THE CIRCULATORY SYSTEM: BLOOD Hematocrit - RBCs as percent of total blood volume

 Female: 37%-48%
The circulatory system is composed of:  Male: 45%-52%
1) the blood (the circulating material)
2) the heart (pump) Hemoglobin
3) blood vessels (conduit)  Female: 12-16 g/100 ml
 Male: 13-18 g/100 ml
Mean RBC count
 Female: 4.8 million/l
 Male: 5.4 million/l

Platelet counts 130,000-360,000/l

Total WBC counts 4,000-11,000/l

Composition of Plasma
Water 92% by weight
Proteins Total 6-9 g/100 ml
Albumin 60% of total plasma protein
Globulin 36% of total plasma protein
Fibrinogen 4% of total plasma protein
Enzymes of diagnostic value trace
Glucose (dextrose) 70-110 mg/100 ml
Amino acid 33-51 mg/100 ml
Internal environment=the interstitium Lactic acid 6-16 mg/100 ml
 H2O Total lipid 450-850 mg/100 ml
 Glucose Cholesterol 120-220 mg/100 ml
 Lipids Fatty acids 190-420 mg/100 ml
 Amino acids High-density lipoprotein (HDL) 30-80 mg/100 ml
 Vitamins Low-density lipoprotein (LDL) 62-185 mg/100 ml
 Minerals Neutral Fats (triglycerides) 40-150 mg/100 ml
 O2 Phospholipids 6-12 mg/100 ml
 pH 7.35-7.45 Iron 50-150 g/100 ml
 ~38° C Vitamins (A, B, C, D, E, K) Trace amount
 280-300 mOsm Electrolytes
External Environment Sodium 135-145 mEq/L
- H2O Potassium 3.5-5.0 mEq/L
- Glucose Magnesium 1.3-2.1 mEq/L
Digestive - Lipids Calcium 9.2-10.4 mEq/L
- Amino acids Chloride 90-106 mEq/L
- Vitamins Bicarbonate 23.1-26.7 mEq/L
- Minerals Phosphate 1.4-2.7 mEq/L
Sulfate 0.6-1.2 mEq/L
Respiratory - O2 Nitrogenous Wastes
Ammonia 0.02-0.09mg/100 ml
Respiratory - pH 7.35-7.45 Urea 8-25 mg/100 ml
Urinary Creatine 0.2-0.8 mg/100 ml
Creatinine 0.6-1.5 mg/100 ml
All tissue cells - ~38° C Uric acid 1.5-8.0 mg/100 ml
Bilirubin 0-1.0 mg/100 ml
Urinary - 290 mOsm Respiratory gases (O2, CO2, and N2)
Endocrine Plasma to serum = clotting proteins – fibrin
Neural

1) Primary Functions of the Circulatory System 3) The Formed Elements (Blood Cells)
1) Erythrocytes (RBCs)
a) Transportation 2) Platelets (cellular fragments)
- Deliver life-supporting materials, i.e., O2, glucose, amino acid, fatty 3) Leukocytes (WBCs)
acids, vitamins, minerals, etc. a) Granulocytes
- Deliver regulating signals, i.e., hormones to tissue cells i) Neutrophils
- Collect waste products from tissue cells and deliver to special organs ii) Eosinophils
(kidney, lung) for disposal iii) Basophils
- Distribute heat throughout the body b) Agranulocytes
i) Lymphocytes
a) Protection ii) Monocytes
- Special components of the blood patrol the whole body and fight
against invaded microorganisms and cancerous cells. Erythrocytes (red blood cells)
Appearance:
The Blood - biconcave disc shape, which is suited for
gas exchange. The shape is flexible so that
RBCs can pass though the smallest blood
vessels, i.e., capillaries.

Erythrocytes are smaller than Leukocytes.

