more permeable to sodium, so lose their biconcave shape and appear spherical and rigid

These are mistaken to be damaged by the spleen and prematurely destroyed in (extravascular haemolysis) – over working of the spleen can cause splenomegaly

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65
Q

What are some signs of spherocytosis?

A

Splenomegaly
- Pallor
- Jaundice
- Tachycardia
- Flow murmur (as body has to work harder to supply body with O2)

Anaemia
Gallstones

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66
Q

Outline the pathophysiology behind abisheks trim

A

DUSTY

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67
Q

What are some symptoms of spherocytosis?

A
  • Fatigue
  • Dizziness
  • Palpitations
  • Right upper quadrant pain: due to gallstones
  • Neonatal jaundice: in 50% of patients
  • Failure to thrive
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68
Q

What is the diagnostic criteria for diagnosing hereditary spherocytosis?

A

No further tests are needed for diagnosis, if:

  • Family history of HSand
  • Typical clinical featuresand
  • Positive laboratory investigations (spherocytes, raised MCHC, increase in reticulocytes)
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69
Q

What are some investigations to consider in spherocytosis?

A
  • FBC:normocytic anaemia with an increased reticulocyte count and raised MCHC
    • MCHC is increased as spherical RBCs lead to water diffusing out of the cell
  • Blood film:spherocytosis
  • LFTs:increased (unconjugated) bilirubin due to haemolysis
  • Coombs test:negativein hereditary spherocytosis. (it is Positive in Autoimmune haemolytic anaemia)
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70
Q

What is the management for spherocytosis?

What should these patients be prescribed and why?

A
  • Blood transfusion:patients should be managed with transfusions for symptomatic anaemia until splenectomy is possible or deemed appropriate
  • Folic acid: all patients require daily folic acid supplementation until splenectomy
  • Splenectomy:removing the spleen reduces haemolysis
    • Patients must bevaccinatedagainst encapsulated bacteria and be prescribed lifelongphenoxymethylpenicillin
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71
Q

How old must patients be before they can have a splenectomy? Why?

A

Splenectomy is delayed until patients are> 6 years oldto reduce the risk of post-splenectomy sepsis

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72
Q

What are some complications of Sphereocytosis?

A
  • Gallstones: the high level of bilirubin due to haemolysis increases the risk of gallstones
  • Aplastic crisis: parvovirus B12 infection attacks erythroid precursors in the marrow, resulting in anaemia with reduced reticulocyte count. Any patient with a haemolytic condition is at risk due to reduced RBC life span

Bone marrow expansion - due to increased demmand for RBC production

Post-splenectomy sepsis

Most patients with HS are asymptomatic with a near-normal Hb post-splenectomy, as this increases RBC lifespan

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73
Q

How can Glucose-6-Phosphate Dehydrogenase Deficiency lead to anaemia? What type of anaemia?

A

A normocytic, Haemolytic Anaemia, where there is a genetic defect in teh G6PD protein

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74
Q

Normal physiology - what does Glucose-6-Phosphate Dehydrogenase normally do?

A

The G6PD enzyme contributes to the production of NADP+ and Gluthione, which reduces the amount of ROS in the cell and protects RBCs from damage by ROS.

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75
Q

What is the epidemiology behind the G6PD deficiency disease? What is the inheritance pattern?

A
  • It is inherited in an X linked recessive pattern, meaning it usually affects males.
  • It is more common in Mediterranean, Middle Eastern and African patients.
  • 6DPD deficiency can be protective against malaria
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76
Q

What are some triggers that lead to deficit G6PD causing anaemia?

A

Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia.

e.g. infections (viral hepatitis or pneumonia), metabolic acidosis, fava beans, soy products, red wine, certain medications

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77
Q

What is the typical presentation of G6PD deficiency?

A

Asymptomatic until exposed to oxidative stressor
Neonatal jaundice – excess bilirubin
Chronic haemolytic anaemia
Acute haemolysis
Rapid anaemia
Jaundice
Back pain
Dark urine
Splenomegaly
Pallor

Caused by
Ingestion of fava beans
Common drugs – quinine, sulphonamides, quinolones and nitrofurantoin

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78
Q

G6PD Deficiency = What do free radicals attacking RBCs lead to specifically?

A

ROS damage the Haemoglobin proteins, and damaged haemoglobin is known as Heinz Bodies - they stay inside the RBC.

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79
Q

What does the spleen do when it sees Heinz bodies

A

The spleen macrophages notice these Heinz bodies and try to remove them by taking a chunk out of the RBCs, leaving them partially devoured. These are known as bite cells.

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80
Q

What investigations would you do for suspected G6PD deficiency anaemia? How can a diagnosis be made?

A
  • FBC: low levels of RBC, high reticulocytes
  • Blood film: heinz bodies and bite cells
    – Bilirubin: elevated
  • Haptoglobin: low
  • Coomb’s test: negative (used to detect immune mediated anaemias)
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81
Q

How can a diagnosis of G6PD defiency be made?

A

Diagnosis can be made by doing a G6PD enzyme assay.

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82
Q

What is the management of G6PD deficiency?

A
  • Avoid trigger of haemolysis e.g. fava beans and certain medications
  • In certain cases, transfusions may be needed
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83
Q

Malaria life cycle in humans starts with an the sporozites infecting the liver, that become shizonts and then burst, releasing Merozoites into the blood. What do the Merozoites go onto the do within the RBC

A

Merozoites infect RBC, making it a trophozoite – this matures into a schizont - which then ruptures and destroy the cell, leading to the release of more merozoites in the blood stream

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84
Q

What are some Haemolysis specific signs of malaria?

A

Anaemia
Jaundice
Hepatosplenomegaly
‘Black Water Fever’- Hb passes into urine

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85
Q

Describe the pathogenesis of p.falciparum?

A
  • Cytoadherence - RBC stick out proteins that adhere to the wall of the endothelium
    Rosetting - Infected RBCs, clump adhere to healthy RBCs - small vessels to become obstructed by clumps of RBCs - this causes hypoxia.
    3️⃣ SequestrationMicroinfarcts form in major organs (brain, heart, lungs, liver, kidney) where they are able to mature and evade the immune system.
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86
Q

What are the symptoms of complicated malaria?

A

Cerebral
ARDS/Pulmonary oedema
Renal failure
Sepsis
Bleeding/Anaemia

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87
Q

What is the ideal first line treatment for severe/complicated malaria?

more detailed malaria flashcards in micro

A

IV Artesunate

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88
Q

What happens in Autoimmune haemolytic anaemia?

A

red blood cells are attacked by either IgM or IgG antibodies

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89
Q

Regarding autoimmune haemolytic anaemia, what triggers IgM mediated destruction of RBCs?

A

cause cold agglutinin - haemolysis happens in the cool extremities, and it’s associated with infections like mycoplasma and mononucleosis

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90
Q

Define what an agglutinin is

A

An agglutinin is a substance in the blood that causes particles to coagulate and aggregate; that is, to change from fluid-like state to a thickened-mass (solid) state.[1]

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91
Q

Regarding autoimmune haemolytic anaemia, what triggers IgG mediated destruction of RBCs?

A

cause warm agglutinin - haemolysis happens when it’s warm, and it’s associated with lupus and drugs like penicillin and cephalosporin.

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92
Q

What happens aplastic anaemia?

A

Is the reduction in the number of pluripotent stem cells causes a lack of haemopoiesis (production of blood cells and platelets). The reduced number of new RBCs produced to replace the old ones causes anaemia.

anaemia, leukopenia, and thrombocytopenia. - low levels of all blood cells!

