Compositon of Blood

Plasma (55%)

Composition

• Water (90%)

• Plasma proteins (7%)

  • Albumins (60%) → major contributor to osmotic pressure regulation in plasma, also transport protein for lipids, and steroid hormones

  • Globulin (35%) → transport protein for ions (ex: iron), hormones (TeBG → testosterone binding globulin), lipids and had immune functions

  • Fibrinogen (4%) → inactive protein essential for the clotting system, can be converted into insoluble fibrin (active from of fibrinogen)

  • Regulatory proteins (<1%) → enzymes, proenzymes and hormones

• Other Solutes (1%)

  • Electrolytes → normal extracellular fluid ion composition for vital cellular activities. Also contribute to osmotic pressure

    • most common ones → sodium (Na⁺), potassium (K⁺), chloride (Cl⁻), magnesium (Mg²⁺), calcium (Ca²⁺), phosphate (P), and bicarbonates (HCO₃-)

  • Organic nutrients → used for ATP production, growth & maintenance of cells, include lipids, carbohydrates, and amino acids

  • Organic waste → carried to cites for breakdown or excretion, include urea, uric acid, creatine, bilirubin and amonium ions

    • most of these are nitrogenous wastes

    • inorganic waste → CO₂

Functions

Primary

• transport

• exchange

Secondary

• pH regulation

• fluid volume regulation

• thermoregulation

  • 90% of it is water → water can absorve a lot of energy without changing temp., aka vasodilation/-constriction

• coagulation

  • ability to form blood clots

• immunity

Formed elements (45%)

White blood cells (WBC) (0.1%)

• Nucleophils (50%)

  • most abundant type of WBC

• Lymphocytes (25%)

  • same size as RBC

• Monocytes (2-8%)

  • migrate btw endothelial cells, fuse to make macrophages and gobble up oxidized LDL to form plaques (atherosclerosis)

• Eosinophils (2-4%)

• Basophils (<1%)

  • least numerous

Red blood cells (RBC)(99%)

• make about 1/3 of all body cells (ab 30 trillion in adult body)

• only living cell without nucleus (anucleate) or organelles

  • make ATP through glycolisis

• contain hemoglobin

  • O₂ transport protein

  • RBC also referred to as “hemoglobin sacs”

• biconcave shape

  • increases SA

  • barely any hemoglobin in the middle making it not pick up any stain leading to making it look like they have hole in the middle under the microscope

  • capillaries are about the same size (or smaller) as the diameter of RBC this makes them have to fold to cruze through them, this shape facilitates this

Platelete (0.1%)

• cell fragments

• huge cells found in bone marrow pinch pieces off their membrane to form platelets

Hematocrit (Hct)

• % of a sample of whole blood that is occupied by RBCs

• multiple ways to do it

Manual Hct:

• derermined by microcentrifugation, followed by dividing the volume of packed RBCs (PCV → packed cell volume) by the total volume of the blood sample

  • Hct = tot. volume RBC/PCV

Automated Hct

• done through the use of a hematology analyzer

• this analyzer counts the # of RBCs and determines their mean corpuscular volume (MCV) then it is multiplied by the # of RBCs to get Hcl

  • Hct = # RBCs x MCV

Hct values

• Males (41-50%) & Females (36-48%)

  • this difference btw males and females is due to testosterone levels

• What affects the values?

  • androgens

  • estrogens

  • erythropoitetin (EPO)

    • RBC profuction stimmulating hormone

• Abnormal Hct typically results from changes in the # of RBCs and or Plasma volume

  • topHat question: Could you be anemic and have a normal Hct?

