Lecture Exam 1 Study BSCI202

sTOPPED ON 14 OF IMMUNE

What type of tissue is blood?

Connective

ORIGIN OF BLOOD TISSUE

Blood is a fluid, specialized connective tissue, containing formed elements, proteins that can form fibers, and fluid ground substance.

BODY’S FLUID COMPARTMENTS

In humans (age, sex differences), approx 55-80% is water… Not all organs are equal!

ICF - 67%

ISF - 25%

IVF - 8%

Intra Cellular Fluid ICF = 2/3

ECF = 1/3

(Inter Stitial Fluid ISF = ¾ and Intra Vascular Fluid IVF = 1/4)

OVERVIEW OF BLOOD

• 8% total body weight

• Males 5-6L; Females 4-5L

• Color varies with O2 content

  • High O2 - scarlet; Low O2 - dark red

• Normal Blood pH: 7.4 (7.35–7.45)

CELLULAR BODY COMPOSITION

84% of our cells are RBCs Importance of transport of O2 for survival → cellular respiration → energy producing mechanism

Plasma - 55% , Red Blood Cells - 45%

FUNCTION OF BLOOD

Distribution & elimination (gases, hormones, nutrients, etc) (waste elimination)

Regulation (pH, Temperature, electrolytes)

Protection (Immune cells, immunoglobulins, complement system, etc)

Blood Composition

Plasma – non-living fluid matrix

Formed elements – living blood "cells", all derive from Hematopoietic Stem Cells (HSC), formed in the red bone marrow:

⚫ Erythrocytes (red blood “cells”, or RBCs)

⚫ Leukocytes (white blood cells, or WBCs)

⚫ Platelets (“thrombocytes”, cell fragments)

HEMATOPOIESIS

• Blood cell formation in red bone marrow

  • In adults,

    • axial skeleton, girdles, and proximal epiphysis of humerus and femur

• Hematopoietic stem cells (Hemocytoblasts)

  • Give rise to all formed elements:

    • RBC

    • Platelets

    • WBC (granulocytes, agranulocytes)

FORMED ELEMENTS – HEMATOPOIESIS

Plasma

• 55% total blood volume

• >90% water

• >100 dissolved solutes

  • Nutrients, gases, hormones, wastes, proteins, inorganic ions

• Plasma proteins: most abundant solutes (7-9%)

  • albumin → osmotic balance and buffers pH

  • globulins → immune response & lipid transport

  • fibrinogen → blood clotting

• Serum is plasma without clotting factors

FORMED ELEMENTS – 1. ERYTHROCYTES

• Simple Biconcave discs contribute to gas transport

  • Biconcave: high surface to Vol ratio → ↗ gas exchange

  • Filled with hemoglobin (Hb) (>97% content) → carries O2

  • High flexibility (spectrin) for passing through thin capillaries No mitochondria; ATP production by anaerobic fermentation; do not consume O2 they transport

  • No protein synthesis, growth, or division Erythropoietin regulates erythropoiesis 4.2-6.1 million cells / μL of blood Life span: 100–120 days

• Complementarity of structure and function

  • Erythropoietin regulates erythropoiesis

  • 4.2-6.1 million cells / μL of blood

  • 4.2-6.1 million cells / μL of blood

ERYTHROCYTES: GAS TRANSPORT

• Hemoglobin: protein binds reversibly to oxygen:

  • reversible, cooperative

  • 4 hemes / hemoglobin (Hb); 1 iron ion / heme

  • 1 O2 mlc / iron ion → 4 O2 mlc per hemoglobin complex

STRUCTURE OF HEMOGLOBIN

• Hemoglobin consists of 4 globins (two alpha and two beta polypeptide chains) and four heme groups.

• The heme group is an Iron-containing pigment that can bind 1 O2 molecule.

