6a: Haematology in systemic disease Flashcards Preview

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Flashcards in 6a: Haematology in systemic disease Deck (43):
1

What three things must we consider when we think about things influencing patient blood counts

  1. Cause
  2. Complications (bc of systemic disease)
  3. Treatment

2

What are the causes of reduced erythropoeisis? 

  1. Empty bone marrow unable to respond to stimulus from EPO eg after chemotherapy or toxic insult such as parvovirus infection or in aplastic anaemia
  2. Marrow infiltrated by cancer cells or fibrous tissue (myelofibrosis) means the normal haemopoietic cells are reduced
  3. Lack of response to the haemostatic loop – eg in chronic kidney disease the kidney stops making EPO

3

What is Anaemia of Chronic Disease/inflammation?

Anaemia of chronic disease (also called anaemia of inflammation) is a common cause of anaemia (2nd worldwide after iron deficiency) associated with chronic inflammatory conditions such as rheumatoid arthritis, chronic infections (e.g. tuberculosis) and malignancy

4

How is RBC production control? 

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5

What is anaemia of chronic disease an example of? 

Dyserythropoiesis

6

How does anaemia of chronic disease occur? 

  1. Iron dysregulation: iron not released for use in bone marrow
  2. The marrow shows a lack of response to erythropoietin
  3. Reduced lifespan of red cells

7

What is a functional iron deficiency? 

Sufficient iron in the body but not available to the developing erythroid cells

8

Describe the importance of macrophages in supplying iron

  • In bone marrow, erythroid cells develop in islands surrounding a nursing macrophage
  • Macrophage takes the iron and gives to RBCs that need it
  • Macrophages ‘eat’ old senescent RBCs and recycle iron
  • Iron recycling is the main source of iron for new rbc
  • Small amount of iron absorbed from gut

9

What is Hepcidin?

  • Degrades ferroportin a protein involved in moving iron out of cells
  • Prevents iron release from macrophages
  • Prevents iron absorption from gut

10

What is hepcidin regulated by? 

  • HFE (hereditary haemochromatosis)
  • Transferrin receptor
  • Inflammatory cytokines - MOST IMPORTANT

11

Outline the causes for Anaemia of Chronic Disease/inflammation due to inflammatory cytokines

  • Iron dysregulation: iron not released for use in bone marrow
  • The marrow shows a lack of response to erythropoietin
  • Reduced lifespan of red cells

12

How does Chronic kidney disease result in anaemia? 

  • Deficiency of erythropoietin production by the damaged kidneys
  • Lower level of erythropoiesis in bone marrow leading to insufficient red cell production and anaemia
  • Reduced clearance of hepcidin from blood
  • Increased hepcidin production due to inflammatory cytokines
  • Reduced lifespan of RBC as a direct effect of uraemia
  • Dialysis-damage to rbc and loss due to bleeding

13

List some investigations for chronic kidney disease 

  • Often normocytic normochromic or microcytic anaemia
  • Normal or high ferritin (iron stores) 
  • Normal or high Reticulocyte Haemoglobin content (CHr)
  • CRP often elevated

14

How do we treat anaemia of chronic disease? 

  • Treat underlying condition – need to reduce inflammation and reduce the number of cytokines circulation
  • Recombinant human erythropoeitin – can be given if associated renal failure. Only effective in patients with sufficient iron, folate and B12 to support an increase in erythropoiesis
  • Vit B12 folate -  to ensure  and iron stores are adequate
  • Transfuse - if all else fails and patient is symptomatic (and sparingly)

15

Describe the management of the chronic renal failure 

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16

Describe how chronic kidney disease can cause uraemia and some consequences of this 

  • Kidney dysfunction can result in uraemia (increase in urine concentration) 
  • Can inhibit erythropoiesis
  • Reduces the lifespan of existing red blood cells as well as inhibiting platelet function
  • Can cause chronic bleeding from the gastrointestinal tract

17

Discuss why there may low or high platelet count in chronic kidney disease 

Low:

  • direct effect of uraemia on platelet production
  • drugs
  • Haemolytic uraemic syndrome

High

  • Reactive
  • bleeding
  • iron deficiency

18

Discuss why there may low or high RBC count in chronic kidney disease 

Low:

  • ARF/ACD (acute renal failure)
  • Blood loss
  • Haematinic causes

High

  • Post renal transplant
  • Renal tumour

19

Discuss why there may low or high WBC count in chronic kidney disease 

Low:

  • Immunosuppression post renal transplant drugs
  • Marrow infiltration eg in myeloma

High

  • Inflammation
  • Connective tissue disease
  • Infection
  • Drugs: steroids

20

What is Rheumatoid Arthritis

  • Chronic immune mediated inflammatory conditions
  • Damage to the synovial joint - Joint inflammation

21

How is Rheumatoid Arthritis treated? 

  • Analgesia often NSAIDs
  • Corticosteroids
  • Chemotherapy

22

How does Rheumatoid Arthritis cause low haemoglobin?

