Blood and Hemostasis Questions

Blood Overview

• Blood is connective tissue
• Consists of blood plasma, cells, and cell fragments
• Blood dissolves and suspends various cells and cell fragments
• Blood is denser and more viscous than water
• Blood is slightly sticky
• Normal blood temperature measures 38°C
• Blood has a pH of 7.35 to 7.45
• Bright red blood contains high oxygen
• Dark red blood contains low oxygen

Components of Blood

• Blood plasma comprises 55% of blood, contains dissolved substances
• Formed elements are 45% of blood
• Red blood cells (RBCs) are a part of formed elements
• White blood cells (WBCs) are a part of formed elements
• Platelets are a part of formed elements

Hematocrit

• The Hematocrit is the packed cell volume (PCV)
• It denotes proportion/percentage of blood made up of cells
• The cell proportion consists of RBCs and a buffy coat(WBCs and platelets)
• Normal PCV measures 0.42 - 0.47
• PCV is generally greater in men than in women
• Polycythemia, dehydration, and dengue fever increase PCV
• Anemia, cirrhosis of the liver, and pregnancy decrease PCV

Blood Plasma

• Blood plasma is a straw-colored liquid
• Blood is 91.5% water
• Blood contains 8.5% solutes
• Solutes include organic and inorganic molecules
• Plasma proteins compromise 7% of blood volume
• Sugar, fats, enzymes, and hormones are organic molecules within blood
• Extracellular inorganic molecules: Na+, Ca2+, Cl-, HCO3-
• Intracellular inorganic molecules :K+, Mg2+, Cu2+, Fe2+, Fe3+, PO4-
• Non-protein nitrogenous substances include urea, uric acid, creatine, and creatinine

Plasma Proteins

• Albumin maintains colloidal osmotic pressure
• Albumin transports proteins for steroid hormones and fatty acids
• Albumin works as a buffering agent
• Albumin maintains viscosity
• Globulins include Immunoglobulins which help attack viruses and bacteria
• Globulins include alpha and beta globulins which transport iron, lipids, and fat-soluble vitamins
• Globulins provide buffering action
• Fibrinogen plays essential role in blood clotting

Formed Elements of Blood

• Formed Elements consist of red blood cells, white blood cells, and platelets
• White blood cells are divided into granular leukocytes and agranular leukocytes
• Granular leukocytes include neutrophils, eosinophils, and basophils
• Agranular leukocytes include lymphocytes and monocytes

Functions of Blood: Transportation

• Transports oxygen from the lungs to the cells
• Transports carbon dioxide from the body cells to the lungs
• Carries nutrients from the gastrointestinal tract to body cells
• Transports waste products to organs for elimination

Functions of Blood: Regulation

• Maintains homeostasis
• Regulates water, pH, and electrolytes to normal limits
• Regulates of body temperature through heat absorption and coolant properties
• Maintains Osmotic pressure through dissolved ions and proteins
• Provides fluid exchange between blood and tissues
• Transports hormones

Functions of Blood: Protection

• Blood clots protect against excessive loss of blood after injury
• WBCs protect against disease by carrying on phagocytosis
• Antibodies, interferons, and complement help to protect against disease

Red Blood Cells

• Red blood cells are also known as erythrocytes
• Red blood cells are biconcave discs with a diameter of 7–8 µm
• Contain hemoglobin molecules without a nucleus, or organelles
• Red blood cells have a life span of 120 days
• Normal RBC count is 5.4 million/µL in adult males
• Normal RBC count is 4.8 million/µL in adult females
• RBCs lack mitochondria and generate ATP by anaerobic mechanisms

Importance of Biconcave Shape (RBCs)

• Flexible and can change shape when squeezing through capillaries
• Increases the surface area for diffusion of gases while decreasing the diffusion distance
• Variations in shape and dimensions of RBCs help differentially diagnose anemias