HEMOGLOBIN (HB)

• O2 loading in lungs

  • Produces oxyhemoglobin (ruby red)

• O2 unloading in tissues

  • Produces deoxyhemoglobin or reduced hemoglobin (dark red)

• CO2 loading in tissues

  • 20% of CO2 in blood binds to Hb → carbaminohemoglobin

    • Carb/amino/hemoglobin

FORMED ELEMENTS – 2. PLATELETS

• Cytoplasmic fragments of megakaryocytes

  • Granules: serotonin, Ca2+, enzymes, ADP, platelet-derived growth factor (PDGF), and more

• Act in clotting process

• aka thrombocytes

• Normal = 150,000 – 400,000 platelets /μl of blood

• Age quickly; degenerate in about 10 days

• Thrombopoiesis: Formation of platelets regulated by thrombopoietin

“Thrombo” = relating to the clotting of blood “poiesis” = poi → to make , esis → process “in” = substance (protein)

FORMED ELEMENTS – 3. LEUKOCYTES

• Complete cells

• Make up <1% of total blood volume

  • “Buffy coat”

  • 4,800 – 10,800 WBCs/μl blood (1/1,000,000th of a liter)

    • Leukocytosis: WBC count >11,000/μl

• Immune System: defense against disease

• ⚫ Diapedesis (aka extravasation)

• Can live hours, days, or decades

CONCEPT REVIEW

• Blood is formed of:

• Plasma: 55% of blood volume (BV): fluid carrying dissolved solutes, including large proteins important for oncotic (colloid osmotic) pressure

• Formed elements:

  • Leukocytes (aka, White blood cells) cells of the immune system (part of buffy coat, <1% BV)

  • Platelets (aka thrombocytes) fragments of cells important in coagulation (hemostasis) (part of buffy coat, <1% BV)

  • Red blood cells (aka erythrocytes) cells that lost their nucleus, and transport O2 . 45% of BV

  
  

• Blood is required to transport O2 and CO2 , distribute nutrients, eliminate waste, distribute/regulate heat, regulate pH, transport immune cells, hormones, etc

• All cells in the blood develop from Hematopoietic Stem Cells (HSC), in the red bone marrow

CONCEPT REVIEW: ERYTHROCYTES

• Erythrocytes are the most numerous cells in the body.

• RBC have a biconcave shape that is adapted to transport and exchange gases across their membrane.

• Spectrin is a protein that provides flexibility to the RBC such that it can travel through very thin capillaries and regain its shape.

• RBCs contain hemoglobin (Hb) which transports O2 bound to the iron in its heme.

  • They do not carry mitochondria, hence can only produce ATP by anaerobic fermentation.

  • Hb transports 20% of the blood’s CO2 bound to its amino acid for release via the lungs

REGULATION OF ERYTHROPOIESIS

• > 2 million RBCs made per second

• Too few → tissue hypoxia

• Too many → ↑ blood viscosity

HypoOxia = Low Oxygen

• Balance of production and destruction

  • Hormonal controls

  • Nutrient access (limiting factors)

    • iron (Fe2+) → Heme

    • amino acids → globin, and

    • B vitamins: B12 & Folic Acid necessary for DNA replication

      • Absorption of B12 requires intrinsic factor expressed by the stomach’s parietal cells

HEMATOCRIT (PACKED CELL VOLUME)

Depends on rates of production and destruction of RBC Percent of blood volume that is RBCs

• 45% of blood volume on average:

• 47% ± 5% for males;

• 42% ± 5% for females

Why is hematocrit taken? What can it tell us?

T/F You can have a normal hematocrit (45%), but still be in hypoxia*.

True

Why / Why not?

Volume RBC? Volume total blood * 100 = Hematocrit

• Hematocrit is a relative value, not an absolute value.

• Hematocrit does not always correlate with the distribution of O2 to the tissues *Hypoxia: Not enough O2 in the tissues

WHAT CAN A LOW HEMATOCRIT MEAN?

• Low hematocrit

  • Not enough healthy red blood cells (anemia)

Volume RBC/Volume total blood times 100 = Hematocrit

• High number of white blood cells (long term illness)

Volume RBC/Volume total blood times 100 = Hematocrit

WHAT CAN A HIGH HEMATOCRIT MEAN?

