Maria Carmela L. DomocmatInstructorNorthern Luzon Adventist College

�Consists of blood and the bone marrow� blood - the major body fluid tissue

� bone marrow - manufactures new blood cells (hematopoiesis)

� transports vital substances

� maintains stability of interstitial fluid

� distributes heat

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� changes in fluid concentration

� changes in electrolyte concentration

� amount of adipose tissue

� about 8% of body weight or about 5 liters

� Let us watch Human Physiology How Does the Body Make Blood.avi

Contents of Blood.avi

� Water

� Ions

� Glucose

� Proteins� Proteins

� Water

� 3 L in average adult; constitutes 90% of plasma

� Ions:

� Sodium, potassium, calcium, phosphorous, and other elctrolytesother elctrolytes

� Glucose

� Prime oxidative metabolite of body cells

� Proteins: act as buffers

� Albumin

� Largest component of plasma protein� Largest component of plasma protein

� Principally responsible for plasma colloid osmotic

pressure (COP)

� Reversibly combines with and transports certain lipids,

bilirubin, thyroxin, and certain drugs, such as

barbiturates

� Proteins

� Alpha and beta globulins

� Help establish COP

� Transport certain vitamins, iron, copper, and cortisol

� Hemostasis (prothrombin and fibrinogen are in this

blood fraction)

� Gamma globulins

� Antibodies

• straw colored• liquid portion of blood• 55% of blood

Albumins• most numerous plasma proteins• originate in liver• help maintain osmotic pressure of blood

Alpha and Beta Globulins• originate in liver• transport lipids and fat-soluble vitamins

Fibrinogen• originate in liver• plays key role in blood coagulation

Gamma Globulins• originate in lymphatic tissues• constitute the antibodies of immunity

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Gases• oxygen• carbon dioxide

Nutrients • amino acids• simple sugars• carbon dioxide

• nitrogen

• simple sugars• nucleotides• lipids• lipoproteins

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Chylomicrons• high concentration of triglycerides• transport dietary fats to muscles and

VLDLs• relatively high concentration of triglycerides• produced in the liver• transport triglycerides fats to muscles and

adipose cells

HDLs• relatively high concentration of proteins• relatively low concentration of lipids• transport remnants of chylomicrons to liver

LDLs• relatively high concentration of cholesterol• formed from VLDLs• deliver cholesterol to various cells

• transport triglycerides from liver to adipose cells

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� molecules containing nitrogen but are not proteins� urea – product of protein catabolism; about 50% of NPN substancessubstances� uric acid – product of nucleic acid catabolism� amino acids – product of protein catabolism� creatine – stores phosphates� creatinine – product of creatine metabolism� BUN – blood urea nitrogen; indicate health of kidney

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• sodium• potassium• calcium• magnesium• magnesium• chloride• bicarbonate• phosphate• sulfate• sodium and potassium most abundant

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� Red blood cells or

erythrocytes

� Platelets or Platelets or

thrombocytes

� White blood cells

or leukocytes

� Mostly in bone marrow from stem cells

� Rate regulated by cytokines & growth factors

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Description

Normal Values

Function

Erythropoiesis

Hemolysis

�7.5 µm in diameter

� in 1 cm – you can put ›1,500 RBCs side by side

� Average life span: 120 days

odeformable

� Average life span: 120 days

�unique shape� biconcave disk shape

� thin center, thick edges – ideal for gas exchange

� deformable

� 1 RBC has 200-300 million Hb

� 1 Hb has 4 globin chains (1 pair of ά chain and 1 pair of β chain)

� 1 globin is bound to 1 heme (red pigment)

� 1 heme has 1 iron atom

� Iron binds O2

�Transport O2 and CO2 to and from body tissues

�Contains hemoglobin

�participate in acid-base balance participate in acid-base balance

� The process begins in the embryonic yolk sac

� maturing fetus - liver, spleen and lymph nodes

� end of pregnancy and after birth- restricted to bone marrowto bone marrow

� As time progresses, the contribution from long bones decreases

� Adult life - only the marrow of membranous bones is involved

� vertebrae, ribs and pelvis,.

