WEEK 5 - Haematological Disorders Flashcards
Blood is classified as?
A specialised connective tissue
What is the function of blood and what are its constituents?
Transports oxygen, food and wastes around the body to maintain homeostasis.
Made up of blood cells (45%) and plasma (55%)
What is plasma made up of?
90% water and 10% solutes (proteins)
Most abundant proteins are albumin, globulins (antibodies) and fibrinogen - made by the liver
What is the function of plasma proteins?
Functions in:
- Transport
- Maintenance of oncotic pressure (esp. albumin)
- Immunity
- Clotting
Name the three types of blood cells?
- Erythrocytes (RBCs)
- Leukocytes (WBCs)
- Thrombocytes (platelets)
Are all blood cells true cells?
NOP
- Mature RBCs = no nuclei
- Platelets = cell fragments
Where do blood cells originate?
From bone marrow, renewed via division of stem cells in bone marrow
Where is bone marrow found (what kind of bones)?
In long bones, vertebrae, cranium and sternum
Primary role of RBCs?
Transport of O2 and CO2
What molecule in RBCs carry O2? How many O2 molecules can each one carry?
Haemoglobin
Each Hb has four Fe = each one carries one O2 = four O2 per Fe
What makes up the cytoskeleton of RBCs?
Spectrin
Rate of RBC production depends on?
EPO production via the kidneys (erythropoietin)
At the end of their life, how are RBCs broken down?
Via macrophages
What are the five types of WBCs?
Which are granulocytes and which are agranulocytes?
Granulocytes:
- Neutrophils
- Eosinophils
- Basophils
Agranuloctes:
- Lymphocyte
- Monocytes
What do neutrophils do?
They are phagocytes - first to respond to injury
What do lymphocytes do?
B and T cells - immunity cells
T = directly attack and kill foreign cells
B = make antibodies that go and do the killing
What do eosinophils do?
Form the immune system of the GIT, have a role against parasitic worms
What do basophils do?
Contain histamines, active in allergic and inflammatory responses
What is the difference between leukocytosis and leukopenia?
Leukocytosis = WBC count higher than normal, may be due to infection
Leukopenia = WBC count lower than normal, may be due to infection or bone marrow suppression
What is the difference between platelets and sticky platelets?
Sticky = name of platelets when they are forming a blood clot ONLY
What are the two roles of platelets?
- Haemostasis - formation of a platelet plug to stop bleeding after injury
- Coagulation - release of chemical mediators by platelets required for blood clotting
Number of platelets in blood depends on?
Thrombopoeitin produced by the liver and kidneys
Define and describe haemataopoiesis?
The process of blood cell formation
Blood cells are made from haematopoietic stem cells, which then differentiate to follow the myeloid (most blood cells) or lymphoid (NK cells or T/B lymphocytes) lines.
What are the four blood types and their present antigens?
A = A antigens B = B antigens AB = A and B antigens O = no antigens
What are the two principles of blood typing?
- Plasma does not contain antibodies against the antigens present on its own RBCs
- Plasma contains antibodies against A/B antigens if they are not present on its own RBCs
How does the Rhesus blood typing work?
Gives positive or negative blood.
Rhesus antigen present = +ve blood
No Rhesus antigens = -ve blood
Those with positive blood = can have both positive and negative blood
Those with negative blood = can ONLY have negative blood, exposure to positive blood = antibody production
What happens if the wrong blood type is give in a blood transfusion?
Mixture of antigens (agglutinogens) and antibodies (agglutinins) = agglutination reaction
Reaction severity depends on the individual and the amount of blood given
What is anaemia and what causes it?
Blood disorder in which there is either a decreased number of RBCs or decreased Hb in RBCs
Caused by:
- Impaired RBC production
- Severe blood loss
- Increased or premature RBC destruction
Anaemia is classified by?
RBC size and Hb content
- ‘-cytic’ refers to cell size
- ‘-chromic’ refers to Hb content
What are some of the clinical manifestations of anaemia?
- Hypoxia
- Diluted blood = increased HR, preload and SV = increased CO
- Increased RR, dyspnoea
- Palpitations, tachycardia, angina
- Dizziness, fatigue
- Yellowed, pale skin
- Thinning, greying of hair
- Numbness and weakness due to myelination disruption
- GI disturbances leading to weight loss
What is megaloblastic anaemia?
- Larger than normal RBCs and smaller nuclei = macrocytic-normochromic anaemia
- Due to defective DNA synthesis as a result of lack of Vit B12 or folate
What is the most common type of megaloblastic anaemia?
Pernicious anaemia, occurs in those 60+, vague, unspecific symptoms
What is the pathophysiology of pernicious anaemia?
Genetic disorder (congenital)/gastric mucosal atrophy (autoimmune)/loss of parietal cells Leads to lack of intrinsic factor (transporter for Vit B12) Leads to Vit B12 deficiency Leads to pernicious anaemia
Lack of B12 may also be due to lack of intake in diet
Evaluation for pernicious anaemia?
- Serology = presence of parietal cell ABs, decrease in B12, IF
- Bone marrow aspirate
- Schilling test (admin of radioactive B12 to determine excretion)
- Gastric biopsy
All to determine if anaemia caused by lack of IF or B12
Treatment of pernicious anaemia? What happens if it is left untreated?