    • Answer: Yes, you can have a normal Hct and be anemic because an anemia can also be caused by issues with hemoglobin or an iron deficiency

Abnormal Hcts

• Anemia - 30%

• Polycythemia - 70%

  • primary (polycythemia vera) - bone marrow cancer causing ↑ #RBC and ↑Hct

  • secondary - normal physiological response to ↓ P_O2 causing ↑ #RBC and ↑Hct

    • used in high altitude training

    • also artificially done through blood doping

• Dehydration - 70%

  • lack of watter

Red Blood Cells

RBC production (erythropoiesis)

• RBC is formed in bone marrow of long bones (sternum, ribs, pelvic bones, and cranium)

  • cranium bones are composed of two layers of bone and in the middle a section of spongy bone (thats where RBC are cranked out)

  • Requires iron & amino acids (for hemoglobin synthesis) and coenzyme vitamin B₁₂

• Gastric intrinsic factor (GIF) is essential for B₁₂ absorption

  • ↓ GIF → pernicious anemia

    • treated with B₁₂ injections

• Erythropoietin (EPO) → hormone released by chemoreceptive kidney (JG) cells during hypoxic conditions (↓ P_O2) which stimulates erythropoiesis

• Erythropoiesis is influenced by EPO, Androgens, Estrogen, GH, T3, etc…

Lifespan & destruction

• On average the RBC lifespan is about 3-4 months

Jaundice

• characterized by a yellow hue on the skin and sclera (white part of the eye)

  • on white skin it shows yellow skin but in dark skin it is more apparent by the yellow sclera

• caused by liver unable to convert bilirubin into less toxic forms

  • seen in sorosis of the liver, and pancreatic, liver and duc cancers

  • also found in premature babies

    • liver has not fully developed

    • treated with UV light (synthesizes bilirubin into less toxic form)

Hemoglobin

• 4-subunits, quaternaty protein complexed with 4 heme groups (phorphyrin ring-Fe²⁺)

types

• oxyhemoglobin (HgbO₂)

• deoxyhemoglobin (Hgb)

• carbaminohemoglobin (HgbCO₂)

  • carbon monoxide bonded with hemoglobin

  • carbon monoxide has a higher affinity to heme than oxigen

    • it’s a competitive inhibitor for it

    • always outcompetes oxigen, this is why its poisonous

• maternal (adult) hemoglobin (HgbA)

• fetal hemoglobin (HgbF)

• sickle-cell hemoglobin (HgbS)

• glycated hemoglobin (HgbA1c)

  • glucose bound to the n-terminus of the polypeptide chains in hemoglobin

  • no change in O₂ affinity

• it binds to CO₂, H⁺, 2,3-BPG, NO, CO, glucose, etc…

  • CO₂, H⁺, 2,3-BPG are byproducts of metabolism that bind to hemoglobin and change the conformation of its 3D shape making it lose its ability to bind to O₂

  • binding cites:

    • CO₂ → polypeptide chain

      • forms an amine

    • H⁺ → some R- groups in the amino acids

      • when it binds it changes the confirmation of hemoglobin decreasing O₂ affinity (due to change in pH)

    • 2,3-bisphosphoglycerate (BPG) → center of hemoglobin

two conformations

• Tense (T-hemoglobin)

  • low O₂ affinity

  • favors the unloading of O₂

  • induced by CO₂, H⁺, and 2,3-bisphosphoglycerate

• Relaxed (R-hemoglobin)

  • high O₂ affinity

  • favors the loading of O₂

Hgbs and Sickle-cell anemia

• Inherited point-mutation in DNA coding for hemoglobin

  • makes it so that it codes for the protein to be nonpolar instead of non-polar thus making it hydrophilic

    

  • this leads to the sickling of RBCs, sickle-cell crises, premature RBC destruction and anemia

    • this small change makes the hemoglobin sticky which causes the hemoglobin proteins to stick with each other creating sickle-cell crises

    • this anemia can cause ischemia, perfusion and lead to organ failure

Trait vs disease

• Sickle-cell disease (HgbSS or HgbAS) → has the disease

  • only has sickle cells

    • treatments:

      • monthly blood transfusions (most common)

      • bone-marrow transplants (not common, a few have been completely cured)

      • gene therapy (currently on the horizon)

• Sickle-cell trait (HgbSs or HgbAS) → carries the gene for the disease

  • also has both sickle and normal RBC

  • 1/13 of African americans in the US are carriers

Malaria and Sickle-cell

• malaria is a superimposable disease to Sickle-cell

  • the malaria parasite uses human RBC to mature (it gets into them)

