Week 10 Haematology Flashcards
define haematopoiesis
formation of the cellular components of red blood cells
define myelopoiesis
formation of blood cells in the myeloid (eg granulocytes, monocytes, erythrocytes, platelets)
define lymphopoiesis
formation of blood cells in the lymphoid cell line (B cells, T cells and NK cells)
outline the haematopoesis pathway
-haematopoietic stem cell (hemocytoblast)
-common myeloid progenitor and common lymphoid progenitor cells
-lymphoid progenitors –> NK, T,B, Plasma cell
-common myeloid progenitor–> erythrocyte, mast, basophil, neutrophil, eosinophil, macrophage
where do lymphoid progenitors differentiate
Bone marrow (B precursors) and thymus (t precursors)
features of haematopoietic stem cells
-precursors to blood cells
-differentiate into progenitor cells
-self renewing
-pluripotent
-mostly found in bone marrow
features of progenitor cells
-multipotent
-limited self renewal
-located in bone marrow
-differentiate into myeloid or lymphoid cells
where is the site of haematopoiesis in embryo (0-3 months)
yolk sac and then the liver
where is the site of haematopoiesis in foetus (3-7 months)
spleen
where is the site of haematopoiesis in foetus (7-9 months)
begins to occur in bone marrow
where is the site of haematopoiesis in birth to maturity
bone marrow and tibia/femur
where is the site of haematopoiesis in adults
bone marrow of skull, ribs, sternum
over production and under production of erythrocytes
polycythaemia and anaemia
over production and under production of platelets
thrombocythaemia/thrombocytosis and thrombocytopenia
over production and under production of leukocytes
leukocytosis and leukopenia
over production and under production of neutrophil
neutrophillia and neutropenia
over production and under production of lymphocytes
lymphocytosis and lymphopaenia
over production and under production of monocyte
monocytosis and monocytopaenia
over production and under production of eosinophil
eosinophilia and eosinopaenia
over production and under production of basophil
basophilic and basopaenia
proportion of WBC in body from most to least abundant
never let monkeys eat bananas
neutrophil-60%
lymphocyte-30%
monocyte-6%
eosinophil-3%
basophil-1%
lifespan of neutrophils
2-5 days
lifespan of lymphocyte
long-lived
lifespan of monocyte
2-5 days
lifespan of eosinophil
7-12 days
lifespan of basophil
12-15 days
function of mast cells
Releases histamine, promotes inflammation, and recruits immune cells.
function of dendritic cells
Captures antigens, presents them to T cells, initiates immunity.
function of macrophages
Engulfs pathogens, removes debris, and activates immune response.
CD4 T cell=
T helper cell
CD8 T cell =
T cytotoxic cell
B cell=
plasma cell
what are the primary lymphoid organs
thymus and bone marrow
what are the secondary lymphoid organs
lymph nodes, spleen, MALT
list the structures of the lymph node
cortex and paracortex
follicles
medulla
sinuses
antibodies
afferent vessels
efferent vessels
trabecular
what is the cortex and paracortex in the lymph node
-cortex contains follicles with B cells
-paracortex contains T cells
-this allows for interactions between these cells and initiates immune response
what are the follicles in the lymph node
-areas of the cortex where B cells proliferate and produce antibodies as part of AIR (adaptive immune)
what is the medulla in the lymph node
-contains plasma cells that produce antibodies and macrophages phagocytose
what are the sinuses in the lymph node
-spaces within lymph nodes where lymph circulates and immune cells meet antigens carried by lymph
-allows for immune surveillance and response
what are the afferent vessels in lymph node
-bring lymph along with pathogens and antigens into lymph node for filtration and immune initiation
what are the efferent vessels in lymph node
carry filtered lymph, including immune cells, and antibodies away from Ln to body
what is the trabecular in lymph node
-fibrous CT partitions within lymph nodes that provide structure support and nutrients to Ln
what is lymph
-tissue fluid carries antigens from the periphery, to the local draining lymph nodes
function of spleen
-filters blood borne antigens
structure of spleen
-white pulp (immune responses) and red pulp (filtration)
