• Albumin- Osmotic pressure of blood

*Protein (made in liver) keeps water in blood

• Globulin- Antibodies
• Fibrinogen- Responsible for clotting

• Red blood cells (RBC)

      - Main Job: Responsible for oxygen transport

      - The amount moved is dependent on the amount of hemoglobin in the red blood cell

      - Hemo= iron, globin= protein

      - These live about 120 days, and are removed by the spleen

     - Plasma makes the blood mold

     - Need fluid and glucose when giving blood

     - Hemotoma= massive blood clot!

• Platelets 

- Need for blood to clot!

-Short lived fragments of a bone marrow cell, responsible for clotting when needed

- Must be replaced continuously

* Blood is made in the bone marrow*

• White blood cells (WBC)

- Many different types, responsible for inflammatory reactions and fighting infections

- Leukocytes= fight bacteria

- Lymphocytes= fight virus and cancer

• Biconcave (due to surface area) flexible discs
• No nucleus in mature state
• Contains hemoglobin (4 mol. of oxygen per hemoglobin)
• Globin portion
• Heme group (women lose ~100mL/day during period)
• Life span- ~120 days
• Erythropoietin (can be made synthetically now) is produced in the kidney & stimulates erythrocyte production
• Wright stain- stains rbc's pinkish, plates look flaky

-Metabolic activity decreases with age

     ~Weakened membranes with age

     ~Corpuscle- no nucleus in rbc

- Eventually, RBCs break as they squeeze through the spleen capillaries

     ~Phagocytes from the spleen, liver, bone marrow, lymph nodes ingest and destroy RBCs

      ~ Heme is processed to bilirubin, where the liver processes it & breaks it down

        ~ High bilirubin levels = jaundice

- Conjugated bilirubin

    ~ Water soluble

    ~Excreted in bile

- Unconjugated bilirubin

   ~If more RBCs are broken down than bilirubin is removed (through the kidney), this will cause jaundice

• Decreased blood oxygen
• The kidneys secrete erythropoietin
• Bone marrow is stimulated and produces:

1. Immature RBC (erythroblast, nucleated)
2. Reticulocytes (will contain more if there is less in the blood, remanent of nucleus, contain ER)
3. Mature RBCs

*Blood typing is based on antigens (proteins) in the plasma membrane of the erythrocytes*

-A B O system

     ~ Based on the presence or absence of specific antigens

     ~ Antibodies in the blood plasma

- Rh sytem

     ~ Antigen D in plasma membrane: Rh+

     ~ Absence of antigen D: Rh-

Most hematopoietic system diseases will cause nonspecific symptoms

    - Physical exam: lymphadenopathy, splenomegaly or hepatomegaly

     - Labratory exams: described on the next slide

    - Biopsy: used to diagnose hematopoietic cancers and diseases

Complete blood count (CBC)

    - Includes total RBCs, WBCs, and platelets

    -Leukocytosis (increased WBCs, neutrophil #1)

         - Associated with inflammation or infection

    - Leukopenia (decreased WBC)

      - Associated with some viral infections, radiation, chemotherapy

     - Increased eosinophils

         - Common in allergic responses

     - Differential count for WBCs

Morphology

- Observed with blood smears

- Shows size, shape, uniformity, maturity of cells

    + Different typed of anemia can be distinguished

Hematocrit (how many rbc)

- Men typically have more due to women periods

- Percent by volume of cellular elements in blood

Hemoglobin

- Amount of hemoglobin per unite volume of blood

- Mean corpuscular volume (MCV)

    + Indicates the oxygen carrying capacity of blood

Reticulocyte count

   - Assessment of bone marrow function in terms of RBC production

Chemical analysis

   - Determines serum levels of components, such as iron, vitamin B12, folic acid, cholesterol (heart disease), urea, glucose

Bleeding time

   - Measures platelet function for clotting

Prothrombin time (PT) and partial thromboplastin time (PTT)

   - Measure function of various factors in coagulation process

  - International normalized ration (INR) is a standardized version

   *Cumatin and Warfin prevent blood clots (blood thinners)*

Anemia (major disorder of rbc)

   - Lack of circulating red blood cells

   - There are several different kinds, with different causes

White blood cell disorders are secondary defects

Anemia causes a reduction in oxygen transport

Basic problem is hemoglobin deficit

Oxygen deficit leads to:

   - Less energy production in all cells

      + Cell metabolism and reproduction diminished

   - Compensation mechanisms

      + Tachycardia and peripheral vasoconstriction

   -General signs of anemia

      + Fatigue, pallor (pale face), dyspnea, tachycardia

*Light pink in eye conjunctiva could indicate anemia*

- Blood loss (acute or chronic) *cut hand vs. hemrhoids*

- Hemolysis (destruction of rbc)

- Impaired RBC production (not enough iron in diet)

- lack of B12 and folic acid (Cheerios are a good source)

Hemolytic anemia

   - Red blood cells are prematurely destroyed (bad blood transfusion)

   - Sickle cell anemia (misshaped hemoglobin)

   - Thalassemia (genetic disorder)

Results from excessive destruction of RBCs

Causes:

   - Genetic defects

   - Immune reactions

   - Changes in blood chemistry

   - Infections such as malaria

   - Toxins in blood

   - Antigen- antibody reactions

      + Incompatible blood transfusions

   + Erythroblastosis fetalis (wrong Rh factor in pregnancy)

Sickle Cell Anemia

(Sickle shaped RBC)

Genetic condition

   - Autosomal (both need to be +)

   - Incomplete dominance

   - Anemia occurs in homozygous recessive

   - Diagnostic testing is available

   - More common in individuals of African ancestry

    + Heterozygous condition is somewhat protective against malaria

      + One in ten African Americans is heterozygous for the trait

• Abnormal hemoglobin (HbS)
• Sickle cell crisis occurs whenever oxygen levels are lowered
• Altered hemoglobin is unstable and changes shape in hypoxemia (low oxygen in blood)
• Sickle shaped cells are too large to pass through the microcirculation
• Obstruction leads to multiple infarctions (blockages) and areas of necrosis
• Increased hemolysis of RBC in spleen= enlarged spleen

-Severe pain because of ischemia of tissues and infarction

- Pallor (pale), weakness, tachycardia, dyspnea (labored breathing)

-Hyperbilirubinemia- jaundice

-Splenomegaly- enlarged spleen

-Vascular Occlusions and infarctions

   + In lungs

      - Acute chest syndrome

   + Smaller blood vessels

      - Hand-foot syndrome

- Delay of growth and development

- Congestive heart failure

- Iron deficiency anemia

-Megaloblastic anemias

   + Cobalamin (Vitamin B12) deficiency- intrinsic factor (stomach) doesn't absorb

       - Also called pernicious anemia

    + Folic acid deficiency

- Aplastic anemia (bone marrow deficiency)

- Chronic disease anemias

    + Chronic inflammation

    + Chronic renal failure

- Insufficient iron impairs hemoglobin synthesis

   + Microcytic, hypochromic RBCs (small, lighter pink)

      - Result of low hemoglobin concentration in cells

- Very common

   + Ranges from mild to severe

   + Occurs in all age groups, but more common in women of childbearing age (due to menstruation

   + Estimated that one in five women is affected

      - Proportion increases for pregnant women

- Frequent sign of an underlying problem

- Dietary intake of iron below minimum requirement

- Chronic blood loss

   + As from bleeding, ulcer, hemorrhoids, cancer

- Impaired duodenal absorption of iron

   + In many disorders, malabsorption syndromes

- Severe liver disease (cirrhosis, hepatitis, etc.)

   + May affect iron absorption as well as storage

• RBC is too big, can't carry enough oxygen
• Vitamin B12 and folic acid deficiencies
• Impaired DNA synthesis→ enlarged red cells
• Erythrocytes are large, often with oval shape

- Basic problem is lack of absorption and vitamin B12 because of lack of intrinsic factor

   + Intrinsic factor secreted by gastric mucosa

   + Required for intestinal absorption on vitamin B12

- Characterized by very large, immature, nucleated erythrocytes

   + Carry less hemoglobin
   + Shorter life span

- Dietary insufficiency is very rarely a cause

- Genetic factors have been implicated

   + More common in light skinned women of northern European ancestry

- Often accompanies chronic gastritis

- May also be an outcome of gastric surgery

- Acute or chronic

- Impairment or failure of bone marrow

- May be temporary or permanent

- Often idiopathic by possible causes include:

   + Myelotoxins

       - Radiation, industrial chemicals, drugs (antibiotics)

   + Viruses

       - Particularly hepatitis C

- Blood count indicate

   + Anemia, leukopenia, thrombocytopenia (less platlets, won't clot)

   + Bone marrow biopsy may be required

   + Erythrocytes often appear normal

- Identification of cause and prompt treatment needed for bone marrow recovery

   + Removal of any bone marrow suppressants

   + Failure to identify cause and treat effectively is life threatening!

