Blood & Lymphatic

I & II

Amit Jha.
Associate Professor
TU
 FUNCTIONS OF BLOOD

• NUTRITIVE FUNCTION
• Nutrients are absorbed from intestine  carried by
blood to different parts of body.
• RESPIRATORY FUNCTION [Transport of respiratory gases]
• EXCRETORY FUNCTION
• Metabolic waste products in tissues are carried by blood
to excretory organs.
• TRANSPORT OF HORMONES AND ENZYMES
 FUNCTIONS OF BLOOD

• REGULATION OF WATER BALANCE

• REGULATION OF ACID-BASE BALANCE [Plasma proteins
& Hb act as buffers]
• REGULATION OF BODY TEMPERATURE
• DEFENSIVE FUNCTION
• Neutrophils and monocytes  Phagocytosis
• β-Lymphocytes  produce antibody.
 FUNCTIONS OF PLASMA PROTEINS

• ROLE IN COAGULATION OF BLOOD [Fibrinogen]

• ROLE IN DEFENSE MECHANISM OF BODY [Gamma globulins (Ig)]
• ROLE IN TRANSPORT MECHANISM
• Albumin transports hydrophobic substance
• α & β globulin transport metals.
• Albumin maintains Oncotic pressure & Viscosity.
• ROLE IN REGULATION OF ACID-BASE BALANCE [Albumin]
Red blood cells [Erythrocytes]

• Non-nucleated [mitochondria and Golgi apparatus also are absent]

• NORMAL VALUE: 4 and 5.5 million/cu mm
• NORMAL SHAPE: disk shaped and biconcave (dumbbell shaped).
• NORMAL SIZE
• Diameter : 7.2 μ (6.9 to 7.4 μ).
• Thickness : Periphery: 2.2 μ, Center: 1 μ
• Surface area : 120 sq μ.
• Volume : 85 to 90 cu μ.
 FUNCTIONS OF RED BLOOD CELLS

• Transport of O2 [Lungs to Tissues]

• Transport of CO2 [Tissues to Lungs]
• Buffering Action in Blood [Hb functions as good buffer]
• In Blood Group Determination [“A antigen, B antigen and Rh factor
helps in determination of blood group]
 PHYSIOLOGICAL VARIATIONS
Increase in RBC Count [Polycythemia]
• Age
• At birth high RBC count [decreases within 10 days after birth]
• Sex
• Before puberty & after menopause RBC count is similar to that in males.
• During reproductive period of females, RBC count is less than in males.
• High altitude
• Hypoxia  stimulates kidney  erythropoietin secreted  stimulate BM
 increase Erythropoiesis.
 PHYSIOLOGICAL VARIATIONS
Increase in RBC Count [Polycythemia]
• Muscular exercise
• Muscular exercise  mild hypoxia  increases sympathetic activity 
secretion of adrenaline  contraction of spleen  stores RBCs released.
• Emotional conditions
• Increases sympathetic activity  secretion of adrenaline  contraction
of spleen  stores RBCs released.
• Increased environmental temperature [Due to increased metabolism]
• After meals [need for more oxygen for metabolic activities]
 PHYSIOLOGICAL VARIATIONS
Decrease in RBC Count
• High barometric pressures
• In deep sea, when O2 tension of blood is higher, RBC count decreases.
• During sleep [Due to decreased metabolism]
• Pregnancy [Increase in ECF volume hemodilution]
 PATHOLOGICAL VARIATIONS
• Pathological Polycythemia [RBC count > 7 million/cu mm of blood].
• Polycythemia is of two types, Primary & Secondary polycythemia.

Primary Polycythemia Secondary Polycythemia

[Polycythemia Vera] • Respiratory disorders like emphysema.
• Myeloproliferative disorders • Congenital heart disease.
[malignancy of red BM]
• Chronic carbon monoxide poisoning.
• characterized by persistent increase in
RBC count [> 14 million/cu mm of • Poisoning by chemicals like phosphorus &
blood] & increase WBC count [> arsenic.
24,000/cu mm of blood]. • Repeated mild hemorrhages.
• All these conditions lead to hypoxia.
 ANEMIA
• Anemia is defined as condition of decreased RBC count, decreased Hb
concentration and decreased oxygen carrying capacity of blood.

MORPHOLOGICAL CLASSIFICATION
 ETIOLOGICAL CLASSIFICATION
Hemorrhagic Anemia
• Acute haemorrhage [Sudden loss of a large quantity of blood (accident)]
• Chronic Hemorrhage [Internal or external bleeding, over a long period of time
(peptic ulcer, purpura, hemophilia & menorrhagia)]

Hemolytic Anemia
• Extrinsic hemolytic anemia: Destruction of RBCs by external factors
[Antibodies, Chemicals & Drugs]
• Intrinsic hemolytic anemia: Destruction of defective RBC [Sickle cell anemia
& Thalassemia]
 ETIOLOGICAL CLASSIFICATION
• Nutrition Deficiency Anemia
• Iron deficiency anemia [Microcytic Hypochromic]
• Protein deficiency anemia [macrocytic and hypochromic]
• Pernicious anemia [IF deficiency]
• Megaloblastic Anemia [B12 or Follic acid deficiency]

Aplastic Anemia [normocytic and normochromic]