-T cell area containing Dc cells which surround periarteriolar lymphoid sheath (PALS)
-adjacent to PALS are follicles in B cell area
-PALS + follicles –> marginal sinus (veins)
-marginal zone surrounds this sinus
what are Colony stimulating factors
factors that stimulate certain elements of erythropoiesis, enabling the differentiation of HSC’s
list the CSF’s
M-CSF
GM-CSF
G-CSF
Thrombopoietin
Function of M-CSF
stimulates the production and differentiation of monocytes and macrophages from haematopoietic stem cells
Function of GM-CSF
promotes growth and maturation of WBC’s, including granulocytes (neutrophils, eosinophils, and basophils)
Function of G-CSF
specifically stimulates the production and release of neutrophils from the bone marrow, helping the body fight infection
function of thrombopoietin
regulates the production and maturation of platelets from megakaryocytes in the bone marrow, maintaining appropriate platelet levels in the blood
what is lymphoid ontogeny
process by which lymphocytes are made and developed into mature b and T cells
describe what happens in lymphoid ontogeny
-B and T cells make unique BCR’s and TCR’s
-these are tested by body before further differentiation to prevent AI conditions
list the functions of blood
nutrition
waste removal
thermoregulation
distribution
describe nutrition as a function of blood
gas exchange, providing oxygen to cells and tissue
describe waste removal as a function of blood
regulating homeostasis of pH and electrolytes; removal of CO2
describe thermoregulation as a function of blood
regulating the internal temperature of the body via vasodilation and vasoconstriction
describe distribution as a function of blood
distribution of immune cells, cytokines, hormones and immunoglobulins
list the components of blood
plasma
Buffy coat
red cells
what is plasma’s proportion in the blood
-55% of blood volume
(91% water, 7% proteins and 2% nutrients)
what is the Buffy coats proportion in the blood
insignificant proportion of blood volume (made of cells)
what is the red cells proportion in the blood
45% of blood volume (haematocrit)
what are the features of bone marrow structure
-bony trabecular
-active marrow
-dissolved fat
what is the bony trabecular of the bone marrow
seen as thick ‘pink’ stripes, structure of the bone itself
what is the active bone marrow in bone marrow
pink/purple cellular elements of the bone marrow
what is the dissolved fat in the bone marrow
leaves behind gaping white spaces (CIRCLES)
where does heme synthesis occur
mitochondria (early and late stages) and cytoplasm (intermediate stages)
Outline the steps in heme synthesis
1.Succinyl-CoA and glycine combine to form delta-aminolaevullinic acid (ALA)
2.ALA is transported into cytoplasm
3.A series of enzymatic reactions in the cytoplasm and mitochondria lead to the formation of porphyrin ring, known as propobilinogen (PBG)
4.Four PBG –> hydroxymethylbilane (HMB), –> urophyrinogen III
5. urophyrinogen III i–> coproporphyrinogen III
6. coproporphyrinogen III i–> protoporphyrin IX
7.iron + protoporphyrin IX –> heme
Describe the structure of haemoglobin
-tetrameric protein with 4 subunits
-2 alpha-like and 2 beta-like subunits , each subunit contains a Fe molecule
-the Fe in heme group is able to bind to oxygen, allowing Hb to carry and release O2 as needed
-Hg has a quaternary structure
features of HbF
-has two alpha and two gamma haemoglobin chains
-present from conception to 6 months
features of HbA
-has two alpha and two beta haemoglobin chains
-present from birth onwards
list the properties of Hb
O2 transport
CO2 transport
cooperative binding
describe O2 transport as a property of Hb
Hb’s primary function is to bind to oxygen in the lungs (oxyhemoglobin) and release it in the body’s tissues (deoxyhemoglobin) to facilitate oxygen transport
describe CO2 transport as a property of Hb
Hb can bind to Co2, aiding in it’s removal from tissues, some CO2 binds directly to Hb, forming carbaminohemoglobin
describe cooperative binding as a property of haemoglobin
Hb exhibits cooperativity, meaning that s one subunit binds to oxygen, it increases the affinity of the the other subunits for oxygen, enhancing its oxygen carrying capacity
what is the Bohr effect vs Haldane effect
Bohr: High CO₂ or low pH encourages O₂ release (tissues).