Structure:
- Primary cell content is
2) General Properties of Whole Blood hemoglobin, the protein that binds oxygen
and carbon dioxide.
- Fraction of body weight 8% - no nucleus nor mitochondria

- Volume Female: 4-5 L Hemoglobin consists of :

Male: 5-6 L globin and heme pigment

- temperature 38 C (100.4 F)

- pH
- Viscosity (relative to water)
- Osmolarity
- Mean salinity (mainly NaCl)
Globin
7.35 - 7.45 - Consists of two  and two  subunits
- Each subunit binds to a heme group
Whole blood: 4.5-5.5 Heme Groups
plasma: 2.0 - Each heme group bears an atom of iron, which binds reversibly with one
molecule of oxygen
280-300 mOsm/L
Carbon monoxide competes with oxygen for heme binding with a much higher
0.85% affinity.
Problem: deoxygenate hemoglobin
Treatment: hyperbaric oxygen chamber
Oxyhemoglobin Ways to increase Red Blood Cell Count in Sports
- bound with oxygen  Legal: raise RBC count by training athletes at high altitude
- red  Illegal: use erythropoietin, androgen, or their analogs
Deoxyhemoglobin Dietary Requirements for Erythropoiesis
- free of oxygen
 Iron
- dark red.
 vitamin B12
Carbaminohemoglobin  folic acid
20% of carbon dioxide in the blood binds to the globin part of hemoglobin, which is More important to women due to the loss of blood during menstruation
called carbamino-hemoglobin.
Life Cycle of Erythrocytes:
Functions of Erythrocytes The average life span is 120
1) Primary Function days.
- Transport oxygen from the lung to tissue cells
and carbon dioxide from tissue cells to the lung
2) Buffer blood pH

Production of Erythrocytes
Erythropoiesis
- refers specifically to red blood
cell production.

Hematopoiesis - refers to whole

blood cell production.
All blood cells, including red and
white, are produced in red bone
marrow.

On average, one ounce, or 100 Erythrocyte Disorders

billion blood cells, are made each Anemia
day. - is a condition in which the blood has an abnormally low oxygen-carrying
capacity.

Hematopoiesis Common causes of anemia include:

- The red bone marrow is a network of reticular connective tissue that  an insufficient number of red blood cells
borders on wide blood capillaries called blood sinusoids. As  decreased hemoglobin content
hemocytoblasts mature, they migrate through the thin walls of the  abnormal hemoglobin
sinusoids to enter the blood. Two such examples are Thalassemias and Sickle-cell anemia, which are caused by
genetic defects.
All of blood cells including red and white arise from the same type of stem cell, the
hematopoietic stem cell or hemocytoblast Erythrocyte Disorders - 2
Polycythemia
- Is an abnormal excess of erythrocytes that increases the viscosity of the
blood, causing it to sludge or flow sluggishly.

Common causes of polycythemia include:

1) Bone marrow cancer
2) A response to reduced availability of oxygen as at high altitudes

Human Blood Groups

- We’ve learned from tragedies (death) caused by mismatch during transfusion in
ancient time.
- ABO blood types were identified in 1900 by Karl Landstein (1930 Nobel laureate).
- Other blood types were identified later.

Blood type is determined by

Agglutinogens
o are specific glycoproteins on red blood cell membranes.
o All RBCs in an individual carry the same specific type of agglutinogens.
ABO Blood Groups
Type A: RBCs carry agglutinogen A.
Type B: RBCs carry agglutinogen B.
Type O: RBCs carry no A nor B agglutinogens.
Type AB: RBCs carry both A and B agglutinogens.

Erythropoiesis Type A blood

Erythrocytes are produced throughout whole life to replace dead cells.  RBCs carry type A agglutinogens.
 Plasma contain preformed antibodies,
Feedback Regulation of  Agglutinin B, against B agglutinogens.
Erythropoiesis
- Regulated by renal oxygen Agglutinins
content. o are preformed antibodies in plasma
o bind to agglutinogens that are not carried by host RBCs
- Erythropoietin, a o cause agglutination --- aggregation and lysis of incompatible RBCs.
glycoprotein hormone, is
produced by renal cells in Type B blood
response to decreased  RBCs carry type B agglutinogens.
renal blood O2 content.  Plasma contain agglutinin against A agglutinogens.
- Erythropoietin stimulates
Type O blood
erythrocyte production in
 RBCs carry neither type A nor type B agglutinogens.
the red bone marrow.
 Plasma contain agglutinin against both A and B agglutinogens.
 The person can accept only type O blood transfusion.
Type AB blood
 Agglutinogen(s) ?
 Agglutinin(s) ?
A drop in renal blood oxygen level can result from:

1) reduced numbers of red blood cells due to hemorrhage or excess RBC

destruction.
2) reduced availability of oxygen to the blood, as might occur at high altitudes or
during pneumonia.
3) increased demands for oxygen (common in those who are engaged in aerobic
exercise).
Summary of ABO
Blood Groups Blood Agglutinogen Agglutinin
Type
(on RBC) (in Plasma)

