BLOOD - Dr. Chintan

- Internal environment- Milieu interieur = ECF of the body

- Homeostasis- Maintenance of constant internal environment

- Transport of ECF- Maintenance of pH of ECF- Regulation of temperature- Maintenance of water & electrolyte balance- Supply of nutrients, O2, enzymes & hormones- Removal of metabolic & other waste products- Reproduction

BLOOD- Blood is a fluid connective tissue which delivers

necessary substances such as nutrients, hormones and oxygen to the cells and transports metabolic waste products away from those same cells.

- it is composed of blood cells suspended in blood plasma

- blood cells – RBC, WBC, Platelets

- Plasma – plasma proteins

BLOOD Functions- Supply of oxygen to tissues (bound to hemoglobin,

which is carried in red cells)

- Supply of nutrients such as glucose, amino acids, and fatty acids (dissolved in the blood or bound to plasma proteins)

- Removal of waste such as carbon dioxide, urea and lactic acid

- Immunological functions, including circulation of white blood cells, and detection of foreign material by antibodies

BLOOD Functions- Coagulation, the response to a broken blood vessel,

the conversion of blood from a liquid to a semi-solid gel to stop bleeding.

- Messenger functions, including the transport of hormones and the signaling of tissue damage

- Regulation of body pH

- Regulation of core body temperature

- Storage functions

Blood plasma- Blood plasma is the pale-yellow liquid component of

blood that normally holds the blood cells in whole blood in suspension. It makes up about 55% of the body's total blood volume.

- It is the intravascular fluid part of extracellular fluid.

- water (up to 95% by volume),- dissolved proteins (6-8%) (i.e.—albumins, globulins, and

fibrinogen),- glucose, clotting factors, - electrolytes (Na+, Ca2+, Mg2+, HCO3-, Cl-, etc.), - hormones, and carbon dioxide.

Blood plasma- Plasma also serves as the protein reserve of the

human body.

- It plays a vital role in an intravascular osmotic effect that keeps electrolytes in balanced form and protects the body from infection and other blood disorders.

- Blood plasma = blood – cells

- Blood serum = plasma - clotting factors

Plasma proteins- transport of lipids, hormones, vitamins and metals in

the circulatory system

- the regulation of the immune system.

- Serum albumin accounts for 55% of blood proteins, and is a major contributor to maintaining the osmotic pressure of plasma, assist in the transport of lipids and steroid hormones.

- Globulins make up 38% of blood proteins and transport ions, hormones, and lipids, assisting in immune function.

Plasma proteins- Fibrinogen comprises 7% of blood proteins; conversion of

fibrinogen to insoluble fibrin is essential for blood clotting.

- The remainder of the plasma proteins (1%) are regulatory proteins, such as enzymes, proenzymes and hormones.

- Viscosity – blood pressure, buffers – acid base balance (NH2 → NH4, COOH → COO -)

- All blood proteins are synthesized in liver except for the gamma globulins.

- The normal laboratory value of serum total protein is around 6.4 – 8.3 g/dL.

Plasma proteinsPlasma Protein

Normal level

 % Function

Albumins 3-5 g/dl 55%maintains colloid osmotic pressure; create oncotic pressure and transport insoluble molecules

Globulins 2-3 g/dl 38%participate in immune system, α β γ Globulin, A/G ratio 1.7 : 1

Fibrinogen 0.3 g/dl 7% Blood coagulation

Regulatory proteins

<1% Regulation of gene expression

Clotting factors

<1% Conversion of fibrinogen into fibrin

Plasma proteins- Prealbumin (Transthyretin) – Binds T3, T4- Albumin – osmotic pressure, carrier

- Lipoproteins (chylomicrons, VLDL β, LDL β, HDL α) – α globulin- Transferrin – β globulin – iron transport- Haptoglobin - α globulin – binds with Hb- Ceruloplasmin - α globulin – binds with copper- globulins (immunoglobulins) - γ immunity- Alpha-2-macroglobulin - Inhibitor of serum endoproteases

- Alpha 1 antitrypsin (neutralizes trypsin that has leaked from the digestive system)