- Increased RBC count and hemotocrit greater than 50%

   + Too many, very thick (viscous), high blood pressure

- Relative polycythemia: loss of plasma volume

   + Too little water can cause this

- Absolute polycythemia: increased red cell mass

   + Primary: neoplastic

   + Secondary: increased erythropoietin

- Primary polycythemia- polycythemia vera

   + Increased production of erythrocytes and other cells in bone marrow

   + Neoplastic disorder

   + Serum erythropoietin levels low

- Secondary polycythemia- erythrocytosis

   + Increase in RBCs in response to prolonged hypoxia (low oxygen)

   + Increased erythropoietin secretion

  + Compensation mechanism to provide increased oxygen transport

• Distended blood vessels, sluggish blood flow
• Increased blood pressure
• Hypertrophied (increased) heart
• Hepatomegaly (increased liver)
• Splenomegaly (increased spleen)
• Dyspnea (difficulty breathing)
• Headaches
• Visual disturbances
• Thromboses and infarctions

• Leukopenia
• Neutropenia (agranulocytosis)
• Aplastic anemia
• Infectious mononucleosis
• HIV

• The result of bone marrow failure is anemia, leukopenia, and thrombocytopenia
• These have the potential to increase the likelihood of infection and bleeding

- Hyperplastic/Neoplastic Disease

   + Leukemias- WBC cancers

   +Lymphomas- WBC cancers (soft tissue, usually in lymph nodes and spleen)

   + Multiple myeloma- cancer of the plasma cells

• Group of neoplastic disorders involving WBCs
• Uncontrolled WBC production in bone or lymph nodes
• Other hemopoietic tissues are reduced
• One or more types of leukocytes are undifferentiated, immature, and nonfunctional
• Large numbers released into general circulation
• Infiltrate spleen, lymph nodes, liver, brain, other organs
• Usually in childhood or older populations

- Acute leukemias (ALL and AML)

   + High proportion of immature nonfunctional cells in bone marrow and peripheral circulation

    + Onset usually abrupt, marked signs of complications

    + Occurs primarily in children and younger adults

- Chronic leukemias (CLL and CML)

    + Higher proportion of mature cells

    + Insidious onset

    + Mild signs and better prognosis

    + Common in older adults

- Usual signs at onset

    + Frequent or uncontrolled infections

    + Petechiae and purpura

    + Signs of anemia

- Severe and steady bone paine

- Weight loss, fatigue, possible fever

- Enlarged lymph nodes, spleen, liver

- Headache, visual disturbances, drowsiness, vomiting

- Diagnostic tests

    + Peripheral blood smears

       - Immature leukocytes and altered numbers of WBCs

       - Numbers of RBCs and platelets decreased

       - Bone marrow biopsy for confirmation

- Treatment

   + Chemotherapy

   + A.L.L. in young children responds well to drugs

   + Biological therapy (interferon)

       - May be used to stimulate the immune system

• Opportunistic infections, including pneumonia
• Sepsis
• Congestive heart failure
• Hemorrhage
• Liver failure
• Renal failure
• CNS depression and coma

- Neoplastic disease that involves increased production of plasma cells (B cells) in bone marrow

- Unknown cause

- Occurs in older adults

- Production of other blood cells is impaired

- Multiple tumors in bone

   + Loss of bone

   + Severe bone pain

- Prognosis poor, with short life expectancy

• Onset usually insidious
• Malignancy well advanced before diagnosis
• Pain caused by bone involvement
• Anemia and bleeding tendency
• Impaired kidney function and eventually failure
• Chemotherapy to encourage remission
• Median survival rate, 3 years