• High hematocrit

  • Dehydration

Volume RBC/ Volume total blood times 100 = Hematocrit

• Disorder/disease

  • Polycythemia vera

    • bone marrow disease creates too many red blood cells

  • Lung/heart

    • low oxygen in blood triggers red blood cell production

Volume RBC/ Volume total blood X 100 = Hematocrit

HORMONAL CONTROL OF ERYTHROPOIESIS

• Hormone Erythropoietin (EPO)

  • Direct stimulus for erythropoiesis

  • Released by kidneys (some from liver)

  • When kidneys sense low O2 in renal tissue

  • Increases circulating reticulocyte (premature RBC that finish maturation in the blood) in 1-2 days

• Testosterone enhances EPO production

  • → higher RBC counts in males

    • males ≅ 47% ; females ≅ 42%

ERYTHROPOIETIN: MECHANISM FOR REGULATING ERYTHROPOIESIS

1) Stimulus: Hypoxia (inadequate O2 delivery)

2) Kidney (and liver to a smaller extent) releases erythropoietin

3) Erythropoietin stimulates red bone marrow

4) Enhanced erythropoiesis increases RBC count

5) O2 carrying ability of blood rises

QUICK FIRE QUESTION

• Kidneys filter blood and make urine (more on this later in the semester).

• When kidneys fail, patients are put on dialysis to artificially filter waste from the blood. What other impacts might kidney failure have on blood?

• Which is likely the case for patients on dialysis…

• Low RBC

• Kidneys → EPO → Erythropoiesis → RBC

HYPOXIA: LOW O2 IN TISSUES

• What causes hypoxia?

  • hemorrhage (RBC loss)

  • increased destruction of RBC

  • decreased production of RBC

• Insufficient hemoglobin per RBC (e.g., iron deficiency)

• Reduced availability of O2

Why are you at increased risk of stroke (blocked artery) while at high altitudes?

Low environmental oxygen levels

→ tissue hypoxia

→ production more red blood cells

→ increased hematocrit

→ thicker blood

→ increased viscosity

→ blood flows slow (clot!)

→ higher block risk

FATE AND DESTRUCTION OF ERYTHROCYTES

• Produced in red bone marrow, under EPO regulation

• Old RBCs become fragile; hemoglobin (Hb) begins to degenerate

• Get trapped in smaller circulatory vessels (capillaries) especially in spleen

  • Macrophages engulf dying RBCs in spleen

LIFE CYCLE OF RED BLOOD CELLS

1) Low O₂ level in blood stimulate kidneys to produce erythropoietin

2) Erythropoietin levels rise in blood

3) Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow

4) New erythrocytes enter blood stream function about 120 days

RBC DESTRUCTION & RECYCLING

RBC Destruction and Recycling

Heme and globin are separated

• Heme: Degraded to yellow pigment bilirubin → liver

  • Liver secretes bilirubin

  • Serves in production of bile → helps in lipid digestion in small intestine

  • Degraded to pigment

  • Pigment leaves body in feces

  • Brown feces

  • Iron salvaged for reuse

  
  

• Globin metabolized into aa Released into circulation Re-uptake for production of proteins

  • Released into circulation

  • Re-uptake for production of proteins

ERYTHROCYTE DISORDERS

• Anemia

  • Blood has abnormally low O₂ - carrying capacity

• Four broad causes

  • Blood loss (hemorrhage)

  • Low RBC production

  • High RBC destruction

  • Hemoglobin abnormalities

CAUSES OF ANEMIA: LOW RBC PRODUCTION

• Iron-deficiency anemia

• Renal anemia

  • Lack of EPO production

  • Often accompanies renal disease

  • Treated with synthetic EPO

• Pernicious anemia

  • Autoimmune disease against stomach parietal cells that produce intrinsic factor

  • Lack of Vit B12, prevents maintaining replication pace of committed cells

CAUSES OF ANEMIA: LOW RBC PRODUCTION

• Aplastic anemia

  • Destruction or inhibition of red bone marrow

  • Treatment

• Hypoplastic Anemia (decline)

CAUSES OF ANEMIA: HIGH RBC DESTRUCTION (1)

• Hemolytic anemias

• Premature RBC lysis

• Caused by

  • Hb abnormalities

  • Incompatible blood transfusions

  • Infections

CAUSES OF ANEMIA: HIGH RBC DESTRUCTION (2)

• Sickle-cell anemia

  • One amino acid mutation in a globin beta chain of hemoglobin (HbS)

  • RBCs with crescent shape and block small vessels

  • RBCs rupture easily and reduced O2 carrying-capacity

SICKLE-CELL ANEMIA

• More prevalent in people from African malarial belt and descendants

MALARIA

• 300–500 million cases each year

• Kills ~2 million each year

• Plasmodium parasite

• If 2 alleles of β chain Hb mutated → lesser survival rate

• If 1 allele mutated → greater survival rate than WT with malaria

ERYTHROCYTE DISORDERS: HIGH RBC NUMBERS

• Polycythemia vera (permanent)

  • Bone marrow cancer → excess RBCs

  • Severely increased blood viscosity

• Secondary polycythemia (temporary)

  • Less O2 available (high altitude) or EPO production increases → higher RBC count

  • Lower plasma volume

  • Blood doping

• ⇒ High RBC numbers increase blood’s viscosity ⇒ increased chances of blood clotting, embolism.