Cause: reduced red bone marrow (replaced by fatty tissues).
1. Repeated exposure to Xray or gamma ray radiation.
2. Presence of bacterial toxins, quinine, gold salts, benzene, radium, etc.
3. Tuberculosis.
4. Viral infections like hepatitis and HIV infections.
• Anemia of Chronic Diseases [Normocytic and normochromic]
• Cause: Disturbance in iron metabolism or resistance to erythropoietin.
• Rheumatoid arthritis.
• Chronic infections like tuberculosis
• Chronic renal failure (Decreased erythropoietin production)
• Neoplastic disorders (Hodgkin’s disease)
 SIGNS & SYMPTOMS OF ANEMIA
• SKIN AND MUCOUS MEMBRANE
• Color of skin and mucous membrane becomes pale.
• Skin looses the elasticity and becomes thin and dry.
• Thinning, loss and early grayness of hair occur.
• The nails become brittle and easily breakable.
• CARDIOVASCULAR SYSTEM
• Increase in heart rate (tachycardia), velocity of blood and cardiac output.
• Heart is dilated and cardiac murmurs are produced.
 SIGNS & SYMPTOMS OF ANEMIA
• RESPIRATION
• Increase in rate and force of respiration.
• Difficulty in breathing.
• ODC shifted to right.
• DIGESTION: Anorexia, nausea, vomiting, abdominal discomfort and
constipation are common.
• METABOLISM: Basal metabolic rate increases in severe anemia.
• KIDNEY: Renal function is disturbed & Albuminuria is common.
• REPRODUCTIVE SYSTEM: In females, the menstrual cycle is disturbed.
 VARIATIONS IN SHAPE OF RED BLOOD CELLS
• Crenation [Shrinked RBC, in hypertonic solution]
• Spherocytosis [in hypotonic solution]
• Elliptocytosis:
• Sickle cell: [in sickle cell anemia]
• Poikilocytosis [Unusual shapes due to deformed cell membrane.
 Erythropoiesis
Colony forming blastocyte
↓
CFU-E
↓
Proerythrocyte [20 μ]
↓
Early Normoblast [15 μ]
↓
Intermediate Normoblast [10 to 12 μ]
↓
Late Normoblast [8 to 10 μ]
↓
Reticulocyte
↓
RBC [7.2 μ]
 FACTORS NECESSARY FOR ERYTHROPOIESIS

General factors Maturation factors Factors necessary for

hemoglobin formation

• B12
• Follic acid • Amino acids
• Erythropoietin
• Intrinsic Factor • Iron
• Thyroxine
• Copper
• Hemopoietic growth
• Cobalt
factors
• Vitamin C,
• Vitamins [C, D, E]
• Riboflavin
• Pyridoxine
 White blood cells [Leukocytes]
• Colourless and nucleated formed elements of blood.

• Granulocytes
• Classified Depending upon the staining property of granules,
• Neutrophils [granules taking both acidic and basic stains]
• Eosinophils [granules taking acidic stain]
• Basophils [granules taking basic stain]
• Agranulocytes
• Agranulocytes have plain cytoplasm without granules.
• Monocytes & Lymphocytes.
• NEUTROPHILS [Polymorphs]
• Have fine or small granules in the cytoplasm.
• Nucleus is multilobed. [2 to 5 lobes].
• Diameter: 10 to 12 μ
EOSINOPHILS
• Have coarse (larger) granules in cytoplasm.
• Nucleus is bilobed [spectacle-shaped]
• Diameter: 10 to 14 μ.
BASOPHILS
• Have coarse granules in cytoplasm.
• Nucleus is bilobed
• Diameter of the cell is 8 to 10 μ.
• MONOCYTES
• Largest WBC [Diameter: 14 to 18 μ]
• The cytoplasm is clear without granules.
• Nucleus: round, oval and horseshoe shaped, bean or kidney shaped.
• Nucleus is placed either in the centre of the cell or pushed to one side.
• LYMPHOCYTES
• No granules in the cytoplasm.
• Nucleus: oval, bean-shaped or kidney-shaped.
• Nucleus occupies the whole of the cytoplasm.
 Types of Lymphocytes

• Depending upon the size:

• Large lymphocytes: Younger cells [diameter: 10 to 12 μ]
• Small lymphocytes: Older cells [diameter of 7 to 10 μ]

• Depending upon the function:

• T lymphocytes: [cellular immunity]
• B lymphocytes: [Humoral immunity]
 PHYSIOLOGICAL VARIATIONS
• Age:
• Infants: 20,000 per mm3 of blood
• Children: 10,000 to 15,000 per mm3 of blood
• Adults: 4,000 to 11,000 per mm3 of blood.
• Sex: Slightly more in males than in females.
• Diurnal variation:
• Minimum in early morning & maximum in afternoon.
• Increases in: Exercise, Anxiety, Pregnancy, Menstruation, Parturition
• Decreases during Sleep
 PATHOLOGICAL VARIATIONS

Leukocytosis Leukemia Leukopenia

Increase in Total WBC count Blood cancer Decrease in total WBC count
• Infections Abnormal & • Anaphylactic shock
• Allergy uncontrolled increase in • Cirrhosis of liver
• Common cold Total WBC count • Disorders of spleen
• Tuberculosis (> 1,000,000/cu mm) • Pernicious anemia
• Glandular fever • Typhoid and paratyphoid
• Viral infections
 Neutrophilia Neutropenia
• Acute infections • Bone marrow disorders
• Metabolic disorders • Tuberculosis
• Injection of foreign proteins • Typhoid
• Injection of vaccines • Vitamin deficiencies
• Poisoning by chemicals [Pb, Hg, camphor, benzene • Autoimmune diseases.
derivatives, insect venom]
• After Acute Hemorrhage.

Eosinophilia Eosinopenia
• Asthma • Cushing’s syndrome
• Allergic conditions • Bacterial infections
• Blood parasitism (malaria, filariasis) • Stress
• Intestinal parasitism • Prolonged administration of drugs [steroids, ACTH,
• Scarlet fever epinephrine]
 Basophilia Basopenia
• Smallpox • Urticaria (skin disorder)
• Chickenpox • Stress
• Polycythemia vera • Prolonged exposure to chemotherapy or radiation therapy.

