HAN 202 Quiz 1 Circulatory system blood

functions of the blood

transportation

protection

regulation

functions of blood —- transportation of

delivers oxygen and nutrients to body cells

metabolic wastes to the lungs and kidneys for elimination

hormones from endocrine organs to target organs

functions of the blood —- protection against

blood loss

• plasma proteins and platelets initiate clot formation (white blood cells)

infection

• antibodies

• complement proteins

• WBCs defend against foreign invaders

functions of blood —- regulation of

body temperature by absorbing and distributing heat

maintain normal pH (7.35 - 7.45) of ECF using buffers

adequate fluid volume in the circulatory system

what is blood

blood is a fluid connective tissue made up of cells and extracellular matrix

• cells == formed elements (45%)

• extracellular matrix == plasma (55%)

blood fractionation - separation of blood into basic components

• can visualize with a centrifuge

blood is mostly plasma

blood fractionation -

separation of blood into basic components

• can visualize with a centrifuge

formed element

make up 45% of blood

erythrocytes — red blood cells (RBCs)

leukocytes — white blood cells (WBCs)

• granulocytes vs agranulocytes

platelets — fragments of certain bone marrow cells

plasma

makes up 55% of blood

matrix of blood — clear, light yellow fluid

mixture of water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones and gases

• water — makes up 90-92% of plasma

• plasma proteins

  • albumins

  • globulins

  • fibrinogen

plasma proteins

albumin

globulins

fibrinogen

plasma proteins —- albumin

smallest but most abundant

contributes significantly to viscosity and osmotic pressure

also helps with solute transport and buffers plasma pH

plasma proteins —- globulins

alpha, beta, gamma globulins

helps with solute transport, clotting, immunity

plasma proteins —- fibrinogen

precursor of fibrin

blood viscosity

— resistance of a fluid to flow

results from cohesion of particles

• red blood cells and albumin are major contributors

impacts how blood flows through vessels

thickness of the blood to increases resistance to want to stay together

blood osmolarity (Osm)

—- total concentration of solute particles

optimum osmolarity achieved by the body’s regulation of sodium ions, proteins, and red blood cells

colloid osmotic pressure (COP) — protein contribution on blood osmotic pressure

• plays important role in water balance

blood osm is too high

• not enough water dehydration

• cells shrink

blood osm is too low

• too much water

• cells swell

• dangerous in the brain

blood production

hematopoiesis — production of blood cells

hematopoietic tissue produces blood cells

• located in bone marrow

lymphoid hematopoiesis vs myeloid hematopoiesis

hematopoietic stem cells (HSCs)

• hemocytoblasts

• found in the bone marrow

what do red blood cells do?

respiratory gas transportation (with assistance from hemoglobin)

• transport oxygen from lungs —> tissues

• transport carbon dioxide from tissues —> lungs

pH balance

• carbonic anhydrase produces carbonic acid from carbon dioxide and water

  • acts as a buffer

determine blood type

red blood cell structure

biconcave discs

no organelles, no nucleus

red blood cell cytoplasm ~ 1/3 hemoglobin

outer membrane has glycolipids

hemoglobin

structure

• 4 protein chains (globins)

• heme group associated with each globin chain

  • ferrous ion at its center

function

• bind with oxygen and sometimes carbon dioxide

  • specifically the iron atom in each heme that can bind to one O2 molecule

erythropoiesis

erythrocytes/RBC production

begins when HSC becomes an erythrocyte CFU

• role of erythropoietin (EPO)

pathway

hematopoietic stem cell HSC —→ colony forming unit CFU ——> precursor cells (erythroblasts to reticulocytes) —→ mature blood cells (erythrocytes)

hormonal control of erythropoiesis

erythropoietin (EPO)

• overall effect of EPO — increase production of RBCs

• but how?