- Alpha 1 fetoprotein - Osmotic regulation; binding and carrier protein- Complement component 3- Complement component 4- C-reactive protein (CRP) - has role in tissue inflammation- Prothrombin – precursor of thrombin - clotting

Plasma proteins - applied- Dietary proteins – essential amino acids – animal protein (Albumin)

– plant protein (Globulin)

- Hypoproteinemia – edema- Dietary deficiency, starvation- Malabsorption syndrome- Liver diseases- Renal diseases- Hemorrhage, burns- Hereditary

- Hyperproteinemia- Acute infection- Chronic infection- Multiple myeloma

Red Blood Cells (Erythrocytes)- major function of RBCs - to transport hemoglobin, which in turn

carries oxygen from the lungs to the tissues.

- they contain a large quantity of carbonic anhydrase, an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water (H2O) to form carbonic acid (H2CO3) = H+ , HCO3-

- this reaction makes it possible for the water of the blood to transport enormous quantities of CO2 in the form of bicarbonate ion (HCO3–) from the tissues to the lungs, where it is reconverted to CO2 and expelled into the atmosphere.

- responsible for most of the acid-base buffering power of whole blood.

RBC- biconcave discs having a mean diameter of about 7.8 micrometers and a thickness of 2.5 micrometers at the thickest point and 1 micrometer or less in the center.

RBC- The shapes of red blood cells can change remarkably

as the cells squeeze through capillaries - the red blood cell is a “bag” that can be deformed into almost any shape.

- In normal men, the average number of RBCs per cubic millimeter is 5,200,000 (±300,000).

- In normal women, it is 4,700,000 (±300,000).

- Persons living at high altitudes have greater numbers of RBCs.

RBC- The whole blood of men contains an average of

15 g of Hb / 100 ml of cells- for women, it contains an average of 14 g / 100 ml

- 1 g Hb is capable of combining with 1.34 ml of O2

- In a normal man, a maximum of about 20 ml of O2 can be carried in combination with Hb in each 100 ml of blood,

- In a normal woman, 19 ml of O2 can be carried

Production of RBC- In the early weeks of embryonic life, primitive,

nucleated RBCs are produced in the yolk sac.

- During the middle trimester of gestation, the liver is the main organ for production of RBCs, but reasonable numbers are also produced in the spleen and lymph nodes.

- Then, during the last month or so of gestation and after birth, RBCs are produced exclusively in the bone marrow.

- the bone marrow of essentially all bones produces red blood cells until a person is 5 years old

Production of RBC- The marrow of the long bones, except for the

proximal portions of the humeri and tibiae, becomes quite fatty and produces no more RBCs after about age 20 years

- After 20 years, most red cells continue to be produced in the marrow of the membranous bones, such as the vertebrae, sternum, ribs and ilia.

- Even in these bones, the marrow becomes less productive as age increases.

Genesis of Blood Cells- The blood cells begin their lives in the bone marrow from a

single type of cell called the pluripotential hematopoietic stem cell (PHSC).

- As these cells reproduce, a small portion of them remains exactly like the original pluripotential cells and is retained in the bone marrow to maintain a supply, although their numbers diminish with age

- The intermediate stage cells are very much like the pluripotential stem cells, even though they have already become committed to a particular line of cells and are called committed stem cells.

- Growth inducers: interleukin-3

erythropoiesis- CFU – E → proerythroblast

- The first-generation cells are called basophil erythroblasts (early normoblast) because they stain with basic dyes; the cell at this time has accumulated very little Hb

- cells become filled with Hb, the nucleus condenses to a small size, and its final remnant is absorbed or extruded from the cell

- ER is also reabsorbed – reticulocyte - contains a small amount of basophilic material, consisting of remnants of the Golgi apparatus, mitochondria, and a few other cytoplasmic organelles – 0.5 to 2 % - 1 to 2 days - mature erythrocyte

Regulation of RBC Production- (1) an adequate number of red cells is always available

to provide sufficient transport of oxygen from the lungs to the tissues,

- (2) the cells do not become so numerous that they inhibit blood flow

- Tissue Oxygenation - Any condition that causes the quantity of oxygen transported to the tissues to decrease