Monocytosis Monocytopenia
• Tuberculosis • Prolonged use of Steroid (immunosuppressant)
• Syphilis • AIDS
• Malaria • Chronic lymphoid leukemia
• Kala-azar

Lymphocytosis Lymphocytopenia
• Diphtheria AIDS
• Infectious hepatitis Hodgkin’s disease (cancer of the lymphatic system)
• Mumps Malnutrition
• Malnutrition Radiation therapy
• Rickets Steroid administration
• Syphilis
• Thyrotoxicosis
• Tuberculosis.
 FUNCTIONS OF WHITE BLOOD CELLS
NEUTROPHILS
• Infection  Neutrophils released in large number  neutrophils move by
diapedesis towards site of Infection  Chemo-attractants increase adhesive
nature of neutrophils  neutrophils attached firmly to infected area 
neutrophil hold microorganisms  destroy via phagocytosis & Oxidative
burst mechanism.
BASOPHILS
• Basophils play an important role in healing processes, allergy or acute
hypersensitivity reactions (allergy).
 FUNCTIONS OF WHITE BLOOD CELLS
EOSINOPHILS
• Eosinophils play an important role in defence against parasites.
• Parasitic infestations  eosinophil move towards affected tissues  attack
larger parasites by cytotoxic substances present in their granules.

Capable of destroying Mechanism of Action

Eosinophil peroxidase Helminths, bacteria, tumor cells
Major basic protein (MBP) Helminths distension (ballooning) and
detachment of tegumental sheath
Eosinophil cationic protein (ECP) Helminths complete disintegration
Eosinophil-derived neurotoxin myelinated nerve fibers
Cytokines [IL-4, IL-5] invading organisms accelerate inflammatory response
 FUNCTIONS OF WHITE BLOOD CELLS
Monocytes
• Along with neutrophils, these leukocytes provide the first line of defense.
• Monocytes are precursors of the tissue macrophages.
• Matured monocytes stay in blood only for few hours.  enter tissues 
become tissue macrophages. [ Kupffer cells (liver), alveolar macrophages ]

• LYMPHOCYTES
• T lymphocytes: cellular immunity
• B lymphocytes: Humoral immunity [Antibody formation]
 Platelets [Thrombocytes]
• Small colorless, non-nucleated.
• Diameter: 2.5 μ (2 to 4 μ)
• Volume : 7.5 cu μ (7 to 8 cu μ).
• Spherical or rod-shaped and become oval or disk-shaped when inactivated.
• NORMAL COUNT: 2,00,000 to 4,00,000/cu mm of blood.
 PHYSIOLOGICAL VARIATIONS
• Age: Less in infants and reaches normal level at 3rd month after birth.
• Sex: No difference [reduced during menstruation]
• High altitude: Platelet count increases.
• After meals: platelet count increases.
 Thrombocytopenia
Thrombocytosis
[Decrease in platelet count]
[Increase in platelet count]
• Acute infections
• Acute leukemia • Allergic conditions
• Aplastic and pernicious anemia • Asphyxia
• Chickenpox • Hemorrhage
• Smallpox • Bone fractures
• Splenomegaly • Surgical operations
• Scarlet fever • Splenectomy
• Typhoid • Rheumatic fever
• Tuberculosis • Trauma
• Purpura
 PROPERTIES OF PLATELETS
ADHESIVENESS
• Injury of blood vessel  endothelium damaged  sub-endothelial collagen
exposed  platelets activated by collagen  platelets adhere to collagen with
help of von Willebrand factor & glycoprotein Ib

AGGREGATION
• Activation of more number of platelets  platelets change their shape [with
elongation filopodia]  Filopodia help platelets aggregation.

AGGLUTINATION [clumping together of platelets]

• Aggregated platelets  actions of some platelet agglutinins  Agglutination
occurs.
 FUNCTIONS OF PLATELETS
ROLE IN BLOOD CLOTTING
• Platelets forms intrinsic prothrombin activator  onset of blood clotting.

ROLE IN CLOT RETRACTION

• Platelets entrapped in blood clot  cytoplasmic contractile protein of
platelets (actin, myosin & thrombosthenin)  responsible for clot
retraction.
HEMOSTASIS
• Platelets secrete 5-HT  vasoconstriction.
• Platelet adhesion & formation of temporary plug  seal damage in blood
vessels.
 FUNCTIONS OF PLATELETS
ROLE IN REPAIR OF RUPTURED BLOOD VESSEL
• Platelet-derived growth factor (PDGF) is useful for the repair of endothelium.
ROLE IN DEFENSE MECHANISM
Platelet agglutination  platelets encircle foreign bodies and destroy them.

Hemostasis [arrest or stoppage of bleeding]

• STAGES OF HEMOSTASIS
I. Vasoconstriction
II. Platelet plug formation
III. Coagulation of blood.
 VASOCONSTRICTION [local phenomenon]
• Injured blood vessels  damaged endothelium  collagen exposed 
Platelets adhere to collagen  platelet activated  secrete serotonin 
vasoconstriction.
PLATELET PLUG FORMATION
• Platelets get adhered to collagen  platelet secrete ADP & thromboxane A2
 attract & activate more platelets  platelets aggregation  form platelet
plug closes ruptured vessel  prevents further blood loss.
COAGULATION OF BLOOD
• Fibrinogen is converted into fibrin.
• Fibrin threads get attached to temporary platelet plug  blocks ruptured
part of blood vessels  prevents further blood loss completely.
 Blood Coagulation [Clotting]
• Process in which blood loses its fluidity and becomes a jelly-like mass few
minutes after it is shed out or collected in a container.
Intrinsic Pathway
• It is initiated by factors present within blood within the blood itself