  • Released by kidneys in response to hypoxia

  • When a hematopoietic stem cell becomes an erythrocyte
    colony-forming unit (CFU) it has receptors for EPO

  • EPO stimulates CFU -> erythroblast

• Other hormonal influences:

  • Testosterone enhances EPO production

nutritional control of erythropoiesis

iron

vitamin b12 and folic acid

vitamin c and copper

nutritional control of erythropoiesis — iron

key for erythropoiesis

• bone marrow needs it for hgb

• but also utilized in muscles and all cells

lost daily through urine, feces, and bleeding

complicated by low absorption rate, requiring increased consumption

nutritional control of erythropoiesis — vitamin b12 and folic acid

required for rapid cell division and DNA synthesis

nutritional control of erythropoiesis —- vitamin c and copper

cofactors for enzymes synthesizing hgb

erythrocyte homeostasis

balance btn RBC production and destruction

• too few RBCs leads to tissue hypoxia

  • why is that bad —- tissue would die

• too many RBCs increases blood viscosity

  • why is that bad —- harder to pump to body, led to clotting

erythrocyte homeostasis — negative feedback

RBC count maintained through negative feedback
○ Example: Low RBC may result in hypoxemia
○ Kidney increases EPO output
○ RBC count increases (within 3-4 days) to counteract hypoxemia

erythrocyte homeostasis — balance btn RBC production and destruction

depends on:

Hormone controls:
■ EPO

Nutritional controls:
■ Adequate supplies of iron, amino acids, B vitamins, etc.

red blood cell death and disposal

RBC proteins deteriorate, cells rupture within spleen & liver

Reuse & recycle:

• Macrophages separate heme from globin

• Globin -> amino acids

• Heme -> iron & bile pigments

erthrocyte disorders

polycythemia (vera)

anemia

sickle cell disease

erthrocyte disorders — polycythemia

Polycythemia: Excess of RBC

• why is that bad —- slower flow bc of thicker blood, increase risk of blood clots

Types:

Primary polycythemia (polycythemia vera):

• Due to bone marrow cancer (within erythropoietic line)

Secondary polycythemia:

• Polycythemia from all other causes

• Causes include dehydration, emphysema, high altitude, physical conditioning

erthrocyte disorders — polycythemia

Types:

Primary polycythemia (polycythemia vera):

• Due to bone marrow cancer (within erythropoietic line)

Secondary polycythemia:

• Polycythemia from all other causes

• Causes include dehydration, emphysema, high altitude, physical conditioning

erthrocyte disorders — anemia

Deficiency of either RBCs or Hgb

Consequences:
○ Tissue hypoxia & necrosis
○ Decreased blood osmolarity
○ Low blood viscosity

Symptoms:
○ Fatigue, Low energy/ lethargy, Lightheadedness, Dizziness,Shortness of breath (on exertion)

Vital sign changes:
○ Rapid heart rate, Low blood pressure

erthrocyte disorders —- anemia

causes of anemia

Causes of anemia can fall into 3 categories:
1. Externally losing RBCs
2. Destroying RBCs
3. Cannot make RBCs or Hgb

Causes of anemia can fall into 3 categories:
1. Externally losing RBCs

Hemorrhagic anemia: from bleeding, blood loss

• Causes include bleeding disorders, trauma, menstruation, ulcer, aneurysm, etc.

• Bleeding disorders:

  • Hemophilia: hereditary clotting deficiency

Causes of anemia can fall into 3 categories:
2. Destroying RBCs

Hemolytic anemia: from RBC destruction

• Causes: drug reactions, poisoning, infections, blood type incompatibilities

  • Hemolytic disease of the newborn

Causes of anemia can fall into 3 categories:
3. Cannot make RBCs or Hgb

Inadequate erythropoiesis or Hgb synthesis

Causes include nutritional deficiencies, kidney insufficiency, destruction of myeloid tissue, aging

Inadequate erythropoiesis anemias:
■ Kidney failure and insufficient erythropoietin
■ Iron deficiency anemia

