Intro To Anemia Flashcards
Define Haematopoiesis
Multi potent HSC
Myeloid
Progenitor
Mast cell
Megakaryocyte
Platelets
-process of creating RBCs
-hematopoietic stem cells - can differentiate into specialised BC
-group of cells play major role in body’s innate immunity
-descendants of SCs that further differentiate into specialised cells
-involved in allergic response
-large cell in bone marrow - produces platelets
-fragments involved in clotting response
Neutrophil functions
Monocyte
Osteoclast
T cell
B cell
Natural killer cell (NK)
Draw on OneNote the flow chart for haematopoiesis
-1st line of defence against infection - type of phagocytes
- largest WBC - can differentiate into dendritic or macrophage cells - find + destroy germs - eliminate infected cells - call on other WBC to help treat injury and prevent infection
- break down old bone to make room for new (bone resorption)
- lymphocyte that produces antibodies and release cytokines - mature in thymus - release performing to kill pathogens
- mature in bone marrow - 2nd response - have memory cells and produce antibodies
-lymphocyte that kills targets w/out prestimulations - use hydrologic enzyme granules - release cytokines/ chemo kinds for adaptive immune response
Whats one explanation for difference in Hb in women vs men
Reference range vs normal range
-testosterone can affect Hb
- reference range covers 95% of reference population - varies between hospitals and areas - normal range is healthy range
What forms plasma
Buffy coat
Hematocrit
Depressed vs elevated hematocrit
Define Anaemia
- water, proteins, nutrients and hormones
- WBC and platelets
-RBC
-Anemia vs Polycythemia
-no. RBCs, Hb or o2 carrying capacity is insufficient to meet physiologic needs
What’s a premature RBC ?
Does it have a nucleus ? RNA?
What about a mature RBC?
Reticulocyte
No nucleus just RNA
RBCs have no RNA
What structure is a Haem group ?
What kind of arrangement ?
What kind of subunit ?
Porphyrin Ring
Cyclic macromolecule
4 pyrrole subunits
What’s the O2 delivery equation ?
DO2 = Q x (Hb x SaO2 x 1.34 + (PaO2 x 0.003))
DO2 = O2 delivery
Q= cardiac output = heart rate x stroke volume
SaO2 = arterial O2 saturation = degree to which Hb in blood is bound to O2
PaO2 = O2 partial pressure = amount of dissolved O2 in blood
Which organ detects low RBC level in blood? what hormone does it release as a response ?
Kidneys increase production of Erythropoietin
What’s normoxia?
Hypoxia?
How do cells detect normal O2 levels in blood? (What factor interacts w O2? Process called? So how are those factors that induce RBC production stopped ? What interacts w O2 complex and what’s the process called ? What enzyme is then triggered ? So what’s the product of all this ?)
Normal O2 blood levels
Low O2 blood levels
Cells have Hif-a (hypoxia induced factor alpha)
If normal O2, proline hydroxylation occurs , as Hif-a reacts w O2 . product reacts w VHL (Von hoppy-lindau protein - regulatory protein in cell development and growth / has role in ECM formation) , which marks Hif-a for degradation
Ubiquitin then binds to the product of that , called ubiquitination, which is a proteasome that degrades proteins
So Hif-a breaks down into peptides, and it doesn’t work to trigger additional RBC formation
Instead, what happens during hypoxia?and how does the body accommodate for those extra RBCs in body ?
Hif-B (aka ARNT) triggered during degreased O2 consumption in vessels , and binds to Hif-a, which bind to HRE (hypoxia response element) in DNA in target genes. This results in changes in metabolism, erythropoesis, and angiogenesis (formation of new BVs from pre-existing ones) to increase blood flow to deprived tissues.
How is erythropoiesis regulated via receptors
Endogenous erythropoietin (EPO) binds to receptor , JAK2 (Janus associated kinase 2) is phosphorylated, triggering the release of various kinases such as MAPK, STAT5 and PI3K/AKT . This is how RBC proliferates
What happens to RBC at the end of its life-cycle ? Globin? Haem? Organs and products and metabolites involved ?
