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Semester 2 - MEH > 11. Haematology in systemic disease > Flashcards

11. Haematology in systemic disease Flashcards

1
Q

What can cause changes to the blood in systemic disease?

A
  • underlying physiological or external cause e.g. over expression of cytokines
  • complications of the disease e.g. bleeding
  • adverse effects of treatment e.g. folate antagonists, immunosuppressants
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2
Q

what might cause reduced or dysfunctional erythropoiesis that might cause anaemia?

A
  • lack of response of kidney to make erythropoietin - chronic kidney disease
  • BM unable to respond to EPO e.g. after chemotherapy, toxic insult, infections such as parvovirus
  • in anaemia of chronic disease e.g. RA, iron is in the body but not made available to the BM for RBC production
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3
Q

What are the three main effects of anaemia of chronic disease?

A
  • iron dysregulation —> iron available is not released for use in BM
  • BM shows lack of response to EPO
  • reduced lifespan of RBCs

all causes by inflammatory cytokines in chronic inflammation

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4
Q

Give examples of conditions where anaemia of chronic disease can occur?

A
  • Rheumatoid arthritis
  • Inflammatory bowel disease (Ulcerative Colitis or Crohns disease)
  • Chronic infections eg bronchiectasis, TB
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5
Q

What is ferroportin?

A

ferroportin is the main exporter of iron out of the macrophage (and out of the gut cell)– so need ferroportin to recycle the iron

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6
Q

What is hepcidin regulated by?

A
  • HFE
  • Transferrin receptor
  • Inflammatory cytokines
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7
Q

What does hepcidin do?

A
  • Prevents iron release from macrophages
  • Prevents iron absorption from gut
  • By degrading ferroportin the protein involved in moving iron out of cells - Inhibits ferroportin: causes its internalisation and degradation
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8
Q

Describe how inflammatory conditions can cause anaemia?

A
  • inflammatory conditions like rheumatoid arthritis, chronic infection, malignancy cause the release of cytokines like IL6 by immune cells.
  • Cytokines cause increased production of hepcidin by liver
  • Hepcidin causes inhibition of ferroportin which decreases iron release from reticuloendothelial system and decreased iron absorption in gut
  • this reduces plasma iron so inhibition of erythopoeiesis in bone marrow and thus results in anaemia
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9
Q

How do we treat anaemia of chronic disease?

A

treat underlying condition:

  • if associated renal failure - give recombinant human EPO
  • ensure vit B12, folate and iron stores are adequate for EPO therapy to work
  • transfuse RBCs if all else fails and patient is very symptomatic
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10
Q

What is the main molecule released in inflammatory conditions which contributes to the anaemia?

A

IL-6

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11
Q

What are the effect of IL-6 on erythropoiesis?

A
  • stimulates production of hepcidin in the liver
  • inhibitory effects on erythropoiesis by limiting proliferation and differentiation of red cell progenitors and blunting the response to erythropoietin.
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12
Q

What size are the RBCs in anaemia of chronic disease?

A

Similar to iron deficiency anaemia, in the early stages of the disease MCV is normal but as the disease progresses microcytic anaemia results

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13
Q

What are the size and colour of RBCs in chronic kidney disease?

A

Normochromic and normocytic (or microcytic)

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14
Q

What is the severity of anaemia in chronic kidney disease proportional to?

A

Proportional to the severity kidney disease

i.e. the lower the GFR (glomerular filtration rate) the higher the severity of the anaemia.

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15
Q

What different factors lead to anaemia in chronic kidney disease?

A
  • deficiency of erythropoietin production by the damaged kidneys (most common)
  • reduced renal clearance of hepcidin from blood combined with Increased hepcidin production by kidneys due to inflammatory cytokines reduce erythropoiesis due to a functional lack of iron
  • uraemia - leads to reduced lifespan of RBC
  • anaemia worsened by dialysis -damage to Red
    blood cells
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16
Q

What is uraemia?

A

a raised level in the blood of urea and other nitrogenous waste compounds that are normally eliminated by the kidneys.

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17
Q

How does uraemia contribute to anaemia?

