Blood part 3 Flashcards
3 clinical indices of interest about blood
Number of RBC, amount of Hb and hematocrit
2 diseases associated with abnormal hematocrit and what hematocrit exactly
Ht < 45% (ex. 30%) -> Anemia. Can be caused by fluid retention.
Ht > 45% (ex. 70%) -> Polycythemia. Can be caused by dehydration.
Normal values and polycythemia values for RBC count per volume and Hb concentration
Normal : 5-5.5 x 10^6 RBC / microliter. 16g % Hb
Polycythemia : > 6x10^6 RBC / microliter. >18g % Hb
Relative vs Absolute polycythemia
Relative = Due to lower plasma volume Absolute = Physiological or Pathological
Physiological polycythemia 4 causes
1) High altitudes
2) Increased physical activity
3) Chronic lung disease
4) Heavy smoking
Pathological polycythemia 2 causes
1) Tumours of cells producing erythropoietin (kidney cells)
2) Unregulated production by bone marrow
What is polycythemia vera and values for RBC count per volume and Hematocrit
Blood cancer. Bone marrow does too many RBCs. 7-8 x 10^6 RBC / microliter. Ht approx. 70%
Problem with polycythemia
High blood viscosity -> sluggish blood flow and more risks of blood cloting
Anemia definition
Decrease in oxygen-carrying capacity of blood
F and M w/ Anemia -> RBC count and Hb content
M : 4x10^6 RBC/microliter and <11 g% Hb
F : 3.2 x 10^6 RBC/microliter and <9g %
Classifications of morphologic anemias
1) Microcytic (<80 u^3), Normocytic (80-94 u^3), Macrocytic (>94 u^3) (about volume so microcytic smaller diameter and macrocytic bigger diameter.
2) Normochromic (=33%) Hypochromic (<33%) (about % of RBC volume occupied by Hb)
On microscope, how to distinguish different morphologic anemias
Microcytic, normocytic and macrocytic -> sizes of RBCs
Normochromic or hypochromic -> colour of RBCs
3 etiologic anemias
1) Diminished (RBC) production 2) Increased (RBC) destruction 3) Ineffective (RBC) maturation
3 causes for diminished production of RBC (first etiologic anemia)
1) Abnormal site 2) Abnormal stimulus 3) Inadequate raw materials
Which anemia associated with diminished production of RBC due to abnormal site + causes (3) + morphologic classification
Aplastic (hypoplastic) anemia. a. uknown cause b. exposure to radiation c. chemicals or drugs.
Morph. class. of anemia : normocytic, normochromic
What causes anemia associated with diminished production due to abnormal stimulus + morphologic classification
Stimulation failure -> renal disease (EPO produced by kidneys)
Morph. class. of anemia : normocytic, normochromic
Which anemia associated with diminished production of RBC due to inadequate raw materials + causes (2) + morphologic classification
Iron deficiency anemia.
a. High requirements (infancy, adolescence, pregnancy)
b. Inadequate supplies due to 1) Failure to absorb Fe (gastrointestinal tract defficiency) 2) Dietary defficiency 3) Loss of Fe in hemorrhage (hemorrhage = loss of RBC + loss of Fe)
Morph. class. of anemia : microcytic, hypochromic
Total amount of iron in body and its % distribution
4g. 65% Hb. 30% stored. 5% myoglobin (muscle cells). 1% enzymes
Daily intake of iron and daily absorption from gut for M + F and what it depends on
15-20 mg daily. Gut absorbs 1 mg daily for males and 2 mg daily for females (depending on need).
Erythropoiesis iron requirement daily
25 mg
Iron that comes from RBC destruction and what happens with it
25 mg (24 mg recycled, 1 mg lost -sweat)
How much iron in 1 g of Hb
3.5 mg
Why women require 2 mg Fe daily
15g Hb/100 mL = 50 mg Fe (because 15 g * 3.5 mg Fe/1 g Hb)
Menstrual loss : 50 mL of blood so 25 mg Fe
25 mg + 28 mg (1 mg lost daily) = 50 mg/month = 2 mg daily
Second anemia type/etiology and names
Ineffective maturation. Maturation failure anemia
Cause of maturation failure anemia and morph. classification
Deficiencies in Vitamin B12 and folic acid (required for normal synthesis of DNA). Macrocytic RBCs, normochromic RBCs
What can cause lack of vitamin B12
Failure to absorb it
What can cause lack of folic acid
Dietary absence, overcooking vegetables
Vitamin B12 absorption mechanism
Vitamin B12 goes in digestive system. Joins intrinsic factor secreted by stomac cells in the stomac to form IF-B12 complex. IF-B12 complex absorbed in ileum by a receptor.