- Non-Hodgkin Lymphoma

   + B cell

   + T cell

   + Distinguished by multiple node involvement

   + Nonorganized, with widespread metastases

-Hodgkin Lymphoma

   + Malignant B cells invade lymphoid organs

-Malignant neoplasms involving lymphocyte proliferation in lymph nodes

- Specific causes not identified

   + Higher risk in adults who received radiation during childhood

- Initially involves a single lymph node

- Cancer spreads to adjacent nodes

   + To organs via lymphatics

   + T lymphocytes seem to be defective; lymphocyte count decreased

   + Presence of Reed-Sternberg Cells

      - Giant cells present in lymph node

   + Four subtypes, based on cell at biopsy

- Symptoms

   + First indicator- usually a painless enlarged lymph node

   + Later- splenomegaly and enlarged lymph nodes

   + General signs of cancer

      - Weight loss, anemia, low grade fever, night sweats, fatigue

- Treatment

   + Radiation, chemotherapy, surgery

- Staging and prognosis dependent on:

   + Number and location of nodes involved

- Increasing in incidence

   + Partially caused by HIV infection

- Similar to Hodgkin's lymphoma

   + Clinical signs and symptoms are similar

   + More difficult to treat when tumors are not localized

- Initial manifestation- enlarged, painless lymph node

Review of Structure and Function

(Chapter 12- Hemostasis disorders)

- Hemostasis is the process that prevents excessive bleeding after an injury

- This complex interaction includes:

   + Blood vessels (constricts)

   + Platelets (platelet plug)

   + Chemical coagulation factors in plasma

• Blood vessels allow blood to circulate, however in the event of an injury, they spasm, thus decreasing blood flow to the area

• Platelets physically obstruct blood flow at the site of injury

• Chemicals released at injury promote coagulation

- Three steps:

   + Vasoconstriction or vascular spasm after injury (slows down blood flow)

   + Platelet clot

   + Coagulation mechanism

- Plasmin (enzyme) will eventually break down the blood clot

- Live 8 to 9 days in circulation

   + Many stored in spleen

   + Released when needed

- Large fragments of megakaryocytes in bone marrow

- Thrombopoietin (hormone)→ platelet production

   + Made in the liver, kidney, smooth muscle, bone marrow

• Constrict blood vessels

• vFW (blood clotting factor) → platelet adhesion

• Degranulation of platelets → ADP, TXA2 → platelet aggregation
• Calcium → coagulation cascade

- Plasma proteins

   + Circulate as inactive procoagulation factors

   + Most are synthesized by the liver

   + von Willebrand factor (vFW) made by megakaryocytes and endothelium

- Calcium (factor IV)

• The process of converting plasma from a liquid to a solid

• The end result is the formation of a thrombus, which contains fibrin with entrapped red blood cells and platelets

• A series of enzymatic steps that must occur in order to develop a thrombus

• Each step depends on the previous one to "activate" the enzymes in the next step (like a line of dominos)

- Decreased platelet levels (thrombocytopenia)

   + Decreased production

   + Increased destruction

   + Platelets used up in forming clots

- Impaired platelet function

- Shock= massive blood loss

- Blood pressure pushes blood to heart, brain, and kidney

• Trauma

• Spontaneous bleeding induced by a secondary illness

• Hereditary coagulation disorders (ex. hemophilia)

- Disorders are characterized by two groups:

   + Disorders characterized by hemorrhage

   + Disorders characterized by thrombosis (making thrombi)

- These are further categorized in subgroups:

   + Vascular disorders

   + Platelet disorders

   + Coagulation disorders

- Persistent bleeding from gums

- Petechiae

   + Pinpoint, flat, red spots on skin and mucous membrane

- More than normal bleeding in trauma

- Bleeding into joint- hemarthroses

   + Or sputum in pulmonary edema

   + Swollen, red, painful

- Hemoptysis

- Fish oil helps blood from clotting

- Hematemesis- vomiting blood

   + Coarse brown particles (coffee ground emesis)

- Blood in feces- or intestines

   + Black or occult

- Anemia

- Feeling faint and anxious

- Low blood pressure

   + Heart will compensate by increasing heart rate

- Rapid pulse

- Classic hemophilia

   + Deficit or abnormality of factor VIII (8)

- Most common inherited clotting disorder

   + X-linked recessive trait (sex linked, like baldness)

   + Manifested in men, carried by women

- Varying degrees of severity (depending on trauma)