- when a person becomes extremely anemic as a result of hemorrhage or any other condition

Regulation of RBC Production- destruction of major portions of the bone marrow by

any means, especially by x-ray therapy, causes hyperplasia of the remaining bone marrow, thereby attempting to supply the demand for RBC

- At very high altitudes, where the quantity of O2 in the air is greatly decreased, insufficient oxygen is transported to the tissues,

- Various diseases of the circulation that cause decreased blood flow through the peripheral vessels, and particularly those that cause failure of O2 absorption by the blood as it passes through the lungs

- cardiac failure and lung diseases

erythropoietin- The principal stimulus for red blood cell production

in low oxygen states is a circulating hormone called erythropoietin, a glycoprotein with a molecular weight of about 34,000.

- about 90 % of all erythropoietin is formed in the kidneys; the remainder is formed mainly in the liver

- renal tubular epithelial cells secrete the erythropoietin

- NE and E and several of the PGs stimulate erythropoietin production

erythropoietin- the important effect of erythropoietin is to stimulate

the production of proerythroblasts from hematopoietic stem cells in the bone marrow

- erythropoietin causes these cells to pass more rapidly through the different erythroblastic stages than they normally do

- The rapid production of cells continues as long as the person remains in a low O2 state or until enough RBCs have been produced to carry adequate amounts of O2 to the tissues despite the low O2

Maturation of RBC- important for final maturation of the RBCs are two

vitamins, vitamin B12 and folic acid - essential for the synthesis of DNA,

- required for the formation of thymidine triphosphate, one of the essential building blocks of DNA

- lack of either causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division

- Larger than normal red cells called macrocytes – irregular and oval - capable of carrying O2 normally, but their fragility causes them to have a short life

Pernicious Anemia- failure to absorb vitamin B12 from the GIT

- Atrophic gastric mucosa that fails to produce normal gastric secretions.

- The parietal cells of the gastric glands secrete a glycoprotein called intrinsic factor, which combines with vitamin B12 in food and makes the B12 available for absorption by the gut

intrinsic factor- (1) IF binds tightly with the vitamin B12. In this bound

state, the B12 is protected from digestion by the gastrointestinal secretions.

- (2) Still in the bound state, IF binds to specific receptor sites on the brush border membranes of the mucosal cells in the ileum.

- (3) Then, vitamin B12 is transported into the blood during the next few hours by the process of pinocytosis, carrying IF and the vitamin together through the membrane

Pernicious Anemia- Once vitamin B12 has been absorbed from the GIT, it

is first stored in large quantities in the liver, then released slowly as needed by the bone marrow.

- The minimum amount of vitamin B12 required each day to maintain normal red cell maturation is only 1 to 3 micrograms, and the normal storage in the liver and other body tissues is about 1000 times this amount.

- Therefore, 3 to 4 years of defective B12 absorption are usually required to cause maturation failure anemia

Deficiency of Folic Acid- Folic acid is a normal constituent of

green vegetables, some fruits, and meats (especially liver). However, it is easily destroyed during cooking

- gastrointestinal absorption abnormalities - sprue

Hemoglobin - Synthesis of Hb begins in the proerythroblasts and

continues even into the reticulocyte stage of the RBCs

- Formation of Hb - succinyl-CoA, formed in the Krebs metabolic cycle binds with glycine to form a pyrrole molecule

- 4 pyrroles combine to form protoporphyrin IX, which then combines with iron to form the heme molecule

- each heme molecule combines with a long polypeptide chain, a globin synthesized by ribosomes, forming a subunit of Hb called a hemoglobin chain

- Each chain has a MW of about 16,000; four of these in turn bind together loosely to form the whole hemoglobin molecule.

Hemoglobin - variations in the different subunit hemoglobin chains,

depending on the amino acid composition of the polypeptide portion

- Alpha (α) chains, beta (β) chains, gamma (γ) chains, and delta (δ) chains

- Most Common adult HbA - two alpha chains and two beta chains - MW of 64,458.