What can cause a failure to absorb B12 and what pathology would occur
Intrinsic Factor deficiency or ileum disease -> Pernicious anemia
Anemia type/etiology other than increased RBC destruction. different names and what may come with it
Survival disorders/Hemolytic anemias - may be accompanied by jaundice
Survival disorders/Hemolytic anemias etiology (2)
1) Congenital
2) Acquired
Congenital survival disorders causes (3)
1) Abnormal membrane structure (less flexible, more fragile) ex. hereditary spherocytosis (spherical RBCs)
2) Abnormal enzyme systems (abnormal metabolism)
3) Abnormal hemoglobin structure ex. sickle cell anemia (half moon shape) ex. Thalassemia - deficient synthesis of globin amino acid chains
Acquired hemolytic anemia causes (3)
Toxins, drugs, antibodies. Kill RBCs
Name for blood loss. 2 types and name of accumulation of blood in tissues
Hemorrhage. External and internal (into tissues). Hematoma = acccum. of blood in tissues
Hemostasis def.
Arrest of bleeding following vascular injury
3 overlaping mechanisms in hemostasis and which part of hemostasis they’re involved in
Vascular response. Platelet response. Clot formation. Vascular resp. and Plat. response = primary hemostasis. Platelet resp. and clot formation = secondary hemostasis
Time for primary hemostasis to occur
couple seconds after injury
4 general hemostasis step
Vascular injury, vasoconstriction, platelet plug formation (temporary), blood clot formation (there until healing)
Vascular response name and 3 levels of response
Vasoconstriction. 1. Nervous reflex (larger vessels) 2. Myogenic response (muscle cells in vessel wall contract) 3. Chemical vasoconstrictors (local release of agents)
Platelet response
Platelet plug (white thrombus - means clot) blocks blood flow
Platelets size, life span and amount
2-4 micrometers diameter. 7-10 days life span. 250 000 per microliter
Platelet structure (composition)
No nucleus, granules, mitochrondion, tubule, submembranous filaments (platelet contractile protein)
What are granules in platelet
Factors for vasoconstriction, platelet aggregation, clotting, growth, etc.
Platelet production name and general scheme
Thrombopoiesis -> pluripotential stem cell -> committed stem cell ….. Megakaryocytes -> release of platelets in blood
Thrombopoiesis committed stem cell size vs megakaryocyte size
15-20 micrometers vs 60-80 micrometers.
When thrombopoiesis process becomes in blood stream
Megakaryocytes in bone marrow but platelets released in blood stream
Name of what regulates thrombopoiesis, what secretes it and what kind of molecule it is
Thrombopoietin. Liver. Cytokine
Platelet plug formation 4 general steps
Adhesion, Activation and release of cytokines, Aggregation, Consolidation.
Name 8 substances that can be related to platelet plug formation
Prostacyclin, NO (nitric oxyde), von Willebrand factor, collagen, PF3, Serotonin, ADP, Thromboxane A2 (TXA2)
What prostacyclin and nitric oxyde do and where come from
Released by endothelial cells and discourage platelets aggregation
What von Willebrand Factor does
grabs platelet at one end and endothelial cells at other end
What collagen does
has affinity with platelets
What is TXA2 and what it does
Thromboxane A2 -> promotes vasoconstriction and promotes aggregation
What ADP does
promotes aggregation
What serotonin does
facilitates hemostasis mechanism
what is PF3 and what it does
platelet factor 3. source of phospholipid activity which participates in coagulation.
First steps in platelet plug formation
Vascular injury -> collagen exposure and von Willebrand Factor facilitate platelet adhesion.
2nd steps in platelet plug formation
Activation and release of cytokines (TX A2, ADP, PF3) and platelet aggregation.
Important things that platelet factors released do
Attract more platelets
Last steps in platelet plug formation
Thrombin (which is critical for clot formation) and the coagulation pathway also promotes platelet plug (white thrombus) adhesion, aggregation, formation. POSITIVE FEEDBACK
Platelets function (5)
1) Release vasoconstricting factors
2) Form white thrombus (platelet plug)
3) Release clotting factors
4) Participate in clot retraction
5) Promote maintenance of endothelial integrity
What is the consequence of an abnormal hemostatic response
prolonged bleeding
What can cause abnormal primary hemostatic response
1) Failure of blood vessels to constrict
2) Platelet defficiencies
Different platelet deficiencies
1) Numerical (less than 75 000 per microliter)
2) Functional (congenital or acquired)
3) Caused by drugs, toxins, antibodies
Exemple of drug than can cause platelet deficiency and what it does
Aspirin (in small doses) inhibits synthesis and release of TX A2 and this inhibits ability of platelets to come together (TX A2 stimulates vasoconstriction but also aggregation of platelets, just like all factors released by platelets)
Blood clot : what do we name it
thrombus
Clot formation is a function ___________. What it involves and what it doesn’t involve.