Haldane: Oxygen binding encourages CO₂ release (lungs).
describe the maturation of erythroblasts to erythrocytes
-born with 300 HSC, they divide once or twice per year (lessens risk of mutations)
-with successive cell divides, the progeny stem cells become committed to a specific lineage
-mature cells lose proliferative potency and acquire specific characteristic functions akin to their type
what is the turnover of red cells
120 days
what is the turnover of granulocytes
few hours (10^13) produced daily)
what is the turnover of platelets
5-10 days
describe stress haematopoiesis
-at times of increased demand, output is increased rapidly in bone marrow
-stress includes exercise and pregnancy
-abnormal stress includes blood loss and infection
source of erythropoietin
kidney
source of thrombopoietin
liver
what is 2,3-DPG
2,3-diphosphoglycerate
increased PCO2 leads to …
right shift (decreased O2 affinity)
increased H+/decreased pH leads to…
right shift (decreased O2 affinity)
increased temperature leads to
right shift (decreased O2 affinity)
increased 2,3-DPG leads to
right shift (decreased O2 affinity)
describe the structure of the thymus
small, bilobular structure
describe the location of the thymus
in the anterior mediastinum of the chest, behind the sternum (breastbone) and just above the heart
describe the structure of the spleen
white pulp (lymphoid tissue, T cells, b cells, Dc)
red pulp (splenic sinusoids, macrophages)
describe the location of the spleen
intraperitoneal in the left upper quadrant of the abdomen, long axis parallel to the 10th rib, mobile with respiration
function of the white pulp
serves as the immune response centre, initiating and coordinating immune reactions against blood-borne pathogens
function of the red pulp
primarily functions to filter and remove damages or aged RBC’s from the circulation, as well to store platelets
structure of the capsule in lymph node
outer protective covering the lymph node
function of the sub capsular sinus
drains lymph into the node and filters it
describe the flow of lymph through the lymph node
- lymph enters through the afferent lymphatic vessels, flowing into the sub capsular sinus
2.lymph flows through the subcapsular sinus where it is filtered (debris/pathogens are trapped)
3.lymph flows into cortex, where B cells in lymphoid produce antibodies
4.lymph flows into the paracortex where T cells enable Cell mediated response
5.Lymph enters the medulla, where dendritic cells macrophages process antigens
6.lymph exits via the efferent lymphatic vessel and returns to circulation
function of the right lymphatic duct vs thoracic duct
collects lymph from the upper right side of the body vs thoracic duct collects lymph from the rest of the body
what lymph nodes are in the occipital area
superficial: occipital nodes
what nodes do scalp and posterior neck drain into
occipital nodes
what lymph nodes are in the auricular area
superficial: pre auricular, post auricular , parotid nodes
what lymph nodes are in the cervical area
superficial: anterior cervical, posterior cervical, supraclavicular nodes
Deep: deep cervical nodes
what nodes do external ear, temple, and cheek drain into
superficial: pre auricular, post auricular , parotid nodes
what nodes do head, neck and superficial structures drain into
superficial: anterior cervical, posterior cervical, supraclavicular nodes
Deep: deep cervical nodes
what lymph nodes are in the axillary area
Superficial: pectoral, sub scapular, humeral nodes , apical
deep: central axilliary nodes
what structures do the the upper limb, breast and superficial thorax drain into
Superficial: pectoral, sub scapular, humeral nodes
deep: central axilliary nodes
what lymph nodes are in the mediastinal area
deep: tracheobronchial and paratracheal nodes
what nodes do the lungs, bronchi and oesophagus drain into
deep: tracheobronchial and paratracheal nodes
what lymph nodes are in the inguinal area
superficial: superficial inguinal nodes
deep: deep inguinal nodes
what nodes do the lower limb, external genitalia, lower abdominal drain into
superficial: superficial inguinal nodes
deep: deep inguinal nodes
what lymph nodes are in the coeliac area
deep: celiac nodes
what nodes do the stomach, liver, pancreas, spleen and upper duodenum drain into
deep: celiac nodes
what lymph nodes are in the external iliac area
superficial: superficial external iliac nodes
deep: deep external iliac nodes
what do the lower abdominal wall, perineum and external genitalia drain into
superficial: superficial external iliac nodes
deep: deep external iliac nodes
what lymph nodes are in the common iliac area
deep: common iliac nodes
what do the pelvic viscera, upper thigh drain into
deep: common iliac nodes
what lymph nodes are in the popliteal area
superficial: popliteal nodes
deep: deep popliteal nodes
what do the foot, calf, posterior knee drain into
superficial: popliteal nodes
deep: deep popliteal nodes
features of Fe3+
-obtained from plant products
-High solubility
-low oxygen affinity
features of Fe2+
-obtained from animal products
-low solubility
-high oxygen affinity
Describe iron metabolism
*Fe³⁺ is reduced to Fe²⁺ by an enzyme, which is then transported into cells by DMT-1.