- B12 replacement via injection or oral dose
- Lifelong supplementation needed if autoimmune
PA left untreated is FATAL - leads to cardiac failure
What is iron deficiency anaemia?
Most common type of anaemia - due to a lack of iron
Abnormally small RBCs with low Hb content = microcytic-hypochromic anaemia
What causes iron deficiency anaemia?
- Blood loss (ulcers and cancer)
- Poor nutritional intake or absorption (most common)
- Increased iron requirements during youth
How to treat iron deficiency anaemia?
- Treat underlying cause = reversible
- Admin of oral or parenteral iron replacement
What is aplastic anaemia? What is it caused by?
Anaemia as a result of a dysfunctional bone marrow
Caused by pancytopenia (failure of bone marrow stem cells), usually autoimmune disease, affects all blood cell types
Treatment for aplastic anaemia?
What happens if it is not treated?
- Immunosuppressants
- Steroids
- Bone marrow transplant
If left untreated will progress to death
What is haemolytic anaemia?
Premature or accelerated destruction of own blood cells
May be due to genetics (autoimmune) or secondary to other diseases
What is leukaemia?
Malignant disorder of the blood in which there is uncontrolled proliferation of WBCs that disrupts normal bone marrow function and function of the body
How is leukaemia classified?
Based on cell origin (myeloid/lymphoid) and maturity of cells (acute-immature/chronic-mature)
What are the four types of leukaemia?
- ALL - Acute lymphoblastic leukaemia (common in children)
- CLL - Chronic lymphocytic leukaemia (common in older population)
- AML - Acute myeloid leukaemia (common in adults)
- CML - Chronic myelocytic leukaemia
What is ALL characterised by and what is the cause?
Characterised by the presence of malignant lymphoblasts in bone marrow or blood
Exact cause is unknown, may be due to radiation or toxins
Describe the pathophysiology of ALL?
Lymphoblasts accumulate in bone marrow and precent normal blood cell production
Leukaemic cells are released into blood to accumulate in blood, spleen, liver, lymph nodes
Worse prognosis associated with presence of Philadelphia chromosome - translocation of genes across chromosomes leads to increased TKR activity = uncontrolled cancer cell proliferation
Clinical manifestations of ALL?
- Bone marrow suppression - fever, fatigue, bleeding and bruising
- GI disturbance - weight loss and muscle wasting
- Hepatomegaly, splenomegaly
- Pts present with cold like symptoms
Diagnosis of ALL?
- Blood tests = anaemia, high WBC count
- Bone marrow aspirate
Treatment of ALL?
- Chemo
- Stem cell transplantation - from bone marrow of donor
- Supportive therapy - blood transfusions, nutritional support, immune system support
Describe the pathophysiology of CLL?
Malignant transformation and accumulation of B lymphocytes in organs and bone marrow
B cells are defective and cannot mature into effector cells, live longer than healthy B cells
Usually occurs in adults over 60
Diagnosis of CLL?
Lab analyses of blood and bone marrow
Treatment of CLL?
No cure
Treated with chemo - chlorambucil - and monoclonal antibodies (immunotherapy)
Transplant is not an option for older patients
Cause of multiple myeloma (MM)?
Unknown - may be due to genetics, radiation or chronic stimulation of the immune system
Pathophysiology of MM?
Defective immunoglobulin is produced - infiltrates organs
Myeloma cells migrate to bone marrow, increase osteoclast activity = lesions in bones
Leads to brittle bones and can lead to kidney failure
Clinical manifestations of MM?
Pain
Infections and anaemia
Renal failure
Diagnosis of MM?
Radiography
Blood and bone marrow analysis
Urine tests
Treatment of MM?
Chemo (thalidomide and dex)
Bortezomib - proteosome inhibitor (chemo)
Stem cell transplant - may be autologous
NOT CURATIVE, only 3-5 year survival
What is the difference between ALL and lymphoma?
ALL - immature cells of the bone marrow are affected
Lymphoma - mature lymphoblasts are affected
What is lymphoma?
Malignant B and T cell tumours that form in:
- Primary lymphoid tissue (thymus)
- Secondary lymphoid tissue (lymph nodes, spleen, tonsils)
What are the two major types of lymphoma?
Hodgkin’s lymphoma and non-Hodgkin’s lymphoma
Pathophysiology of Hodgkin’s lymphoma?
- Trigger of malignant proliferation is unclear
- Cytokines released by Reed-Sternberg cells = inflammatory damage
- Usually starts in a single lymph node = progression to formational of masses at different body sites and organs
Clinical manifestations of Hodgkin’s lymphoma?
- Painless swelling or mass in the neck or chest
- Enlargement of cervical, axillary, inguinal lymph nodes
- Fever/sweating
- Weight loss, fatigue
Diagnosis of Hodgkin’s lymphoma?
- CXR
- Biopsy
- Lymphangiography
- Staging via Cotswold staging classification system (1-4)
Treatment of Hodgkin’s lymphoma?
- Chemo
- Radiotherapy
- Stem cell transplant