Extrinsic Pathway
• It is initiated by tissue thromboplastin, released from the injured tissues.
Intrinsic Pathway

Extrinsic Pathway

Common Pathway
 Role of Vitamin K in coagulation
Vitamin K (Cofactor] increases activity of γ- Carboxylase
↓
Responsible for γ- carboxylation of ‘Glutamate” residue of
Coagulation factor [II, VII, IX, IX, XI]
↓
↑ in -ve charge
↓
↑ binding with Ca++
↓
↑ Coagulation cascade
 Hemophilia
• A group of blood disorders in which there is defect in clotting factors.
• 70% are X-linked recessive disorder & 30% spontaneous mutation.
• The bleeding patterns of haemophilia are similar.
• Types :
Hemophilia A [Deficiency in factor VIII] (classic haemophilia)
Hemophilia B [Deficiency in factor IX] (Christmas disease)
Hemophilia C [Deficiency in factor XI]
 Clinical manifestation
• Haemarthrosis (spontaneous bleeding in muscle or joints - painful)
• Illiapsoas bleeding
• Joint Swelling
• Easy bruising
• Epistaxis
• Haematuria
• Intracranial hemorrhage
 Hemophilia A [classic hemophilia]
• Inherited [X-linked recessive]
• Cause: decreased or defective factor VIII
• Usually affects males & homozygous females.

• Hemophilic gene is carried on X chromosome.

• Fathers can’t pass hemophilia to children.
• If son inherits hemophilic gene, will have hemophilia.
• If Daughters inherit hemophilic gene, [healthy X chromosome from
father] will be a carrier (pass gene on to her children).

50
 Classification Clinical Manifestation
• Manifest in infancy [toddler stage]
Severe • Spontaneous bleeding – in muscles or joints
(<0.01U/mL) • Excessive bleeding after minor trauma, surgery, or
intramuscular childhood vaccinations.
Moderate • Manifest after 2 years of life
(0.02-0.05 U/mL) • Moderate trauma causes bleeding episodes
Mild •Diagnosed in teenagers & adults
(>0.05U/mL) • Significant trauma to induce bleeding

Symptoms
Patients often, bleed longer than normal people.
Internal or external bleeding episodes, called "bleeds“.

Bleeding into joints with associated Bruising Spontaneous bleeding

pain and swelling
GIT & urinary tract hemorrhage Nose bleeds
Blood in urine or stool Prolonged bleeding from Cuts,
Tooth extraction, Surgery
 Bleeding time
• Principle: Bleeding time is time in minutes which is taken for a standardized
skin puncture to stop bleeding. Bleeding ceases when a platelet plug seals the
breach in the vessel.

• MATERIAL REQUIRED:-
DUKE’SMETHOD • 70% alcohol.
DEFINITION:- Time in minutes, • Cotton balls.
which it takes for a standardized • Sterile lancet.
skin wound to stop bleeding.
• Filter.
• Stop watch
• TECHNIQUE:-
• Clean ear lobe , finger or heel with 70% alcohol swab.
• Hold that part between thumb & forefinger.
• Make a stab wound of 2.4mm deep in margin with help of sterile lancet.
• Start the stopwatch as soon as the stab is made.
• Using the edge of a piece of filter paper blot the blood gently touch the
paper to the drop of which forms over the wound every 30 seconds.

NORMAL VALUE: 1-3 min.

 Clotting Time
• Time taken by blood to coagulate after it has been shed.
 Capillary tube method

• Procedure:
• Prick a finger with a sterile lancet, fill 2 non heparinzed capillary tube with
blood (capillary tube should touch the bleeding point), wipe any excess
blood from the outside of the tube.
• Wait for 4 minutes, then cut the tube after each 30 seconds.
• Note the time if the fibrin thread is formed between the 2 broken capillary
tubes.
 ABO BLOOD GROUPS
• Landsteiner found
• Two antigens (agglutinogens) on surface of RBCs “A antigen & B antigen”.
• Corresponding antibodies (agglutinins) in plasma “anti-A antibody & anti-
B antibody”.
LANDSTEINER LAW
1. If a particular agglutinogen (antigen) is present in RBCs, corresponding
agglutinin (antibody) must be absent in serum.
2. If a particular agglutinogen is absent in RBCs, corresponding agglutinin
must be present in serum.
 ABO BLOOD GROUPS
ABO SYSTEM
• Based on the presence or absence of antigen A & antigen
B, blood is divided into four groups:
 DETERMINATION OF ABO GROUP

