Hematology Flashcards
Why is average water intake important?
Water intake maintains constant body temperature
Why does obesity decrease the percent of average water in body weight?
Fat is hydrophobic so it retains less water than lean tissue
Water turnover
Maintains water balance in the body
Majority of water we intake is from food or liquids we ingest. Water is lost through breathing, exercising, and production of waste.
Two main fluid compartments
- Intracellular (inside cells)
2. Extracellular (blood plasma, interstitial fluid)
Lymphatic system
Designed for movement of macromolecules paired with the circulatory system
Where is does interstitial fluid originate from?
Filtration from capillaries. Consists of same components as plasma except for large proteins that exists at lower levels
Why is [Ca] zero in intracellular compartments?
Because free Ca is stored until needed.
Why is total osmotic pressure higher for extracellular fluids (plasma)?
Because it allows solutes to move into the blood more readily
Cellular clefts
Channels for fluid and solutes between cells
Polarity, size, and permeability
Increased polarity and size decreases permeability of a substance
Major proteins of the plasma
- Albumin
- Globulin
- Fibrinogen
1>2>3
Albumin
Most abundant plasma protein, acts as non-specific protein carrier, provide colloid pressure in plasma
Globulin
Specific carrier proteins
Fibrinogen
Important for blood clotting, polymerizes into long fibrin threads during blood coagulation
Fluid movement out of capillary due to pressure from …
Capillary pressure and plasma colloid osmotic pressure
Fluid movement into capillary due to pressure from…
Interstitial fluid pressure and interstitial fluid colloid osmotic pressure
When does colloid pressure increase?
When protein content increases
Why does net outward force of capillaries need to be greater than inward force?
To maintain constant filtration to interstitial compartments
Components of the interstitial compartment
- Collagen fibres
- Proteoglycan filaments entrap fluid to form a “gel”
- Small amount of free flowing water is stored and exchanged between small vesicles
Endema
Result of fluid buildup in the interstitial compartment
Importance of gel formation in the interstitial compartment
- Uniform distribution of fluid compartments
- Prevention of fluid accumulation due to gravity
- Maintain optimal intercellular distance (hold cells apart)
- Give shape to body parts
Lymphatic system
Accessory route for transport of fluid and macromolecules from interstitial space to veins.
Lymph
Fluid in lymphatic system, absorbed from surrounding tissue into tubes that lead to lymph nodes
Lymph nodes
Filter lymph to remove blood contaminants before drainage into the veins, allowing clean blood to flow back to the heart
Lymph flow and fluid pressure
Flow is function of interstitial fluid pressure. Flow occurs in one direction due to presence of valves.
Negative effect by blockage of lymph valves
Blockage causes build up of lymph leading to inflammation. Continued increase in back flow pressure causes filtration rate to decrease. Tissues stop getting important nutrients and start dying. Sever cases involve amputations.
Hemopoeisis
The production of blood cells, formed from the differentiation of PLEURIPOTENTIAL HEMOPOIETIC STEM CELLS
Cytokines
Small proteins important in cell signalling, important for regulation of blood proliferation, maturation and growth of blood cells.
Interleukins and stem cell factors
Increase production of all HEMOPOIETIC stem cells
Erythropoietin
Stimulate differentiation into erythrocytes
Thrombopeitin
Stimulate differentiation into megakaryocytes
Granulocytes monocytes colony stimulating factors
Stimulate differentiation into granulocytes and monocytes
Interleukins
Type of cytokines synthesized by helper cells
Myeloid stem cell derived blood cells
Erythrocytes
Platelets
Leukocytes (neutrophil, eosinophil, basophils)
Monocytes
Lymphoid stem cells derived blood cells
B and T lymphocytes
Plasma cells
Structure of red blood cells (erythrocytes)
Mature RBC has no nucleus
Membrane is deformed into biconcave disk
Has ability to change shape and pass through capillaries
Advantage of biconcave structure for RBC
Maximize surface area for gas exchange
Hematocrit
Volume of RBC in the blood
Function of RBC
- Transport hemoglobin (oxygen carrier)
- Hemoglobin in blood acts as a acid base buffer
- Contains carbonic anhydrase to catalyze production of bicarbonate (prevent accumulation of co2)
Production of RBC
- Birth from stem cell of bone marrow
- Erythropoietin stimulate differentiation into RBC
- Committed cells differentiate into RBC or colony forming unit erythrocyte (CFUE)
Hemoglobin composition
4 Pyroles + 1 Fe = 1 Heme
1 Heme + 1 Globin (peptide chain: a,b,c,d) = 1 Hemoglobin subunit
4 Hemoglobin subunits = 1 functional Hemoglobin
Most abundant hemoglobin in an adult
Hemoglobin A: units consist of 2 alpha and 2 beta globin chains
How many oxygen molecules can bind to a hemoglobin?