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93
Q

Outline the pathophysiology behind aplastic anaemia

A

Alterations in the immunologic appearance of haematopoietic stem cells because of genetic disorders, or after exposure to environmental agents, like radiation or toxins, or autoimmune

  • ## This means that the hematopoietic stem cells start expressing non-self antigens and the immune system subsequently targets them for destruction.
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94
Q

What are some symptoms/signs for Aplastic anaemia?

A

Anaemia
Increased susceptibility to infection
Increased bruising
Increased bleeding (especially from nose and gums)

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95
Q

What investigations would you do for suspected aplastic anaemia

A

FBC – would show pancytopenia (low levels of all blood cells i.e. RBCs, WBCS etc.)
EPO levels may be raised, to try and stimulate RBC production
Reticulocyte count – low or absent
BM biopsy – hypocellular marrow with increased fat spaces

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96
Q

What are some treatments for aplastic anaemia?

A

Remove causative agent
Blood/platelet transfusion
BM transplant
Immunosuppressive therapy –

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97
Q

How can CKD cause anaemia?

A

kidneys normally produce a hormone called erythropoietin (EPO), which stimulates the bone marrow to produce red blood cells.

When the kidneys are not working properly, EPO production decreases, leading to a decrease in the number of red blood cells in the body. As a result, anaemia can occur.

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98
Q

What is macrocytic anaemia characterised by?
What are it’s 3 main causes?

A

Characterised by MCV >100

3 main causes:
Megaloblastic
B12 deficiency (pernicious anaemia)
Folate deficiency
Non-megaloblastic
Alcohol excess

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99
Q

What can you often see regarding neutrophils in Macrocytic anaemia?

A

Neutrophil hypersegmentation =

the presence of neutrophils whose nuclei have six or more lobes or the presence of more than 3% of neutrophils with at least five nuclear lobes

The presence of hyper segmented neutrophils is an important diagnostic feature of megaloblastic anaemia.

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100
Q

Why can B12 and folate deficiency’s be referred to as Megaloblastic? What does Megalobastic mean?

A

Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a larger, abnormal cell. This is caused by a vitamin deficiency. (hence the macrocytosis)

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101
Q

Normal physiology -what does Vitamin B12 do? Where is it commonly found?

A

Vitamin B12 (cobalamin) is found in meats and diary products. It is an essential vitamin for DNA synthesis in cells undergoing rapid proliferation.

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102
Q

Name some causes of vitamin B12 deficiency

A
  • Inadequate intake(e.g. strict vegetarians, vegans)
  • Inadequate secretion of intrinsic factor(e.g. pernicious anaemia, gastrectomy)
  • Malabsorption(e.g. Crohn’s, tropical sprue, patients who have had gastric bypass)
  • Inadequate release of B12from food(e.g. gastritis, alcohol abuse)
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103
Q

Where in the gut is Vitamin B12 absorbed?

How is it absorbed?

A

Vitamin B12 is absorbed in the terminal ileum bound to Intrinsic Factor (IF) produced by parietal cells

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104
Q

What are some signs and symptoms of vitamin B12 deficiency?

A
  • Signs
    • Pallor
    • Signs of neurological deficit e.g. confusion, ataxia etc
  • Symptoms
    • Shortness of breath
    • Fatigue
    • Palpitations
    • Headaches
    • Glossitis
    • CNS involvement
      • Personality change
      • Depression
      • Memory loss
      • Visual disturbances
      • Numbness, weakness and paraesthesia affecting the lower extremities
      • Ataxia
      • Loss of vibration sense or proprioception
      • Autonomic dysfunction (e.g. bladder/bowel dysfunction)
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105
Q

Name some high risk groups for people to get folate deficiency

A
  • Elderly
  • Poverty
  • Alcoholic
  • Pregnant
  • Crohn’s or coeliac disease
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106
Q

What pathophysiological manifestations will occur due to Folate (B9) deficiency?

A
  • This means that folate deficiency can eventually lead to pancytopenia. In response to the anaemia, the bone marrow compensates by releasing megaloblasts into the blood - and the final result is macrocytic, megaloblastic anaemia.
  • Other rapidly dividing cells, include mucosal epithelial cells of the tongue. These are affected, preventing healing. This leads to glossitis.
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107
Q

Due to the respective amounts being able to be stored in the body, how long until Folate and B12 Deficiencies begin to manifest?

A

folate deficiency can develop after months, compared to vitamin B12 deficiency, which tends to develop over years

fOlate = mOnths

B12 = years.

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108
Q

What is the pathophysiology behind Pernicious Anaemia?

A

Pernicious anaemia is an autoimmune condition in which the parietal cells are attacked 🡪 atrophic gastritis and loss of IF production 🡪 B12 malabsorption

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109
Q

What investigations would you carry out for suspected Pernicious Anaemia?

A

Investigations:
FBC
Blood film – would show macrocytic RBCs
Autoantibody screen – check for IF and parietal cell antibodies (present in 50% and 90% of cases respectively)
Serum B12 - low

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110
Q

What is the treatment for Pernicious Anaemia?

A

Treatments:
Artificial Vitamin B12 (hydroxocobalamin) tablets/injections
NOT FOLIC ACID – causes fulminant neurological deficits

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111
Q

What do you correct first in someone a combined B12 and folate deficiency??

A

In a combined B12 and folate deficiency, you MUST replace B12 before replacing folate

B12 deficiency is sometimes misdiagnosed as a folate
deficiency so you always correct the B12 as it can cause neurological
complications left untreated.

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112
Q

How can hypothyroidism lead to anaemia

A

hypothyroidism leads to Less production of EPO, can lead to decreased production of RBCs

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113
Q

What is leukaemia?

A

Leukaemia is the name for cancer of a particular line of the stem cells in the bone marrow.

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114
Q

How is leukaemia classified?

A

How fast the production is (slow = chronic or fast = acute)

What cell line is affected (myeloid or lymphoid)

make four main types with different characteristics:

Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia

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115
Q

What is the pathophysiology behind leukaemia

A

Leukaemia is a form of cancer of the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.

116
Q

What type of leukaemia is most common in
Under 5 and over 45
Over 55
Over 65
Over 75 year olds?

A

“ALL CeLLmates have CoMmon AMbitions”
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)

117
Q

Outline the pathophysiology behind Acute Myeloid Leukaemia and Acute Lymphoblastic Leukaemia?

A

Characterised by a mutation 🡪 clonal proliferation of myeloid or lymphoid precursors
Precursor blood cells lose ability to differentiate and are stuck in the blast stage of development and don’t function effectively

Makes blast cells divide uncontrollable so other blood cells in BM are “crowded out” 🡪 cytopenia (anaemia, thrombocytopenia and leukopenia)

118
Q

Outline what happens in Acute Lymphoblastic Leukaemia

A

Malignant change in a Lymphocyte precursor cell, causing the acute proliferation of a single type of lymphocyte, usually B-lymphocytes.

Leads them to replace the other cell types being created in the bone marrow, leading to a pancytopenia.

119
Q

What groups of people is Acute Lymphoblastic Leukaemia (ALL) assosicated with most?

A

Most commonly affects with children
Highest prevalence between 2-4 years
Associated with Down’s syndrome

120
Q

What are some signs/Symptoms of Acute Lymphblastic leukaemia?

A

-Anaemia 🡪 breathlessness, fatigue, pallor
Infection
Hepatosplenomegaly
Peripheral lymphadenopathy (swollen lymph nodes)
CNS involvement 🡪 headache, cranial nerve palsies
SVC obstruction, dilated superficial chest veins
Bone marrow failure and bone pain

121
Q

What are some investigations to do for acute lymphoblastic leukaemia?