- HbA2 - two alpha chains and two delta chains

- Fetal – HbF - two alpha chains and two gamma chains

Hemoglobin - each Hb chain has a heme prosthetic group containing

an atom of iron, and because there are 4 Hb chains in each Hb molecule - 4 iron atoms in each Hb molecule;

- each of these can bind loosely with 1 molecule of O2, making a total of 4 molecules of O2 (or 8 O atoms) that can be transported by each Hb molecule

- The types of Hb chains in the Hb molecule determine the binding affinity of the Hb for O2.

- Abnormalities of the chains can alter the physical characteristics of the Hb molecule

sickle cell anemia- The amino acid valine is substituted for glutamic

acid at 6th position in each of the two beta chains.

- When this type of hemoglobin is exposed to low oxygen, it forms elongated crystals inside the red blood cells.

- These make it almost impossible for the cells to pass through many small capillaries, and the spiked ends of the crystals are likely to rupture the cell membranes

Iron Metabolism- Iron is important for the formation not only of hemoglobin

but also of other essential elements in the body (e.g., myoglobin, cytochromes, cytochrome oxidase, peroxidase, catalase)

- The total quantity of iron in the body averages 4 to 5 grams,

- About 65 per cent of which is in the form of hemoglobin.- About 4 per cent is in the form of myoglobin,- About 0.1 per cent is combined with the protein transferrin

in the blood plasma, - About 15 to 30 per cent is stored for later use, mainly in the

reticuloendothelial system and liver parenchymal cells, principally in the form of ferritin.

Iron Metabolism- Iron is absorbed from the small intestine, it immediately

combines in the blood plasma with a beta globulin, apotransferrin to form transferrin, which is then transported in the plasma

- The iron is loosely bound in the transferrin and, consequently, can be released to any tissue cell at any point in the body

- In the cell cytoplasm, iron combines mainly with a protein, apoferritin to form ferritin.

- when the total quantity of iron in the body is more than the apoferritin storage, Smaller quantities of the iron in the storage pool are in an extremely insoluble form called hemosiderin

Iron Metabolism- When the quantity of iron in the plasma falls low, some of

the iron in the ferritin storage pool is removed easily and transported in the form of transferrin in the plasma to the areas of the body

- the transferrin is ingested into the erythroblasts by Endocytosis, there it delivers the iron directly to the mitochondria, where heme is synthesized

- When RBC destroyed → Hb released from the cells is ingested by monocyte-macrophage cells

- There, iron is liberated and is stored mainly in the ferritin pool to be used as needed for the formation of new Hb

Iron Metabolism- A man excretes about 0.6 mg of iron each day, mainly into

the feces. Additional quantities of iron are lost when bleeding occurs.

- For a woman, additional menstrual loss of blood brings long term iron loss to an average of about 1.3 mg/day.

- Iron is absorbed from all parts of the small intestine.

- The liver secretes moderate amounts of apotransferrin into the bile, which flows through the bile duct into the duodenum → binds with free iron and also with certain iron compounds, such as hemoglobin and myoglobin from meat → transferrin

Iron Metabolism- Transferrin is attracted to and binds with receptors in the

membranes of the intestinal epithelial cells.

- Then, by pinocytosis, the transferrin molecule, carrying its iron store, is absorbed into the epithelial cells and later released into the blood capillaries beneath these cells in the form of plasma transferrin.

- Iron absorption from the intestines is extremely slow, at a maximum rate of only a few milligrams per day.

- When the body has become saturated with iron, the rate of additional iron absorption from the intestinal tract becomes greatly decreased & vice versa.

Fate of RBC- When RBCs are delivered from the bone marrow into the circulatory

system, they normally circulate an average of 120 days before being destroyed

- Once the red cell membrane becomes fragile, the cell ruptures during passage through some tight spot of the circulation

- Many of the red cells self-destruct in the spleen, where they squeeze through the red pulp of the spleen.

- There, the spaces between the structural trabeculae of the red pulp, are only 3 micrometers wide, in comparison with the 8-micrometer diameter of the red cell.

