Haematology in systemic disease

Question 1

Physiological life cycle of blood cells

Answer 1

Blood cells made in bone marrow—> sent out to the periphery and then removed by the spleen (reticulocytes-endothelial system)

Question 2

Haematological changes associated with

Answer 2

1. Anaemia of chronic disease and anaemia of renal disease
2. Rheumatoid arthritis
3. Liver disease / alcohol excess
4. Post-operative state and infection
5. Cancer

Question 3

Changes to the blood is systemic disease are often multi-factorial due to…

Answer 3

• Physiological causes e.g. inflammatory cytokines (IL-6)
• Complications of the disease
  
  • e.g. UC loss of blood and unable to absorb nutrients
• Treatment- adverse effects e.g. methotrexate

Question 4

Anaemia results due to

Answer 4

• Lack of response from haemostatic loop
  
  • E.g. in chronic kidney disease the kidney stops making EPO
• Bone marrow unable to respond to EPO
  
  • E.g. after chemotherapy, toxic insult or infections (parvovirus)
• In anaemia of chronic disease e.g. rheumatoid arthritis, iron is not made available to marrow for RBC production

Question 5

which cells produce erythropoietin in response to hypoxia

Answer 5

pericytes in the kidney

Question 6

EPO binds to

Answer 6

receptros on erythroblasts in bone marrow and stimualtes red cell production

Question 7

anaemia of chronic disease: examples of chronic disease

Answer 7

Rheumatoid arthritis, IBD, chronic infections e.g. TB

Question 8

mode of actiom of anaemia of chronic disease

Answer 8

IL- 6 released by immune cells due to inflamamtory condition

• increased production of hepicidin by the liver
• hepcidin
  
  • inhibits ferroprotion
    
    • decreased iron release from RES
    • decreased iron absorption in the gut
    • leads to plasma iron reduced
• plasma iron reduction leads gto inhibition of EPO in bone marrow –> anaemia

Question 9

anaemia of chronic disease leads to what sort of iron deiciency

Answer 9

Functional iron deficiency- sufficient iron in the body but not available to develop erythropoiesis cells

à due to hepcidin

Question 10

hepcidin prevents

Answer 10

iorn release from macrophages and iron absorption from the gut

Question 11

anaemia of chronic kidney disease

Answer 11

• Kidney becomes damaged and less functional throughout disease
• Will need renal replacement therapy e.g. dialysis or intraperitoneal dialysis
• Underlying cause of CKD often associated with raised cytokines
  
  • Reduced clearance of hepcidin and increase hepcidin production due to inflammatory cytokines
• Dialysis- damages red blood cells- shear stress e.g. of the dialysis tubing
• Reduced lifespan of RBC as a direct effect of uraemia - high levels of urea
  
  • Ureamia also inhibits megakaryocytes- leading to low platelet count

Question 12

ureamia

Answer 12

inhibits megakaryocytes leading to low platelet count

Question 13

Treatment of anaemia of chronic disease

*

Answer 13

• Treat underlying condition
• Associated with renal failure
  
  • Give recombinant human EPO
  • Ensure Vit B12 folate and iron stores are adequate
• Transfuse red cells- only if all else fails and patient symptomatic
• Absorption given in IV form due to absorption being impaired

Question 14

with A of CKD what csan be used to assess function iron deficiency

Answer 14

reticulocyte haemoglobin content

Question 15

how to treat A of CKD low iron

Answer 15

give ferritin

• iron should be given in intravenous form as absorption

Question 17

possible haematological abnormalities in kidney disease

Answer 17

Question 18

3. Rheumatoid arthritis

Answer 18

A chronic immune mediated inflammatory condition

Question 19

treatment of RA

Answer 19

• Pain relief (NSAIDS)
• Disease modifying agents (DMARDs)
  
  • Corticosteroids
  • Chemotherapy e.g. methotrexate
  • Biological agents – monoclonal antibodies against cytokines

