4 Flashcards
List 5 signs of anaemia
Signs: pallor, tachycardia, glossitis, koilonychia, dark urine
List 4 symptoms of anaemia
Symptoms: weakness, SoB, palpitations, fatigue
What is glossitis?
Swollen, red, painful tongue (vitamin B12 deficiency)
Koilonychia
Spoon nails (caused by iron deficiency)
Tinnitus
A sensation of noise (such as a ringing or roaring) that is typically caused by a bodily condition.
What are the 3-main type of anaemias?
Microcytic, normocytic, macrocytic
What is the consequences of less RBCs/haemoglobin?
Anaemias
What role does vitamin B12 (cobalamin) play in RBC production?
A water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system, and the formation of red blood cells. It is one of eight B vitamins.
How can anaemia lead to confusion and loss of consciousness?
When not enough oxygen is getting to the brain
What are erythropoiesis?
Production of red blood cells
What is EPO?
Erythropoietin, which regulates erythropoiesis
What is the difference between microcytic, normocytic and macrocytic anaemia?
Microcytic – Small RBC size (decreased MCV)
Normocytic – normal RBC size (MCV normal)
Macrocytic – large RBC size (increased MCV)
What do these mean: hypochromic, normochromic?
Hypochromic – erythrocytes are paler than normal
Normochromic – normal MCV (erythrocyte size)
In what kind of anaemia is dark urine common?
Haemolytic anaemia
Define haematopoiesis.
Formation of the cells of immune system + blood cells.
What are haematopoietic stem cells (HSCs) + where do they reside?
Cells which can give rise to all the different blood cells.
Why are HSCs known as being self-renewing?
They reside in the bone marrow + when they proliferate, at least some of their daughter cells remain as HSCs so stem cell pool is not depleted (asymmetric division).
What is asymmetric division? Give an example.
Asymmetric cell division produces two daughter cells with different cellular fates. E.g. HSC proliferation.
What are the daughter cells of HSCs? Can they renew themselves?
HSCs – can renew themselves
Myeloid progenitor cells – cannot renew themselves
Lymphoid progenitor cells – cannot renew themselves
All blood cells are divided into which 2 lineages?
Lymphocytes and myelocytes
What do myelocytes include?
Granulocytes: neurotrphil, eosinophil, basophil
Monocyte —> Macrophages + myeloid DC
What is the lymphoid lineage primarily composed of?
Lymphoid progenitors such as T-cells and B-cells
What is a proerythroblast?
A precursor cells that will eventually become a RBC
Which vitamin are essential for DNA synthesis?
Vitamin B12
Vitamin B9
Define proliferation.
Rapid reproduction of a cell or organism.
What 2 things cause anaemia?
Reduced production of functional erythrocytes or production of defective haemoglobin
Increased destruction of erythrocytes
List 3 essential micronutrients that are critical in the production of erythrocytes and haem synthesis.
Vitamin B6
Vitamin B12 + B9
Iron
What do the abbreviations in a full blood count mean: MCV, HCT, MCH, MCHC, RDW?
MCV – mean corpuscular volume (RBC size)
HCT – haematocrit (PCV – proportion of RBCs in blood)
MCH – mean corpuscular haemoglobin (average amount of haemoglobin in RBCs)
MCHC – MCH concentration (average % of haemoglobin in the RBCs)
RDW – red blood cell distribution width
What are does SCA cause?
Increased haemolysis
Vaso-occlusive crises
Visceral sequestration crisis
Haemolytic crises
What are the common causes of macrocytic anaemia (increased MCV)?
Vitamin B12 deficiency, folate deficiency, liver disease, hypothyroidism, reticulocytosis
Which receptors do IgE antibodies bind to on mast cells?
FcεRI on mast cell where the Fc region of IgE binds to
What is the difference between folic acid + vitamin B12?
Folic acid is vitamin B9
What is sideroblastic anaemia?
Form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy erythrocytes.
