Hematology Flashcards
Medullary region of bones
Inner most layer, cite of erythrocyte production-
Starts around 5 months gestation
2 big factors in RBC production
Eryhtropoetin
And
Iron
What stimulates erythropoiesis?
Hypoxia
Chemoreceptors in carotid bodies detect and release hypoxia-inducible factor
-at the tissue level!!! Hypoxia not hypoxemia
Cascade following hypoxia-inducible factor stimulation
EPO release from renal parenchyma cells
EPO binds to progenitor cells in the bone marrow to promote differentiation and growth
Reticulocyte
Immature red blood cell with reduced carry capacity- secreted in emergencies (surgery) to compensate for acute loses
Why do you see chronic anemia in renal failure?
Kidneys produce EPO! Sometimes we give exogenous EPO to compensate
Normal composition of erythrocytes
Four heme groups containing Fe
Two pairs of alpha and beta chains
Where do we store iron?
Hemoglobin mostly
-bone marrow
-hepatocytes (iron compounds-ferritin)
-spleen
Two compounds iron is stored as
Ferritin and hemosiderin
What do Hepatocytes regulate?
SERUM iron levels
Have nothing do to with EPO/hypoxia!
Hepcidin
A hormone produced by the liver
Disables iron transport from the intestines to the blood
Activated when serum iron is high
Describe 3 characteristics of RBCs
Bi-concave
Lifespan 110 days
Do not have mitochondria!!
What allows RBCs to exist without mitochondria?
Glucose can passively cross the cell membrane via glut-1 transporters
Why is the A1c measured every three months?
It’s based on the lifespan of an RBC
And looks at level of glycosilation? Level of glucose in the Hb
Affinity of gasses for Hb
CO about 300x the affinity of O2
O2>CO2
Type of competition between O2 and CO
Competitive…
CO2 is non-competitive
What is expressed to signal for cell death to start?
Fas ligand
Steps in RBC cell death
Recruitment of macrophages
Conjugation of bilirubin- to hydrophilic substance that can be pooped out
Residual iron is recycled
Microcytic anemia
Most common-
Small diameter
Hypochromic- pale (less red)
Thalassemia
Genetic- maybe evolutionary to combat malaria
Autosomal recessive- lack of alpha or beta subunit
Microcytic/hypochromia- but body compensates with HIGH RBC production
Can be complicated by extramedullary erythropoiesis
Macrocytic anemia
Large diameter
Hypochromic
Sickle cell/pernicious/Alcohol abuse
Role of intrinsic factor in pernicious anemia
Pernicious- destruction of parietal cells that produce intrinsic factor
Intrinsic factor-Binds B12 so it can be absorbed in GI tract
Sickle cell anemia
Autosomal recessive
Macrocytic/ sickle shaped erythrocytes
Risk of vaso-occlusive crisis
Aplastic anemia
Pancytopemnia (everything super low)
Acquired via environmental toxins
Polycythemia
Too many RBCs
Hyperchromic
Rare disorde of progenitor cells in bone marrow
Can also be caused by hypoxia and elevated testosterone
Hemochormatosis
Too much iron
Primary-rare neoplastic disorder
Secondary- blood transfusion- high iron intake
Chronic liver disease-hepicidin-loss of ability to regulate iron levels
Macrocytic/hyperchromic
TPO
Thrombopoietin
From hepatocytes- produce platelets
High levels of EPO inhibit what?
TPO
Low levels of EPO will stimulate what?
TPO
Our potent procoagulatory factors… big ones for clots?
Factor X and factor V
Both coagulation pathways do what
Promote conversion or prothrombin to thrombin
Ion involved with thrombin activation
Calcium
3 clotting steps
Conversion of fibrinogen to fibrin
Binding of thrombocytes to collagen
Stabilization of clot
How are our clots broken down?
tPA
Tissue plasminogen activators
-enzymatic destruction of fibrin and local thrombocyte aggregation
What does tPA do?
Converts plasminogen to plasmin
Von willebrand factor
Normally promotes adherence of thrombocytes to collagen and transports Factor VII
When impaired it cannot promote coagulation
Hemophilia factor
Factor VIII
Genetic cannot convert prothrombin to thrombin
Immune thrombocytopenic Purpura
ITP
Type II hypersensitivity reaction (=destruction of thrombocytes)
Virchows triad
Stasis of blood flow
Endothelial injury
Hypercoagulability
Causes of hypercoagulability
Chronic inflammation
Pregnancy
Acute trauma
Metastatic disease
Causes of endothelial injury
Atherosclerosis
High blood pressure
Oxidative stress
Unprovoked thrombi is what?
Cancer until proven otherwise
Factor V Leiden
Hypercoagulability!!
Autosomal dominant
Impacts intrinsic and extrinsic
Creates unprovoked thrombi
Antiphospholipid syndromes
Hypercoagulable
Complex-vasculitis
IgM IgG autoimmune impacting intrinsic and extrinsic