A

FBC 🡪 anaemia, thrombocytopaenia, neutropoenia, low reticulocyte count
Blood film 🡪 leukaemic blast cells
Bone marrow aspiration and trephine biopsy: diagnosis can be made if ≥ 20% of the cells in the sample are lymphoblast’s

CXR and CT 🡪 lymphadenopathy

122
Q

What is the most common gene abnormality for children who develop ALL?

A

Most common gene abnormality T (12;21), a translocation between genes 12 and 21

123
Q

What is the most common acute leukaemia in adults?

A

Acute myeloid leukaemia

124
Q

What cells does acute myeloid leukaemia involve? What is the most common group for it

A

Affects the myeloblasts Over 75 males

Progresses very rapidly; 20% 3 year survival
AML is a medical emergency

125
Q

What are some signs and symptoms of Acute myeloid leukaemia?

A

Anaemia 🡪 breathlessness, fatigue, pallor
Infection
Hepatosplenomegaly
Peripheral lymphadenopathy
Gum hypertrophy
Bone marrow failure and bone pain

126
Q

What are some investigations you would do for suspected acute myeloid leukaemia?

A

FBC 🡪 anaemia, thrombocytopaenia, neutropoenia
Blood film 🡪
Bone marrow biopsy 🡪
Cytogenetic analysis and immuno-phenotyping

127
Q

What would you see on a blood film for someone with acute myeloid leukaemia?

A

A blood film will show a high proportion of blast cells. These blast cells can have rods inside their cytoplasm that are named Auer rods.

128
Q

What is the treatment for acute myeloid leukaemia and acute lymphoid leukaemia?

A

Supportive treatment (blood/platelets/fluids/antibiotics)
Correction of anaemia, thrombocytopenia and coagulation abnormalities
Treatment of infection with IV antibiotics

Allopurinol - prevention of acute tumour lysis syndrome
Chemo needed to induce remission
BM transplant and steroids to maintain

129
Q

What are some side effects from chemo

A

Alopecia, nausea, vomiting, fatigue, neutropenia, sexual dysfunction, increased infection susceptibility, anaemia…

Long term - tumour lysis syndrome

130
Q

Following chemo, patients can get neutropenic sepsis - what anbtx do you give for this?

A

IV piperacillin/tazobactam, both beta lacatams

131
Q

What is tumour lysis syndrome? What can it lead to?

A

Tumour lysis syndrome is caused by the release of uric acid from cells that are being destroyed by chemotherapy.

The uric acid can form crystals in the interstitial tissue and tubules of the kidneys and causes acute kidney injury.

132
Q

What can cause tumour lysis syndrome? How can you treat it?

A

Can see it in chemotherapy, as uric acid is released in the cells destroyed in it

Allopurinol or rasburicase are used to reduce the high uric acid levels. Other chemicals such as potassium and phosphate are also released so these need to be monitored and treated appropriately.

133
Q

What are the electrolye abnormalites caused by tumour lysis syndrome?

A

Hypocalcaemia, hyperphosphatemia, hyperuricemia, hyperkalaemia

think of what is in cells (potassium and phosphate) which will leak out. The hypocalcaemia is secondary to hyperphosphataemia.

134
Q

Define Lymphocytosis

A

Lymphocytosis is an increase in the number of lymphocytes in the blood. This is usually seen as an increase in the percentage of lymphocytes in a person’s complete blood count

135
Q

What is the most common age for developing chronic myeloid leukaemia?

A
  • CML is generally considered a condition of the elderly, with a peak age of diagnosis between 65 and 74 years
  • Slight male predominance
136
Q

Name a difference between AML + ALL compared to CML + CLL

A

Both CML and CLL leads cells to mature partially, however in active acute leukaemia’s the cells don’t mature at all

137
Q

What is the pathophysiology that leads to Chronic myeloid leukaemia?

A

The most common cause is a chromosome translocation which results in a Philadelphia chromosome.

138
Q

What actually is a Philadelphia chromosome - what does it contain?

A

The Philadelphia chromosome = a specific genetic abnormality in chromosome 22, seen in all cases of CML, and can also be seen in AML

This chromosome is defective and unusually short because of reciprocal translocation, of genetic material between chromosome 9 and chromosome 22,

contains a fusion/hybrid gene called BCR-ABL1.

The presence of this translocation is required for diagnosis of CML; in other words, all cases of CML are positive for BCR-ABL1

139
Q

Pathophysiology behind Chronic myeloid leukaemia - how is hte Philadelphia chromosone formed?

A

As a result of Translocation between chromosomes 9 and 22, which brings together parts of the BCR (breakpoint cluster region) gene on chromosome 22 and the ABL1 (Abelson leukemia viral oncogene homolog 1) gene on chromosome 9

Leads to production of abnormal BCR-ABL1 fusion gene. This fusion gene produces a protein that is constantly switched on that causes the growth of CML cells.

it is a t(9:22) translocation.

140
Q

Pathophysiology behind Chronic myeloid leukaemia - what does the BCR-ABL1 gene code for?

A

BCR ABL protein, which is constantly active (always turned on) tyrosine kinase

Tyrosine Kinase plays an important role in cell signalling and regulation, and are involved in a wide range of cellular processes such as cell growth, differentiation, and proliferation.

141
Q

What are the phases of Chronic myeloid leukaemia, and what symptoms would a patient experience in each one?

A

Chronic - 5 years, asymptomatic

Accelerated - blast cells go outta control, anaemia and immunocompromised

Blast crisis - ). This phase has severe symptoms and pancytopenia. It is often fatal.

142
Q

What percentage of blast cells do you see in each phase of Chronic myeloid leukaemia?

A

Chronic phase - <10% of cells in the bone marrow are blast cells
Accelerated phase - 10-19% of cells in the bone marrow are blast cells
Blast crisis - >20% of cells in the bone marrow are blast cells

143
Q

What changes can be seen in the Blast crisis stage of chronic myeloid leukaemia?

A

In this stage there is a high chance of mutation, eg A the formation of a trisomy on chromosome number 8, or the doubling of the Philadelphia chromosome.

144
Q

What investigations would you do for suspected chronic myeloid leukaemias?

A
  • FBC:leukocytosis, (high numbers of WBC) anaemia with a reduced reticulocyte count, and reduced leukocyte Alkaline Phosphatase ALP may be seen. Thrombocytosis is found in 30% of patients.
  • Blood film:an**increase in all stages of maturing granulocytes. Precise findings depend on the disease phase (e.g. blast transformation)
  • Bone marrow biopsy:myeloblast infiltration in the bone marrow
  • Cytogenetic and molecular studies:Philadelphia chromosome t(9;22)(q34;q11)
145
Q

What is the management of chornic myeloid leukaemia in the chronic and accelerated phases?

A

Tyrosine Kinase inhibitor IMATINIB

– if Philadelphia chromosome positive - can be combined with Interferon Alpha
Watchful waiting
Chemo
Stem cell transplant
BM transplant

146
Q

What is the management of chronic myeloid leukaemia in the blast crisis phase?

A
  • Tyrosine kinase inhibitor - IMATINIB plushigh dose inductionchemotherapy, followed bystem cell transplantation
  • Patients may have pancytopaenia requiring blood and platelet transfusion
  • If remission is not achieved through the above measures, death is imminent
147
Q

What is the main complication that can arise from CML?

A

Progression to acute myeloid leukaemia - you would find AUER RODS on blood film

148
Q

What are some differentials for Leukaemia?

A
  • Meningococcal septicaemia *Bacteria release toxins that damage vessels
  • Vasculitis

Disseminated Intravascular Coagulopathy

  • Henoch-Schonlein Purpura (HSP) -autoimmune disorder that damages vessels in body
  • Idiopathic Thrombocytopenia Purpura (ITP) - autoimmune disorder that destroys platelets, so will also lead to bruising
  • Non-accidental injury
149
Q

What is the most common leukaemia?