Other nutritional anemias
■ Pernicious anemia: intrinsic factor, vit B12
■ Hypoplastic & aplastic anemia

Inadequate Hgb synthesis:
■ Thalassemias
■ Sickle-cell anemia

Antigens

molecules on cell membrane surface used to distinguish self from non-self

• proteins, glycoproteins, glycolipids

Agglutinogens - antigens of the red blood cell that trigger agglutination (clumping)

Agglutinogens -

antigens of the red blood cell that trigger agglutination (clumping)

Antibodies

proteins that bind to antigens, marking them for destruction

agglutination — Ab binds to multiple foreign cells and sticks them together

agglutinins — Ab that bind agglutinogens

agglutination

— Ab binds to multiple foreign cells and sticks them together

agglutinins — Ab that bind agglutinogens

Human blood groups

RBC antigens (agglutinogens)

• Antigen A

• Antigen B

ABO group antibodies

• Agglutinins

  • Anti A

  • Anti B

RBC Antigens (Agglutinogens)

Glycolipids on RBC surface

• Antigen A

• Antigen B

their presence (or absence) determines ABO blood group

• Blood types A, B, AB, O

ABO Group Antibodies

Agglutinins:

• Anti A

• Anti B

reacts against any A or B antigens except one’s own

Blood type AB ha no antibodies because you dont want to attack yourself

Blood type O have both anti a and anti b

ABO Group Antigens

Agglutinogens

• Antigen A

• Antigen B

Type O blood have no antigens

Type AB blood have both antigens

Rh Group

Rhesus D factor

(+) or (-) refers to the Rh factor

includes numerous RBC antigens (C, D, and E)

Rh- positive (Rh+) vs Rh- negative (Rh-)

hemolytic disease of the newborn

breaking down blood

aka erythroblastosis fetalis

Rh- mom with 2nd Rh+ baby

Anti-D antibodies

RhoGAM

Blood transfusion

delivery of a blood product from donor to recipient

• blood bank

requires blood type compatibility

• transfusion reaction

AB+ —→ universal recipient

O- —→ universal donor

what do WBCs do

(leukocytes)

protect against infection and other diseases

• leukocytosis (WBC count > 11,000/mm3) is a normal response to bacterial or viral invasion

transiently in bloodstream

• can leave capillaries via diapedesis (leaving bloodstream)

move through tissue spaces by ameboid motion and positive chemotaxis

WBC structure

Have a nucleus

Retain their organelles

Granules in cytoplasm

• All WBCs have lysosomes called nonspecific granules

• Granulocytes (a group of WBCs) have specific granules that contain enzymes and other chemicals employed in defense against pathogens

types of leukocytes

granulocytes (3)

• neutrophils

• eosinophils

• basophils

agranulocytes (2)

• lymphocytes

• monocytes

never let monkeys eat bananas

granulocytes

AKA polymorphonuclear cells

• many shape nucleus (multi-shape nucleus)

Contain specific granules

Three types:
○ Neutrophils
○ Eosinophils
○ Basophils

granulocytes types —- Neutrophils (neutral)

Most numerous (60-70% circulating WBCs)

Appearance:

• Barely visible granules

• Three- to five-lobed nucleus

Function:
■ Anti-bacterial
■ Phagocytic — cell engulf or eat another cell
■ Release antimicrobial chemicals

granulocytes types —- Eosinophils (rosy)

2-4% circulating WBCs

Appearance:

• Large rosy-orange granules

• Bilobed nucleus

Function:
■ Phagocytic
■ Allergies
■ Release enzymes that weaken/ destroy parasites

granulocytes types —- basophils (basic)

<0.5% circulating WBCs

Appearance:

• Coarse, dark violet granules

• S- or U-shaped nucleus

Function:
■ Secrete histamine (allergy)
■ Secrete heparin (blood clotting)

agranulocytes

AKA mononuclear cells

Lack specific granules

Two types:
○ Lymphocytes
○ Monocytes

agranulocytes types —- lymphocytes

25-33% circulating WBCs

Mostly in lymph tissue

Appearance:

• Variable amounts of bluish cytoplasm

• Ovoid/round, uniform dark violet nucleus

Function:
■ Crucial to long-term immunity
■ T cells & B cells
■ APCs — antigen presence cell

agranulocytes types —- monocytes

3-8% circulating WBCs

Appearance:

• Usually largest WBC

• Ovoid, kidney-, or horseshoe-shaped nucleus

Function:

• Phagocytic — when they are mature they become macrophage

  • Macrophages

• APCs

leukopoiesis

== leukocyte/WBC production

• HSC differentiates into distinct CFUs

• Distinct CFUs go on to form distinct precursor cells

  • Myeloblasts (bone marrow)

  • Monoblasts

  • Lymphoblasts

blasts - immature cells

leukocytes disorders

Leukopenia: low WBC count (<5k WBCs/μL)

• why is that bad —- body isnt able to protect or heal you

• Causes: radiation, poisons, drug induced, infections

Leukocytosis: high WBC count (>10k WBCs/μL)

• Causes: infection, allergy, disease

Leukemia

Differential WBC count: identifies what percentage of the total WBC count consists of each type of leukocyte

Leukemia

cancer of hematopoietic tissue

• Typically causes very high circulating WBCs however nonfunctional

• Disrupts normal cell percentages

Types:
○ Myeloid leukemia
○ Lymphoid leukemia
○ Acute leukemia
○ Chronic leukemia

Leukopenia:

low WBC count (<5k WBCs/μL)

• why is that bad —- body isnt able to protect or heal you

• Causes: radiation, poisons, drug induced, infections

Leukocytosis:

high WBC count (>10k WBCs/μL)

• Causes: infection, allergy, disease

what do platelets do

Secrete vasoconstrictors

Form platelet plugs

Secrete procoagulants

Initiate formation of clot-dissolving enzyme

Chemically attract neutrophils & monocytes to sites of inflammation

Phagocytic

Secrete growth factors

platelet structure

Small fragments of megakaryocytes found in bone marrow

• 2-4 μm in size

• No nucleus

Contain granules filled with platelet secretions

Open canalicular system

Capable of amoeboid movement

thrombopoiesis

production of platelets

• begins when HSC becomes a megkaryoblast

  • role of thrombopoietin

pathway

• stem cell (hemocytoblast) —→ developmental pathway —→ platelets

clotting overview

hemostasis

clot retraction

clot repair

fibrinolysis

clotting — hemostasis

= cessation of bleeding (stop blood from moving)

Involves three mechanisms:
a. Vascular spasm
b. Platelet plug formation
c. Coagulation: Blood clotting

• i. Formation of Prothrombin Activator (intrinsic/ extrinsic pathways)

• ii. Prothrombin to Thrombin

• iii. Fibrinogen to Fibrin Mes

hemostasis

1. vascular spasm

Constriction of broken blood vessel (decrease amount of blood)

Provides:
○ Protection from blood loss
○ Time

Triggers:
○ Nociceptors
○ Smooth muscle injury
○ Positive feedback from inflammatory chemicals

hemostasis

2. platelet plug formation

Platelet pseudopods stick to damaged vessel and other platelets
○ Collagen fibers — keep everything inside

Platelets undergo degranulation

Positive feedback cycle

hemostasis

3. coagulation

A set of reactions transforming blood from liquid to a gel

Reinforces platelet plug

Three phases of coagulation:
1. Formation of Prothrombin Activator (intrinsic/ extrinsic pathways)
2. Prothrombin to Thrombin
3. Fibrinogen to Fibrin Mesh

Three phases of coagulation:

1. Formation of Prothrombin Activator (intrinsic/ extrinsic pathways)
2. Prothrombin to Thrombin
3. Fibrinogen to Fibrin Mesh

Three phases of coagulation:

1. Formation of Prothrombin Activator (intrinsic/ extrinsic pathways)

● Intrinsic mechanism

• Initiated when plts release factor 12

• Uses only clotting factors found in the blood itself

• Cascades to factor 11 -> 9 -> 8 -> 10

● Extrinsic mechanism

• Cell trauma exposes blood to

• Tissue Factor

• Initiated by tissue thromboplastin (factor 3)

• Cascades to factors 7, 5, and 10

● Common Pathway

• Begins with activation of factor 10

• Leads to production of prothrombin activator

Three phases of coagulation:

2. Prothrombin to Thrombin

The enzyme prothrombin activator (from phase 1) converts factor 2 (prothrombin) to thrombin

Three phases of coagulation:

3. Fibrinogen to Fibrin Mesh

Thrombin (from phase 2) converts fibrinogen into fibrin monomers, which bind to form fibrin polymer
● Factor 13 crosslinks fibrin polymer strands, creating fibrin mesh

cloting overview — hemastasis

a. Vascular spasm
b. Platelet plug formation
c. Coagulation
i. Prothrombin Activator

• Intrinsic vs. extrinsic pathways

ii. Prothrombin->Thrombin
iii. Fibrinogen->Fibrin Mesh

clotting overview —- clot retraction

a. Platelet pseudopods adhere to fibrin strands and contract
b. Clot becomes more compact
c. Draws together ruptured edges of blood vessel

clotting overview —-clot repair

a. Platelet-derived growth factor (PDGF):

• i. Secreted by platelets & endothelial cells

• ii. Stimulates fibroblasts & smooth muscle cell mitosis

clotting overview — fibrinolysis

a. The dissolution of a clot — remove the blood clot
b. Factor 12
c. Plasminogen -> plasmin

• i. tPA — tissue plasminogen activator

d. Plasmin: fibrin-dissolving enzyme

• break down fibrin

clotting controls

Platelet repulsion

• Smooth lining of prostacyclin-coated endothelium

• Endothelial cells secretes antithrombotic substances

  • Nitric oxide and prostacyclin

• Vitamin E

Dilution of thrombin

Anticoagulants

• Antithrombin

• Heparin

clotting disorders —Bleeding Disorders:

• Hemophilia:

  • Group of hereditary diseases related to clotting factor deficiencies

• Most common types are sex-linked recessive traits:

  • Hemophilia A (classical): missing factor VIII

  • Hemophilia B: missing factor IX

• Thrombo (clot) cyto penia (decrease) :

  • Decreased # of platelets

clotting disorders — thrombo (clot) embolic(blood clot travels) disorders

Abnormal formation of a clot in unbroken vessel

Thrombus: stationary clot; ie DVT

Embolus: traveling clot

• Can become an embolism if it wedges in a vessel; ie PE

Prevented by/ treated with: anti-coagulants, thrombolytics

diagnostic blood tests

Complete Blood Count (CBC):

• Total count for RBCs, WBCs, and platelets

• Hematocrit

• Hemoglobin concentration

• RBC size

• Differential WBC count

Coagulation studies:

• Prothrombin time

medications

Medical management of blood clotting goal is either to prevent formation of clots or dissolve existing clots

Anticoagulant:

• Vitamin K antagonists: ie coumarin, warfarin (Coumadin)

  • Vit K required for synthesis of factors 2, 7, 9, 10

• Heparin

Thrombolytics:

• Streptokinase

• tPA (Tissue plasminogen activator)

Medications —Anticoagulant:

Vitamin K antagonists: ie coumarin, warfarin (Coumadin)

• Vit K required for synthesis of factors 2, 7, 9, 10

Heparin

Medication —-Thrombolytics:

Streptokinase

tPA (Tissue plasminogen activator)