Procedure
1. One drop of antiserum A is placed on one end of a
glass slide & one drop of antiserum B on the other end.
2. One drop of RBC suspension is mixed with each
antiserum.
3. The slide is slightly rocked for 2 minutes.
4. The presence or absence of agglutination is observed.
5. Presence of agglutination is confirmed by the presence
of thick masses (clumping) of RBCs.
6. Absence of agglutination is confirmed by clear mixture
with dispersed RBCs.
Inheritance of ABO group
 Rh FACTOR
• Rh factor is an antigen present in RBC.
• Discovered by Landsteiner and Wiener in Rhesus monkey [thus so named]
• Person having D antigen are called ‘Rh positive’ & those without D antigen are
called ‘Rh negative’.
• If Rh positive blood is transfused to a Rh negative person anti-D is developed in
that person.
• On the other hand, there is no risk of complications if the Rh positive person
receives Rh negative blood.
 HEMOLYTIC DISEASE OF FETUS & NEWBORN
[ERYTHROBLASTOSIS FETALIS]
• Cause: due to Rh incompatibility, (i.e. difference between Rh blood group of
mother & baby).
• When a mother is Rh negative & fetus is Rh positive, usually first child escapes
complications of Rh incompatibility. (Rh antigen cannot pass from fetal blood
into mother’s blood through placental barrier).
• During parturition, Rh antigen from fetal blood leak into mother’s blood.
• During postpartum period, mother develops Rh antibody in her blood.
 HEMOLYTIC DISEASE OF FETUS & NEWBORN
[ERYTHROBLASTOSIS FETALIS]
• When mother conceives for second time & if fetus is Rh positive again  Rh
antibody from mother’s blood crosses placental barrier  enters fetal blood
 causes agglutination of fetal RBCs  Hemolysis.
• To compensate, there is rapid production of RBCs, not only from bone
marrow, but also from spleen and liver.
• Large & immature cells (proerythroblastic stage) are released into circulation.
[thus known as erythroblastosis fetalis]
 HEMOLYTIC DISEASE OF FETUS & NEWBORN
[ERYTHROBLASTOSIS FETALIS]
• Complications:
• Severe anemia
• Hydrops fetalis
• enlargement of liver and spleen and cardiac failure.
• In severe condition, it may lead to intrauterine death of fetus.
• Kernicterus (brain damage due to deposition of bilirubin)
 Physiological basis of Blood Transfusion
• During blood transfusion, only compatible blood must be used.
• During blood transfusion,
• Antigen of donor & antibody of recipient are considered.
• Antibody of donor & antigen of recipient are ignored mostly.
• RBC of ‘O’ group has no antigen  agglutination doesn’t occur with any blood
group  can be given to any blood group persons (‘universal donors’).
• Plasma of AB group blood has no antibody  This does not cause
agglutination of RBC from any other group of blood. People with AB group can
receive blood from any blood group persons. (‘universal recipients’).
 Precautions to be taken before transfusion of blood
• Donor must be healthy, without any diseases (like STD, viral disease)
• Only compatible blood must be transfused.
• Both matching and cross-matching must be done.
• Rh compatibility must be confirmed.

Precautions to be taken while transfusion of blood

1. Apparatus for transfusion must be sterile
2. Temperature of blood to be transfused must be same as body temperature.
3. Transfusion of blood must be slow. [sudden rapid infusion of blood into body
increases the load on heart, resulting in many complications]
 MATCHING AND CROSS-MATCHING
• For blood matching, RBC of individual (recipient) and test sera are used.
Matching = Recipient’s RBC + Test sera.
• Cross-matching is done to find out whether the recipient’s body will accept
the donor’s blood or not.
• Cross-matching is always done before blood transfusion.
• Cross-matching is done by mixing recipient’s serum & donor’s RBCs.
Cross-matching = Recipient’s serum + Donor’s RBC.
• If agglutination of RBCs from a donor occurs during cross-matching, the blood
from that person is not used for transfusion.
 HAZARDS OF BLOOD TRANSFUSION
1. Reactions due to mismatched blood transfusion – transfusion reactions

2. Reactions due to massive blood transfusion

3. Reactions due to faulty techniques during blood transfusion

4. Transmission of infections. [HIV, Hepatitis B and A, Infectious

mononucleosis, Herpes , Bacterial infections]
 HAZARDS OF BLOOD TRANSFUSION
• Reactions due to mismatched blood transfusion – transfusion reactions
• If recipient’s plasma contains agglutinins against donor’s RBCs  immune
response (IgG/IgM)  Donor RBCs agglutinated  Transfusion reactions.
Hemolysis  increase Bilirubin  Jaundice
Hemolysis 
• Release of Hb  increase viscosity of blood  increase work
load on Heart.
• Release of toxic substance  decreased BP  Circulatory
shock.

Hemolysis 
• Release of toxic substance causes Vasoconstriction.
• Release of Hb  precipitates in tubule  obstruction  Anuria.
 HAZARDS OF BLOOD TRANSFUSION
• Reactions due to massive blood transfusion (> patient’s own blood volume)
• Circulatory shock
• Hyperkalemia [increased potassium in stored blood]
• Hypocalcemia [due to massive transfusion of citrated blood]
• Hemosiderosis
• REACTIONS DUE TO FAULTY TECHNIQUES DURING BLOOD TRANSFUSION
• Thrombophlebitis (inflammation of vein  thrombus formation)
• Air embolism (entry of air  obstruction of blood vessel).
 Immunity