*Fe2+ then can be converted into Fe3+ and stored as ferritin or
*Ferroportin transports Fe²⁺ from cells (like enterocytes) into the bloodstream.
*Transferrin binds to Fe²⁺ and oxidises it to Fe³⁺, increasing its solubility, so it can transport it through blood
*Hepcidin regulates iron homeostasis by degrading ferroportin, preventing iron release into the bloodstream.
Cells can later reduce Fe³⁺ back to Fe²⁺ if they need it for active processes, like heme synthesis.
list the factors effecting iron absorption
hypoxia
increased erythropoietin
inflammation
haemochromatosis
describe how hypoxia influences iron absorption
increased DMT-1
decreased hepcidin
increased iron absorption
describe how a need for increased erythropoietin influences iron absorption
decreased hepcidin
increased release of iron into blood stream
describe how inflammation influences iron absorption
increased hepcidin
decreased release of iron into bloodstream
describe how haemochromatosis influences iron absorption
decreased hepcidin
increased release of iron into bloodstream
what is the role of ferritin
globular protein found in most organisms, primarily stores/contains iron and, in its empty form , circulates in the blood, reflecting iron demand
role of transferrin
blood glycoprotein that transports Fe3+ throughout the body (from site of absorption and site of storage to cells)
ferric vs ferrous
Ferric =Fe3+
Ferrous = Fe2+
what is the male anaemic haemoglobin
<130 g/L
what is the female anaemic haemoglobin
<120 g/L
what is the pregnant female anaemic haemoglobin
<110 g/L
what is macrocytic anaemia + eg’s
> 100 fL/cell
FAT RBC
foetal
alcohol
thyroid disease
reticulocytosis
b12/folate
cirrhosis and liver disease
define mean cell volume
average size or volume of a red blood cell
define mean cell haemoglobin
average amount of Hb in a red cell
define mean corpuscular Hb concentration(MCHC)
amount of Hb per unit volume in a red cell
what is thalassemia
is defined as a reduction or absence of synthesis of a globin chain resulting in an imbalance of alpha and beta globin chains
what are haemoglobinopathies
defined as mutations in the Hb genes resulting in changes in the normal amino acid sequence of a globin chain, resulting in an abnormal structure
what is alpha thalassaemia (a+)
reduced or partial production of alpha globin chains
what is alpha thalassaemia (a0)
absence of production of alpha globin chains
what is beta thalassaemia (b+)
reduced or partial production of beta globin chains
what is beta thalassaemia (b0)
absence of production of beta globin chains
what is normocytic anaemia + eg’s
80-100 fL/cell
acute blood loss
bone marrow defieincy
chronic disease of anaemia
destruction of RBC’s (hemolytic)
enzymatic
what is microcytic anaemia +eg’s
<80 fL/cell
thalassemia, anaemia of chronic disease, iron deficiency, lead poisoning, seroblastic anaemia (TAILS)
what is the main difference between alpha and beta thalassaemia
-alpha thalassaemias are mostly due to deletions in the Hb alpha locus (chromosome 16)
-beta thalassemia is due to mutate in Hb beta gene locus (chromosome 11)
what are the consequences of thalassaemia on red blood cells
-genetic alterations that affect the production of alpha and beta globin chains of Hb, leading to abnormal Hb molecules
-RBC’s become fragile and prone to hemolysis
-leading to anaemia as RBC have shorter lifespan and reduced oxygen carrying capacity
list the clinical exam presentation of thalassaemia
pallor
jaundice
splenomegaly
dyspnoea
describe pallor in thalassaemia
skin appears usually pale due to anaemia and reduced oxygen supply
describe jaundice in thalassaemia
yellowing of the skin and eye caused by breakdown of RBC’s (bilirubin increases=yellow)
describe splenomegaly in thalassaemia
an enlarged spleen is common, enlarged due to increased workload in filtering abnormal red blood cells
describe dyspnoea in thalassaemia
SOB, especially during physical exercise, due to reduced oxygen carrying capacity in blood
Outline the severity of thalassaemia
-determined by the specific mutations in the alpha or beta globin chains
-thalassemia minor if individuals carries one normal and one mutated gene (heterozygous)
