Week 10 Haematological System Flashcards
Haematopoeisis and Haemopoesis
Interchangeable terms —> describes formation of blood cells
Myelopoiesis
Formation of blood cells in the myeloid line (e.g., granulocytes, monocytes, erythrocytes, and platelets).
Lymphopoiesis
Formation of blood cells in the lymphoid cell line (e.g., B cells, T cells, and natural killer (NK) cells.
Haematopoietic stem cells (HSCs)
• The precursor cell to blood cells and begin the differentiation process.
• They are self-renewing and can make any blood cell in the body, (e.g., erythrocyte, B cell, T cell, etc.).
• They can also make other non-haematopoietic cells, when required, and are hence classed as pluripotent.
• HSCs are found predominately in the bone marrow in adults.
Haematopoietic Stem Cells vs Progenitor cells
BOTH
- Located in bone marrow
Heamatopoeitc Stem Cells
- High self renewal tendency
- Differentiate into progenitor cells
- Pluripotent
Progenitor Cells
- Limted self renewal tendency
- Differentiate into myeloid or lymphoid
- Multipotent
Site of haematopoiesis in an embryo
Yolk sac and then liver
Site of haematopoiesis in 3-7 month old foetus
Spleen
Site of haematopoiesis haematopoiesis in a 7-9 month old foetus
Begins to occur in bone marrow
Site of haematopoiesis between birth and maturity
Bone marrow and the tibia/femur
Site of haematopoiesis in adults
Bone marrow of the skull ribs and sternum
Types of WBCs
Neutrophils, Lymohocytes, monocytes eosinophil, basophil
Primary lymphoid organs
Where lymphocytes undergo ontogeny (get made and develop in mature B and T cells)
Thymus and Bone Marrow
Naive lymphocytes
Precursor lymphocytes that differentiate into effector lymphocytes
CD4 T cell —> Helper T Cell
CD8 T cell —> Cytotxic T cell
B Cell —> Plasma cell
Primary lymphoid organs
Thymus and bone marrow (where cells develop)
Secondary Lymphoid organs
Lymph nodes
Spleen
Mucosal associated lymphoid tissues MALT
Function of Lymph Nodes
Filters tissues borne antigens in regions rich with naive B and T cells —> allowing them to interact (which happens in the Cortex, paracortex and medulla of the lymph node)
Spleen Function
Filters blood born antigens
Has white pulp for immune response and red pulp for filtration
M-CSF
Stimulates the production and differentiation of monocytes and macrophages from hematopoietic stem cells
GM-CSF
Stimulates growth and maturation of WBC
G-CSF
Specifically stimulates the production and release of neutrophils from the bone marrow helping body fight infections
Thromboprotein
Regulates the production and maturation or platelets (thrombocytes)( from megakaryocytes in the bone marrow, marinating appropriate platelet levels in the blood
What does multipotent myeloid stem cell differentiate into
Myeloid progenitor and Lymphoid progenitor
What does myeloid progenitor differntiate into
Megakaryocyte —> Platelets
Erythroblast —> Reticulocytes —> RBC
Myeloblast —> Monocyte, Neutrophil, Basophil, Eosinophil
What does Lymphoid progenitor differntiate into
B-lymphocyte —> B plasma
T Lymphocyte
Natural Killer Cell
Function of RBCs
Nutrition (gas exchange)
Waste removal (pH and electrolytes; removal of carbon dioxide)
Thermoregulation (via vaso constriction and dilation)
Distribution (immune cells, cytokines, hormones and Immunoglobulins)
Bony Trabeculae in histology
Seen as thick pink stripes; structure of the bone itself
Active Bone marrow in histology
Pink/purple cellular elements of the bone marrow
Dissolved Fat in bones in histology
White spaces
In adults makes about about 30-70%
Haeme synthesis
- Succinyl-CoA and glycine combine to form δ-aminolaevulinic acid (ALA).
- ALA is transported into the cytoplasm
- A series of enzymatic reactions in the cytoplasm and mitochondria lead to the formation of the porphyrin ring, known as porphobilinogen (PBG).
- Four PBG molecules combine to form hydroxymethylbilane (HMB), which is then converted into uroporphyrinogen III.
- Uroporphyrinogen III is converted to coproporphyrinogen III.
- Coproporphyrinogen III is further modified to form protoporphyrin IX.
- Iron is incorporated into protoporphyrin IX to produce heme.
What is Haeme
• Haeme is a crucial component of haemoglobin and other hemoproteins, which play a vital role in oxygen transport and various biological processes.
• Haeme synthesis occurs in the mitochondria (early and late stages) and the cytoplasm of the cell (intermediate stages).
Structure of Haemoglobin
Consists of 4 different protein chains (two alpha like sub units and two beta like subunits)
Each subunit contains iron
Bohr Effect
Haemoglobin exhibits cooperativity, meaning that as one subunit binds to oxygen, it increases the affinity of the other subunits for oxygen. This enhances its oxygen-
carrying capacity.