A

Inhibit erythropoiesis and reduces the lifespan of existing red blood cells as well as inhibits megakaryocytes leading to low platelet counts

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18
Q

What is the effect of inhibition of platelet function by uraemia?

A

chronic bleeding from the gastrointestinal tract

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19
Q

How does dialysis worsen anaemia?

A

Loss and mechanical destruction of red blood cells

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20
Q

How does chronic kidney disease affect ferritin and CHr?

A

Normal or high for both

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21
Q

What is commonly used to manage renal anaemia and what is given in addition to this to support the increased rate of erythropoiesis?

A

Recombinant human EPO

  • must ensure sufficient iron, folate and B12
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22
Q

What are some adverse effects of EPO (recombinant human forms)?

A

Hypertension, seizures, and blood clotting during dialysis

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23
Q

What type of iron deficiency does anaemia of chronic inflammation cause?

A

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

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24
Q

Why is there a reduced life span of RBCs in anaemia of chronic disease?

A

In AOCD at the start of the condition the MCV is normal however as the disease progresses RBC become microcytic.
These abnormal RBCs will be removed by macrophages causing a reduction in the lifespan of the RBCs.
As well as this increased activity of macrophages in the underlying chronic inflammatory condition also reduces the lifespan of red blood cells.

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25
Q

Explain the level response of the bone marrow to erythropoietin in anaemia of chronic disease

A

Cytokines that are released from the underlying condition exert inhibitory effects on erythropoiesis.
This is done by limiting the proliferation and maturation of the progenitors of RBCs (e.g reticulocytes) as well as by reducing the bone marrows abiltity to respond to erythropoietin so it means that RBCs will be reduced in production.

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26
Q

When treating anaemia of chronic disease with associated renal failure, what needs to be done if all else fails and patient is symptomatic?

A

Transfuse red cells, only if all else fails and patient is symptomatic

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27
Q

How can a deficiency of EPO result in the development of CKD?

A

Damaged kidneys will result in a reduction in the amount of EPO produced and released. The lower levels of EPO will lead to a reduction in RBC production and anaemia.

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28
Q

What role does hepcidin play in the development of anaemia as a result of CKD?

A

The increased hepcidin results in less iron absorption from the gut and less release of iron from stores.
This is done by decreasing ferroportin expression and promoting internalisation of ferroportin molecules.

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29
Q

What are the NICE guidelines for management of anaemia of chronic renal failure?

A
  • Use CHr (or % hypochromic cells) to assess for functional iron deficiency
  • Give iron if ferritin <200µg/L (normal range 15-
    400µg/L ) or CHr low
  • Iron given in intravenous form as absorption is impaired (….Hepcidin)
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30
Q

How might renal disease cause high or low RBC count?

A

Low:
• ARF/ACD • Blood loss • Haematinic causes

High
• Low O2 level detected e.g. Post renal transplant etc • Renal tumour •how

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31
Q

How might renal disease cause high or low neutrophil count?

A

Low:
• immunosuppression due to post renal transplant drugs
• marrow infiltration eg in myeloma

High
• inflammation • connective tissue disease
• Infection • drugs: steroids cause neutrophilia

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32
Q

How might renal disease cause high or low platelet count?

A

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

High
• reactive • bleeding • iron deficiency

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33
Q

What is Rheumatoid arthritis?`

A

It’s a chronic immune mediated inflammatory condition.

34
Q

What is rheumatoid arthritis treated with?

A 
◦ Analgesis often NSAIDs
disease modifying agents:
◦ Corticosteroids
◦ Chemotherapy eg methotrexate
◦ Biological agents - monoclonal antibodies
35
Q

Why is iron deficiency more common in rheumatoid arthritis?

A

Need for NSAIDs and corticosteroids which can cause gastrointestinal blood loss
- majority iron in body is from recycled RBCs

36
Q

What effect do disease-modifying anti-rheumatic drugs

(DMARDs) have on platelets and neutrophils and how?

A

Cause thrombocytopenia and/or neutropenia through marrow suppression, immune causes or folate-inhibition.

37
Q

What kind of anaemia can develop in asssociation with rheumatoid arthritis?

A

You can get the development of anaemia of chronic disease or autoimmune haemolytic anaemia

38
Q

What effect does rheumatoid arthritis and the treatments associated have on blood cells?