� Red Blood Cell Production

� Requirements in production of healthy RBCs

� Precursor cells (reticulocytes)

� Adequate supplies of iron, Vitamin B12, folic acid or folate, protein, pyridoxine, and acid or folate, protein, pyridoxine, and traces of copper

1. Pluripotent stem cells or hemocytoblast2. Proerythroblast2. Proerythroblast3. Erythroblast 4. Normoblast5. Reticulocyte 6. Erythrocyte – mature RBC

� hemocytoblast reticulocyte3-7 days (in bone marrow)

� reticulocyte erythrocyte

24-48 hrs (in blood)

� erythrocyte lifespan 100-120 days

� STIMULUS: Decreased oxygen level in blood (hypoxia) due to:

� Less RBCs from bleeding

� Less RBCs from excess RBC destruction

� Low oxygen levels (high altitude, illness)� Low oxygen levels (high altitude, illness)

� Increased oxygen demand (exercise)

� Causes kidneys and liver to release of erythropoietin

� Kidneys produce 90%; liver 10%

� Erythropoietin: the hormone that stimulates RBC production

� Takes several days to effect

� Red bone marrow increases production of RBC RBC

� Reach maximum production after 5 days from stimulation

� Increased number of RBC in the circulation result to increased oxygen-carrying capacity of the blood

� Detected by the liver and kidneys

Negative feedback to the kidney and liver : � Negative feedback to the kidney and liver : Inhibition of the erythropoietin production

� Note: if with kidney failure – hypoxia has little or no effect on RBC production

� RBC lacks mitochondria –no source of energy

� Relies on glucose ad glycolytic pathway for its metabolic needs

� Enzyme-mediated anaerobic metabolism of glucose glucose

� Generate the ATP needed for normal membrane function and ion transport

� Depletion of glucose or functional deficiency of one of glycolytic enzymes leads to premature death of RBC (G6PD deficiency)

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� RBC destruction

� Rate of RBC destruction: 2.5 million/sec or 1% of RBCs per day

� RBC destruction = RBC production

� RBC circulate for about 120 days

� macrophages ingest and destroy worn out and defective RBCs in spleen, liver, bone marrow and lymph nodes

� hemoglobin is broken down into heme and globin

� Let’s watch

� Hemoysis and crenation of RBC

� Crenation: the formation of abnormal notching around the edge of an erythrocyte; the an erythrocyte; the notched appearance of an erythrocyte due to its shrinkage after suspension in a hypertonic solution.

� Let’s watch Hb breakdown

� Heme

� in the spleen - heme is converted to unconjugated bilirubin

� heme attaches to plasma protein for transport in the blood

� removed from the blood by the liver and conjugated with

glucuronideglucuronide

� becomes conjugated bilirubin

� conjugated bilirubin and biliverdin are secreted in bile and

excreted in feces and urine

� Globin: neutralized or recycled into amino acids

� heme releases iron

� iron attaches to biliverdin for transport

� return to bone marrow to be reused or stored in the spleen and liver for future use

� 33% of cell mass

� the O2-carrying substance that gives blood its

red colorred color

� 1 liter of water has 3ml of dissolved O2

� hemoglobin can transport 70 times this amount

� 20ml of O2= 100ml of blood

� large molecules with globin and hemes

� heme group – iron-containing pigment part of

hemoglobin to which oxygen bindshemoglobin to which oxygen binds

� globin - complex protein with 4 polypeptides

(2 alpha and 2 beta polypeptide chain)

� each polypeptide has one heme group; each

heme carries one O2

� oxyhemoglobin - when oxygen is bound to iron

� deoxyhemoglobin - no oxygen bound to iron

� carbaminohemoglobin - when carbon dioxide is bound (to polypeptide chain) to iron is bound (to polypeptide chain) to iron

� essential for hemoglobin to carry oxygen

� Found in several compartments

� 80% is in heme of blood

� ‹20% stored in bone marrow, liver, spleen, other organsorgans

� Small amount in myoglobin in muscles, cytochromes, iron-containing enzymes

� daily Fe loss: 0.9 mg men/l.7 mg women

� Dietary iron helps maintain body stores

� Absorbed in small intestines (especially duodenum) (10-15% is absorbed)

� Most iron enter the circulation

� Some are sequestered in intestinal epithelial � Some are sequestered in intestinal epithelial cells and is lost in feces as these cells slough off