What causes low MCV + high RBC count?
Thalassemia
What causes low MCV and low RBC count?
ron deficiency, Pb poisoning
What is pancytopenia?
Conditions affecting production of other cell types in addition to RBCs.
What is PRCA pure red cell aplasia?
Conditions affecting specifically erythropoiesis in the bone marrow.
What leads to pancytopenia?
Failure of HSCs to self-renew eventually leads to HSC exhaustion and pancytopenia.
What is haemolytic anaemia?
Premature destruction of functional erythrocytes by intrinsic or extrinsic mechanisms.
What are the 2 reasons why erythrocyte destruction usually occurs (extrinsic and; intrinsic)?
- Nothing wrong w/ the erythrocyte but they are destroyed by external pathological processes such as drugs, toxins, auto-antibodies or infection.
- Something intrinsically wrong w/ the erythrocyte so it’s destroyed. E.g. abnormal Hb, lacks certain enzymes
What is SCA caused by?
Mutation in the beta-globin gene
What does a RBC get broken down into (in the spleen/liver/red bone marrow)?
Globin - aa - reused for protein synthesis
Heme - liver (bilirubin and ferritin) - excretion
What are haemoglobinopathies?
Give an example.
Autosomal co-dominant genetic defects resulting in abnormal structure of 1 globin chain of Hb molecule.
E.g. SCA
What does SCA affect?
Due to abnormally shaped SC erythrocytes issues w/ passage through circulatory system and ability to carry O2
What is a splenic sequestration crisis?
Intrasplenic sickling prevents blood from leaving the spleen and acute splenic engorgement ensues
What is a haemolytic crisis?
The rapid destruction of large numbers of red blood cells (haemolysis)
The destruction occurs much faster than the body can produce new red blood cells.
What is a vaso-occlusive crisis and its causes?
Sickle-shaped RBCs block blood vessels. Blood and oxygen cannot get to tissues, causing pain.
What characterises hypochromic and microcytic RBCs?
Hypochromic – pale RBCs
Microcytic – small RBCs
What is sideroblastic anemia caused by and characterised by?
Characterised by failure to incorporate iron into haem in erythrocyte precursor cells.
Caused by mutations/deletions of genes regulating expression of key enzymes in haem synthesis.
Describe what happens to broken down heme components.
Heme –> biliverdin and Fe3+ –> bilirubin and Fe3+ (goes to liver) –> bilirubin secreted in bile into the SI where it become urobilinogen –> urobilin (urine) / stercobilin (faeces)
What is the role of transferrin in the breakdown of haemoglobin?
Carries Fe3+ in the blood from macrophage to liver and liver to red bone marrow.
What does bilirubin get broken down into in the kidney and large intestines?
Kidney – urobilin
LI – stercobilin
What 2 components is heme broken down into?
Biliverdin and Fe3+
What happens to the globin broken down from RBCs?
Breaks down into amino acids and are reused for protein synthesis
Put these in order in starting from RBC being phagocytosed in liver, spleen, or red marrow: bilirubin, urobilinogen, biliverdin, urobilin.
Biliverdin, bilirubin, urobilinogen, urobilin
List the components of blood cells.
Erythrocytes, thrombocytes, leukocytes
List the components of blood plasma.
Water, proteins, inorganic ions, organic substances
What are the blood cells of the innate immune system?
Neutrophils, monocytes, basophils, eosinophils, mast cells, natural killer cells.
Type 1 hypersensitivity reactions are mediated by which type of antibody in humans?
IgE
In hypersplenism is MCV high, low or normal?
Normal
In liver disease is MCV high, low or normal?
High
In thalassemia is MCV high, low or normal?
Low
In iron-deficiency anaemia is MCV high, low or normal?
Low
What is the difference between sideroblastic anaemia and haemolytic anaemia?
Sideroblastic – Low MCV and few RBCs (failure of iron incorporated in Hb)
Haemolytic – Normal MCV (RBCs breakdown > formation)
Does vitamin B12 deficiency cause macrocytic, normocytic or microcytic anaemia?