  • carriers of the disease have both sickle and normal RBC, meaning that some of their RBC carry low oxygen capacity and it can stick together a little bit

    • Malaria is unavle to live in those and it messes up their lifecycle

    • as a result the individuals who are gene carriers are most likely to survive Malaria in comparison to someone who is HgbSS (disease) or HgbAA (normal)

      • this is why the trait is still in our gene pool → natural selection

        • those who live pass the gene down to their offspring

HgbA1c and diavetes

• HgbA1c is glycated hemoglobin (i.e. covalently bound to monosacharides)

  • glycated hemoglobin is a high indicator for diavetes (lasts 3-4 months)

RBC blood typing

ABO blood group system

• blood type is determined by the antigens attached to the end of the base unit

  • type O has no antigens (its only the base unit) but has both A and B antibodies → makes it the universal donor (there are no antibodies for type O)

    • 60% of all blood transfusions are type O

  • type AB has both A and B antigens and has no antibodies → makes it the universal receiver (can get blood from any type)

What happens if you get the wring type of blood?

• the antibodies attack bind to the surface antigens causing Agglutination and Haemolysis (destruction of the blood cells)

Rh blood group system

• where we get + or - in our blood types

• Rh hemolytic disease

  • occurs in mothers who are Rh- that have Rh+ after first pregnancy

    • treatment: at 28 weeks and within 72h of delivery they are given doses of RhoGAM (Rh+ antibody) that will bind to them when the blood of the foetus mixes with the mother during the hemorrhaging occurring during delivery preventing her from getting sensitized

      • her immune cells are unable to detect the Rh+ antigens thus preventing the disease from occurring in the following pregnancy

ABO types + Rh blood

Blood typing: ABO and Rh blood group systems

• + types can donate only to other + types

• - types can donate to both -/+ types

  • true universal donor → O-

  • true universal recipient → A-

Leukocytes (WBC)

• unlike RBC they do have nuclei and organelles

• function → immunity, removal of waste, toxins and damage cells

• primary site of action → lose connective tissue (CT)

Types of WBCs

Granulocytes

• Nucleophils (50%)

  • most abundant type of WBC

  • soecualized in attacking and digestin “marked” backteria

  • phagocytosis → lysosomes → respiratory burst (H₂O₂ and O₂)

• Eosinophils (2-4%)

  • attack and phagocytose objects coated with antibodies

    • will be in high ammounts during allergic or anaphylactic reactions

      • phagocytosis of pollen granules that have antibodies bound to them

    • also common in parasitic worm infections

  • exocytose cytotoxic compounds

    • In parasitic worm infections: eben though they are way smaller than the multicellular parasitic worms they exocytose chemicals that damage them

• Basophils (<1%)

  • least numerous WBC

  • histamine (inflammation) and heparin (anticoagulant) granules

    • histamine makes blood vessel walls leaky (increase gaps btw epithelial cells) allowing blood to crowl

    • heparin prevents blood clots in blood vessesl

  • analogous to mast cells (resident cells in lose CT)

    • mast sells are in the connective tissue, basophils are in the blood

Agranulocytes

• Monocytes (2-8%)

  • largest WBC

  • enter CT to become macrophages (syncytium)

  • phagocytosis

• Lymphocytes (25%)

  • smallest WBC

  • abundant in CT and lymphoid tissue

  • 3 functional classes →

    • T-cells → cell-mediated immunity

      • physically bind to cells to destroy them

    • B-cells → antibody- mediated immunity

      • secrete antibodies into the blood

    • NK cells → immune surveillance

      • Natural Killers, don’t need sensitizing

      • cruise around the body making sure you got normal sugars and stuff

      • sometimes they go haywire leading to autoimmune diseases

WBC production

• occurs in red bone marrow (just like RBC)

CBC and differential WBC counts

• CBC count (#WBC, #RBCs, #platetes, hemoglobin, hematocrit, etc.)

• differential WBC count provides relative numbers of WBCs (#/100)

• what does count indicate?

  • ↓ WBC → leukopenia

  • ↑ WBC → leukocytosis

    • could be leukemia (WBC cancer)