- When the spleen is removed, the number of old abnormal red cells circulating in the blood increases considerably.

Destruction of Hb- When RBCs burst and release their Hb, it is phagocytized

almost immediately by macrophages in many parts of the body, but especially by the Kupffer cells of the liver and macrophages of the spleen and bone marrow.

- During the next few hours to days, the macrophages release iron from the Hb and pass it back into the blood, to be carried by transferrin either to the bone marrow for the production of new RBCs or to the liver and other tissues for storage in the form of ferritin.

- The porphyrin portion of the Hb molecule is converted by the macrophages, into the bile pigment bilirubin, which is released into the blood and later removed from the body by secretion through the liver into the bile

bilirubin- greenish yellow bile pigment

- The first substance formed is biliverdin, but this is rapidly reduced to free bilirubin, which is gradually released from the macrophages into the plasma

- The free bilirubin immediately combines strongly with plasma albumin and is transported in this combination throughout the blood and interstitial fluids.

- Even when bound with plasma protein, this bilirubin is still called “free bilirubin”

bilirubin- Within hours, the free bilirubin is absorbed through the

hepatic cell membrane.

- In passing to the inside of the liver cells, it is released from the plasma albumin and soon thereafter conjugated about 80 per cent with glucuronic acid to form bilirubin glucuronide,

- about 10 per cent with sulfate to form bilirubin sulfate, and about 10 per cent with a multitude of other substances

- In these forms, bilirubin is excreted from the hepatocytes by an active transport process into the bile canaliculi and then into the intestines

bilirubin- Once in the intestine, about half of the “conjugated”

bilirubin is converted by bacterial action into the substance urobilinogen, which is highly soluble.

- Some of the urobilinogen is reabsorbed through the intestinal mucosa back into the blood.

- Most of this is re-excreted by the liver back into the gut, but about 5 per cent is excreted by the kidneys into the urine.

- After exposure to air in the urine, the urobilinogen becomes oxidized to urobilin; alternatively, in the feces, it becomes altered and oxidized to form stercobilin.

Jaundice- Jaundice refers to a yellowish tint to the body

tissues, including a yellowness of the skin as well as the deep tissues.

- The usual cause of jaundice is large quantities of bilirubin in the extracellular fluids, either free bilirubin or conjugated bilirubin.

- The normal plasma concentration of bilirubin, which is almost entirely the free form, averages 0.5 mg/dl of plasma – yellow skin above 1.5 mg/dl.

Jaundice- (1) increased destruction of RBCs, with rapid release of bilirubin

into the blood - hemolytic jaundice, pre hepatic jaundice- (2) obstruction of the bile ducts or damage to the liver cells so

that even the usual amounts of bilirubin cannot be excreted into the GIT - obstructive jaundice, hepatic or post hepatic jaundice

- In hemolytic jaundice, the excretory function of the liver is not impaired, but RBCs are hemolyzed so rapidly that the hepatic cells simply cannot excrete the bilirubin as quickly as it is formed.

- Therefore, the plasma concentration of free bilirubin rises to above normal levels. Likewise, the rate of formation of urobilinogen in the intestine is greatly increased, and much of this is absorbed into the blood and later excreted in the urine.

Jaundice- In obstructive jaundice, caused either by - obstruction of the bile ducts (which most often occurs when a

gallstone or cancer blocks the common bile duct)- by damage to the hepatic cells (which occurs in hepatitis),

- the rate of bilirubin formation is normal, but the bilirubin formed cannot pass from the blood into the intestines.

- The free bilirubin still enters the liver cells and becomes conjugated in the usual way.

- This conjugated bilirubin is then returned to the blood, probably by rupture of the congested bile canaliculi and direct emptying of the bile into the lymph leaving the liver.

Jaundice- A test called the van den Bergh reaction can be used to

differentiate jaundice

- In hemolytic jaundice, almost all the bilirubin is in the “free” form; indirect +ve

- In obstructive jaundice, it is mainly in the “conjugated” form; direct +ve

- In obstructive jaundice, no bilirubin can reach the intestines to be converted into urobilinogen by bacteria. Therefore, no urobilinogen is reabsorbed into the blood, and none can be excreted by the kidneys into the urine.