-thalassaemia major if individuals inherit two mutated genes (homozygous)
-intermediate is between the two above
what is iron overload
-occurs when body absorbs too much iron from the diet, often when there is no efficient mechanism for iron regulation
-can be due to genetic mutations or medical conditions
list the consequences of iron overload in beta thalassaemia major
cardiac complications
liver damage
endocrine disorders
bone marrow suppression
weakened immune system
skin discoularation
describe cardiac complications as a result of iron overload in beta thalassaemia major
iron overload in the heart can result in cardiomyopathy and HF, which can be life threatening
describe liver damage as a result of iron overload in beta thalassaemia major
iron deposits in the liver can lead to liver fibrosis, cirrhosis, and impaired liver function
describe endocrine disorders as a result of iron overload in beta thalassaemia major
iron overload can disrupt hormone regulation , causing growth and puberty delays, diabetes and thyroid dysfunction
describe bone marrow suppression as a result of iron overload in beta thalassaemia major
iron accumulation in the bone marrow can interfere with red blood cell production, exacerbating anaemia
describe weakened immune system as a result of iron overload in beta thalassaemia major
iron excess can impair the immune system function, increasing susceptibility to infections
describe skin discolouration as a result o firon overload in beta thalassaemia major
skin may developer a bronze or slate-grey hue due to iron deposits
what are the causes of iron deficiency anaemia
chronic blood loss
diet
malabsorption
increased iron demand
impaired iron recycling
how does diet lead to Fe deficiency anaemia
-lack of dietary Fe
-depleted Fe reserved in the body
-decreased Fe absorption
-Fe defieicny anaemia
how does chronic blood loss lead to Fe deficiency anaemia
-chronic blood loss
-Fe removal without replenishment
-depleted Fe reserved in the body
-decreased Fe absorption
-Fe deficiency anaemia
how does increase in Fe demand lead to Fe deficiency anaemia
-increased Fe demand
-Fe removal without replenishment
-depleted Fe reserved in the body
-decreased Fe absorption
-Fe deficiency anaemia
How does malabsorption lead to Fe defiency anaemia
-absorption pathologies eg coeliac
-decreased Fe absorption
-Fe deficiency anaemia
how does impaired Fe recycling lead to Fe deficiency anaemia
-impaired Fe recycling
-Fe removal without replenishment
–depleted Fe reserved in the body
-decreased Fe absorption
-Fe deficiency anaemia
what is coeliac disease, briefly
- autoimmune disorder in which the immune system mistakenly reacts to the consumption of gluten, causing damage to the small intestine.
- Celiac disease can cause malabsorption of nutrients, including iron (Fe), in the small intestine.
- Damage to the intestinal villi reduces the surface area available for nutrient absorption.
- In coeliac disease, the immune system’s reaction to gluten can create chronic inflammation, exacerbating the
anaemia.
Describe the pathogenesis of anaemia of inflammation/ anaemia of chronic disease
-inflammation
-release of cytokines (IL-6)
-increased hepcidin produced (decreases Fe availability for pathogens)
-hepcidin inhibits the release of recycled iron from macrophages causing decreased serum iron
-decreased serum iron
-reduced EPO production
-bias of hamaetopoiesis towards myeloid cell production
-TNFa molecule inhibits erythropoiesis and promotes erythrophagocytosis
-more myeloid cells and less erythrocytes are produced
features of iron deficiency anaemia (Hb, MCV/MCH, Ferritin, Transferrin)
low Hb
low MCV/MCH
low Ferritin
high transferrin/low transferrin saturation
features of thalassaemia (Hb, MCV/MCH, Ferritin, Transferrin)
low Hb
low MCV/MCH
high Ferritin
low transferrin
features of iron overload (Hb, MCV/MCH, Ferritin, Transferrin)
high Hb
normal MCV/MCH
high Ferritin
low transferrin
features of chronic inflammation anaemia (Hb, MCV/MCH, Ferritin, Transferrin)
low Hb
low MCV/MCH
high Ferritin
low transferrin
epidemiology of anaemia
Globally, 24.8% of the population are anaemic; the highest prevalence is pre-school age children (47.4%).
