Haematological Response to Infection and Bone Marrow Failure Flashcards
Why is IL-3 so important for production of several different WBCs and platelets?
It acts on all cell lineages from the start.
How are megakaryocytes formed?
Within cytoplasm you have mitosis occuring within the cytoplasm several times creating exponential growth of nucleus numbers
How do platelets form in the nucleus of megakaryocytes?
Platelets are beginning to form when the nucleus is starting to die. When the nucleus dies it is deconstructed into the various components it is made up of
Where are plasma cells most common?
Plasma cells are very few in the blood and most frequent at the bone marrow
What are the types of haemotlogical response?
Neutrophilia
Lymphocytosis
Reactive bone marrow hyperplasia; aplasia
What do neutrophils do?
They are attracted to and move to site of infection they then adhere to foreign particle and encircle the particles and start to form a phagosome and consume the pathogen releaseing the fused primary and secondary granules.
What do neutrophil rleased granules do?
The released granules cause destruction of invading organism.
What causes neutrophilia?
Infection (bacteria or viruses)
Acute inflammation
Stress
Exertion
Pregnancy
Surgery, trauma
What happens with high neutrophil counts?
Increased granulation (toxic environment for bacteria)
What are the common symptoms from bacterial infections?
Fever, pain and lethargy
What kind of infections can bacterial infections cause?
Localised (in skin, tonsil, bone)
Generalised (Causing hypotension, fluid shifts, and organ failure)
How does the bone marrow respond to bacterial infection?
Bone marrow produces more granulocytes (granulocytic hyperplasia)
Blood neutrophilia
Left shift (presence of band forms in neutrophils in blood)
Toxic granulation
Dohle bodies
What signal stimulates pluripotent stem cells to produce more neutrophils?
IL-3 and granulocyte colony stimulating factor
How long does granulopoeisis take typically?
5 - 7 days (5 under lots of stress)
What happens to neutrophil count immediately after bacterial infection?
It drops briefly due to neutrophils moving into the sites of infection
What are the most common neutrophilia causing organisms?
Staphylococcus, streptococcus and neisseria
What are Dohle bodies?
Blue lines in neutrophils found after long-standing severe bacterial sepsis.
They may be aggregates
What does multi-organ failure look like on blood film?
Causes fragmentation haemolysis (schistocytes) with toxic neutrophils and thrombocytopenia.
(might not always look like this so don’t take as fact)
What morphological changes happen in neutrophils in response to bacterial infections?
Granulation (toxic granulation)
Dohle bodies
Bacteria
Vacuolation containing bacteria as well as some toxic changes
What is the result of hypercellular bone marrow during bacterial infections?
Granulocytic hyperplasia
Increased macrophages with phagocytosed debris
Hypercellular bone marrow trephine and aspirate
What is a good indication of reactive granulocytic hyperplasia?
Presence of less white fat blobs in bone marrow
What happens in response to mycobacterium infection?
Production of more monocytes
What do monocytes form in the bone marrow in response to mycobacterial infection?
Granulomas which have negatively stained rod-like appearace
What are the symptoms of viral infections?
Fever, lassitude (lethargy)
Enlarged lymph nodes, liver and spleen
Pharyngitis
Thrombocytopenia (can be a complication of EBV)
Muscle and joint pain
Reactive lymphocytosis
Which viral infections exhibit reactive lymphocytosis?
Infectious mononucleosis
Cytomegalovirus
Varicella infection
Viral hepatitis
Dengue fever
What does lymphocytosis look like on the blood slide?
Change in look from small circular nucleus to cell with long morphology and nucleus. Pale sites present where there are lots of golgi and ER structures. Cytoplasm looks greyish.
This greatly resembles monocytes.
What is infectious mononucleosis caused by?
Epstein-Barr virus (EBV)
Who gets EBV most often?
Teenagers and young adults
What are the symptoms of infectious mononucleosis?
Lassitude (lethargy)
Fever
Pharyngitis
Lymphadenopathy
Hepatosplenomegaly
Thrombocytopaenia is common
Haemolytic anaemia (spherocytes (immune mediated)) [this is in rare cases and in some cases total bone marrow failure]
What does blood film of infectious mononucleosis look like?
Virally infected B lymphocytes and activated reactive T lymphocytes
How common is haemolytic anaemia in people with EBV?
It is rare and in some cases can cause total bone marrow failure which is extremely rare
What do lymphocytes look like in infectious mononucleosis?
Large lymphocytes with round or irregularly shaped nuclei, abundant flowing cytoplasm that is basophilic with a dark staining periphery
What are the clinical features of cytomegalovirus?
Indistinguishable from EBV
What ages is cytomegagalovirus most common in?
20 - 50
Which cells are infected by cytomegalovirus?
Neutrophils
Which cells are infected by cytomegalovirus?
B Lymphocytes
What does blood film show with cytomegalovirus?
Reactive T lymphocytes in the blood
What is commonly seen in EBV, cytomegalovirus and varicella infections?
Thrombocytopenia
Which viral infections do we commonly see activated T lymphocytes?