YOU PLAY 3: CRS

What is EPO?

1- a biogenic amine hormone produced by the liver if high O2

in blood

2- a steroid hormone produced in males by the gonads if low O2

in blood

3 - a peptide hormone produced primarily by the

kidney if low O2 in blood

4- a steroid hormone produced by the liver when no access to O2

3 - a peptide hormone produced primarily by the kidney if low O2 in blood

METABOLISM: CONVERT INGESTED FOOD INTO USEABLE ENERGY

• Metabolism = transformation of energy into biological useable forms

• Adenosine-5'-triphosphate (ATP)

• Energy is maximized through aerobic respiration (w/↑ O2 )

• No negative byproducts as in anaerobic fermentation

CONCEPT REVIEW

• Erythropoiesis is the process of RBC formation, it is highly dependent on Erythropoietin (EPO), and will determine hematocrit (% vol of RBC in blood)

• Imbalances (high or low) in hematocrit have damaging consequences:

  • low hematocrit may be caused by an increase in RBC destruction or decrease in RBC production

  • High hematocrit may be caused by an increase in RBC production or a decrease in RBC destruction. '

• They can be temporary or permanent:

  • Low hematocrit: Anemias, low EPO

  • High hematocrit: Polycythemia vera, secondary polycythemia

Recall: testosterone increases EPO

HEMOSTASIS ≠ HOMEOSTASIS

HEMOSTASIS:

• Series of reactions to stop bleeding

• Requires clotting factors & substances released by platelets and injured tissues

• Three steps

1. Vasoconstriction by vascular spasm

2. Platelet plug formation

3. Coagulation (blood clotting)

HEMOSTASIS 1. VASOCONSTRICTION

Constriction of vessels by contraction of smooth muscle surrounding arterioles, even muscular arteries if needed.

→ Limit the flow… to limit the loss

HEMOSTASIS 2: PLUG FORMATION

• Activated platelets → temporary platelet plug

  • Stick to collagen fibers

von Willebrand factor (plasma protein)

• Swell, become spiked and sticky,

• release chemical messengers

  • ADP

  • Serotonin

  • thromboxane A2

  • Ca2+

• Positive feedback loop: activated platelets further activate platelets

INTACT BLOOD VESSEL

1. Connective tissue

2. Smooth Tissue

3. Connective

HEMOSTASIS 3: COAGULATION

• Intrinsic Pathway = triggered by factors from within blood

• Extrinsic Pathway = triggered by factors from outside

Fibrin & clotting factors → Blood clot (aka, Thrombus)

COAGULATION PATHWAYS

• Contact activation or Intrinsic pathway

  • Internal trauma

  • Triggered by negatively charged surfaces

• Contact with collagen

• Activated platelets

Tissue Factor or Extrinsic pathway

• Triggered by exposure to tissue factor (TF) (aka, coagulation factor III) released by lysed tissue cells

• Faster (few reactions

• Ca 2+ is an essential coagulation factor (cf IV)

COAGULATION: COMMON PATHWAY

• Common Pathway activated by Intrinsic and Extrinsic pathways

• Reinforces platelet plug with fibrin meshwork

• Blood transformed from liquid to gel

• Three phases of coagulation

1. Prothrombinase formation

2. Prothrombin converted to enzyme thrombin

3. Thrombin catalyzes fibrinogen → fibrin → fibrin mesh

EVENTS OF HEMOSTASIS

Step 1 Vascular spasm

• Smooth muscle contracts, causing vasoconstriction

Step 2 Platelet plug formation

• Injury to lining of vessel exposes collagen fibers; platelets adhere.

• Platelets release chemicals that make nearby platelets sticky; platelet plug forms

Step 3 Coagulation

• Fibrin forms a mesh that traps red blood cells and platelets, forming the clot.