Macrocytic anaemia - RBCs larger than normal
What does the common lymphoid progenitor develop into?
T and B lymphocytes, NK cells, lymphoid dendritic cells.
Where to T cell develop and migrate to?
Develop in the thymus and migrate to spleen.
Where does the common myeloid progenitor develop?
In the red bone marrow and completes in lymphatic tissue
Name 3 granulocytes.
Eosinophil, basophil, neutrophil
Name all the agranulocytes (mononuclear).
Monocytes (macrophages, DC), lymphocytes (B and T cells)
What is the suffix of all granulocytes?
-phil
What is the suffix of most agranulocytes?
-cyte
What does a monocyte differentiate into and where?
Macrophage or dendritic cells when they migrate from bloodstream to tissues.
What does the B lymphocyte become once activated?
B effector cells.
What do megakaryocytes develop into?
Thrombocytes (platelets)
What is the bone marrow a site of?
Blood formation
How does haematopoiesis change as we develop and age?
Prenatal months – blood produced: yolk sac, liver, spleen
Postnatal years – bone marrow of tibia (0-20), femur (0-25), vertebrae and pelvis, sternum and ribs forever.
Where is most blood produced in prenatal foetuses?
Liver
CTLA-4 is an important negative regulator of T cell activation. How does it function?
Is a protein receptor that functions as an immune checkpoint, downregulates immune responses. Is expressed in Tregs.
In prenatal and postnatal years, what type of Hb is produced?
Prenatal – alpha and gamma
Postnatal – alpha and beta
In postnatal years, over 25 where is blood produced?
Bone marrow of vertebrae, pelvis, sternum and ribs
What regulates haematopoiesis?
GFs including: IL-1,2,3,7, GM-CSF, G-CSR, M-CSF, TPO, EPO
Protein regulators that determine the fate of haematopoietic cells drive what?
Self-renewal, cell death, expansion and differentiation.
What does EPO, TPO and cytokines regulate formation of?
EPO – RBCs, TPO – platelets, Cytokines – WBCs
Bone marrow contains which distinct features?
Trabecular bone, granulocytes, megakaryocytes, erythroid islands, steatocytes
What are steatocytes?
Fat cells, they maintain metabolic state by storing energy needed for proliferation
What are erythroid islands?
Erythroblasts making erythrocytes
What are megakaryocytes?
A large bone marrow cell w/ a lobulated nucleus. It produces thrombocytes.
What is trabecular (spongy) bone? Where is it found?
a.k.a. cancellous bone. It is very porous and contains red bone marrow, where blood cells are made.
Found at ends of long bones, pelvic bones, ribs, skull and vertebrae (spinal).
What are granulocytes?
A white blood cell with secretory granules in its cytoplasm, e.g. an eosinophil or a basophil.
Immature blood cells initially interact with which type of cells in the marrow?
Stomal cells in the marrow.
Delta, epsilon and zeta chains are associated with what and when do they disappear?
The yolk sac, disappear v. early (9 weeks)
What is the point of having LT-HSC (long term haematopoietic stem cells?
They divide rarely so little chance of mutations/damage etc. so they last entire lifespan.
What do LT-HSC differentiate into?
LT-HSC, ST-HSC
What are MPPs (multipotent progenitor cells)?
Cells committed to either the lymphoid or myeloid lineages and give rise to more differentiated precursors.
Why is foetal haemoglobin different from adult haemoglobin?
Because it must bind oxygen at lower partial pressure (from mother) so it must have a higher affinity for oxygen than adult Hb
What is made in the bone marrow at a rate of 2.4 x 106 per second?
RBCs
What does gamma interferon induce?
Activation of macrophages and inducer of MHC class II expression
What is the key role of macrophages in the spleen?
Removal of damaged RBCs
What is the life span of RBCs?