EBV, cytomegalovirus, hep A+B and varicella infections
What does viral hepatitis cause?
Mononucleosis-like syndrome
Also causes reactive lymphocytes
What causes Dengue Fever?
any one of 4 closely related virus serotypes of the genus flavivirus
How is dengue fever transmitted to humans?
Aedes aegypti mosquito
What are the clinical symptoms of dengue fever?
Sudden onset fever
Severe headache
Muscle and Joint pain
Petechial rash on the lower limbs and the chest
mild neutropenia
What does blood film look like in dengue fever?
Reactive lymphocytes with eccentrically placed nucleus
Basophilic cytoplasm
What does blood film of bordatella pertussis look like?
leucocytosis (15 - 50 x 10^9/L)
Lymphocytosis
How does bordatella pertussis avoid lymphocyte activity?
Lymphocytes are mature (but not activated) with nuclear clefts and folds and don’t migrate to tissue due to ‘lymphocyte promoting factor’ produced by B pertussis that inhibits this migration pattern
What is haemophagocytosis?
Macrophages mistake haemopoietic cells and RBCs in the bone marrow for foreign pathogens and “eat them”
When do we typically see haemophagocytosis?
May be associated with viral infections or with bacterial, fungal, or protozoal infections
What are the symptoms of haemophagocytosis?
Fever, lethargy, and myalgia
Pancytopenia: severe anemia, leucopenia, thrombocytopenia
How is haemophagocytosis mediated?
Cytokine mediated
What does the bone marrow of someone with haemophagocytosis look like?
Increased macrophages
Phagocytosed erythrocytes, leucocytes, and platelets
Variable residual haemopoiesis
What are the clinical symptoms of parvovirus B19?
Repiratory symptoms
Anaemia
Reticulocytopenia
Giant pronormoblasts with viral inclusions
What is a potential complication of parvovirus B19?
In patients with sickle-cell disease it can cause bone marrow failure
How are people with parvovirus B19 treated?
With blood transfusions because controlling the infection is very difficult
Do parasitic infections and worms always cause symptoms?
No sometimes they can be completely asymptomatic
What are some examples of parasitic infections and worms?
Malaria
Leishmaniasis
Trypanosomiasis
Filaria
What are the symptoms of malaria?
Fever
Malaise
Anaemia (haemolytic)
Thrombocytopenia
Increased monocyte count
What is the condition caused by malaria called?
Blackwater fever (intravascular haemolysis)
What species cause malaria?
Plasmodium species:
P. falciparum (kills people by damaging brain and severe haemolysis)
P. vivax
P. ovale
P. malariae
How does malaria cause anaemia?
Through intravascular haemolysis causing splenic pooling and dilution.
What are the symptoms of leishmaniasis?
Hepatosplenomegaly
Anaemia
BM with macrophages containing intracellular Leishman-Donovan bodies which get released on macrophage death but this can be treated.
Where is leishmaniasis located?
Africa most commonly
What are the symptoms of filariasis?
Can be seen in blood but asymptomatic with very little affect on blood count
What is bone marrow failure?
Inability of bone marrow to produce sufficient blood cells
What does bone marrow failure lead to?
Pancytopenia
What are the clinical features of bone marrow failure?
Symptoms and signs of anaemia
Infections
Bruising and bleeding
Symptoms and signs of the underlying cause
What causes bone marrow failure?
Primary reduction in haemopoietic activity
Bone marrow replacement by malignant cells
Ineffective haemopoiesis
Marrow infiltration
What causes primary reduction in haemopoietic activity?
Aplastic anaemia
Chemotherapy
Radiotherapy
What causes bone marrow replacement by malignant cells?
Primary:
Leukaemia
Myeloma
Lymphoma
Secondary:
Metastatic cancer
What causes ineffective haemopoiesis?
Megaloblastic anaemia
Myelodysplasia
What causes marrow infiltration?
Marrow fibrosis (myelofibrosis)
Inherited disorders:
Osteopetrosis (thickening of bone);
Gaucher disease
What is aplastic anaemia?
Pancytopenia due to BM failure. Hypoplastic or aplastic bone marrow
What does BM failure look like on Blood Film?
Blood film shows no abnormal cells and leucoerythroblastic
What does BM failure look like on Full Blood count?
Anaemia, leucopenia, thrombocytopenia, Low/absent reticulocytes
What does BM failure look like on Bone marrow examination?
Bone marrow examination: Used to establish cause and diagnosis
What causes aplastic anaemia?
Congenital cause: Fanconi anaemia
Acquired:
Idiopathic
Chemotherapy
Chemicals/toxins
Infections
SUMMARY
Describe how the bone marrow and blood
respond to bacterial and viral infections.
• Specific leucocytes due to their function
• Numerical and morphological changes in blood
cells
• Bone marrow response
• Appropriate and inappropriate responses
• Bone marrow failure
Can aplastic anaemia be completely idiopathic?
Yep (it can also be caused by infection and recover after infection is recovered)
How is idiopathic aplastic anaemia treated?
Immuno suppression and blood product transfusion
Haemopoietic growth factors (GCSF)
Potential for BM transplantation