* most common cause of anaemia in the world is iron deficiency, (approximately 50% of all cases)
.
list the risk factors for anaemia
malnutrition
commorbidities
GI disorders
menstruation
pregnancy
surgery/trauma
how is malnutrition a risk factor for anaemia
-inadequate intake of key nutrients like iron, vitamin B12, folate, necessary for RBC production
how are comorbidities a risk factor for anaemia
CKD, cancer, inflammatory conditions can disrupt RBC production or lifespan of RBC
how are GI disorders risk factors for anaemia
conditions like celiac disease or crohns can impair nutrient absorption, leading to anaemia
how is menstruation a risk factor for anaemia
heavy prolonged menstrual bleeding in women can result in iron deficiency anaemia
how is pregnancy a risk factor for anaemia
increased iron demands during pregnancy can lead to anemia if dietary intake is insufficient
how is surgery/truama a risk factor for anaemia
acute blood loss due to surgery or GI bleeds can readily deplete RBC’s or anaemia
Describe the process of erythropoiesis
-Driven by hypoxia and low renal perfusion
-renal release of EPO
-EPO extends pro-erythrocyte life in bone marrow to increase chance of maturation
-increased RBC production
-HSC differentiates into myeloid/lymphoid progenitor
-myeloid progenitor–>erythroblast–>pro-erythrocyte–>reticulocyte–>erythrocyte
Describe the red blood cell breakdown
involves the phagocytosis of aged or damaged RBCs by macrophages, degradation of hemoglobin into globin and heme, conversion of heme into bilirubin, and recycling of iron for new red blood cell synthesis.
describe the role of iron in erythropoiesis
iron is required to produce haemoglobin, and it’s deficiency leads to reduced oxygen carrying capacity to anaemia
describe the role of vitamin B12 in erythropoiesis
vitamin B12 or cobalamin, plays a role in DNA synthesis and the maturation of red blood cells, a deficiency can result in megaloblastic anaemia and neurological complications, affecting the nerves that control muscle movement
describe the role of folate in erythropoiesis
folate, also known as vitamin B9, is essential for DNA synthesis, which is critical in the rapid cell division that occurs during erythropoiesis, a deficiency can lead to megaloblastic anaemia, characterised by large, immature red blood cells
outline the pathophysiology of macrocytic anaemia (B12)
-B12 deficiency leads to reduced conversion of m-CoA to s-CoA
-formation of macrocytic cells
-low Hb concentration
outline the pathophysiology of macrocytic anaemia (folate)
-folate deficiency leads to impaired DNA synthesis
-formation of macrocytic cells
-low Hb concentration
sources of vitamin B12
-meat/poultry/fish
-dairy
-algae/seweed
-mushrooms
sources of folate
-leafy green (spinach, kale)
-legumes
-fortified grains/cereals
-sunflower seeds
examples of megaloblast macrocytic anaemia
-B12 deficiency eg pernicious anaemia
-Folate deficiency eg dietary insufficiency
examples of non megaloblast macrocytic anaemia
-alcohol
-reticulocytosis (haemolytic)
-liver disease
-hypothyroidism
intrinsic vs extrinsic haemolytic anaemia
intrinsic is due to abnormalities within the RBC itself whereas extrinsic is due to abnormalities outside the RBC’s
intrinsic causes of haemolytic anaemia
thalassaemia
G6PD deficiency
extrinsic causes of haemolytic anaemia
stress from mechanical valve
thrombotic state
pathophysiology of haemolytic anaemia from mechanical valves and thrombotic state
-mechanical valves and/or thrombotic state
-shear force exerted upon RBC’s
-premature RBC breakdown (haemolysis)
-RBC count reduction
-haemolytic anaemia
pathophysiology of haemolytic anaemia from infectious agent
-infectious agent
-agent invades RBC’s
-premature RBC breakdown (haemolysis)
-RBC count reduction
-haemolytic anaemia
pathophysiology of haemolytic anaemia from thalassaemia
-impaired Hb content
-premature RBC breakdown (haemolysis)
-RBC count reduction
