Lecture 11 Flashcards
What is the lifecycle of a RBC?
Bone marrow (haemopoiesis)
Peripheral blood cells
Removal (RES)
What is methotrexate used to treat?
Rheumatoid arthritis (folate antagonist)
Why does anaemia develop in anaemia of chronic disease due to inflammatory cytokines?
- iron dysregulation (available iron not released for use in bone marrow)
- marrow shows lack of response to EPO
- reduced lifespan of RBC’s
Is iron recycled?
Yes, by macrophages phagocytosing the old RBC’s (recycling is main source of iron)
What happens in anaemia of chronic disease?
Hepcidin is regulated by inflammatory cytokines (IL-6)
-this increases production of hepcidin from liver
-increased inhibition of ferroportin
-decreased iron release from RES/decreased iron absorption in gut
= plasma iron reduced (inhibition of erythropoiesis in bone marrow leading to anaemia)
What are some chronic diseases causing anaemia of chronic disease?
- Rheumatoid arthritis
- inflammatory bowel disease (Crohns disease/ulcerative colitis)
- chronic infections (TB)
What is anaemia of chronic kidney disease?
- reduced EPO production due to damage to kidneys
- reduced clearance of hepcidin + increased hepcidin due to imfammtory cytokines
- dialysis induced damage to RBC’s
- high levels of urea= uraemia (which reduces lifespan of RBC)
What is an underlying cause of chronic kidney disease?
Raised cytokines
What does uraemia cause?
Inhibits megakaryocytes leading to low platelet count
How do you treat anaemia of chronic disease? (CKD)
Treat underlying cause
(Renal failure- recombinant EPO injected + vit B12/folate/iron levels are adequate asall of these are required for EPO therapy to work)
-transfuse red cells if all else fails
What is reticulocyte Hb content used to assess?
CHr: Assess for functional iron deficiency
Give some haematological abnormalities in kidney disease:
Red cells
- anaemia (CKD, blood loss,dietary causes)
- secondary polycythemia (renal transplant/tumour)
Neutrophils
- neutropenia (autoimmune kidney disease, immunosupression)
- neutrophilia (inflammation, infection, drugs-steroids)
Platelets
-thrombocytopenia (uraemia, drugs, haemolytic uraemic syndrome-Ecoli)
-High (inflammation, bleeding, iron deficiency)
-
What is rheumatoid arthritis + what is it treated by?
Chronic immune mediated inflammatory condition
(see high neutrophils/platelets)
Treated by:
-pain relief (NSAIDS)
-disease modifying agents (DMARDS): drug to slow down process e.g. corticosteroids, chemotherapy, biological agents- monoclonal antibodies against cytokines that mediate inflammation (block cytokines)
Give examples of disease modifying agents:
- steroids
- methotrexate
- monoclonal antibodies against cytokines (block cytokines and stop damage being done)
Is anaemia in RA mutlifactorial?
Yes
- anaemia of chronic disease
- GI loss of blood due to chronic NSAID use
- increased risk of autoimmune haemolytic anaemia as RA is an autoimmune disease
What is Felty’s syndrome?
Combination of RA, splenomegaly, neutropenia
Neutropenia due to:
-spleen is large so destruction takes away neutrophils
-failure of bone marrow to produce neutrophils (myeloid cells in marrow become insensitive to stimulator GCSF)
What is liver disease?
Nodules and reduced function of liver (cirrhosis)
What does chronic liver disease cause?
- Portal hypertension (includes oesophagus) (back pressure leading to splenomegaly-leading to low blood count)
- leads to oesophagus/gastric varices (dilated veins which can burst causing massive acute blood loss)
- clotting factors are made in liver and some are dependent on vit K (in liver disease= low level of clotting factors)
- endothelial dysfunction
- low platelet count (platelets around don’t work well)
What are some haematological features of liver disease?