A

Chronic lymphocytic leukaemia

150
Q

What cells do you see lots of in chronic lymphocytic leukaemia?

A

B CELLS!

Accumulation of mature B cells that have escaped programmed cell death and undergone cell-cycle arrest in the G0/G1 phase is the hallmark of CLL

151
Q

Outline the basic pathophysiology behind Chronic Lymphocytic leukaemia

A

Pathology – characterised by an uncontrolled proliferation and accumulation of mature B lymphocytes that have escaped apoptosis. Don’t die as they should 🡪 too many premature cells 🡪 accumulate in BM 🡪 crowding out 🡪 cytopenia (anaemia, thrombocytopenia, leukopenia etc.)

152
Q

What is the most common cause of Chronic Lymphocytic leukaemia?

A

Chromosomal abnormality in haematopoietic stem cells that are destined to become leukocytes is the most common cause of chronic leukaemia.

Some examples of abnormalities include a chromosomal deletion, a trisomy, and a translocation

153
Q

How many chronic lymphocytic leukaemia present?

A

Often none, presenting as a surprise finding on a routine FBC (eg done
pre-op).

  • Fatigue
  • Loss of appetite
  • Weight loss
  • Fever
  • Easy bruising and bleeding: due to thrombocytopaenia
  • Recurrent infections: due to hypogammaglobulinaemia
  • Abdominal fullness: due to hepatosplenomegaly
  • Localised pain at lymph node
154
Q

What are some signs of Chronic lymphocytic leukaemia

A

Enlarged, rubbery, non-tender nodes (fig 3). Splenomegaly, hepatomegaly

155
Q

What investigations would you carry out for suspected chronic lymphocytic leukaemia?

What test confirms the diagnosis?

A

FBC
Shows lots of lymphocytes
Hypogammaglobulinemia as no plasma cells
Anaemia
Thrombocytopenia

Blood film – shows small lymphocytes of mature appearance with “smear or smudge cells” (artefactual finding due to rupture while film is being made)

Immunophenotyping essential to exclude reactive lymphocytosis and other lymphoid neoplasms - confirms diagnosis

156
Q

What is the management of chronic lymphocytic leukaemia?

A

Treatment:
Varies depending on stage:
Early - watchful waiting, Advanced - Chemo

Radiotherapy to shrink lymphadenopathy
Splenectomy
BM transplant

Stem cell transplant

157
Q

What is Richter’s Syndrome? What can it be a complication of, and what % of people with initial disease get this??

A

Seen as a complication of Chronic Lymphocytic Leukaemia where CLL is Transformed into an aggressive, large B - cell lymphoma

(a transformation into a Non-Hodgkinson lymphoma)

Seen in 3 to 10% of cases of Chromic lymphocytic leukaemia

158
Q

What has been associated as a trigger of Richter syndrome? What is necessary for its diagnosis?

A

Epstein-Barr virus may play a role in transformation
Lymph node biopsy is necessary for diagnosis.

Patients will often present with:
weight loss
fever
night sweats
muscle wasting
increasing hepatosplenomegaly
lymphadenopathy

159
Q

Define lymphadenopathy

A

lymph nodes, which are part of the immune system, become abnormally enlarged

160
Q

Define lymphoma - what does it lead to?

A

Malignant proliferation of lymphocytes which accumulate in lymph nodes 🡪 lymphadenopathy

161
Q

What are the two types of Lymphoma?

A

Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.

Hodgkin’s lymphoma is a specific disease

Non-Hodgkins lymphoma encompasses all the other lymphomas. Hodgkin’s lymphoma is the most likely specific lymphoma to appear in your exams.

162
Q

What are the risk factors of Hodgkin’s Lymphoma?

A
  • Bimodal age distribution: 15-35 years and > 60 years
  • Epstein Barr Virus: mixed cellularity subtype
  • HIV infection:lymphocyte-deplete subtype
  • Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
  • Family history
163
Q

In Hodgkin’s lymphoma, what do infected B cells not express?

A

In classical HL these cells don’t express CD45 or CD20, which are typically seen on B-cells.

164
Q

What are some signs of Hodgkinsons lymphoma?

A
  • Lymphadenopathy (may be cervical, axillary, or inguinal)
    • Painless
    • Hard
    • Rubbery
    • Fixed
    • Contiguous spread (to nearby nodes) unlike in NHL
  • Splenomegaly: rarer compared to NHL
165
Q

What are some symptoms of Hodgkinson’s Lymphoma?

A
  • B symptoms: occur in around 30% of cases
    • Fever
    • Weight loss
    • Night sweats
  • Pel-Ebstein fever: an intermittent fever every few weeks
  • Alcohol-induced lymph node pain
  • Pruritus
  • Dyspnoea: due to mediastinal lymphadenopathy
166
Q

What are two types that Hodgkinson’s lymphoma can be further classified into?

A

2 types - Classic Hodgkinson’s lymphoma - See Classic Reid Steinberg cells, most common and more aggressive

Nodular lymphocyte predominant Hodgkin lymphoma - rare and slower growing where you see Popcorn variant of the Reed - Sternberg cell - see picture, bottom left

credit Copyright © 2011 Michael Bonert, MD, FRCPC ( https://commons.wikimedia.org/wiki/User:Nephron

167
Q

What is the Hallmark cell to diagnose Hodgkin’s lymphoma?

What antigens are almost always expressed on these cells?

A

Reed-Sternberg cell (aka lacunar histiocytes). These are giant malignant cells seen on light microscope

CD15 and CD30 antigens are almost always expressed on these cells in HL.

USED TO DISTINGUISH BETWEEN HODGKIN AND NON HODGKIN LYMPHOMA

Picture credit unknown

168
Q

What investigations would you do for Hodgkin’s Lymphoma?

A

CT/MRI of chest, abdomen and pelvis – show staging (Ann Arbor)
Lymph node biopsy and histological examination - shows Reed-Sternberg cells
FBC – may be normal of show normochromic, normocytic anaemia
CXR
WCC is often not raised in HL!!

169
Q

Investigating Lymphoma - What is the Ann Arbour Staging? What does it focus on? How many stages are there

A

Used in Both Hodgkin’s and Non - Hodgkin’s Lymphoma

Its a system that looks at whether affected nodes are above or below diaphragm. Done on CT/MRI

There are 4 stages - USED TO GUIDE TREATMENT

170
Q

Investigating Lymphoma - outline the 4 stages of the Ann - Arbour System

A

Stage 1: Confined to one region of lymph nodes.
Stage 2: In more than one region but on the same side of the diaphragm (either above or below).
Stage 3: Affects lymph nodes both above and below the diaphragm.
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.

picture source unknown

171
Q

Investigating Lymphoma - What can the Ann Arbour system be prefixed with, and what do these mean?

A

Prefixed with A or B
A – absence of B symptoms
B – present of B symptoms

‘A’—no systemic symptoms other than pruritus (itchiness)
‘B’—presence of symptoms:
weight loss >10% in last 6 months, unexplained fever >38°C, or night sweats (needing change of clothes).

‘B’ indicates worse disease, can guide management

172
Q

What is the management of early stage Hodgkinson Lymphoma

A

A Short course of Chemo - with 4 drugs ABVD
Adriamycin
Bleomycin
Vinblastine
Dacarbazine

Followed by radiotherapy

173
Q

What is the management of later stage Hodgkinson Lymphoma?
What does relapse respond well to?

A

A Longer course of Chemo ,
And radiotherapy

Relapse responds well to autologous bone marrow transplantation

174
Q

What is the prognosis for Hodgkin’s lymphoma?