Turnover rates of RBCs, Granulocytes, and Platelets
RBC= 120 days
Granulocytes = mere hours
Platelets = 5-10 days
Right shift/decreased O2 affinity factors
Increased pCO2
Increased H+
Increased temp
Increased 2-3DPG (has to do with lactate)
Think right=exercise
Role of thymus
Site of development and maturation of t lymphocytes
Role of Spleen
Including red and white pulp
Acts as a filter for blood, removing damaged or old blood cells, pathogens and cellular debris
White Pulp: Serves as the immune response centre, initiating and coordinating immune reactions against blood borne pathogens and antigens
Red Pulp: Primarily functions to filter and remove damaged or aged blood cells from the circulation as well as to store platelets
Role of lymph nodes
Filter lymph to remove pathogens and antigens, innate immune reactions and facilitate activation of T and B cells
Lymph Node Cortex
Outer region contains B cells and follicles
Lymph nodes Medulla
Inner region contains plasma cells and macrophages
Lymph node paracortex
Middle region constraint T cells and High endothelial venules
Lymph node follicles
Contractions of B cells for antibody production
Flow of lymph through lymph node
- Afferent vessels
- Subcapsular sinus
- Lymph flows into the cortex, where B and T cells enable cell mediated immune responses
- Lymph flows into the paracortex where T cells enable cell mediated immune responses
- Medulla (dendritic and macrophages process antigens)
- Exits via lymphatic vessels
Iron types, where they come from, solubility and oxygen affinity
Fe3+
Source: Plants
Solubility: High
Oxygen Affinity: Low
Fe2+
Source: Animal Products
Solubility: Low
Oxygen Affinity: High
How is Fe3+ converted to Fe2+
By a transporter protein called DNMT-1
Iron Metabolism
Iron is converted to Fe2+ by DMT1 (if not already)
Ferroportin enables Fe2+ to travel from the enterocytes (cells in intestine) into the blood stream
When iron is not needed, Hepcidin is produced by the liver, and actively degrades Ferroportin, preventing more Fe2+ uptake into blood
Transferrin (a transporter protein) oxides iron into Fe3+, increasing solubility in blood
How does Hypoxia effect Iron absorption
Increases levels of DMT1
Leads to decreased hepcidin
Leads to increased absorption of iron
(And thus more RBCs can be made)
How does Increased EPO (erythropoietin) levels effect iron absorption
Leads to decreased hepcidin
Leading to increased released of iron into blood stream
How does Inflammation effect iron absorption
Leads to increased hepcidin
Leading to decreased released of iron into blood stream
How does Haemochromatosis (iron overload) effect iron absorption
Leads to decreased hepcidin
Leading to increased released of iron into blood stream
DMT1
A membrane [protein that transports dietary iron into interstitial cells
Ferroportin
A protein responsible for exporting iron from enterocytes (cells in intestine) into the blood stream
Channel protein facilitating absorption of iron into intestinal cells from the lumen
Macrocytic Anaemia
MCV Value: >100
Causes: B12 deficiency, folate deficiency, alcoholic liver disease
Normocytic anaemia
MCV Value: 80-100
Causes: Renal failure, anaemia of chronic disease, leukaemia
Microcytic anaemia
MCV Value: <80
Causes: Iron Deficiency, anaemia of chronic disease
Consequences and Clinical Presentation of thalassaemia
Consequences: RBCs are fragile and prone to haemolysis —> anaemia
Presentation: Pallor, Jaudice, Splenomegaly, Dyspnoea
Consequences of Iron Overload
Cardiac complications: cardiomyopathy and heart failure
Liver damage: fibrosis, cirrhosis, impaired function
Endocrine disorders: growth and puberty delays, diabetes, thyroid dysfunction
Bone marrow suppression
Weakened immune system
Skin discolouration: bronze of slate gray hue
Causes of iron deficiency
Chronic Blood loss
Diet
Malabsorption
Increased iron demand (ie pregnancy or growth)
Impaired iron recycling
Prevelance and incidence of anaemia
24.8% of people globally, 47.4% of pre-school aged children
Most common cause is iron deficiency- 50% of cases
Causes of Haemolytic Aaemia
Thalasseamia
Stress from mechanical Valve
G6PD deficiency
Thrombotic state
Anaemia Investiagtions
CBE: for classification and aetiology (MCV)
Iron studies
B12/folate
LDH: Hugh may suggest haemolytic anaemia
Hb electrophoresis: suickle cell or thallassemia
how to differeintate btwn iron deficiency anaemia and anaemia of chronic disease?
serum ferrotin
also a little bit total iron binding capacity
the pattern of inheritance in Haemophilia A & B?
X Linked reccessive
What gives rise to platelets
megakaryocytes