-circulate for 120 days and then broken down by hepatocyte kupffer feels by phagocytosis -Globin broken down into AAs and reused in protein synthesis
-heme into
1)Fe3+ group + transferrin = ferritin - releases Fe3+ + globin+ Vitamin B12 + erythropoietin in red bone marrow = new RBC
2)biliverdin - reduced to bilirubin - bile pigment secreted from liver into small intestine - bilirubin + bacteria = urobilinogen = secreted into urine (as urobilin) or feces (as stercobilin)
How do u obtain blood sample and what machine do u use?
how does machine analyse cells
venepuncture
automated blood count analyser
RBCs lyses and Hb directly measured bvia photo metric method (w light intensity)
What does full blood count involve ?
Red cells indices?
Include any units
Hb (g/L)
WBC count
Platelet count
MCV (mean cell/corpuscular volume) fL(10^ -15)
Red cell distribution width (variability of RBC size) (RDW %)
PCV (packed cell volume) (hematocrit)
RBC count
Reticulocyte count
What’s used to classify anemia primarily ? reference range ?
3 subtypes ?
MCV (80-100 fL)
Microcytic, Normocytic and macrocytic
How distinguish 2 types of microcytic anemia ?
What are the 2 types and what causes them?
Fe deficiency- high RDW - low iron means little Hb in RBCs, making them smaller as they have less contents
Thalassemia - low or normal RDW - abnormal Hb affects RBC size
How distinguish 2 types of normocytic anemia ?
What are the 2 types and what causes them?
Second type has 2 causes - what are they and how to distinguish them ?
Anemia of chronic disease (Marrow hypo plasma ) - normal or low Reticulocyte count - autoimmune diseases - stem cells damaged in bone marrow
Haemolysis - high Reticulocyte count (bone marrow responding) - do DAT test (direct anti globulin test
Positive DAT = autoimmune haemolysis (AIHA)
Negative DAT = sickle cell anaemia (HbSS) , G6PD deficiency (error of metabolism so RBC breakdown), or mechanical cause (smth destroying RBCs )
2 types of mechanical anemia and what they mean?
March haemoglobinura (running for long time)
Microongiopathic haemolytic anaemia - abnormal BVs
2 types and causes of macrocytic anaemia and how to distinguish them.
Do B12/folate test
If low = deficiency in one or both, so RBCs don’t form correctly (growth not restricted)
If normal or high = chronic alcoholism active haemolysis -linked w haemolysis and erythrocyte membrane alterations
Define haematinics
Iron studied incl ferritin, B12 and folate
Suggest 4 additional tests above FBC to test for haemolysis
Bilirubin (how much RBCs broken down and is the liver dealing w it right)
LDH (lactate dehydrogenate)
Hepatoglobin - for X free hemogobins neutralisation of oxidation denase
DAT (direct antiglobulin test)
Define Haemoglobinopathy
What test is used to look for it
Group of single-gene inherited blood disorders that involve Hb
Hb electrophoresis
Study and try and identify abnormal blood films
What would be abnormal about the following blood films
1)Iron deficiency anaemia
2)Sickle cell
3)Megaloblastic anaemia
4)G6PD deficiency haemolytic anaemia
5)Autoimmune haemolytic anaemia
6)Thalassaemia
1) thrombocytosis - excess platelet count , hypo-chromatic cells, large area of central pallor, pencil cells (hypo-chromic variants of elliptocytes), microcytic cells
2)moon shaped RBCs, bulls eye shape, hyper-segmented neutrophils
3) central pallor - RBCs almost as large as neutrophils
4) ‘eaten from’ cells (happens in spleen), cells burst w sharp edges and deflation
6) abnormal Hb production - cells fragmented and very hypo-chromic, and very small fragments
What are spherocytes ? Shape and cause
Small RBC w no central paralor - microcytic - insufficient Hb top stretch membrane into making cells biconcave.