A

relatively slow progression so Good long term survival – therefore must minimise long term effects of treatment

175
Q

What is the difference between lymphoma and leukaemia?

A

LYMPHOMA - NEOPLASTIC CELLS IN LYMPH NODES,
LEUAKAEMIA - INVOLVES BONE MARROW AND BLOOD

176
Q

What is more common and HL or NHL and what is the most common type of lymphoma overall?

A

NHL is far more common
B-cell lymphoma are more common that T-cell lymphomas

177
Q

What is Non Hodgkin’s lymphoma?
What cells do the tumours originate from

A

These are malignant tumours of lymphoid tissue, that do not contain Reed-Sternberg cells
70% are B cell in origin
30% are T cell in origin

“This includes all lymphomas without Reed–Sternberg cells —a diverse group”

178
Q

Name 3 types of notable non hodgkin lymphoma

A

Burkitt lymphoma is associated with Epstein-Barr virus, malaria and HIV.

MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.

Diffuse large B cell lymphoma often presents as a rapidly growing painless mass in patients over 65 years

179
Q

What are the risk factors for Non Hodgkin’s Lymphoma?

A

HIV and Epstein-Barr virus - seen in Burckett’s
H.Pylori seen in MALT lymphoma
Hepatitis B or C
Exposure to pesticides ( trichloroethylene)
Family history

180
Q

Outline basic pathophysiology behind non hodgkin lymphoma

A

===> You will see a genetic mutation in a Lymphocyte - Either a B or T cell ==> Instead of undergoing apoptosis, they divide uncontrollably, becoming a neoplastic cell

181
Q

What is a
a) Nodal Lymphoma
b) Extra Nodal Lymphoma

A

Nodal Lymphoma - A lymphoma that develops in Nodes
Extra Nodal Lymphoma - a lymphoma that develop in other tissue or organs, like stomach or skin

182
Q

What could happen in a lymphoma gets in GI tract, bone marrow or spine?

A

lymphoma in GI tract = can grow and cause bowel obstruction.

Lymphoma in Bone marrow = can crowd out normal bone marrow progenitor cells and cause pancytopenia.

Lymphoma in Spinal chord = can cause spinal cord compression.

183
Q

What are some signs of Non hodgkin lymphoma?

A
  • Lymphadenopathy
    • Painless
    • Hard
    • Rubbery
    • Fixed
    • Non-contiguous spread unlike in HL
  • Splenomegaly: more common in NHL compared to HL
  • Extranodal disease: bone marrow, thyroid, salivary gland, GI tract, CNS
184
Q

What are some symptoms of Non Hodgkin lymphoma?

A
  • B symptoms:
    • Fever
    • Weight loss
    • Night sweats
  • Related to extranodal involvement:
    • GI tract: bowel obstruction
    • Bone marrow: fatigue, easy bruising, or recurrent infections
    • Spinal cord: weakness and a loss of sensation - usually in the legs
185
Q

Investigating cancer - what does ESR stand for, and what does it mean?

A

ESR stands for erythrocyte sedimentation rate, which is a measure of the rate at which red blood cells settle to the bottom of a test tube in one hour. It is used to measure inflammation in the body

A high ESR may indicate an increased level of inflammation in the body, which can be caused by a variety of conditions, including infection, autoimmune diseases, and certain types of cancer. It may also be the result of other factors such as pregnancy, anemia, or dehydration.

186
Q

What investigations would you do in suspected non Hodgkin lymphoma

A

CT – for staging
Lymph node biopsy - no Reed-Sternberg Cells
FBC - *could show Anaemia, Elevated WBC or thrombocytopenia, Raised ESR -(Erythrocyte sedimentation rate)
CXR
PET scan
BM aspirate and trephine biopsy to confirm marrow involvement

187
Q

What is the management for Non - Hodgkin Lymphoma?

A

Steroids
Rituximab - targets CD20 on B cells

CHOP regimen: (A Chemotherapy regimen)
Cyclophosphamide
Hydroxy-daunorubicin
Vincristine
Prednisolone

188
Q

Treatment for Non - Hodgkin lymphoma - what is Rituximab, and what does it do?

A

Rituximab: monoclonal antibody targets CD20 on lymphocytes and is used in CD20+ lymphoma

189
Q

What are the main differences between Hodgkin and non Hodgkin lymphoma?

A

Hodgkin’s -
- Contiguous (only spreads to adjacent nodes/structures, due to flow of Lymph) - rarely extra nodal
-Affects a particular type of B-cell: Reed-Sternberg Cells
-Younger age of onset
- Painful nodes on drinking alcohol
-Better Prognosis than Non - Hodgkin Lymphoma

Non-Hodgkin’s -
Non-contiguous (multi-centric - can arise in several unlinked structures,) - extra nodal
No RS cells
Older age of onset (7th decade)
-Worse Prognosis than Hodgkin Lymphoma

190
Q

What is a myeloma?
What is a multiple myeloma?

A

Myeloma is a cancer of the plasma cells.
Multiple myeloma is where the myeloma affects multiple areas of the body.

191
Q

What are the most common antibodies that there ends up being large amounts of in the blood in myeloma?

A

IgG (2/3) and IgA (1/3)

192
Q

In what age and group is myeloma most common?

A
  • The median age of diagnosis is 72 years in Europe
  • More common in Afro-Caribbeans than caucasians
193
Q

Risk factors for Myeloma - what is MGUS?

A

Monoclonal gammopathy of undetermined significance (MGUS) =

Excess of a single type of antibody, but without other features of myeloma/cancer it’s often found in a healthy person and its significance is unclear ==> but people with it need to be monitored it may progress to a myeloma

194
Q

Risk factors for Myeloma - what is a smouldering myeloma?

A

progression of MGUS with higher levels of antibodies or antibody components. More likely to progress to myeloma than MGUS

195
Q

Outline the pathophysiology of a myeloma

A

There is clonal proliferation of the plasma cells
Normally plasma cells produce a wide range of immunoglobulins (antibodies) such as IgG, IgA, IgM and IgD
In myeloma, malignant plasma cells produce an excess of one type of immunoglobulinusually IgG and IgA.
Bence Jones protein deposition in urine

196
Q

Pathophysiology of myeloma - what is the name given to the specific type of antibody that is specifically produced by the malignant plasma cell?

A

monoclonal paraprotein

(only consisting of light chains rather than a light and heavy chain)

197
Q

Pathophysiology of Myeloma - what do these neoplastic plamsa cells do that can lead to symptoms?

A

Neoplastic cells release Cytokines, that lead to activating of osetoclasts via RANKL

Light chains from the pathological antibodies Known as Bence Jones proteins can interrupt/impair renal function

Bone marrow can get infiltrated by plasma cells - reduced haematopoesis, leading to anaemia

198
Q

What are the symptoms of Myelomas?

A

CRAB

Calcium raised (Hypercalcaemia) cancer symptoms, Confusion (hyperviscosity, hypercalcaemia), repeat infections, pathological fractures

Renal failure – nephrotic syndrome
Immunoglobulin light chains deposit in organs especially kidneys

Anaemia, infections and bleeding due to BM infiltration (anaemia, thrombocytopenia, leukopenia)

Bone pain – increased osteoclastic activity cause bone destruction (backache most common symptom)
Osteolytic lesions, easy fractures, Spinal cord compression

CRAB

199
Q

Where are common places for Myeloma bone disease, due to increased osteoclast activity?

A

Common places for myeloma bone disease to happen are the skull, spine, long bones and ribs.

NICE suggest considering myeloma in anyone over 60 with persistent bone pain, particularly back pain, or an unexplained fractures!!!!!