CLOT RETRACTION & VESSEL REPAIR

• Actin and myosin in platelets contract

• Contraction pulls on fibrin strands, squeezing serum from

clot

• Clot retraction stabilizes clot, by excluding fluid

• Draws ruptured blood vessel edges together

• Platelet-derived growth factor (PDGF)

• → proliferation of smooth muscle and fibroblasts (CT)

• → rebuild blood vessel outer wall

• Vascular endothelial growth factor (VEGF)

• → restores endothelial lining

FIBRINOLYSIS

• Removes unneeded clots after healing

• Begins within two days; continues for several days

Plasmin is a fibrin-digesting enzyme

• Produced by activating Plasminogen

  • Trapped during clot formation → Negative feedback loop

⚫ Plasmin deficiency leads to thrombosis, due to inadequate

degradation of clots.

DISORDERS: THROMBOEMBOLIC CONDITIONS

Thrombus = blood clot Embolus = unattached mass that travels in the bloodstream

DISORDERS: BLEEDING DISORDERS

Thrombocytopenia: deficient number of circulating platelets

• Platelet count <50,000/μl is diagnostic

• Treated with transfusion of concentrated platelets

• Petechiae appear due to spontaneous, widespread

hemorrhage

Bleeding Disorders

Inability to synthesize procoagulants

• due to impaired liver function

• Causes: vitamin K deficiency*, hepatitis, and cirrhosis (most clotting factors are produced in the liver)

BLEEDING DISORDERS

Hemophilia includes several similar hereditary bleeding

disorders

• Hemophilia A: factor VIII deficiency

  • 77% of all cases

• Hemophilia B: factor IX deficiency

• Hemophilia C: mild type; factor XI deficiency

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

• Widespread clotting in intact vessels

And

• Severe bleeding

  • by reduced availability of clotting factors and platelets

  • residual blood unable to clot

• Causes: Usually pregnancy complication; incompatible blood transfusions = transfusion reaction

HEMOSTASIS

1. Vascular Spasm

Smooth muscle in vessel wall contracts → ↘ vessel diameter → ↘ blood loss

2. Plug Formation

• Platelets adhere to collagen fibers

• •Release chemicals Ca2+ , ADP, Serotonin and Thromboxane A2

• •attract more platelets, sustain vasoconstriction

• •Temporary physical barrier is created (clot)

• Triggers intrinsic/extrinsic pathways

3. Coagulation

Intrinsic pathway

Clotting factors are activated by contact with cut edges of vessel wall and activated platelets

Extrinsic pathway

Clotting factors activated by tissue factor from damaged neighboring tissue

(Ca2+) + (Ca2+)

Prothrombinase (activator)

Prothrombinase (activator) → Thrombin →Fibrinogen →Fibrin

Blood cells and platelets adhere to fibrin and form a clo

WHY IS ASPIRIN PROHIBITED BEFORE MOST SURGERIES?

Aspirin = Acetylsalicylic Acid (ASA)

→ antithrombotic drug (blood thinner)

→ Prevents synthesis of

Thromboxane and Prostaglandin

1) platelet aggregation

2) pain information temperature regulation inflammation

BLOOD TRANSFUSIONS

• Multiple types of transfusion

  • Whole blood transfusion

    • plasma, RBC, platelets, WBCs

  • Packed red blood cells transfused to restore oxygen-carrying capacity (plasma, WBCs, platelets removed)

• Transfusion of incompatible blood can be fatal

RBC PRESENT ANTIGENS ON THEIR MEMBRANE

Blood groups are determined by the type of Antigen (Ag) at the surface of RBC.

Antigens are glycoproteins that can generate an immune response by triggering the generation of antibodies

ANTIGEN-ANTIBODY COMPLEX

• Antigens (Ag, Antibody generator) are macromolecules, that trigger an immune response, usually proteins from foreign entities (bacterium, allergen, virus, etc).

• Ag are recognized by Antibodies (Ab, immunoglobulins = Ig) produced by the host (= self) immune cells.

• Ab are specific to the Ag, but cross-reactivity can occur.