- tests for urobilinogen in the urine are completely negative.

Jaundice- In obstructive jaundice, the stools become clay colored

owing to a lack of stercobilin and other bile pigments.

- kidneys can excrete small quantities of the highly soluble conjugated bilirubin but not the albumin-bound free bilirubin.

- Therefore, in severe obstructive jaundice, significant quantities of conjugated bilirubin appear in the urine.

- This can be demonstrated simply by shaking the urine and observing the foam, which turns an intense yellow.

Function testPre-hepatic

JaundiceHepatic Jaundice

Post-hepatic Jaundice

Conjugated bilirubin

Normal Increased Increased

Unconjugated bilirubin

Increased Increased Normal

Van den Bergh test indirect +ve Biphasic direct +ve

Urine Urobilinogen Increased Decreased Decreased / Absent

Fecal stercobilinogen

Increased Decreased Absent

Stool Color Dark brown Pale Clay

Alkaline phosphatase levels

Normal (excreted in bile)

Increased (less/not excreted in bile)

Bilirubin in Urine Not Present Present (filtered, not bound to albumin)

PS Hemolysis, anemia N N

Albumin N Decreased N

Physiological Jaundice of newborn

- Neonatal jaundice - Appears within 2-5 days of birth & disappears in 2 weeks

- Excessive destruction of RBCs in 1st few days- Hepatic immaturity

- Prevention – hepatic microsomal enzyme inducer (phenobarbital) to mother or newborn – glucuronyl transferase

- Rx – phototherapy – white light → photo isomerization of bilirubin to water soluble lumirubin – excreted in bile without requiring conjugation

Anemias- Anemia means deficiency of Hb in the blood, which can be

caused by either too few RBCs or too little Hb in the cells

- Blood Loss Anemia- After rapid hemorrhage, the body replaces the fluid portion of

the plasma in 1 to 3 days, but this leaves a low concentration of RBCs.

- If a second hemorrhage does not occur, the RBC concentration usually returns to normal within 3 to 6 weeks.

- In chronic blood loss, a person frequently cannot absorb enough iron from the intestines to form Hb as rapidly as it is lost.

- Red cells are then produced that are much smaller than normal and have too little hemoglobin inside them, giving rise to microcytic hypochromic anemia

Aplastic Anemia- Bone marrow aplasia means lack of functioning bone

marrow.

- a person exposed to gamma ray radiation from a nuclear bomb blast can sustain complete destruction of bone marrow, followed in a few weeks by lethal anemia.

- excessive x-ray treatment, certain industrial chemicals, and even drugs to which the person might be sensitive can cause the same effect.

Megaloblastic Anemia- Deficiency of vitamin B12, folic acid, and intrinsic factor - slow

reproduction of erythroblasts in the bone marrow.

- As a result, the red cells grow too large, with odd shapes, and are called megaloblasts.

- atrophy of the stomach mucosa, as occurs in pernicious anemia, or loss of the entire stomach after surgical total gastrectomy

- Intestinal sprue, in which folic acid, vitamin B12, and other vitamin B compounds are poorly absorbed

- the erythroblasts cannot proliferate rapidly enough to form normal numbers of RBCs, those red cells that are formed are mostly oversized, have bizarre shapes, and have fragile membranes - rupture easily

Hemolytic Anemia- Different abnormalities of the RBCs, many of which

are hereditarily acquired, make the cells fragile, so that they rupture easily as they go through the capillaries, especially through the spleen.

- Even though the number of RBCs formed may be normal, or even much greater than normal in some hemolytic diseases,

- the life span of the fragile red cell is so short that the cells are destroyed faster than they can be formed, and serious anemia results

Hemolytic Anemia- In hereditary spherocytosis, the red cells are very

small and spherical rather than being biconcave discs.

- These cells cannot withstand compression forces because they do not have the normal loose, baglike cell membrane structure of the biconcave discs.