200
Q

how does multiple myeloma cause hypercalcaemia

A

due to increased osteoclastic activity in response to cytokines released by the myeloma cells

Patients can often present with hypercalcaemia and have an underlying diagnosis of multiple myeloma hence it is important to investigate patients.

201
Q

What are the first line investigations for suspected myeloma?

A

FBC (low white blood cell count in myeloma)
Calcium (raised in myeloma)
Erythrocyte sedimentation rate (raised in myeloma)
Plasma viscosity (raised in myeloma)

202
Q

What is the second line investigations for suspected myeloma?
What is necessary to diagnose the disease?

What specific things would you see on blood film and xray

A

B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis

Raindrop skull on xray - random patterns of dark spots on skull

Rouleax formation - the stacking of RBC on blood film

Electrophoresis = separating molecules based on charge

Bone marrow biopsy is necessary to confirm the diagnosis of myeloma

203
Q

What complication can the light chain proteins of the antibodies from the malignant plasma cells lead to in myeloma?

A

In myeloma, light chains can clump together and form insoluble deposits, they are called amyloid deposits.

Theses amyloid deposits will damage the organs and tissues they are in, leading to amyloidosis

204
Q

What is the treatment for myeloma?

A

Treatment:
Chemo
BM transplant
Bisphosphonates e.g. zolendronate
Correction of anaemia with transfusions of RBCs and EPO

205
Q

What is the chemotherapy given to older, frailer patients in multiple myeloma?

A

CTD 🡪 Cyclophosphamide, thalidomide and dexamethasone

206
Q

What is the chemotherapy given to younger, fitter patients in multiple myeloma?

A

VAD 🡪 Vincristine, Adriamycin, dexamethasone (for fitter people)

207
Q

Define haematocrit.

A

Haematocrit is a measure of the ratio of red blood cells to the total blood volume.
It is expressed as a percentage and is usually measured using a centrifuge

208
Q

What is seen in relative polycythaemia?

A

Decreased plasma volume, normal RBC mass. This is due to dehydration

209
Q

Define Polycythaemia.

A

Defined as an increase in haemoglobin, packed cell volume (PCV) and RBCs/haematocrit. (opposite of anaemia).

210
Q

What is the cause of primary polycythaemia?
What is the cause of secondary polycythaemia?

A

Primary - Increased RBC production due a genetic disorder or mutation

Secondary = too many red blood cells due to an underlying disease or condition

211
Q

Give 2 examples of Primary Polycythaemia

A

Polycythaemia rubra vera – genetic mutation in JAK2 gene
Primary familial and congenital Polycythaemia – mutation in EPO receptor gene

212
Q

Give two examples of Secondary polycythaemia

A

Due to chronic hypoxia (Like COPD) or erythropoietin producing tumours e.g. renal and hepatocellular carcinoma
Poor oxygen delivery e.g. high altitude
Dehydration

213
Q

Outline the pathphysiology behind Polycythaemia Vera

A

Normally, EPO from the kidneys binds to hemopoietic stem cells, activating JAK2 gene ===> activation of JAK2 gene leads to RBC production

In Polycythaemia vera, there is a mutation in JAK2 gene, so it is constantly activated and causing RBC production, even with no EPO bound to it

214
Q

What are some signs of polycythaemia vera?

A
  • Splenomegaly: because the excess red blood cells buildup in the spleen, which usually helps with removing excess cells.
  • Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
  • Plethoric appearance - flushing cheeks
  • Palmar erythema - red and inflamed hands
  • Hypertension
215
Q

What are some symptoms of polycythaemia vera?

A
  • Fatigue
  • Dizziness
  • Headache
  • Blurred vision
  • Increased sweating
  • Facial flushing
  • Pruritus: characteristically exacerbated by hot water, such as after a bath. This is due to the increased number of basophils and mast cells which contain histamine.
  • Erythromelalgia: pain, redness and swelling esp in hands and feet
216
Q

What are some diagnostic differences between primary and secondary polycythaemia?

A

Primary
EPO is low
Hepatosplenomegaly – result of extramedullary haemopoiesis
Raised WBC and platelets

Secondary
EPO is high
No splenomegaly
Normal WBC and platelets

217
Q

What are the investigations for Polycythaemia?

A

FBC (would have elevated haematocrit in both, WBC and platelets high in primary and normal in secondary)
Serum EPO (low in primary high in secondary)

BM biopsy
Genetic testing for JAK2 gene

218
Q

What is the management for polycythaemia?

A

Treatment:
Blood letting (venesection) – removal of 400-500ml blood, aim to keep haematocrit below 0.45
Aspirin
JAK2 inhibitor
Secondary – treat the cause

NICE recommends that cardiovascular risk factors are managed, such as diabetes, hyperlipidaemia, hypertension and smoking

219
Q

Treatment of polycythaemia - name a common JAK2 inhibitor given

A

ruxolitinib.

220
Q

What is myelofibrosis? What can it lead to?

A

It’s a myeloproliferative neoplasm, where healthy bone marrow tissue gets replaced with scar tissue.

This scar tissue means that body can’t produce enough blood cells, ===> leads to anaemia, increased risk of infection, and easy bruising and bleeding.

221
Q

How can polycythaemia lead to myelofibrosis?

A

in polycythaemia Vera, bone marrow cannot produce enough red blood cells to meet the body’s needs ==> it begins to produce abnormal cells and scar tissue

This can interfere with the production of healthy blood cells, eventually leading to myelofibrosis.

222
Q

Define thrombocytopaenia

A

Deficiency of platelets in bloods

223
Q

Name some causes of thrombocytopaenia

A

Problems with Production:
- Sepsis
- B12 or folic acid deficiency
- Leukaemia
- Liver failure Reduced thrombopoietin production

Problems due to the destruction of platelets
- Medications
- Alcohol
- Immune thrombocytopenic purpura
- Thrombotic thrombocytopenic purpura
- Heparin-induced thrombocytopenia

224
Q

What is Immune Thrombocytopaenic Purpura?

A

ITP is a condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.

225
Q

Name some causes of Immune thrombocytopenic purpura.

A
  • Primary ITP: when ITP occurs by itself
  • Secondary ITP: triggered by another condition e.g. hepatitis C, HIV, or lupus, malignancies
226
Q

Where are
a) Primary Immune Thrombocytopenic purpura
b) Secondary Thrombocytopenic purpura

Most common?
What is more acute?

A

ITP in children (acute/primary) often follows viral infection, there is rapid onset or purpura which is usually self-limiting
ITP in adults (chronic/secondary) is usually less acute than in children and characteristically seen in young women

227
Q

Outline the pathophysiology behind Immune thrombocytopenic purpura.

A

Autoanitbodies (mainly IgG) bind to platelet receptor Gp2B3A, and target platelets for destruction in the spleen.

Often triggered by viral infection or malignancy

228
Q

What are some symptoms of Immune thrombocytopaenia purpura?

A

Think - easy bleeding!

  • Purpura (red or purple spots on the skin caused by bleeding underneath skin)
  • Petechiae small, pinpoint spots on the skin - like purpura but smaller
  • Easy bruising
  • Epistaxis (nose bleed)
  • Menorrhagia (heavy menstruation)
  • Gum bleeding
  • Major haemorrhage is rare
  • Splenomegaly is rare
229
Q

What is the first line investigation you would do for suspected immune thrombocytopaenia purpura?

What would you see?

A

FBC: isolated low platelet count, with a normal haematocrit and leukocyte count

230
Q

What other tests are key to carry out in suspected immune thrombocytopenic purpura?