HUMAN BLOOD GROUPS: ABO

• RBC membranes bear glycoprotein antigens (A, B)

  • if Ag present → Promote agglutination; called agglutinogens

  • co-dominance of IA & IB alleles vs i (recessive)

    • Do not express MHC surface proteins → won’t induce T-cell mediated immunity

• Presence or absence of each agglutinogen is used to classify blood cells into different groups: A, B, AB, O

ABO BLOOD GROUP & AB EXPRESSION

Person 1: Type A Blood: A agglutinogens (Ag) + anti-B antibodies expressed at birth (agglutinins; IgM)

ANTI B= anti-B antibodies (agglutinins, ⍺B IgM)

Person 1: Type A Blood: A agglutinogens (Ag) + anti-B antibodies (agglutinins; IgM)

Receives Type B blood from donor.

A = “A” Antigen (agglutinogens, A Ag)

T/F A person who carries RBC with B Ag … will carry anti-B Ab

False

T/F2. A person who is AB type can donate plasma that will have no anti-A nor anti-B Ab.

True

T/F3. A person who is type O, can receive packed RBC from type A or type B, but cannot receive whole blood transfusions from these donors.

False

DETERMINING BLOOD TYPE

The spots on the card or buffers in the tubes contain specific antibodies.

If Ag exist → Ag-Ab reaction → agglutination

TRANSFUSIONS: RBC VS WHOLE BLOOD

• Packed red blood cells transfusion

= plasma, platelets, and WBCs removed, RBCs transfused to restore oxygen-carrying capacity of receiver

Whole blood transfusion

= donor antibodies included in plasma

• Transfusion of incompatible blood can be fatal

PACKED RBC

No plasma = no donor antibodies!

Blood type compatibility: life or death!

WHAT ABOUT RH+/- ??

• Rh Factor (Rhesus factor)

• “D” antigen = + = Rh positive

• Anti-D Antibodies not present at birth

  • Require a second exposure to Rh+ blood → equivalent to a typical transfusion reaction

  • due to IgG developed by Rh- individual

MORE BLOOD GROUPS

• Other blood groups (MNS, Duffy, Kell, and Lewis) usually weak agglutinogens

• Antigens of ABO and Rh blood groups cause vigorous transfusion reactions

THINK PAIR SHARE

What blood types could Malfoy receive?

⇒ Packed RBC transfusion.

• Malfoy’s Antigens on RBC: A indicates there are A antigens; + indicates there are Rh antigens.

• Malfoy’s Antibodies: anti-B antibodies.

INCOMPATIBLE TRANSFUSION REACTIONS (MISMATCHED BLOOD)

Donor's cells

• Attacked by recipient's plasma agglutinins (Ab)

• Agglutinate and clog small vessels RBC lysis and release hemoglobin into bloodstream

• Result in

  • Diminished oxygen-carrying capacity

  • Diminished blood flow beyond blocked vessels

  • Hemoglobin in kidney tubules → renal injury

HOMEOSTATIC IMBALANCE: HEMOLYTIC DISEASE OF THE NEWBORN

Also called erythroblastosis fetalis

• Only occurs in Rh– mom carrying Rh+ fetus

• Anti-Rh Ab (=anti-D) do not exist until exposure to Rh+ blood.

Rh– mom exposed to Rh+ blood of fetus during delivery of first baby

• baby healthy

• Mother’s immune response is activated against Rh+ Ag (“D”)

• Mother synthesizes anti-Rh antibodies and Memory B cells

Second pregnancy (= Re-exposure)

• Mom's memory B cells are activated → ⍺-Rh IgG

• anti-Rh IgG cross placenta and destroy RBCs of Rh+ baby

NOTE: Anti-A and anti-B Abs (IgM) appear early on in infancy; too large to pass the placenta barrier

ERYTHROBLASTOSIS FETALIS

• To the mother’s immune system: Rh antigen is a potential threat → Immune response → anti-Rh Ab

• During healthy pregnancy, mother’s and fetus’ bloods do not mix. → Increased risk at birth: placenta delivery, miscarriage, ectopic pregnancies, others

• 2nd pregnancy: Memory B cells of mother are activated and produce anti-Rh IgG antibodies that pass the placental barrier →

• anti-Rh IgG of mother agglutinate Rh+ RBC of the fetus!

PREVENTING ERYTHROBLASTOSIS FETALIS

• If mother Rh– , and possibility of Rh+ fetus:

• Administer anti-D antibodies to prevent the mother’s IS to build an initial IR during pregnancy/ delivery! ⇒

• Who develops anti-D Ab to donate?