Function of PLASMA. RBCs and WBCs are bystanders and are not necessary for the process
Clotting def
Sequential activation and interaction of plasma proteins or clotting factors (some act as enzymes and some act as co-factors), in presence of calcium and phospholipid agents
3 stages of clotting -> which stage is visible and which is not
stage 1 -> beginning. stages 1 and 2 molecular changes that aren’t visible. stage 3 : final form
How protein factors in cloting were named
Roman numerals I to XIII in order of discovery
Stage 1 of clotting 2 pathways involved, the time they take and what induces them
Intrinsic pathway activated by blood vessel damage (3-6 minutes)
Extrinsic pathway activated by tissue outside vessel (15-20 seconds)
Stage 3 of clotting what happens
Fibrinogen is converted into fibrin (some a.a removed) in presence of thrombin
Stage 2 of clotting what happens (2)
1) Prothrombin is converted into thrombin in presence of prothrombinase and Ca 2+.
2) Thrombin activates factor XIII (becomes XIIIa) which consolidates/cross-links fibrin molecule to make the network they form more compact
Stage 1 of clotting how intrinsic pathway starts, what it uses and what it leads to
Starts with collagen exposure. Uses plasma factors, Ca 2+ and PF3. Leads to prothrombinase formation (complex of Va, Xa, PF, Ca 2+)
Stage 1 of clotting what extrinsic pathway uses and what it leads to
Uses tissue factors (protein and phospholipid), plasma factors, Ca 2+ and tissue phospholipid. Leads to prothrombinase formation
Why extrinsic AND intrinsic pathway
Small amounts of thrombin generated rapidly by extrinsic scheme trigger strongly positive feedback on intrinsic scheme to generate more thrombin
3 things thrombin does
1) Catalyzes formation of fibrin from fibrinogen
2) Activates factor XIII into XIIIa
3) Positive feedback on intrinsic pathway
What downregulates clotting (2)
1) Inhibitors of platelet adhesion
2) Anticoagulants (naturally occuring chemicals that block reactions in coagulation scheme)
Exemples of coagulants and what they do
Heparin and antithrombin III work together to block IX, X, XI and XII
Protein C inhibits factors V and VIII
3 factors in coagulation and if we can lack them
Ca 2+, phospholipid (always present sufficiently) and protein plasma factors (can be deficient - congenital)
Congenital cloting factor deficiencies
Heredity deficiencies of a single factor (ex. VIII -> hemophilia)
Acquired cloting factor deficiencies and 2 exemples
Multifactor deficiencies (ex. liver disease, vitamin K deficiency)
Clot retraction meaning
Clot moves away from vessel walls/sides
Obtaining serum in vitro
Induce cloting in presence of plasma, cloting factors get involved in cloting and liquid left is plasma
What clot retraction depends on
Platelets. (release a contractile protein named thrombosthenin which influences clot retraction)
How clot helps healing
Tends to shrink after it retracts and this pulls walls of damaged vessel together
Clot lysis what it means and other name for it
Clot dissolution/destruction. Fibrinolysis
Scheme of fibrinolysis
Plasmin dissolves fibrin into fibrin fragment. Plasmin derives from plasminogen. Plasminogen activator transforms plasminogen into plasmin.
2 types of plasminogen activators
1) Intrinsic proactivators (ex. XIIa) and endothelial cell factors.
2) Extrinsic proactivators (ex. tissue factors)
Anticoagulants 3 types
1) Inhibitors of platelet adhesion
2) Anticoagulant drugs (interfere with clot formation)
3) Thrombolytic drugs (promote clot lysis)
Exemple of inhibitor of platelet adhesion
aspirin
2 exemples of anticoagulant drugs
1) Coumarin (blocks synthesis of functional prothrombin, VII, IX, X)
2) Heparin (inhibits thrombin activation and action)
2 exemples of thrombolytic drugs
1) Tissue plasminogen activator (t-PA)
2) Streptokinase