• It is the ability of body to resist entry of different types of foreign bodies like
bacteria, virus, toxic substances, etc.
• Immunity is of two types:
• Innate immunity.
• Acquired immunity.
Innate immunity or Natural or Non-specific immunity
• Inborn capacity of body to resist pathogens.
• It represents the first line of defence against any type of pathogens.
Component of Innate immunity
GI Tract • Digestive enzymes, gastric HCl, Lysozyme in saliva are responsible.
Respiratory System • Defensins and cathelicidins in epithelial cells of Respiratory tract.
• Neutrophils, lymphocytes, macrophages & NK-cells present in lungs.
Urinogenital system • Acidity in urine & vaginal fluid destroy bacteria.
Skin • Keratinized stratum corneum of epidermis
• β-defensins in skin & Lysozyme secreted in skin.
Phagocytic cells • Neutrophils, monocytes and macrophages.
Interferons • MoA: Inhibit multiplication of viruses, parasites and cancer cells.
Complement proteins • MoA: Accelerate the destruction of microorganisms
 Skin • Provide anatomical barrier to all body tissues.
Anatomical • Retards entry & growth of microbes.
Barrier Mucous • Entrap microbes.
membrane • Cilia propels microbes out of body
Temperature • Normal body temperature inhibits growth of
microbes.
• Fever response inhibit growth of pathogens.
Low pH • Gastric HCL lills most ingested microbes.
Physiological
Chemical mediators • Lysozyme: cleaves bacterial cell wall.
barriers
• Interferon: induces antiviral state.
• Complement: lyses microbes, facilitates phagocytosis.
Phagocytic barrier • Neutrophil, Monocyte, Tissue Macrophage internalize microbes
 kill & digest micro-organism.
Inflammatory barrier • Infection  tissue damage  Inflammatory response.
 Acquired Immunity or Specific Immunity
• It is the resistance developed in body against any specific foreign body like
bacteria, viruses, toxins, vaccines or transplanted tissues.
• Types:-
1. Cellular immunity [mediated by T Lymphocyte] [T cell immunity]
2. Humoral immunity [mediated by B Lymphocyte]
Major histocompatiblility complex (MHC)
Found on Responsible for presentation of
Class I MHC molecule Every cell in human body Tumor antigens to cytotoxic T cells
Class II MHC molecule Antigen-presenting cells Exogenous antigens (bacteria or viruses) to
helper T cells
Human Leulocyte Antigen: Genetic matter present in molecule of class II major
histocompatiblility complex (MHC).
 T-Lymphocyte
• Thymus secretes a hormone called Thymosin:
• Accelerates proliferation & activation of lymphocytes in thymus.
• Increases activity of lymphocytes in lymphoid tissues.
• During processing (in thymus), T lymphocytes are transformed into:
• T-Helper cells [CD4 cells]
• T-Cytotoxic [CD8 cells]
• T-Suppressor cells.
• T-Memory cells.
• After transformation, T lymphocytes are stored in lymphoid tissues of lymph
nodes, spleen, BM & GI tract.
 B-Lymphocyte
• 1st discovered in bursa of fabricius in birds, [thus so named].
• Bursa is absent in mammals, processing of B lymphocytes takes place in liver (IUL)
& bone marrow (after birth).
• B lymphocytes  processing  transformed into Plasma cells & Memory cells.
• After transformation, B lymphocytes are stored in lymphoid tissues of lymph
nodes, spleen, bone marrow & GI tract.
 DEVELOPMENT OF CELL-MEDIATED IMMUNITY
• Role of Antigen-presenting Cells (Macrophages, Dendritic cells, B
lymphocytes)
• Foreign organisms engulfed by macrophages or trapped by dendritic cells
 Antigen is digested into small peptide  peptide move towards surface
of antigen-presenting cells  bind HLA present their class II MHC
molecules together with antigen-bound HLA to helper T cells.
• Sequence of Events during Activation of Helper T cells
• Helper T cell recognizes antigen via T cell receptor Initiates interaction
between helper T cell receptor & antigen  activates helper T cells.
• Simultaneously, macrophages release IL-1  facilitates activation &
proliferation of helper T cells  proliferated cells enter circulation for
further actions.
 ROLE OF HELPER T CELLS
• Helper T cells enter circulation activate all other T cells & B cells.
Concerned with Secrete
TH1 cells Cellular immunity • IL-2 [activates other T cells]
• Gamma interferon [stimulates phagocytic
activity of cytotoxic cells, macrophages & NK
cells
TH2 cells humoral immunity • IL-4 & IL-5 [concerned with activation of B
cells, proliferation of plasma cells,
production of antibodies by plasma cell
 ROLE OF CYTOTOXIC T CELLS
• Helper T cells activate Cytotoxic T cells  circulate through blood, lymph &
lymphatic tissues directly attack invading organisms.
• Cytotoxic T cells can also destroy cancer cells, transplanted cells, body’s own
tissues affected by viruses.
• Mechanism of Action of Cytotoxic T Cells
• Receptors on cytotoxic T cells tightly bind antigens or organisms.
• Cytotoxic T cells enlarge & release cytotoxic substances  destroy
invading organisms.
 ROLE OF SUPPRESSOR T CELLS
• Suppressor T cells suppress activities of killer T cells & helper T cells & play an
important role in prevention of destroying body’s own tissues along with
invaded organisms.

ROLE OF MEMORY T CELLS

• Some of the activated T cells remain in lymphoid tissue [memory T cells].
• In later periods, the memory cells migrate to various lymphoid tissues
throughout the body.
• When body is exposed to same organism  memory cells identify organism
 immediately activate other T cells  Invading organism destroyed very
quickly with powerful response.
 DEVELOPMENT OF HUMORAL IMMUNITY
• Humoral immunity is mediated by antibodies (γ- globulins) secreted by B
lymphocytes into the blood & lymph.
• Antibodies fight against invading organisms.
• Presentation of Antigen
• Antigen-presenting cells present the antigenic products bound with HLA to
B cells.
• Sequence of Events during Activation of B Cells
• B cell recognizes antigen via B cell receptor  initiates a complex
interaction between B cell receptor & antigen  activates B cells.
• Simultaneously, macrophages release IL-1  facilitates activation &
proliferation of B cells  carry out further actions.
 ROLE OF PLASMA CELLS
• Plasma cells destroy foreign organisms by producing antibodies
(immunoglobulins).
• Each plasma cell produces about 2000 molecules of antibodies per second
• Antibodies are produced until end of lifespan of each plasma cell [several days
to several weeks].
• Antibodies are released into lymph & then transported into circulation.