Hemoglobin Molecules

• Each RBC contains about 280 million Hb
• Hb consists of a protein called globin
• Globin is composed of four polypeptide chains: two alpha and two beta chains
• Heme is a nonprotein pigment ring
• Heme binds to each of the four chains
• The center of each heme ring is an iron ion (Fe2+)
• Fe2+ combine reversibly with one O₂ and each molecule binds four O₂
• Normal hemoglobin levels are 14 – 17 g/100 ml in men
• Normal hemoglobin levels are 11-14 g/100 ml in women

Fate of Red Blood Cells

• Red blood cell blood stream life is 60-120 days
• Old RBCs become rigid and fragile
• Hemoglobin begins to degenerate
• Dying erythrocytes are engulfed by macrophages
• After being lysed, cellular components mainly undergo extravascular process in reticuloendothelial system
• Broken parts processed in liver, spleen, and bone marrow

Fate of Red Blood Cells (cont.)

• Heme is degraded to a yellow pigment called bilirubin
• Liver secretes bilirubin into the intestines as bile
• Intestines metabolize bilirubin and excrete it through the feces (stercobilin)
• The kidneys excrete bilirubin as urobilin
• Globin is catabolized into amino acids and released into the circulation

Hemopoiesis

• Hemopoiesis refers to the development of formed elements of the blood
• Before birth hemopoiesis first occurs in the yolk sac and later in the liver, spleen, thymus, and lymph nodes
• In the last three months of development, hemopoiesis occurs in the red bone marrow
• After birth hemopoiesis occurs in the red bone marrow

Hemopoiesis (cont.)

• Red bone marrow cells from mesenchyme, are pluripotent stem cells
• They develop into different types of cells
• All bone marrow is red in newborns
• Red bone marrow in the long bones becomes inactive in adulthood
• Red marrow is replaced by yellow marrow, resulting in a decreased rate of blood cell formation

Hemopoiesis (cont. again)

• Pluripotent stem cells produce two types of stem cells
• Myeloid stem cells give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils
• Lymphoid stem cells give rise to lymphocytes

Erythropoiesis

• Erythropoiesis refers to the production of RBCs
• Begins in the red bone marrow
• Proerythroblast is the precursor cell
• The proerythroblast divides several times
• Erythroblasts synthesize hemoglobin and eject their nucleus
• They become reticulocytes, then RBCs after 1 to 2 days

Factors Affecting Erythropoiesis

• Erythropoietin
• Vitamins (Vitamin B12, Folic acid, Pyridoxine, Vitamin C, Riboflavin, and Pantothenic acid)
• Minerals (Iron, Copper, and cobalt)
• Hormones (Growth hormone, Thyroid hormones, Cortisol, Testosterone, and Adrenocorticotropic hormone)
• Proteins (Globin synthesis of hemoglobin)

White Blood Cells

• White blood cells are also known as leukocytes
• 5,000-10,000 cells per µL of blood
• Granular leukocytes exhibit distinct staining
• Agranular leukocytes have granules are not visible under a light microscope

Neutrophils

• Neutrophils are polymorphonuclear leukocytes, comprising 60-70% of WBCs
• Diameter 10-12 μm
• Cytoplasm has very fine, pale lilac granules
• Nucleus has 2–5 lobes connected by thin chromatin strands
• Perform Phagocytosis
• Destroys bacteria with lysozyme, defensins and strong oxidants

Eosinophils

• Comprise 2-4% of WBCs
• The cell diameter is 10-12 μm
• Cytoplasm of eosinophils contains large red-orange granules
• Its nucleus has 2 lobes connected by a thick chromatin strand
• Granules usually do not obscure the nucleus
• Eosinophils combat histamine effects in allergic reactions
• They phagocytize antigen-antibody complexes
• They destroy certain parasitic worms

Basophils

• Basophils comprise 0.5-1% of all WBCs
• They are between 8-10 μm in diameter
• They have large cytoplasmic granules which appear deep blue-purple
• Granules obscures the nucleus and has 2 lobes
• Basophils release heparin, histamine, and serotonin in allergic reactions, intensifying the inflammatory response