  • Anaemia of chronic disease
  • Blood loss due to NSAIDs or corticosteroids > erosions in stomach > bleeding > reduced iron to support > reduced erythropoesis
  • Haematinic
  • Immune dysfunction: AB production against RBCsa

23

Why may WBC count be high for rheumatoid arthritis? 

 

  • Infection: steroid could increase susceptibility to infections
  • Associated inflammation
  • Drug reactions

24

Why may the WBC count be low for individuals with rheumatoid arthritis? 

  • Drugs e.g. methotrexate and not taking their folic acid. Methotrexate interferes with folic acid cycle
  • Immune – associated with folate deficiency

25

Explain why the platelet count may be low or high for rheumatoid arthritis? 

High platelet count

  • Reactive
  • Bleeding – increase in platelet count
  • Iron deficiency

Low platelet count

  • Drugs autoimmune splenomegaly  (Felty’s)......
  • Immune dysfunction leading to disruption of their platelets

26

What is Felty's syndrome? 

Triad of rheumatoid arthritis, splenomegaly and thrombocytopenia

27

What is neutropenia? 

  • Occurs secondary to splenomegaly
  • Peripheral destruction of neutrophils, and failure of bone marrow to produce neutrophils
  • High level of G-CSF, insensitivity of myeloid cells to cytokines

28

How do changes in the blood flow in the liver cause anaeamia of chronic disease? 

Liver disease has many associated blood changes

Increases portal hypertension: 

 

29

How do changes in portal hypertension occur in chronic liver disease? 

  • Increase in resistance bc the blood is not flowing through v well
  • Increase in blood resistance from gut
  • Backup of blood
  • Enlarged spleen

30

How does portal hypertension cause splenomagaly

 

  • Causes splenomagaly
  • Leading to sequestration of cells
  • Because they are spending longer in spleen, more change for: Overactive removal of the cells

31

Describe the effects of esophageal and gastric varices  in chronic liver disease

  • Portal hypertension also leads to esophageal and gastric varices  (back up of blood)
  • Can have little bleeds chronic bleeds or massive bleeds
  • Clotting factors are produced in the liver – more susceptible to bleeding
  • Causes blood loss
  • Endothelial dysfunction
  • Thrombocytopenia
  • Defective platelet function - platelets don't work as well as they should do due to

32

What is Zeive's syndrome? 

  • Acute haemolytic anaemia
  • Associated with the changes in lipid in the cell membrane for patients with liver disease
  • This alters the shape of the cells > leading to macrocytosis, target cells and can lead to haemolysis

33

Describe how Thrombocytopaenia in Liver disease arises

  • Liver produces thrombopoetin
  • Impaired production as thrombopoietin is made in the liver
  • Splenic pooling - because of splenogomagaly
  • Increased destruction - platelets don't work properly 

34

Describe the three other main haematological features of liver disease? 

  1. Alcohol excess - toxic to bone marrow cells; secondary malnutrition (folic acid deficiency)
  2. Hepatitis - because of bone marrow failure
  3. Immune - immune mediated anaemia

35

Explain why low/ high WBC count arises from liver disease

 

Low

  • Impaired production (iron or folate deficiency, alcohol toxicity)
  • Splenic pooling
  • Increased destruction

High: steroids 

36

Explain why low/ high WBC count arises from liver disease

 

Low

  • Impaired production (iron or folate deficiency, alcohol toxicity)
  • Splenic pooling
  • Increased destruction

High: steroids 

37

Explain why low/ high platelet counts arise from liver disease

 

Low

  • Impaired production (iron or folate deficiency, alcohol toxicity)
  • Splenic pooling
  • Increased destruction

High:

  • Bleeding

38

How do post operative changes cause anaemia? 

  • Following major surgery patients often have a mild thrombocytosis or neutrophilia which should settle.
  • Anaemia can be present due to blood loss or dilution

39

Describe how post operative changes would affect RBC, WBC and platelet counts

RBC

  • Low - Bleeding
  • High - Dehydration 

WBC 

  • Low - infection/ sepsis; high: sepsis 

Platelet count

  • High: Bleeding, Infection, Reactive
  • Low: Medication (heparin); sepsis; DIV 

40

Give some examples of anaemia of chronic disease 

  1. Chronic kidney disease/ chronic renal failure
  2. Rheumatoid arthritis 
  3. Liver disease 
  4. Post op reactive changes
  5. Infection

41

Outline some haematological changes associated with infection? 

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42

What term would be used to describe a blood film where Granulocyte precursors and nucleated RBCs are present?

Leucoerythroblastic film

43

Describe the effects of ureaemia in kidney dysfunction

Kidney dysfunction can result in uraemia (as they can't excrete urea as efficiently) an increase in urea concentration in blood acts to inhibit erythropoiesis and reduces the lifespan of existing red blood cells as well as inhibiting platelet function, which can cause chronic bleeding from the gastrointestinal tract.