A

BM examination/Blood film – Could see increased megakaryocytes

  • Platelet autoantibodies (present in 60-70%) - not needed for diagnosis
  • Abdominal ultrasound can be done to rule out splenomegaly, and hepatitis C virus and HIV, since ITP is being triggered by those infections.
231
Q

What are the management options for immune thrombocytopenic purpura?

A

Prednisolone (steroids) -low dose in chronic ITP patients
IV immunoglobulins
Rituximab (a monoclonal antibody against B cells)
Splenectomy
Secondary ITP: treat underlying cause

In acute severe cases, can consider platelet transfusion, although this isn’t commonly used

232
Q

What monitoring should be given for patients with Immune thrombocytopenic purpura?

A

Need to monitor platelet count, and need to educate pt on concerning signs - eg persistent headaches/melaena

Need to control and monitor blood pressure and consider suppressing menstrual periods

233
Q

Outline the pathophysiology behind Thrombotic Thrombocytopenic purpura

A

Abnormally high levels and hence overactivity of VWF causes excessive/unnecessary clots in micro vessels. This uses up platelets in the body leading to a low platelet count (due to platelet consumption) and organ damage, and also haemolysis

234
Q

What is the cause of Thrombotic thrombocytopenic purpura?

A

It is due to a deficiency in the ADAMTS 13 gene - the ADAMTS 13 protein degrades VWF.

Deficiency of ADAMTS 13 can be due to;
- Inherited genetic
- Autoimmune, where antibodies can be created against the protein

235
Q

What diseases can TTP be assossicated with?

A

Associated with HIV, cancer and SLE
More common in adults
More common in females (3:2)

236
Q

What are some first things to look for in Thrombotic thrombocytopenic purpura?
What would the coombes test be for it?

A

FBC: thrombocytopenia and normocytic normochromic anaemia

Blood film - would see schistocytes (fragmented red blood cells)

Urinalysis - would see proteinuria and haematuria
- Unconjugated bilirubin: raised
- Lactate dehydrogenase: raised

Coombes test negative - would rule out autoimmune haemolytic anaemia

237
Q

What would the first line management for TTP be?

A

plasma exchange - (replenishes ADAMTS13 and removes
antibody)

PLUS –
corticosteroids

CONSIDER –
rituximab (a monoclonal antibody against B cells).

don’t give platelets, can increase the which of thrombosis!

238
Q

Normal physiology - what does Von Willebrand Factor do?

A
  • When there is injury, histamine and thrombin stimulate the endothelial cells and megakaryocytes to produce vWF.
  • vWf then attaches to the exposed collagen fibres, which allows platelets to adhere.
  • In addition to this, vWF is also needed as a carried for factor VIII and protects it from degradation.
239
Q

Normal physiology - what makes VWF?

A

It is synthesised and stored in the endothelial cells and megakaryocytes.

240
Q

Normal physiology - outline the clotting factors that make up the intrinsic, and then common pathway.

What test can be used to measure this?

A

Intrinsic 12 > 11 > 9 > 8 >10
Common 10 > 5 > 2 > 1

Factor 2 is called Prothrombin, when activated becomes thrombin
Factor 1 is called fibrinogen activated becomes fibrin
10 is initiator of common pathway

Activated Partial Thromboplastin Time test aPTT will measure it

think TT for table tennis, play indoors, aka INtrinsic

241
Q

Normal physiology - outline the clotting factors that make up the extrinsic, and then common pathway.

What test can be used to measure this?

A

Extrinsic pathway - from damage outside more common, 3 > 7 > 10

Both lead to common pathway, 10 > 5 > 2 > 1

Prothromin Time test (PT) will measure it

242
Q

Outline Von Willebrand disease.

A

Most common hereditary coagulopathy
Can be congenital or acquired
Also called pseudohaemophilia
Caused by von Willebrand factor deficiency
This assists platelet plug formation
vWF binds to factor VIII preventing clearance from plasma
More common in females

243
Q

What are some key clinical manifestations of VWF disease?

A
  • Easy, prolonged or heavy bleeding e.g.
    • Bleeding gums with brushing
    • Nose bleeds (epistaxis)
    • Heavy menstrual bleeding (menorrhagia)
    • Heavy bleeding during surgical operations

Easy bruising

244
Q

What investigations do you need to do for suspected VWF and what would you see in them in order to make a diagnosis?

A
  • Platelets count: usually normal except in type IIB
  • Prothrombin time: tests the extrinsic and common pathway and so is normal
  • Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged
  • Measurement of vWF antigen
    Factor VIII levels 🡪 can be decreased as vWF is not present to protect it

FAMILY HISTORY IS VERY IMPORTANT IN VWF

245
Q

What is the management for VWF disease?

A

Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):

  • Desmopressin:can be used to stimulates the release of VWF
  • VWFcan be infused
  • Factor VIIIis often infused along with plasma-derived VWF
246
Q

What do you treat specific women with VWF disease for?

A

Heavy periods!

Managed by a combination of:

  • Tranexamic acid (antifibrinolytic agent)
  • Mefanamic acid
  • Norethisterone
  • Combined oral contraceptive pill
  • Mirena coil

Hysterectomymay be required in severe cases.

247
Q

What is HIT?

A

Where heparin causes antibodies to be produced against platelets (they target platelet factor 4)

248
Q

What do the HIT antibodies cause?

A

They bind to platelets and activate clotting mechanisms. This causes a hypercoagulable state (leading to thrombosis)
They also bind to platelets and break them down leading to thrombocytopenia

249
Q

What is haemophilia?

A

Haemophilia A and haemophilia B are inherited severe bleeding disorders. Both causes by a deficiency in clotting factors

250
Q

What clotting factor is deficient in Haemophilia A?

A

Haemophilia A is caused by a deficiency in factor VIII.

251
Q

What clotting factor is deficient in Haemophilia B?

A

Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX

252
Q

Haemophilia can either be inherited or acquired - (X-linked condition so all male) - What are some of the causes of acquired haemophilia?

A

Inherited (X-linked condition so all male)
Acquired, Liver failure, vitamin K deficiency, autoimmunity against clotting factor, Disseminated intravascular coagulation

253
Q

What are the mutated genes seen in Haemophilia A called? What about haemophilia B?

A

The mutated genes in haemophilia A are called F8, and in haemophilia B they’re called F9. These are both on the X chromosome.

254
Q

What are the symptoms of haemophilia?

A

Abnormal bleeding
Excessive bleeding
Easy bruising
Spontaneous haemorrhage
Haematomas: collections of blood outside the blood vessels
Hemarthrosis: bleeding into joint

255
Q

Does Haemophilia affect bleeding time?

A

Haemophilia does not affect bleeding time

Haemophilia is a disorder of secondary haemostasis and does not affect platelets. Therefore bleeding time, a measure of primary haemostasis, is usually normal in haemophilia.

256
Q

Where would be common places for bleeding to occur in haemophilia

A

Gums
Gastrointestinal tract
Urinary tract causing haematuria
Retroperitoneal space
Intracranial

257
Q

What would the main investigations be for haemophilia?

A

activated partial thromboplastin time (aPTT) would be increased
Plasma VIII and IX assay
Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing.

258
Q

What is the management for haemophilia?

A

Infusions of deficient factor
Desmopressin to stimulate the release of vWF factor
Antifibrinolytics e.g., tranexamic acid

259
Q

What is a complication of the treatment for haemophilia?

A

Antibodies are created against the clotting factors being infused

260
Q

What are the normal ranges for neutrophils in the blood?

A

Neutrophils ( x10^9/L ) 1.7 - 6.5

40-75% of WCC
Above - Neutrophilia
Below - Neutropenia

261
Q

What are the normal ranges of Lymphocytes in the blood?