Question 20

features of RA

Answer 20

• Anaemia is multifactorial
  
  • ACD
  • GI blood loss due to NSAIDS and steroids
  • Risk of autoimmune haemolytic anaemia
• High platelets and neutrophils when disease is active (CRP will also be up)
• Low platelets and neutrophils may occur due to treatment, autoimmune reactions or to hypersplenism (splenomegaly can occur in this condition)
  
  • Feltys syndrome

Question 21

Felty’s syndrome

Answer 21

Triad: Rheumatoid arthritis, splenomegaly and neutropenia

• Neutropenia due to splenomegaly contributing to peripheral destruction of neutrophils and failure of bone marrow to respond to GCSF (myeloid cell stimulator)

Question 22

liver disease

Answer 22

Chronic liver disease will cause portal

hypertension which causes splenomegaly

which leads to:

• Splenic sequestration of cells
• Overactive removal of cells
• Low blood count

Question 23

Haematological features of liver disease

Answer 23

Thrombocytopenia in 75% of patients

• Impaired production of thrombopoietin is made in the liver
• Splenic pooling
• Increased destruction
• Those platelet made often have reduced function which contributes to bleeding

*Target cells often seen in liver disease- due to increased cholesterol: phospholipid ratio

Question 24

why does chronic kliver diseas elead to splenomegaly

Answer 24

portal hypertneson

Question 25

Portal hypertension also leads to

Answer 25

**oesophageal and gastric varices** (dilated veins prone to bleeding due to higher than normal pressure) * Most **clotting factors** are made by the liver, synthesis of some dependent on vitamin k- patients will become quickly deficiency in clotting factors

Question 26

blood loss in chronic liver disease contributed to by

Answer 26

* Deficiencies of coagulation factors * Endothelial dysfunction * Thrombocytopenia * Defective platelet function

Question 27

**Other haematological features of liver disease are depending on the underlying cause**

Answer 27

**Alcohol excess** * Directly toxic to bone marrow cells- pancytopenia * Secondary malnutrition **–** folic acid deficiency **Viral hepatitis** * Bone marrow failure (hypoplastic/aplastic marrow) can develop after hepatitis **Autoimmune liver disease** * Immune mediated anaemia, thrombocytopenia or neutropenia

Question 29

**5. Post operative reactive changes**

Answer 29

Question 30

**6. Haematological changes with infection**

Answer 30

**Red blood cells- chronic infection can cause anaemia of chronic disease e.g. malaria can cause haemolytic anaemia**

Question 31

neutrophil reaction to bacterial infection

Answer 31

* Neutrophilia- associated with bacterial infections * Neutropenia- associated with severe bacterial infection/sepsis

Question 32

neutrophil reaction to paracytic infection

Answer 32

eosinophilia

Question 33

neutrophil reaction to viral infection

Answer 33

lymphocytosis and neutropenia

Question 34

thrombocytes and infection

Answer 34

* Infection can cause reactive thrombocytosis * Severe infection can cause thrombocytopenia * Thrombocytopenia may be associated with with disseminated intravascular coagulation (DIC) in severe sepsis

Question 35

S**epsis can lead to clotting abnormalities- disseminated intravascular coagulation (DIC)**

Answer 35

* Pathological activation of coagulation * Numerous microthrombi are formed in the circulation * Consumption of clotting factors and platelets and a consequence microangiopathic haemolytic anaemias (MAHA) * Clotting tests * Clotting time ling * Low fibrinogen * Raised D-dimers * **Risk of both bleeding and thrombosis**

Question 36

**Leucoerythroblastic film** *

Answer 36

**Granulocyte precursors and nucleated RBC seen on blood film** * Spilling out from the marrow into the blood when the marrow is under stress * Sepsis * Bone marrow infiltration by carcinoma or haematological malignancy * Severe megaloblastic anaemia * Primary myelofibrosis * Leukaemia * Storage disorder

Question 37

haematological changes in cancer

Answer 37