4 molecules due to 4 Fe (sum from all subunits)
Why can fetal hemoglobin have greater affinity for oxygen?
Fetal hemoglobin have a gamma globin chain rather than a beta. This decreases levels of BPG to favour oxygen binding to hemoglobin. This higher affinity for oxygen is required to extract maternal oxygen across the placenta
Haldane effect
Oxygenation of blood decreases affinity for CO2. De oxygenation of blood increases affinity for CO2. This is achieved by the confirmation change of hemoglobin when it binds to CO2 or O2.
Sickle cell anemia affect on hemoglobin
Point mutation causes structural change of hemoglobin. Sickle cells are more rigid and cannot bind to oxygen as well, and gets stuck in vessels which lead to degeneration of blood cells causing anemia.
Erythropoietin
Produced in the kidney, stimulated by low oxygen levels (hypoxia) to induce differentiation of blood cells to RBC
Hypoxia Anemia Low hemoglobin Poor blood flow Pulmonary disease
How long does RBC production take?
About 5 days
Blood doping
Moving from a lower altitude to higher altitude to increase blood production for maximum oxygen loading.
Megaloblastic anemia
Anemia resulting from lack of vitamin B12 and folic acid. Enlarged blood cells cannot diffuse through membranes so the degenerate causing anemia which triggers increase in erythropoietin
Why is vitamin B12 and folic acid important?
Involved in DNA synthesis and the cell cycle (nuclear maturation required to sustain proliferation of RBC)
Pernicious anemia
Inability to absorb vitamin B12 and Folic acid leading to anemia
Ferritin
Intracellular protein in the liver which binds to iron and reserves it for blood production
Transferrin or beta globulin
Plasma protein that binds to iron.
- Direct iron to mitochondria for heme production
- Increase iron absorption from gut
- Prevent anemia
Average lifetime of an RBC
120 days
What is inside RBCs?
No nucleus
No organelles
Cellular enzymes capable of limited metabolism to form ATP and other compounds
Metabolic capacity of RBC
Metabolic capability decrease with time because they run out of metabolites. This leads or membrane weakening and the RBC ruptures
What happens to ruptured RBC?
They are phagocytosis by macrophages.
What happens to iron from ruptured RBC?
Iron binds to transferrin.
What happens to the porphyrin portion of the ruptured RBC?
It is converted to bilirubin which is incorporated into bile. Build up can lead to hepatitis.
Porphyrin
Portion of the heme without Fe
Bilirubin
Possible antioxidant?
Platelets
Small oval disc cells derived from large megakaryocytes in the bone marrow. (Basically the membrane fragments of megakaryocytes).
No nucleus, but does have organelles.
Short life span.
How are platelets activated?
Activated by contact with college through recognition by surface glycoprotein.
Why do platelets have actin, myosin, and thrombosthenin?
To give them protrusion and adhesion abilities
What can platelet cells make?
They contain residuals of Golgi apparatus and endoplasmic reticulum that allow them to make enzymes, ATP, ADP, eicosanoids, and store Ca++
Hemostasis
Maintain blood levels by preventing loss of blood
How is hemostasis achieved?
- Vascular spasm and constriction
- Formation of platelet plug
- Blood coagulation
- Tissue repair
Vascular constriction
Cut or rupture of a blood vessel releases thromboxane A2 from platelet cells which contact collagen.
Or
Pain reception causes some degree of vasoconstriction
Forming a platelet plug
Cut allows platelets to contact collagen. Results in production and release of ADP and thromboxane A2 to activate other platelet cells. Aggregation of platelets from a plug that can stop minor bleeding.
What enzyme releases thromboxane A2 upon platelet activation?
Cyclo-oxygenase 2
Why is ADP important in a platelet plug formation?
ADP stimulate platelets to swell and protrude podia to adhere to the damaged site.
How is a platelet blog stabilized?
Required fibrin stabilizing factor
How is more sever blood loss stopped?
Blood clotting
Importance of vitamin K
Presence allow production if prothrombin, the precursor of thrombin important in blood coagulation
Tissue thromboplastin (factor 3)
Activate extrinsic pathway due to tissue trauma
Hagemen factor (factor 12)
Activate intrinsic pathway due to blood trauma leading to coagulation.
Anticoagulants
Factors that prevent blood clots
Glycocalyx
Anticoagulant: Absorbs to inner surface of endothelium and repels clotting factors
Thrombomodulin
Anticoagulant: binds to and deactivates thrombin to prevent clotting
Heparin
Anticoagulant: activate factors that remove thrombin to ensure blood doesn’t clot when not necessary.
Clot formation and dissolution
- Clot form
- Healing initiated
- Plasmin activates fibrolysin which breaks down stable fibrin
- Clot starts dissolving due to phagocytosis
Why is platelet activation local?
Because it need only cause vasoconstriction and clotting at site of injury.