Monocytes

• Monocytes comprise 3-8% of all WBCs and have a diameter of 12-20 μm
• Nucleus is kidney shaped or horseshoe shaped
• Cytoplasm is blue-gray and has a foamy appearance
• Fine azurophilic granules (Lysosomes)
• Perform phagocytosis

Macrophages

• Blood transports monocytes from the blood into the tissues
• In tissues, monocytes differentiate into macrophages: either fixed or wandering
• Fixed macrophages reside in a particular tissue (alveolar- lungs, kupffer- liver or neuroglia-brain),
• Wandering macrophages roam the tissues and gather at sites of infection or inflammation.

Lymphocytes

• Lymphocytes comprise 20-25% of WBCs
• Lymphocyte diameters range from 6–9 µm (small) or 10–14 µm (large)
• Their cytoplasm stains sky blue and forms a rim around the nucleus
• Spherical with slightly indented nucleus
• Lymphocytes mediate immune responses
• T lymphocytes (T cells) attack invading viruses, cancer cells, and transplanted tissue
• B lymphocytes (B cells) develop into plasma cells, which secrete antibodies
• Natural killer (NK) cells attack infectious microbes and tumor cells

Clinical Connections: Leukocytosis

• Leukocytosis denotes an elevated number of WBCs above 10,000/μL
• Can be due to infections, allergy, common cold, tuberculosis and glandular fever

Clinical Connections: Leukopenia

• Leukopenia is an abnormally low level of WBCs below 5000/μL
• Can be due to anaphylactic shock
• Other causes are cirrhosis of liver, disorders of spleen, pernicious anemia, and typhoid

Clinical Connections: Anemia

• Anemia is a condition in which the oxygen-carrying capacity of blood is reduced
• Anemia is shown by low levels of RBCs
• Anemias consist of Leukemia, Sickle Cell Anemia, Thalassemia, and Myeloma

Iron Deficiency Anemia

• Occurs due to inadequate absorption of iron/excessive loss of iron
• Megaloblastic anemia occurs due incomplete intake of vitamin B12 or folic acid
• Pernicious anemia is the inability of the stomach to produce intrinsic factor
• Hemorrhagic anemia is the excessive loss of RBCs through bleeding
• Hemolytic anemia is the rupture of RBC plasma membranes prematurely

Clinical Connections (cont.)

• Thalassemia denotes deficient synthesis of hemoglobin
• RBCs are small (microcytic), Pale (hypochromic)
• Aplastic anemia is bone marrow destruction
• It can occur due to exposure to toxic chemicals (benzene), radiation or autoimmune disorder
• Sickle-Cell Disease is an abnormal kind of hemoglobin
• RBCs become a sickle shape and rupture easily
• Leukemia refers to red bone marrow cancers where white blood cells multiply uncontrollably

Blood Types

• Human blood cells contains antigens
• 30 commonly occurring antigens and hundreds of rare antigens
• Antigens can cause antigen-antibody reactions
• Most antigens are weak
• Inheritance of genes are important when studying blood type for crime detection
• Antibodies (agglutinins) are present in the plasma
• Antigens (agglutinogen) are present on the surfaces of the RBCs and cause blood transfusion reactions

Agglutinogens

• Agglutinogens are found on the surfaces of RBCs
• There are four major O-A-B blood types: O, A, B, and AB
• Type O blood has neither A nor B agglutinogen present
• Type A blood possesses only A agglutinogen
• Blood type B possesses only B agglutinogen
• Blood type AB possesses both A and B agglutinogens

Genetic Determination of the Agglutinogens

• Two genes determine the O-A-B blood type
• The Type O gene has no agglutinogens on RBCs
• Type A & B genes are agglutinogens present on the RBCs

Agglutinins

• Absence of A agglutinogen in the RBCs, signifies creation of anti-A agglutinins (Agglutinin a)
• Absence of B agglutinogen in the RBCs, signifies creation of anti-B agglutinins (Agglutinin B)
• No agglutinogens in RBCs. triggers creation of anti-A and anti-B agglutinins
• Alpha- and beta-agglutinins are IgM type of immunoglobulins