ROLE OF MEMORY B CELLS

• Memory B cells occupy lymphoid tissues throughout body.
• when exposed to same organism for second time Memory cells become
active  produce more quantity of more potent antibodies at a faster rate
[basic principle of vaccination]
 IMMUNE DEFICIENCY DISEASES
• Group of diseases in which some components of immune system is missing
or defective.
• Organisms of even low virulence produce severe disease.
• Two types: Congenital & Acquired
1. Congenital immune deficiency diseases
• Occur due to defects in B cell or T cell or both.
I. DiGeorge syndrome (due to absence of thymus)
II. Severe combined immune deficiency (due to absence of
lymphoid tissue).
2. Acquired immune deficiency diseases. [Eg: AIDS]
 AUTOIMMUNE DISEASES
• It is the condition in which immune system mistakenly attacks body’s own
cells and tissues.
• Normally, body has tolerance against self antigen (autoantigens).
• In some occasions, tolerance fails  activation of T lymphocytes or B
lymphocytes  Cytotoxic T cells or autoantibodies attack body’s normal cells
(self antigen or autoantigen).
• Autoimmune diseases are of two types:
• Organ specific diseases which affect only one organ
• Organ nonspecific [affect many organs]
• Common autoimmune diseases are:
• Insulin-dependent diabetes mellitus [Autoimmune destruction of
beta cells of Pancreas]
• Myasthenia gravis [Autoantibodies against Nicotinic receptor]
• Hashimoto thyroiditis [[Autoantibodies against Thyroid tissue]
• Graves disease [Autoantibodies against Thyroid receptor]
• Rheumatoid arthritis [Due to formation of RA factor]
 Allergy & Immunological Hypersensitivity reactions
• It is defined as abnormal immune response (Innate or Acquired) to a chemical
or physical agent (allergen).
• During 1st exposure to an allergen, immune response does not produce any
reaction in body.
• Subsequent exposure to allergen causes variety of inflammatory responses.
(allergic reactions or immunological hypersensitivity reactions) mediated
mostly by antibodies (In some conditions by T cells)
• Common symptoms include sneezing, itching & skin rashes.
• Common allergic conditions are Food allergy, Allergic rhinitis, Bronchial
asthma, Urticaria.
• ALLERGENS are substance that produces the manifestations of allergy is
called an allergen.
• Allergens are introduced by Contact, Inhalation, Ingestion, Injection.

Common Allergens Example

Food substances Wheat, egg, milk and chocolate
Inhalants Pollen grains, fungi, dust, smoke, perfumes, disagreeable odor
Contactants Chemical substances, metals, animals, plants
Infectious agents Parasites, bacteria, viruses, fungi
Drugs Aspirin and antibiotics
Physical agents Cold, heat, light, pressure & radiation
• Hypersensitive reactions are classified into five types:
• Type I reactions [Anaphylactic]
• Type II reactions [Cytotoxic]
• Type III reactions [Antibody-mediated]
• Type IV reactions [Cell-mediated]
• Type V reactions [Stimulatory/blocking]
Type I [Anaphylactic Reactions or Immediate hypersensitive reaction]

• Exaggerated reactions of body to an antigen or other agents to which body is

sensitized already.
• Body exposed to an allergen  IgE produced  IgE bind surface receptors of
mast cells & basophils.
• Subsequent exposure to same allergen  Allergen IgE reaction occurs 
leads to degranulation of mast cells and basophils  release of some
chemical mediators (Histamine)  Chemical mediators produce
hypersensitivity reactions.
• Most serious reactions are fall in BP (due to vasodilatation), obstruction of air
passage & difficulty in breathing (due to bronchoconstriction) and shock.
 Type II or Cytotoxic Reactions
• Involve mainly IgG  IgG bind antigens on the surface of blood cells 
affected cells are destroyed.
• Example: Hemolytic diseases of newborn, autoimmune hemolytic anemia.

Type III or Antibody-mediated Reactions

• Excess amounts of antibodies like IgG or IgM are produced.
• Antigen-antibody complexes are precipitated & deposited in localized areas
like joints (arthritis), heart (myocarditis) & glomeruli (glomerulonephritis).
 Type IV or Cell-mediated Reactions
[delayed or slow type of hypersensitivity]

• Mediated by T lymphocytes
• It is also seen in
• Allergic reactions due to bacteria, viruses and fungi
• Contact dermatitis (chemical allergens)
• Rejection of transplanted tissues.
• Example: delayed reaction after intradermal injection of tuberculin (Mantoux
test).
 Type V or Stimulatory/Blocking Reactions

• It is seen in autoimmune diseases:

• Graves’ disease (stimulatory reactions) and
• Thyroid-stimulating antibodies binds TSH receptor  stimulate thyroid 
increase synthesis of Thyroid hormones
• Myasthenia gravis (blocking reactions).
• Due to development of Autoantibodies (IgG) against Nicotinic receptor.
Reticuloendothelial system [Tissue macrophage system]
• System of primitive phagocytic cells.
• Play an important role in defence mechanism of body.
• RES cells are found in:
• Endothelial lining of vascular & lymph channels.
• Connective tissue
• Organs [Spleen, liver, lungs, lymph nodes, BM etc.
• Classification
• Fixed RE cells or tissue macrophages.
• Wandering RE cells.
FIXED RETICULOENDOTHELIAL CELLS [Located in tissues]

Connective Tissue RE cells in connective tissues & serous membranes

like pleura, omentum, mesentery
Endothelium of Blood Sinusoid In BM, liver, spleen, lymph nodes, adrenal glands,
pituitary glands
Reticulum Reticulum of spleen, lymph node & BM
CNS Meningocytes of meninges and microglia.
Lungs Alveolar Macrophage
Subcutaneous Tissue Fixed RE cells are present in subcutaneous tissue also
 WANDERING RE CELLS [Free Histiocytes]
• Free Histiocytes of Blood
• Neutrophils
• Monocytes  Macrophages  migrate to site of injury or infection.
• Free Histiocytes of Solid Tissue
• During emergency, fixed histiocytes from connective tissue & other organs
become wandering cells and enter the circulation.
 FUNCTIONS OF RETICULOENDOTHELIAL SYSTEM