-haemolytic anaemia
pathophysiology of haemolytic anaemia from G6PD deficiency
-exposure to trigger
-premature RBC breakdown (haemolysis)
-RBC count reduction
-haemolytic anaemia
describe the difference between intravascular and extravascular haemolytic anaemia
intravascular=haemolysis occurring within the vasculature (i.e in the bloodstream)
extravascular=haemolysis occurring outside the vasculature (reticuloendothelial system)
what is sickle cell anaemia
-caused by specific genetic mutation in the HBB gene (which encloses the beta globin subunits of Hb)
-single base pair change results in sub of glutamic acid wth valine at position 6 on beta-globin chain
-inherited autosmal recessive
-the mutation leads to the production of HbS
-this can lead to RBC deformities into a sickle shape-> vasocclusive events
list the consequences of sickle cell disease
-Hb structure
-RBC morphology
-Oxygen transport
-haemolysis
-blood viscosity
describe abnormal Hb structure in sickle cell disease
Substitution of valine for glutamic acid at position 6 of the beta-globin chain results in
the formation of abnormal haemoglobin S (HbS). HbS tends to polymerise under
certain conditions.
describe RBC morphology in sickle cell disease
HbS polymerisation causes red blood cells to become rigid and assume a sickle
shape, leading to the characteristic sickling of cells.
describe oxygen transport in sickle cell disease
Sickle-shaped cells have reduced flexibility and difficulty passing through small blood
vessels, leading to vaso-occlusive events. This impairs oxygen delivery to tissues and
organs, contributing to tissue damage and pain.
describe haemolysis in sickle cell disease
sickle cells have a shorter life span and are more prone to rupture, leading to haemolysis and chronic anaemia
describe blood viscosity in sickle cell disease
sickle cell increases blood viscosity, making it more difficult for blood to flow through the vessels, which can further impede circulation and contribute to complications
list the symptoms and signs of anaemia
fatigue
pallor
dyspnoea
weakness
tachycardia
jaundice
splenomegaly
glossitis
how does anaemia present with fatigue
reduced oxygen carrying capacity of blood (anaemia) leads to tissue hypoxia and fatigue
how does anaemia present with pallor
Anaemia results in decreased haemoglobin levels, causing pale skin due to reduced
oxygen delivery to tissues.
how does anaemia present with dyspnoea
Anaemia forces the heart to work harder to compensate, resulting in rapid or laboured
breathing.
how does anaemia present with weakness
Insufficient oxygen supply to muscles and tissues due to anaemia leads to overall
weakness.
how does anaemia present with tachycardia
Anaemia triggers the release of compensatory hormones, increasing heart rate to enhance oxygen delivery.
how does anaemia present with jaundice
Haemolysis (red blood cell breakdown) in certain anaemias results in the release of
bilirubin, causing yellowing of the skin and eyes.
how does anaemia present with splenomegaly
The spleen may enlarge to compensate for anaemia by producing more red blood
cells or by filtering abnormal ones
how does anaemia present with glossitis
When iron levels are low in the blood, myoglobin, a protein necessary for muscle formation, including the tongue muscle, is low
affecting taste and appearance
list the investigations of anaemia
CBE
iron studies
B12/Folate
LDH
Hb electrophoresis
haptoglobin studies
blood films
why do CBE in anaemia
classification of aetiology via microcytic/macrocytic/normocytic
why do iron studies in anaemia
low serum iron or ferritin suggests iron deficiency anaemia
why do B12/folate studies in anaemia
low levels of B12 or folate may indicate megaloblastic anaemia (pernicious anaemia due to B12 deficiency)
why do LDH studies in anaemia (lactate dehydrogenase)
High LDH may suggest haemolytic anaemia due to various causes, including hereditary disorders or acquired conditions.