- On passing through the splenic pulp and some other tight vascular beds, they are easily ruptured by even slight compression.

Hemolytic Anemia- In sickle cell anemia, which is present in 0.3 to 1.0

% of West African and American blacks, the cells have an abnormal type of Hb called Hb S, containing faulty beta chains

- When this Hb is exposed to low concentrations of oxygen, it precipitates into long crystals inside the RBC.

- These crystals elongate the cell and give it the appearance of a sickle rather than a biconcave disc - damages the cell membrane - highly fragile

Hemolytic Anemia

- Sickle cell patients frequently experience a vicious circle of events called a sickle cell disease “crisis,”

- in which low oxygen tension – sickling - ruptured red cells - further decrease in oxygen tension - more sickling – more red cell destruction.

- Once the process starts, it progresses rapidly, eventuating in a serious decrease RBCs within a few hours and, often, death

Hemolytic Anemia- In erythroblastosis fetalis, Rh-positive RBCs in the

fetus are attacked by antibodies from an Rh-negative mother.

- These antibodies make the Rh-positive cells fragile, leading to rapid rupture and causing the child to be born with serious anemia.

- The extremely rapid formation of new red cells to make up for the destroyed cells causes a large number of early blast forms of red cells to be released from the bone marrow into the blood.

Classification of Anemias- Anemias may be classified etiologically based on the causative

mechanism (Whitby’s):

- Deficiency: iron, megaloblastic, protein, vitamin C- Blood loss or hemorrhagic: Acute, chronic

- Hemolytic:- Hereditary; thalassemia, sickle cell, spherocytosis, G6PD

deficiency- Acquired; immunohemolytic, toxic (malaria, snake venom, drugs,

chemicals), splenomegaly, PNH

- Aplastic: bone marrow failure- Chronic diseases: TB, chronic infection, cancer, chronic Lung

diseases

Classification of Anemias- Anemias may be classified morphologically based on

the average size of the cells and the Hb concentration (Wintrobe’s):

- Macrocytic: megaloblastic

- Normochromic, normocytic: Acute post hemorrhagic, hemolytic, aplastic

- Hypochromic, microcytic: Iron deficiency, thalassemia, chronic post hemorrhagic

Effects of Anemia- The viscosity of the blood depends almost

entirely on the blood concentration of RBCs.

- In severe anemia, the blood viscosity may fall - decreases the resistance to blood flow in the peripheral blood vessels,

- so that far greater than normal quantities of blood flow through the tissues and return to the heart, thereby greatly increasing CO.

Effects of Anemia- hypoxia resulting from diminished transport of oxygen

by the blood causes the peripheral tissue blood vessels to dilate,

- allowing a further increase in the return of blood to the heart and increasing the CO to a still higher level

- increased pumping workload on the heart.

- a person with anemia begins to exercise, the heart is not capable of pumping much greater quantities of blood than it is already pumping - acute cardiac failure

Rx of anemia

Polycythemia - Secondary Polycythemia

- Whenever the tissues become hypoxic because of too little oxygen in the breathed air, such as at high altitudes,

- or because of failure of oxygen delivery to the tissues, such as in cardiac failure

- the blood-forming organs automatically produce large quantities of extra RBCs - 6 to 7 million/cumm

- physiologic polycythemia – high altitudes, newborns

Polycythemia- Polycythemia Vera (Erythremia) – pathological –

primary Polycythemia

- genetic aberration in the hemocytoblastic cells that produce the blood cells – The blast cells no longer stop producing red cells when too many cells are already present

- excess production of WBCs and platelets as well

- entire vascular system becomes intensely engorged - viscosity of the blood increases - many blood capillaries become plugged by the viscous blood

Effect of Polycythemia- blood flow through the peripheral blood vessels is

often very sluggish

- increase peripheral resistance – hypertension

- blood passes sluggishly through the skin capillaries before entering the venous plexus, a larger than normal quantity of hemoglobin is deoxygenated

- a person with polycythemia vera ordinarily has a reddish complexion with a bluish (cyanotic) shade to the skin.

Thank you…