Origin of Agglutinins

• The agglutinins are gamma globulins
• Mostly IgM and IgG type of immunoglobulins
• Alpha- & beta-agglutinins are also IgM type of immunoglobulins
• No agglutinins are present Immediately after birth
• Agglutinins begin to produce with 2 to 8 months after birth
• The titers reaches maximum between 8 to 10 years old

Landsteiner's Law

• A particular antigen is present on an RBC and the plasma doesn't contain corresponding antibodies
• An absent antigen means the plasma contains the corresponding antibody
• Group A blood has beta agglutinin
• Group O blood has both alpha and beta agglutinins

O-A0B Blood Types (cont.)

• Type A blood contain A-Ag surface antigens contains anti-B plasma w/Antibodies (Auto-lgs)

• Type A blood can receive transfusion’s from only A and AB

• Type B blood contain B-Ag surface antigens contains anti-A plasma w/Antibodies (Auto-lgs)

• Type B blood can receive transfusion’s from only B and AB

• Type AB blood contain A + B-Ag surface antigens contains no plasma w/Antibodies (Auto-lgs)

• Type ABblood can receive transfusion’s from only AB (Universal. Recipient)

• Type O blood contain no surface antigens, only the plasma

• Type O blood can only receive transfusion from A,B, AB-O (Universal Donor)

RH Blood Types

• Important for transfusing blood/difference from group O-A-B system

• Group O-A-B system requires transfusions and plasma agglutinins

• Rh system involves transfer of spontaneous agglutinins which never occur

• Three types(Rh Factor): C,D,E

• D antigen is widely prevalent in the population

• Presence of type D is Rh+ (90 percent of population)

• • Absence of type D is Rh- (10 percent of population)

Hemolytic Disease of the Newborn

• Due to Rh + individual’s possibly having DD or Dd genotype

Formation of Anti Rh Agglutinins

• Rh Antibodies: when Rh Antibodies are injected into a Rh person
• Rh negative person transfusions Rh positive blood/ Rh negative female gives birth to Rh positive infant.

Transfusion reactions caused by reactions: Anti Aglutins usually don’t develop 2 to 4 months later/usually has mild impact in transfer Subsequence is transfusion, greatly enhanced/ cause immediate and severe transfusion reactions

Erythroblastosis Fetalis (disease)

• Fetus and new born child are diseases where red blood cells aggregate and spread Mother is Rh - and father is Rh + baby, from placenta transfer anti-Rh antibodies diffuse into fetus
• These Agglutinations are known a fetus blood Agglutination ( RBC breaks) which leaks into the blood

Fetus macrophages convert Hb into bililrubin

• Baby skin becomes jaundice
• 3 % of Rh + exhibits signs of erythroblastosis fetalis/Incidence rises progressively w/sub transfers

Clinical Pictures of Erythroblastosis

Include having enlarged liver with anemia, where nucleared blastic cells cause impairment And jaundice

• Damage to motor areas of the brain cause precipitation and death
• In motor neurals
• Kernicterus

Treatment and Prevention of Erythroblastosis

If baby is born is give Rh positive or negative transfusion/400mm is infused hours at at time Where RH Blood is removed from the Neoconate

• Prevents a process is involves in the red blood cell by 6 or more weeks Anti-D anti body ( Rho) is administered to the expecting mother between 28 to. 30 weeks of gestation
• Anti D antibody is administered to Rh- Women ho deliver to Rh Positive babies and prevent sensitization of mothers to D antigen

Blood Typing

• Separation from the plasma is diluted with saline then mixed in anti A,B, and d agglutinin
• Then put the solutions into a microscope
• Matching blood

Cross Matching of Blood

Match RBCs of serum (of receptor ) & serum w/ (RBC’s) of receptor

Cross Matching of Blood ( 2 types)

• Testing patient’s serum w donor cells, most important, testing most serum Which determines which patient may have hemolyctic transfusions w/ anitbodies