A A B

B B A

O A&B

AB A&B

Blood Type
Match
A B O AB

A Yes No Yes? No

B No Yes Yes? No

O No No Yes No

AB Yes? Yes? Yes? Yes

Rh Blood Groups
Classify blood groups based on Rh agglutinogens other than A/B agglutinogens
Rh positive
- RBCs contain Rh agglutinogens.
- The majority of human beings is Rh positive.
Rh negative
 The RBCs contain no Rh agglutinogens.
 Agglutinins against Rh-positive RBCs are produced after Rh-negative
blood sees Rh-positive RBCs.
The problem with a Rh-negative mother and her Rh-positive fetus.

Leukocytes (White Cells)

Leukocytes are grouped into two major categories:
1. Granulocytes
- contain specialized membrane-bound cytoplasmic granules
- include neutrophils, eosinophils, and basophils.
2. Agranulocytes
- lack obvious granules
- include lymphocytes and monocytes

Leukocytes (WBCs) Count

4,000-11,000 / L

Function of Leukocytes:
1. Defense against diseases
2. Leukocytes form a mobile army that helps protect the body from
damage by bacteria, viruses, parasites, toxins and tumor cells.

Leukocytes circulate in the blood for various length of time.

Life span
 several hours to several days for the majority
 many years for a few memory cells
1. Margination Coagulation Disorders
- slow down by cell adhesion molecules secreted by endothelial cells
2. Diapedesis:  Thrombosis
- Leukocytes slip out of the capillary blood vessels. o The abnormal clotting of blood in an unbroken vessel.
3. Chemotaxis:
- Gather in large numbers at areas of tissue damage and infection by  Thrombus
following the chemical trail of molecules released by damaged cells or o A clot that attaches to the wall of blood vessel.
other leukocytes
4. Phagocytosis  Embolus
- Destroy foreign substances or dead cells o A clot that comes off the wall of blood vessel and travel in the
blood stream?
Leukocyte Disorders
Normal Leukocyte Count: 4,000 – 11,000/l  Embolism
o The blockage of blood flow by an embolus that lodges in a
Leukopenia: < 4,000/l normal leukocytes small blood vessel.
Leukocytosis: > 11,000/l normal leukocytes
 Infarction
Leukopenia is one major side effect of chemotherapy. o Refers to cell death that result from embolism. Infarction is
Why Leukopenia during chemotherapy? responsible for most strokes and heart attacks.
 Cancerous cells grow fast, which distinguish themselves from most of Bleeding Disorders
normal cells.
 Chemotherapy is designed to kill fast-growing cells by interrupting 1) Thrombocytopenia
mitotic cell division. - The number of circulating platelets is deficient (<50,000/l )
 Chemotherapy also kills a few normal fast-growing cells including: - causes spontaneous bleeding from small blood vessels all over the body
 leukocytes
 hair 2) Deficiency of clotting factors due to impaired liver function
 intestinal epithelial cells
3) Hemophilias
Leukemia - Hereditary bleeding disorders due to deficiency of clotting factors
- Leukemia refers to a group of cancerous conditions of white blood cells.
- Descendants of a single stem cell in red bone marrow tend to remain
unspecialized and mitotic, and suppress or impair normal bone marrow
function.
- Extraordinarily high number of abnormal (cancerous) leukocytes

HEMOSTASIS
- Hemostasis refers to the stoppage of bleeding.
Hemostatsis = Homeostasis
Maintaining balance

Three phases occur in rapid sequence.

Function of Platelets
1. Secrete vasoconstrictors that cause vascular spasms in broken vessels
2. Form temporary platelet plugs to stop bleeding
3. Secrete chemicals that attract neutrophils and monocytes to sites of
inflammation
4. Secrete growth factors that stimulate mitosis in fibroblasts and smooth
muscle and help maintain the linings of blood vessels
5. Dissolve blood clots that have outlast their usefulness
Coagulation (Clotting)
- Many clotting factors in plasma are involved in clotting.
- These factors are inactive in the blood.
- They are activated when:
1) blood vessel is broken, or
2) blood flow slows down.
- The sequential activation (reaction cascade) of the clotting factors finally
leads to the formation of fibrin meshwork.
- Blood cells are trapped in fibrin meshwork to form a hard clot.