A

When the disease is active it can cause high platelets and neutrophils counts (there’ll also be high CRP levels).

However when treatment has been implemented you’ll get low platelets and neutrophils through marrow suppression, immune causes or folate-inhibition

39
Q

How might rheumatoid arthritis cause low RBC count?

A
  • ACD
  • blood loss eg due to NSAIDs/corticosteroids
  • Haematinic (reduced appetite, less B12 and folate)
  • Immune haemolytic anaemia
40
Q

How might rheumatoid arthritis cause high or low neutrophil count?

A

High
•Associated inflammation
•infection
•drug reactions…..

Low
•drugs eg methotrexate
•immune

41
Q

How might rheumatoid arthritis cause high or low platelet count?

A

High
• reactive
• bleeding
• iron deficiency

Low
• drugs autoimmune
• splenomegaly
• (Felty’s)……

42
Q

What is Felty’s syndrome?

A

It’s a triad of conditions between rheumatoid arthritis, splenomegaly and neutropenia.

43
Q

How does neutropenia occur in Felty’s syndrome?

A

◦ Is thought to be due to splenomegaly contributing to peripheral destruction of neutrophils, and
◦ failure of bone marrow to produce neutrophils as there is insensitivity of the myeloid cells to the stimulator GCSF (Granulocyte colony stimulating
factor)

44
Q

What are the different ways alcohol consumption can lead to anaemia?

A
  • direct effect on bone marrow
  • autoimmune response against RBCs due to metabolite of ethanol
  • cirrhosis
  • portal hypertension
  • folic acid deficiency (due to malnutrition in alcohol abuse)
45
Q

What direct effect does heavy alcohol consumption have on bone marrow?

A

Generalised toxic effect on bone marrow leading to the suppression of haematopoiesis and resulting in the production of structurally abnormal blood cell precursors that cannot mature into functional cells.
- RBCs can become macrocytic and thrombocytopenia is common

46
Q

What is the metabolite of ethanol and what effect does this have on RBCs?

A

Acetaldehyde produced from ethanol metabolism can produce protein-acetaldehyde adducts on red blood cells leading to an immune response against these modified proteins

47
Q

How does cirrhosis contribute to anaemia?

A

Result in abnormal production of some of the clotting factors and this contribute to gastrointestinal bleeding contributing to anaemia

48
Q

How can portal hypertension contribute to anaemia?

A

May lead to congestive splenomegaly and splenic trapping of red cells, white cells and platelets resulting in progressive pancytopaenia

Also leads to oesophageal and gastric varices
(dilated veins prone to bleeding due to higher than normal pressure)

49
Q

How can alcohol abuse lead to megaloblastic anaemia?

A

Alcohol abuse is also a common cause of folic acid deficiency leading to a megaloblastic anaemia.

50
Q

What is portal hypertension?

A

excessive alcohol consumption can lead to an increase in pressure in the portal veins (between the liver and the stomach/ intestines) this is known as portal hypertension

51
Q

What is the effect of splenomegaly as a result of portal hypertension?

A

It results in an increase in the trapping of blood cells in the spleen and an overactive removal of cells.
This means that you’ll have a low blood count.

52
Q

Give the factors that contribute to blood loss in liver disease (alcoholic)

A 
Blood loss, contributed to by:
• deficiencies of coagulation factors
• endothelial dysfunction
• thrombocytopenia
• defective platelet function
53
Q

Why is thrombocytopenia common in patients with liver disease?

A

In 75% patients with liver disease:
• Impaired production as thrombopoietin is made in the liver
• Splenic pooling
• Increased destruction

Those platelets made often have reduced function
which contributes to the bleeding

54
Q

What type of infections may cause neutropenia or neutrophilia?

A

Neutropenia: post-viral infection
Neutrophilia: bacterial infection

55
Q

What kind of RBCs is often seen in liver disease ?

A

Target cells, this is due to an increased cholesterol: phospholipid ratio.

56
Q

What type of infections may cause lymphocytosis or lymphopenia?

A

Lymphocytosis: Viral infection in children e.g. Bordatella Pertussis

Lymphopenia: HIV

57
Q

What type of infections may cause Eosinophilia?