• Minor testing = determine whether the patient has cell plasma where is can be directed to antigen to patient cells

Transfusion Reactions

• Mismatched blood type (Agglutination)
• In a rare occasion blood becomes deluted and results in a transfer
• Plasma (portions of the donor) becomes diluted

Agglutination

• RBCs can cause 2 agglutinogens w/ 2 (IgG) / 10( IgM) binding sites
• Clumps causes distruction and hemolysis in cells released from Hb
• Opposing anti bodies (agglutination)

Transfusion reactions can cause

• Hb to release (RBC ) and create bilirubin for for phagocytosis. Which excretes bile in the Liver

• Poor liver function can normal bile pigments from the liver

• Jaundice caused by not appear in the adults and a day unless more than 400mm is hemisized

Transfusion Reactions ( can cause)

• Lead to Kideny Failue
• Power Vasocontrictions (release hemolyzed blood)
• Shock with loss of RBCs from vasoconstriction

This causes Blood pressure to decrease. Urine blood outputs increases blood pressure leading to tubular blockage

• Which means tubular blockage to tubular shutdown.

Clinical connections Need of something to stop transfer and replace it with

• Crystalloids (normal saline and dextrose) can replace the blood

Platelets

• Undergo thrombopoietin (myeloid stem cell to create mega)

• Megacarocytes split into 2000- 3000 sections

• Each = (thromobocyte) called and they all promote clothing chemicals

• Platelets stop blood clots from damaged blood clots and vesicles

• Granules of chemcial in a platelet release

• The platelet count blood levels for platelets are (150,000 and 400,000) mL of clots.

• Disc shaped

• Life Span is (5-9 days) from a diameter of 2-4mm

• They include vessels but no nucleus

• Platelets also include factors, ADP, ATP, Ca2 AND serotonin

• All vessel includes what’s needed to strenghten clots _Includes hormone platelets and ednothelliel

Hemostasis steps (3)

1. Vasor Spasms: is were vessels muscle contrast/

• arteries that are usually damage need smooth muscles to contrast
• which reduce blood loss for a day

2. Vessel Damage causes :

• Exposed collagen from vessle that can lead to activation and contraction.
• Which forms and becomes attached

3. Collgen: Platelets (stick to damaged side

• The adheasion is a contact w platelets that cause the connecitve tissues underlying adhisiaon

4. Released reaction :

• Platelets and their contacts become active and liberated vessels which reduce blood in injury location

Hemostasis (4)

• Aggregation (makes platelets sticky as well as activating them)
• Calls/gathers platelets and attaches them to forms mass

5. Serum: a Blood plasma (without protein in clott

Process that causes : gel ( series of chemical reactions leading thread like fibrin)

• Blood cells have to be created to create different stages (Extrinsic to Intrinsic ) leading back tp common stages.
• Prothombrinase is formed to lead prothrombin and thrombins (leading soluble fabrics to fabrin.

Extrisnic and Intrinsic pathways

Extrinsic: Tissue becomes damaged which causes the need of more lipids (with clotting of factorX 15 sec in blood stream

Intristic:

• Damaged endohellium Causes colaggen as well a platelts to create CA to help for activate plasma with phospholipids

Factor- (Causes Vasocontrac to platlettes or other Aspiration prevents this damage as well/ (clotting in body is caused

Clott Pathwats

Positive feedBack loops Thrombin

Q a lot can cause aceleration to tromboginse to to accelerate thrombin

Aggregation of cell and phosphates

• Clott = pulled together Forms of Clotting Clot is pulled togethers to heal

Also platelets from the blood vessels

Red clot

Pulled edges form damage (to for some for more

AntiCoagulate

• People which are at risk can’t be anticulated.

• Warfrin ( Coumadin) attacks an anganistc and synthesis (for cxlpttoing

• EDTA Used the vent

• CLotting Subanates that

Hemopila = Inhearitied of clotting factores Thrombolitc is what leads in the deficnties a a and b