INCOMPATIBLE TRANSFUSION

Incompatible transfusion

• Decreased oxygen-carrying capacity

• Blocked vessels

• Renal failure

CONCEPT REVIEW - Blood 4

• RBC carry Ag at their surface

• Ag can elicit an immune response that produces Ab specific to the Ag.

• Ab against the A and B Ag of the ABO group are IgM and do not pass the placental barrier. They are present early in life.

  • eg, Anti-A IgM agglutinate Type A RBC.

• Determination of blood type and matching blood transfusions is essential to save lives.

• A person that carries a specific Ag on their RBC does not carry Ab against that Ag.

• Anti-Rh (anti-D) IgG are present after sensitization by exposure of a Rh– person to Rh+ RBC.

• Erythroblastosis fetalis can lead to miscarriage, stillbirths.

FUNCTIONS OF THE LYMPHATIC SYSTEM

• Drains excess interstitial fluid (ISF) → return to blood

  • maintains circulating blood volume → blood pressure -

• Transports dietary lipids

  • lipids absorbed by gastrointestinal tract

  • fat-soluble vitamins (A, D, E, K)

• Carries out immune responses

  • includes lymphoid tissue, lymphoid organs

  • contains most lymphocytes (B, T)

THE LYMPHATIC SYSTEM

• Exudation → rush of self and foreign material into lymphatic vessels

Lymphatic system

• Recovers fluid in ISF leaked from blood vessels, back to blood (approx 3L/day!)

• Immune system: Main structures include primary organs (red bone marrow, thymus) and secondary organs (spleen, tonsils, lymph nodes and vessels).

LYMPHOID TISSUE CELLS

• Lymphocytes Produced in red bone marrow Mature into one of two main varieties

• T lymphocytes → Thymus

• B lymphocytes → bone marrow

Other cells of lymphatic system

• Macrophages → phagocytosis

• Dendritic cells → phagocytosis

• Epithelial cells → help select lymphocytes

• Reticular cells produce reticular fibers

Lymph node (SEM): Reticular cells (brown) make up a connective tissue mesh of reticular fibers. White blood cells (lymphocytes, yellow), red blood cells (red) and macrophages (pink).

LYMPH NODES

Cleanse the lymph: ISF returning to blood via lymph → Lymph node houses macrophages → phagocytic cells (invaders, debris, etc)

Immune system

activation site: dendritic cells circulate from the tissues to lymph vessels to lymph nodes → APC to T/B Ly → Activation of the adaptive immune response

LYMPHATIC SYSTEM

Consists of three parts

1) Network of lymphatic vessels (lymphatics)

2. Lymph – fluid in vessels

3. Lymph nodes – cleanse lymph (⌀ 1-25mm)

• Lymph journey: ISF → ly capillaries → ly vessels → ly trunks → ly ducts → [cisterna chyli] → thoracic & right lymphatic ducts join veins → blood (systemic circulation)

WHY DOES ISF FLOW TO THE LYMPHATIC CAPILLARIES? Why not directly back to the systemic venous capillaries?

Out of 20 L/day that leave the capillaries, 17L return to the venous circulation. → 3 L in lymphatic vessels

WHY DOES ISF FLOW TO THE LYMPHATIC CAPILLARIES? Why not directly back to the systemic venous capillaries?

Out of 20 L/day that leave the capillaries, 17L return to the venous circulation. → 3 L in lymphatic vessels

• NO backflow:

  • ○ Endothelial flaps orientation and

  • ○ backflow prevention flaps ○

  • Smooth muscle

LYMPHATIC CAPILLARIES AND RETURN TO BLOOD

• Pressure gradients flow fluid from ISF to lymph.

  • Hydrostatic pressure: HPISF > HPLV

  • Oncotic (colloid osmotic) pressure: large soluble proteins in lymph → Pulls fluid into lymph: OP _LV > OP_ISF

• NO backflow: orientation of endothelial flaps and unidirectional valves.

LYMPHATIC CAPILLARIES AND RETURN TO BLOOD

• HP_ISF > HP_LV

• OP_LV > OP_ISF

OP: pressure exerted by the presence of proteins that pulls fluid into the compartment

HP: pressure applied by the fluid on the walls of the container

Greatest HP pushes water out Greatest OP pulls water in

HYDROSTATIC PRESSURE & ONCOTIC PRESSURE

• Hydrostatic pressure (HP): Force applied by fluid on the walls of its compartment → pushes fluid out of the compartment.