120 days
95% of the blood in the body filters through the spleen in what time frame?
3 minutes
What is the straw-coloured liquid component of the blood called?
Blood plasma
Name the methods of analysis of blood.
Spectrometry and impedance, cytochemistry, flow, cytometry, immunoassays, microscopy.
What are the 3 plasma proteins and what synthesises them?
Albumins, globulins, fibrinogen
What are gamma globulins?
Plasma proteins, a.k.a. immunoglobulins (Ab)
What determines blood type?
Antigen A and B on surface of RBCs
What naturally occurring antibody type in the serum targets non-present ABO antigens?
IgM
Circulating platelets have a life span of what?
5-9 days
What controls the lifespan of circulating platelets?
Integral apoptotic regulating pathway
What 3 types of granules do platelets contain?
Dense – ADP, ATP, calcium ion, magnesium, serotonin
Lambda – hydrolytic enzymes
Alpha – PF-4, TGF-beta-1, vWF, fibrinogen (factor I), factor V, fibronectin
What does dense granules in platelets contain?
ADP, ATP, calcium ion, magnesium, serotonin
What does alpha granules in platelets contain?
PF-4, TGF-beta-1, vWF, fibrinogen (factor I), factor V, fibronectin
Platelet reserves in spleen can be released by what?
Splenic contraction
What does thrombopoietin regulate?
Formation of platelets
Platelets form from what of the megakaryocyte?
Cytoplasm
Each megakaryocyte releases how many platelets?
2000-5000
What does vWF do?
A blood glycoprotein involved in haemostasis.
What does fibrinogen do?
a.k.a factor I – is a blood plasma protein made in the liver. It’s a coagulation factor responsible for normal clotting
What is myeloproliferative neoplasms?
Too much proliferation of myeloid cells
What is polycythemia vera?
Excess of RBCs in circulation
What is the difference between primary and secondary polycythemia?
1 – genetic problems in RBCs, e.g. PV, congenital/familial
2 – conditions promote RBC development, e.g. hypoxia, EPO secreting tumours, neonatal polycythemia.
What the EPO secreting tumours cause?
Too much EPO secretion which upregulates the production of erythrocytes –> secondary polycythaemia
What is relative polycythemia?
When RBCs are normal but reduced plasma volume e.g. dehydration is causing the problem.
What is essential thrombocythemia?
Excess platelets
What is idiopathic myelofibrosis?
Too few RBCs. Too many platelets and WBCs
Which JAK gene is involved in myeloproliferative neoplasms?
JAK-2; Makes HSCs more sensitive to growth factors
What is parasitism?
One organism benefits at the expense of the other
What is mutualism?
Both organisms benefit
What is commensalism?
One organism benefits, the other is unaffected
From smallest to largest list all the pathogens.
Virus, intracellular bacteria, extracellular bacteria, archaea, protozoa, fungi, parasites
In what 3 ways does the innate immune system protect against pathogens?
Anatomical barriers
Complement/antimicrobial protein activation
Inflammation
Is the innate or adaptive immune response more efficient?
Adaptive due to high specificity of antigen recognition by its lymphocytes
What is complement?
Part of the innate immune system that enhances the ability of Ab and phagocytic cells to clear microbes and damaged cells from an organism.
Promotes inflammation and attacks pathogen’s plasma membrane. Consists of a number of small proteins syn by liver.
Where are macrophages found?
In almost all tissues
Many tissue-resistant macrophages arise when?
During embryonic development
List the granulocytes and agranulocytes
Granulocytes:
- Neutrophils
- Basophils
- Eosinophils
Agranulocytes:
- Monocytes (macrophages)
- Lymphocytes (T + B cells, NK cells)
What are proethryoblasts (pronormoblasts) precursors of?
Erythroblasts (RBCs)
Precursors of platelets (thrombocytes)?
Megakaryocytes –> pro-megakaryocyte –> megakaryoblast –> common myeloid progenitor –> Hematopoietic stem cell