� Fe in blood bound to transferrin

� Iron – transferrin complex

� Those iron that enter the circulation combines with betaglobulin transferrin in order to be transported to the plasma

� Iron – transferrin complex is then transported to plasma where:

� (1) Bone marrow uses iron to make Hb

� (2) Excess iron is stored in the liver as ferritin

� When RBC age or destroyed in spleen heme releases iron into circulation

� Returned to:

� (1) to bone marrow to be reused for heme synthesis or synthesis or

� (2) to spleen and liver for storage

� If there is iron overload – there will be increased iron excretion

� Serum ferritin levels

� blood measurement which provide an index of body iron stores

� If decreased –indicate a need for iron supplements supplements

� Antigens - substances that trigger formation of antibodies that interact specifically with that antigen

� Determine a person’s blood group or blood type

� Type A

� RBCs contain A antigen

� antibodies to B in plasma

� Compatible with type A or O

� Type B

� RBCs contain B antigen

� antibodies to A in plasma

� Compatible with type B or O

� Type AB

� RBCs contain A and B antigens

� no antibodies in plasma

� Compatible with type A, B, AB or O

� Type O

� RBCs do not contain A or B antigens

� antibodies to both A and B in plasma

� Compatible with type O

� Rh-positive

� blood with Rh antigen

� Rh-negative

� blood without Rh antigen

no antibodies to Rh+ unless exposed to Rh+ � no antibodies to Rh+ unless exposed to Rh+ antigen)

� hemolytic disease of newborn

� Rh- mom and Rh+ fetus (treatment) Rhogam

�plasma contain antibodies (immunoglobulins) that interact with these antigens—causing cells to agglutinate (clump together)

But plasma cannot contain antibodies to its � But plasma cannot contain antibodies to its own cell antigen—or it would destroy itself

� Thus- type A blood –does not have anti-A antibodies; but have anti-B antibodies

Anemias

Polycythemias

Normal RBCs

RBCs of person with hemolytic anemia

Patient's peripheral blood smear illustrating marked hypochromic microcytic red cells, numerous target cells, polychromasia, poikilocytosis, and anisocytosis with numerous small teardrop forms, ovalocytes, and schistocytes (red cell fragments).

• iron deficiency anemia

• hemoglobin deficient• lack of iron

• sickle cell anemia

• abnormal shape of RBCs• defective gene

• aplastic anemia

• bone marrow damaged• toxic chemicals• radiation

• hemolytic anemia

• RBCs destroyed• toxic chemicals

• pernicious anemia

• excess of immature RBCs• inability to absorb B12

• thalassemia

• hemoglobin deficient• RBCs short-lived• defective gene

Table 16-3: Causes of Anemia

� chelitis

Riboflavin deficiency mostly manifests itself at the edge of the mucosa.

Spoon-shaped Nails

� Beefy red tongue

poikilocytosis anisocytosis

� Excellent sources of iron: beans, carrots, cauliflower, celery, egg yolk, graham bread, kidney, lettuce, liver, oatmeal, soybeans, spinach, whole wheat

Good sources of iron: beef, beets, cabbage, � Good sources of iron: beef, beets, cabbage, cucumbers, dates, duck, goose, lamb, molasses, mushrooms, oranges, peanuts, peas, peppers, potatoes, prunes, radishes, raisins, pineapples, tomatoes

� Thalassemia major is an inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. This is the most severe form of anemia, and the oxygen depletion in the body becomes apparent within the becomes apparent within the first 6 months of life. If left untreated, death usually results within a few years. Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major. The darker cells likely represent normal RBCs from a blood transfusion.

� Thalassemia minor is an inherited form of hemolytic anemia that is less severe than thalassemia major. This blood smear from an individual with thalassemia shows small thalassemia shows small (microcytic), pale (hypochromic), variously-shaped (poikilocytosis) red blood cells. These small red blood cells (RBCs) are able to carry less oxygen than normal RBCs.

� Frontal bossing

� Prominence of facial bones

� Forward protrusion of upper teeth and depression of nasal bridge

� Chelation therapy is the administration of chelating agents to remove heavy metals from the body

� Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in bloodstream and enhancing its elimination in the urine. By removing excess iron, the agent reduces the damage done to various organs and tissues, such as the liver. A recent study also shows that it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma).

� Let’s watch