• Oncotic pressure (OP, π): Force drawing fluid into the compartment to balance the concentrations of large solutes that cannot cross the walls of the compartment

CONCEPT REVIEW LYMPHATIC SYSTEM - session 5

Lymphoid tissue

• houses lymphocytes and provides a site for maturation, activation and proliferation

• allows for organism’s surveillance (infection and filtration) through lymphocytes and macrophages

Lymphoid organs

• produce, mature, and differentiate immune cells

• remove pathogens and aged red blood cells

• Lymphatic vessels

• Return excess ISF as lymph to systemic blood circulation

• Pressure gradients determine the flow of fluid between the blood vessels, ISF, lymphatic vessels I

• Important impact on blood pressure and blood volume (next)

IMMUNITY

• Resistance to disease

  • Extrinsic (infection, injury)

  • Intrinsic (cancer cells)

• Immune system

  • Two main systems

    • Innate (nonspecific) defense system

    • Adaptive (acquired, specific) defense system

• Innate defense system has two lines of defense

  • First - external body membranes (skin and mucosae)

  • Second - antimicrobial proteins, phagocytes, and other cells, chemical mediators

    • Prevent infection,

    • Inhibit spread of invaders

    • Inflammation process

    • Clean dead tissue/cells

    • “Quick and dirty”

• Adaptive defense system

• Third line of defense attacks specifically a particular foreign substance

  • Takes longer to react than innate system

  • It is specific and highly effective “Slow and targeted”

OVERVIEW OF INNATE AND ADAPTIVE DEFENSES

INNATE DEFENSES: 1ST LINE

• Surface barriers ward off invading pathogens

  • Skin, mucous membranes, and their secretions

    • Physical barrier to most microorganisms

    • Acid secretion

    • Phagocytes & dendritic cells

    • Enzymes - lysozyme of saliva, respiratory mucus, and lacrimal fluid

    • Antimicrobial secretions: Defensins

SURFACE BARRIERS BREACHED …

→ second line of defense must protect other/deeper tissues

INNATE DEFENSES: 2ND LINE

• Internal Defenses: Cells and Chemicals

• Leukocytes:

  • Phagocytic cells (Neutrophils, macrophages [“tissue monocytes”])

  • Natural killer (NK) cells (type of Lymphocyte)

  • Additional cells that promote immune response (basophil, eosinophils)

• Antimicrobial proteins (interferons and complement proteins, defensins, Antimicrobial Peptides)

• Fever

• Inflammatory response

LEUKOCYTES: TWO CATEGORIES

• Granulocytes (PMN)– Visible cytoplasmic granules

  • Neutrophils, eosinophils, basophils, NKC

• Agranulocytes – No visible cytoplasmic granules

  • Lymphocytes*, monocytes

GRANULOCYTES

• Neutrophils

  • aka Polymorphonuclear leukocytes (PMNs or polys)

  • Very phagocytic

• Eosinophils

  • Lysosome-like granules

  • Allergies, asthma, and general immune response

• Basophils

  • Granules contain histamine

    • Histamine = inflammatory chemical → vasodilator → ↑ WBCs to inflamed sites

• Natural Killer Cells

  • Large granular cytotoxic LY

  • attack virus-infected, cancerous cells

AGRANULOCYTES

• These cells do not have visible granules

• Lymphocytes

  • Mostly in lymphoid tissue few circulate in blood

  • T lymphocytes (T cells) against virus-infected cells and tumor cells

  • B lymphocytes (B cells) → antibody producing cells

• Monocytes

  • Leave circulation → enter tissues and differentiate into macrophages

  • Actively phagocytic cells that present antigens

  • Activate lymphocytes

PHAGOCYTIC CELLS

• Cells that detect and ingest harmful foreign particles

• Neutrophils most abundant but die fighting

  • Become phagocytic on exposure to infectious material

  • Phagocytize 1 bacterium and die

  • Macrophages differentiate from monocytes – chief phagocytic cells – robust cells

    • Can phagocytize up to 200 bacteria

    • Free macrophages wander through tissue spaces

    • Fixed macrophages permanent residents of some organs (eg, Langerhans cells (skin), Microglia (CNS))