- Prolonged bleeding after minor tissue trauma

- Spontaneous bleeding into joints

- Possible hematuria or blood in feces

- Most common hereditary clotting disorder

- Three major types

- Signs and symptoms include:

   + Skin rashes

   + Frequent nosebleeds

   + Easy bruising

   + Bleeding of gums

   + Abnormal menstrual bleeding (usually heavy)

- Treatment based on type and severity

•  The pathophysiological changes that lead to the development of thrombosis are described by Virchow's Triad

• Endothelial cell injury (most prominent), turbulent flow stasis, hypercoagulable state

- Involves both excessive bleeding and clotting

- Excessive clotting in circulation

   + Thrombi and infarcts occur

- Clotting factors are reduced to a dangerous level

- Widespread, uncontrollable hemorrhage results

- Very poor prognosis, high fatality rate

- Complication of many primary problems

   + Obstetrical complications

   + Infections

   + Carcinomas

   + Major trauma

   + Septic shock

- In very basic terms, patients develop microemboli in small vessels, perhaps due to inflammation

- The body "uses up" the clotting factors on these small clots, and then the patient bleeds extensively from everywhere else

- More women then men die from heart disease

- The heart is divided into systemic (left) and pulmonary (right) systems

   + The pulmonary system has low vascular resistance, this the right side is less muscular

   + Each side has an atrium and a ventricle, separated by valves

- Heart generates blood pressure

- Worst electrical for the heart is fibulation

   + Shock is to stop the heart to reset it for the pace maker to kick in

- Located in the mediastinum

- Located in the pericardial sac

   + Parietal pericardium (outer layer)

   + Epicardium (visceral pericardium)

   + Pericardial cavity

   + Myocardium (middle layer)

   + Endocardium (inner lining)

- Heart valves

   + Atrioventricular valves

   + Semilunar valves

- Septum

   + Where heart is divided between right and left side

• Cardiac muscle is highly dependent on a large oxygen supply, supplied by the right and left coronary arteries

• Heart gets energy from fat

• The flow of electricity through the heart is what produces contraction

• The sinoatrial (SA) node is the pacemaker for the heart (by vagus and sympathetic nerve)

• The SA node then sends the signal to the atrioventricular (AV) node, and finally down the bundle of his to stimulate the ventricles to contract

- Conduction pathway

   + SA Node

       - Pace maker

       - Sinus rhythm

- AV Node

   + Located in floor of the right atrium

- AV bundle (Bundle of His)

   + Right and left branches

- Purkinje fibers

   + Terminal fibers

- Too much potassium causes heart to go through hyperpolarization

- Atherosclerosis blocks coronary arteries

   + No blood getting to arteries, heart cells and muscles die, gets replaced by scar tissue

- Ischemia may cause:

   + Angina (blockage)

   + Heart attack

   + Cardiac arrhythmias

   + Conduction deficets

   + Heart failure

   + Sudden death

- Exercise prevents congestive heart failure (scar tissue)

*Women symptoms differ from men*

- Chest pain

   + Severe, crushing, constrictive or like heartburn

- Sympathetic nervous system response

   + GI distress (needed to go to bathroom), nausea, vomiting

    + Tachycardia and vasoconstriction

    + Anxiety, restlessness, feeling of impending doom

- Hypotension (low bP) and shock

   + Weakness in arms and legs

- Massive heart attack= first and last

- Shortness of breath could mean blockages

- EKG changes

   + T-wave inversion

   + ST-segment depression or elevation

   + Abnormal Q wave

- Serum cardiac markers

   + Proteins released from necrotic heart cells (heart muscle will break down and show in blood)

         - Myoglobin, creatine kinase, troponin

- Imbalance in blood supply and the heart's O2 demands

   + Less blood

      - Atherosclerosis- inflammatory plaques that can burst

      - Vasospasm- happens more in women (back pain)

   + Higher oxygen deman

      - Stress

      - Exercise

      - Cold

- LDL= bad cholesterol

- Anxiety can mimick a heart attack

- Hypertension takes more work for the heart

- Occurs when there is a deficit of oxygen to meet myocardial needs

- Chest pain may occur in different patterns

   + Classic or exertional angina

   + Variant angina

       - Vasospasm occurs at rest

   + Unstable angina

    - Prolonged pain at rest- may precede myocardial infarction