A

Parasitic infections

58
Q

What type of infections cause DIC?

A

Sepsis

59
Q

Give an example of an infection that causes MAHA?

A

E. coli diarrhoea in children

60
Q

Give examples of infections that cause splenomegaly

A

Malaria, glandular fever

61
Q

What type of infection causes aplastic anaemia?

A

Viral hepatitis

62
Q

Explain how viral hepatitis and autoimmune liver disease can result in the haematological features of liver disease

A
  1. Viral hepatitis
    The virus causes bone marrow failure (hypoplastic/ aplastic marrow), this can develop after an episode of hepatitis.
  2. Autoimmune liver disease
    This can result in immune mediated anaemia as well as thrombocytopenia or neutropenia
63
Q

Why might anaemia be present post op?

A

Due to blood loss or dilution (by peri-operative intravenous fluid)

64
Q

What would worsening thrombocytosis or neutrophilia or presence of DIC post op represent?

A

Infective complication

65
Q

What are immobile patients post-op at increased risk of?

A

Deep vein thrombosis

66
Q

What are the common reactive haematological changes post op?

A

Mild thrombocytosis and neutrophilia

- which should settle

67
Q

Why might patients have Temporary relative polycythaemia post op?

A

dehydration

68
Q

Why might patients have Neutropenia or neutrophilia post op?

A

Neutropenia
• Severe sepsis

Neutrophilia
• Post-op reactive
• Infection
• Severe bleeding

69
Q

Why might patients have Thrombocytopenia or thrombocytosis post op?

A

Thrombocytopenia
• Drugs
• Sepsis
• D.I.C

Thrombocytosis
• Post-op reactive
• Infection
• Bleeding

70
Q

What are the haematological changes post-splenectomy?

A

Immediately post-splenectomy there is often a very high rebound thrombocytosis and lymphocytosis and this can persist in some patients long-term. Howell-Jolly bodies will be seen in the red cells.

71
Q

What is Disseminated intravascular coagulation (DIC)?

A
  • Pathological activation of coagulation

- Numerous microthrombi are formed in the circulation

72
Q

What are the effects of DIC?

A

Consumption of clotting factors
- risk of bleeding and thrombosis

MAHA (due to thrombi)

73
Q

How can non-haematological cancers e.g. lung, breast cause a fall in Hb?

A
  • anaemia of chronic disease
  • blood loss
  • haemolytic anaemia
  • infiltration of the bone marrow
  • chemotherapy interrupting blood cell production
74
Q

What are patients receiving chemotherapy at risk of?

A

Neutropenic sepsis

75
Q

What may patients on chemotherapy require?

A

may need blood product support (donor red cells or platelets)

76
Q

What type of blood film may be seen if bone marrow is infiltrated by a metastatic cancer?

A

Leucoerythroblastic blood film

77
Q

What is seen in a leucoerythroblastic blood film?

A

Immature white cells and nucleated red blood cells seen in the blood, often in the context of a
pancytopenia

78
Q

When might a leucoerythroblastic blood film be seen?

A
  • Sepsis/shock
  • Bone marrow infiltration by carcinoma or haematological malignancy
  • Severe megaloblastic anaemia
  • Primary Myelofibrosis
  • AML/MDS
  • Storage diseases
79
Q

What are 3 adaptation to anaemia?

A
  • increased EPO
  • increased BPG (curve shifts to right, Hb gives up more oxygen)
  • decrease in systemic vascular resistance leading to increased CO
80
Q

Describe the haematological changes that can be seen in patients with cancer

A 
Anaemia
• Bleeding eg bowel, stomach, bladder, endometrium
• Iron deficiency
• ACD
• Treatments – chemotherapy

Polycythaemia
• EPO producing tumours

Neutropenia
• Chemotherapy
• Marrow infiltrated by cancer cells

Neutrophilia
• Inflammation
• Infection

Thrombocytopenia
• Chemotherapy
• Sepsis
• D.I.C
• Marrow infiltrated
Thrombocytosis
• Inflammation
• Infection
• Bleeding
• Iron deficiency

Semester 2 - MEH (23 decks)

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