why do Hb electrophoresis in anaemia
helps diagnose and differentiate types of haemoglobinopathies such as sickle cell or thalassemia
why do haptoglobin studies in anaemia
test for sickle cell anaemia (haptoglobin is released from haemolytic anaemia)
why do blood film in anaemia
checks for abnormalities in red cell shape, size etc
indications and contraindications for diet control in treating anaemia
-indication is iron deficiency -contraindications are non iron deficient anaemia
indications and contraindications for oral iron in treating anaemia
-indications are severe iron deficiency
-contrainidcations are Malabsorption-based iron-deficiency
indications and contraindications for IV iron therapy in treating anaemia
-indications are pt who are Unable to receive transfusions
-contraindications are Hypersensitivity prone individuals
indications and contraindications for B12/folate supplement in treating anaemia
-indications are b12/folate deficiency
-contraindiications are unrelated causes of anaemia
indications and contraindications for blood transfusion
-indication are anaemia with acute threat
-contraindications are Jehovah witness
describe the recommended follow up for a patient with anaemia
-depends on cause and severity of anaemia
-the frequency of blood tests needed vary greatly between causes and should be assess case-by-case
-in anaemia due to acute leukaemia, bloods needed multiple times day, in iron deficient bloods needed multiple times per day
why is infancy a vulnerable stage of life to iron dependency
rapid growth and development, high iron needs for building RBC’s and the brain
why is adolescence a vulnerable stage of life to iron dependency
period of growth spurt and increased physical activity, which requires additional iron for muscle growth and oxygen transport
why is pregnancy a vulnerable stage of life to iron dependency
Increased iron demand to support the growing foetus and prevent maternal iron
deficiency anaemia.
why is menstruation a vulnerable stage of life to iron dependency
Monthly blood loss through menstruation necessitates adequate iron intake to
prevent iron-deficiency anaemia
list some sources of dietary iron
red meat
seafood
fortified cereals
legumes
dark leafy greens
poultry
how does Fe2+ and Fe3+ effect the bioavailability of iron
Heme iron (animal based) is more readily absorbed (15-35% absorption) compared to non heme iron (found in plant-based sources), which is less efficiently absorbed (2-20% absorption)
how does vitamin C effect the bioavailability of of iron
Vitamin C (ascorbic acid) enhances the absorption of non-haeme iron. Consuming
vitamin C-rich foods with iron-rich meals can improve iron absorption
how does calcium effect the bioavailability of iron
Calcium can inhibit the absorption of both heme and non-heme iron. Avoiding high-
calcium foods with iron-rich meals may help improve iron absorption.
how do tannins effect the bioavailability of iron
Tannins in tea and coffee can interfere with iron absorption. It’s advisable to consume
these beverages separately from iron-rich meals.
how do GI disorders effect the bioavailability of iron
Conditions such as celiac disease and inflammatory bowel disease can affect iron absorption due to damage to GI tract
how does cooking method effect the bioavailability of iron
Cooking in iron cookware can increase the iron content of food. Conversely,
overcooking, or excessive heat, can reduce iron content
outline food pairing to maximise iron absorption
combining foods in a way that enhances the body’s ability to absorb non heme iron eg steak and broccoli
common causes of folate deficiency
-Old age, poverty, famine, institutions
-Gluten-induced enteropathy
-anticonvulsants
-liver disease, alcoholism
common causes of b12 deficiency
Veganism
Pernicious Anaemia
Gastrectomy
Ileal resection
Crohn’s disease
Atrophic gastritis
what is packed cell volume
a measurement of the proportion of blood that is made up of cells
what is red blood cell distribution width
blood test measures how varied your red blood cells are in size and volume
why are reticulocytes tested
Tested as an assessment of the function of the bone marrow, more reticulocytes means increased risk of clotting, less reticulocytes means more risk of anaemia
what is haemoglobin electrophoresis
-Hemoglobin electrophoresis is a test that measures the different types of hemoglobin in the blood. It also checks for hemoglobinopathy disorders involving abnormal types of hemoglobin
-Uses electric current to seperate proteins based on charge
Mainly used to dx sickle cell disease, anaemia
what is haptoglobin
Binds to and gets rid of Hb outside red blood cells (in the blood)
how are direct coombs test interpreted
Determines if RBC circulating in the bloodstream are covered with antibodies
-can mean autoimmune, chronic leukaemia, blood disease