- target cells (due to increased cholesterol to phospholipid ratio so membrane is ‘baggy’)
- low platelet count (thrombocytopenia, as hormone thrombopoietin is mainly made in liver)
- splenic pooling
How does liver disease caused by alcohol excess cause haematological features?
Alcohol excess
- toxic to bone marrow cells (causing low platelet/pancytopenia)
- secondary malnutrition common (less money spent on food-especially folic acid deficiency-megaloblastic anaemia)
What does viral hepatitis cause?
Bone marrow failure
What are some post operative/ major trauma changes to blood?
RBC’s
-anaemia (blood loss pre/post op)
-temporary polycythaemia (anaesthetist not keeping patient hydrated)
White cells
-severe sepsis (neutropenia)
-post op to help with healing/post op infection/severe bleeding (neutrophilia)
Platelets
- drugs/sepsis (thrombocytopenia)
- thrombocytosis- common after operation (post-op, infection, bleeding): if doesn’t settle later look for blood loss
What are some haematological changes with infection?
- infection with malaria causes haemolytic anaemia
- bacterial infection (neutrohphilia), sepsis/severe bacterial infection (all neutrophils used up- neutropenia)
- parasitic infections (eosinophilia)
- viral infection (lymphocytosis/neutropenia)
- infection can cause a reactive thrombocytosis
What is DIC?
Disseminated intravascular coagulation
(Lots of fragmented blood cells, immature RBC’s with nuclei, low platelets)
-pathological activation of coagulation
-clots in vascular system
-many small clots in circulation (using platelets/fibrinogen), RBC’s get stuck getting through clots causing microangiopathic haemolytic anaemia
=long clotting times
=low fibrinogen
=risk of bleeding/thrombosis
What are some haematological changes in cancer?
Cancers not affecting bone marrow
INCREASED RISK OF VENOUS THROMBOSIS IN PEOPLE WITH CANCER - can break off and form clots in lungs (pulmonary emboli)
Anaemia
- ACD
- chronic bleeding causing iron deficiency
- chemotherapy (causing temporary stop in blood cell production)
- some EPO producing tumours = polycythaemia
Neutropenia (chemotherapy- neutropenic sepsis, marrow infiltrated bone marrow)
Neutrophilia- inflammation/infection
Thrombocytopenia (chemo, sepsis, DIC, marrow infiltrated)
Thrombocytosis (inflammation, infection, bleeding, iron deficiency)
What is a leucoerythroblastic film & what causes it?
Blood film showing immature white and red cells circulating in peripheral blood (spill out of bone marrow when it is under stress)
(Granulocyte precursors/ nucleated RBC’s seen)
- sepsis
- shock
- bone marrow infiltrated by carcinoma causing marrow to push out anything it has in it
- primary myelofibrosis (if has tear drop RBC’s)
- leukaemia
- severe megaloblastic anaemia (folate/B12 deficiency-often has oval RBC’s)
What is anaemia of chronic disease caused by?
Chronic inflammation
What is ‘functional’ iron deficiency?
There is sufficient iron in the body, but not available to developing erythroid cells
What is needed to recycle iron from macrophages?
Ferroportin is main exporter of iron out of the macrophage & gut cell
What is an important inflammatory cytokine released involved in iron regulation?
Interleukin 6 which are cytokines released from immune cells
When do you give your patient iron in anaemia of chronic renal failure?
If ferritin/CHr is low.
Iron given as IV form as absorption is imparied due to high levels of hepcidin.
What changes do you see to a patients hand with RA?
Swan neck deformity of fingers
Ulnar deviation
Boutonnière deformity of thumb
What do you see when RA is active?
High platelets and neutrophils
CRP (acute phase protein) will also be high
(Low platelets/neutrophils can occur due to treatment of disease/autoimmune reactions/hypersplenism)
How do viruses cause haematological features of liver disease?
Viral hepatitis
-bone marrow failure
How are clotting tests affected in DIC?
Clotting times are long as all the clotting factors have been used up
(Low fibrinogen/fibrin degredation products)
Therefore risk of bleeding AND thrombosis