A

Lymphocytes ( x10^9/L ) 1.0 - 3.0
20-45% of WCC
Above/below = * Lymphopenia/philia

262
Q

What are the normal ranges of Platelets in the blood?

A

Platelets ( x10^9/L ) 150 - 400

Above/Below = Thrombocytopenia/philia

263
Q

What are the normal ranges for Red Blood cells in
a) Men
b) Women

A

Men = 4.5 - 6.5 (x 10^12/L)
Women = 3.9-5.6 (x10^12/L)

264
Q

How does HIV attach and enter a cell?

A
  • GP120 on HIV virus binds to CD4
  • This induces a conformational change in GP120
  • This enables co-receptor binding
  • This results in membrane fusion between virus and CD4 cells
265
Q

HIV affects CD4+ cells. (this includes T Helper Cells, Macrophages and Dendritic Cells). CD4 + molecule helps immune cells communicate,

How does HIV get into them?

A

HIV attaches a CD4 cell via BOTH gp120 protein and a co receptor

CXCR4 - In T Cells
CCR5 - In T cells, macrophages, monocytes, dendritic cells

People with mutations to co proteins can be protected from HIV

266
Q

What type of Virus is HIV? What does reverse transcriptase do?

A

A single stranded RNA retrovirus

The Virus injects a single strand of RNA into the cell.
Retrovirus - needs reverse transcriptase enzyme to transcribe a piece of complimentary proviral DNA,

267
Q

When in the cell, what does HIV virus do?

A

Uses reverse transcriptase enzyme to transcribe a piece of complimentary proviral DNA, to make a double strand with the original RNA strand.

This double stranded DNA then pops itself into the DNA of the cell (via integrase enzyme.) , ready to be transcribed into another virus cell, when the old immune cell becomes activated and starts trying to transcribe proteins for the immune response. (sneaky)

268
Q

How does HIV go from entering the body to infecting loads of cells at the lymph node? What does this lead to?

A
  1. Enters, say, through Genito urinal mucosa
  2. Macrophage recognise virus as forgein and phagocytose it, and then present HIV antigens on its surface
  3. Antigen presenting macrophage present HIV virus to a reservoir of immune cells T cells at lymph node.
  4. HIV virus can infect all these cells, leading to a massive spike of HIV in the blood, leading to flu like symptoms
269
Q

HIV infection - How long is the acute phase? What happens after this? How long is the chronic phase and what happens here?

A

12 weeks, After this the immune system will launch a counterattack and the number of normal T cells will begin to rise again.

The chronic phase then starts, lasting from 2 - 10 years, as the virus slowly increases and T cell number slowly start to decrease

270
Q

HIV infection: What do patients with 200-500 T cell/mm^3 present with?

A

Swollen lymph nodes
Hairy leukoplakia (white patch tongue)
Oral Candidiasis (Yeast infection in mouth)

271
Q

What do patients with <200 T cell/mm^3 present with?

A

Persistent fever, fatigue, Weight loss and diarrhoea

AIDS defining conditions appear

eg Recurrent bacterial pneumonia
Pneumocystis pneumonia
Fungal infections

272
Q

What are the percentages of the different modes of transmissions of HIV?

A

75% Sexual contact
the rest IV drug abuse
Mother to child (via placenta or breast milk)

Accidental needlestick injury and error in blood transfusion are least likely.

273
Q

What tests can you do for HIV. What is recommend as the first test?

A

Antibody tests (look for antibodies against HIV)
Antibody/Antigen (Look for virus directly and also antibodies
RNA tests - (look for viral RNA)
DNA tests -( look for Copies of the viral RNA)

Antibody/antigen test is recommended first

274
Q

If your first test for HIV is postive (Antibody/antigen test), what tests should you do next?

A

Antibody test, and RNA tests

275
Q

Once it has been diagnosed,how can we go about treating HIV?

A

With HAART drugs Highly active antiretroviral therapy (HAART)

==> It usually consist of 3+ antiretroviral drugs, that suppress viral replication, eg Nucleoside reveres transcriptase inhibitor

276
Q

What is Disseminated intravascular Coagulation?

A

A serious disorder occurring in response to an illness or disease process which results in dysregulated blood clotting.

In health, there is usually a balance between the clotting and fibrinolytic systems. However, in DIC inappropriate activation of one or both systems leads to a paradoxical tendency to both bleeding and thrombosis simultaneously, set off by various triggers

277
Q

What some things may trigger Disseminated intravascular coagulation?

A

Shock
Sepsis/severe infection, eg meningococcal sepsis in children. these lead to the massive release of pro-inflammatory cytokines in a systemic inflammatory response. These cytokines can activate the coagulation system.

Major trauma or burns
Malignancies: including both solid organ and haematological malignancies. Acute promyelocytic leukaemia (APML) is strongly associated with DIC.
Obstetric emergencies

278
Q

What are some typical symptoms of DIC?

A

Bleeding from unusual sites: ears, nose, gastrointestinal tract, genitourinary tract, respiratory tract or sites of venepuncture or cannulation. Bleeding from three unrelated sites is highly suggestive of DIC.
Widespread or unexpected bruising without a history of trauma
New confusion or disorientation: a sign of microvascular thrombosis affecting cerebral perfusion

Signs of haemorrhage: bleeding from cannula sites/venepuncture sites, melaena, haematemesis, rectal bleeding, epistaxis, haemoptysis, haematuria
Petechiae or purpura (Figure 3)
Livedo reticularis: a mottled lace-like patterning of the skin (Figure 4)
Purpura fulminans: widespread skin necrosis
Localised infarction and gangrene for instance of the digits

279
Q

What are some investigations for DIC, and what would you see in them?

A

Diagnosis suggested by history (severe sepsis, trauma, malignancy), clinical presentation and presence of severe thrombocytopenia
Prolonged PTT, APTT and Thrombin Time (TT)
Decreased fibrinogen
Increased fibrogen degradtion products like D-Dimer
Blood film – shows fragmented red cells - Schistocytes (‘helmet cells’)

280
Q

What is some management options you would see in DIC?

A

Platelet transfusions should be considered if the patient is bleeding. The platelet count should be maintained >50 x 109/L in the presence of bleeding.

prolonged PT and/or APTT, = fresh frozen plasma

Concentrated solutions of clotting factors may also be considered such as prothrombin complex concentrate, or specific factor infusions.

Severely low fibrinogen = transfusions of cryoprecipitate or fibrinogen concentrate (Cryoprecipiate = an extract rich in a blood-clotting factor obtained as a residue when frozen blood plasma is thawed.)

If thrombosis is a prominent feature, then therapeutic doses of heparin should be considered.

281
Q

What would you see in a biopsy in a patient with MM?

A

More than 10% of the bone marrow is occupied by plasma cells

282
Q

What are two coagulation tests you can do in thrombus formation?

A

aPTT - activated prothrombin time

PT - Prothrombin time

283
Q

For both coagulation tests, what pathway does aPTT measure, and what factors does it look at?

A

aPTT - activated prothrombin time

Looks at clotting factors 12, 11, 9 , 10 - intrinsic (TT - table tennis indoors)

284
Q

For both coagulation tests, what pathway does PT measure, and what factors does it look at?

A

PT - Prothrombin time - looks at factors 7 5 10 2 1 - extrinsic pathway

(T - tennis - outdoors )

285
Q

What clotting factors are consumed most rapidly in DIC?

A

Factors V and VIII are most rapidly consumed in DIC (according to passmed)

286
Q

In what conditions would you see sphereocytes on a blood film?

A

Hereidatory sphereocytosis
Autoimmune haemolytic anaemia

287
Q

factor 5 Leiden results in hypercoagulability due to what?

A

reduced activation of protein c

Phase 2a Sam (18 decks)

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