• Phagocytic Function
• Macrophages [large phagocytic cells invade foreign body]
• Lysosomes of macrophages [lysosomal enzymes digest foreign bodies]
• Secretion of oxidants (Superoxide (O2–), H2O2, OH–  kills bacteria [not
digested by lysosomal enzymes].
• Secretion of Interleukins
• IL-1: Maturation & proliferation of specific B & T lymphocytes.
• IL-6: Growth of B lymphocytes & production of antibodies.
• IL-12: Influences T helper cells.
 FUNCTIONS OF RETICULOENDOTHELIAL SYSTEM
• Secretion of Tumor Necrosis Factors
• TNF-α: Causes necrosis of tumor & activates immune responses in body.
• TNF-β: Causes necrosis of tumor & Stimulates immune system.
• Secretion of
• Transforming Growth Factor [prevent rejection of transplanted organs]
• Colony-stimulation Factor [accelerates growth of granulocytes, monocytes
& macrophages]
• Platelet-derived Growth Factor [Accelerates repair of damaged blood vessel
& wound healing]
• Destruction of Senile RBC & of Hb.
 STRUCTURE OF SPLEEN
• Largest lymphoid organ.
• Covered by an outer serous coat & an inner fibromuscular capsule.
• The parenchyma of spleen is divided into red and white pulp.
• RED PULP [consists of venous sinus & cords of structures like blood
cells, macrophages and mesenchymal cells.
• WHITE PULP [Structure similar to that of lymphoid tissue.
 FUNCTIONS OF SPLEEN
• FORMATION OF BLOOD CELLS
• Hepatic stage, spleen produces blood cells along with liver.
• Myeloid stage, it produces blood cells along with liver & BM.
• DESTRUCTION OF BLOOD CELLS [Older RBCs, lymphocytes and thrombocytes]
• BLOOD RESERVOIR FUNCTION
• ROLE IN DEFENSE OF BODY
• Macrophages in splenic pulp destroy microorganisms & other foreign
bodies by phagocytosis.
• Spleen contains 15% of B lymphocytes & forms site of antibody
production.
 THYMUS
• Thymus is situated in front of trachea, below thyroid gland.
• Small in newborn infants, gradually enlarges till puberty & then decreases in
size.

• Thymus has lymphoid function and endocrine function.

• Processing the T Lymphocytes: Lymphocytes produced in BM are processed in
thymus into T lymphocytes. [between 3 months before birth and 3 months
after birth]
• Endocrine Function of Thymus
• Thymosin: accelerates lymphopoiesis and proliferation of T lymphocytes.
• Thymin: suppresses neuromuscular activity by inhibiting acetylcholine
release.
• LYMPHATIC SYSTEM: closed system of lymph channels or lymph vessels,
through which lymph flows.
• One-way system, allows lymph flow from tissue spaces toward blood.

DRAINAGE OF LYMPHATIC SYSTEM

• Larger lymph vessels form:
• Right lymphatic duct [opens into right subclavian vein]
• Thoracic duct [opens into left subclavian vein]
• Drains lymph from > 2/3rd of the tissue spaces.
• Lymphatic system arises from tissue spaces as lymph capillaries.
• Lymph capillaries
• Start as enlarged capillary bulbs having valves [allow one way flow
of lymph].
• Contraction of muscle fibres around capillary bulbs push lymph
through vessels.
• Capillaries unite  form large lymphatic vessels  become larger &
larger [due to joining of many tributaries along their course].
 SITUATION OF LYMPH VESSELS
• Deeper layers of skin
• Subcutaneous tissues
Lymph vessels are absent in :
• Diaphragm
1. Superficial layers of skin
• Wall of abdominal cavity
2. Central nervous system
• Omentum
3. Cornea
• Linings of respiratory tract (except alveoli),
4. Bones
digestive tract, urinary tract, genital tract
5. Alveoli of lungs.
• Liver
• Heart.
 LYMPH NODES [Lymph glands or lymphatic nodes]
• Small glandular structures located in the course of lymph vessels.
• STRUCTUTRE OF LYMPH NODES
• Masses of lymphatic tissue, covered by a dense connective
tissue capsule.
• Structures are arranged in three layers:
• Cortex
• Paracortex
• Medulla
• Cortex
• Consists of primary and secondary lymphoid follicles.
• Primary follicle develops first  Antigens reach lymph nodes
 primary follicle proliferate  forms secondary follicle.
• Cortex also contains some B lymphocytes & Macrophages.
• Paracortex (between cortex & medulla) [contains T lymphocytes]
• Medulla
• Medulla contains B & T lymphocytes, macrophages.
• Blood vessels of lymph node pass through medulla.
• Distribution of Lymph Nodes
• Along the course of lymphatic vessels in elbow, axilla, knee & groin.
• Certain points in abdomen, thorax & neck.
• FUNCTIONS OF LYMPH NODES
• Filtration of lymph.
• Defence barriers: Bacteria & other toxic substances are destroyed
by macrophages of lymph nodes.
COMPOSITION OF LYMPH
 FORMATION OF LYMPH
• When blood passes via blood capillaries 1/10th of fluid passes into lymph
capillaries (have more permeability than blood capillaries).
• Composition of lymph in lymph capillaries is almost similar to IF.
• Proteins (large size) can’t enter lymph capillaries, thus proteins enters via
lymph vessels.
• Addition of Proteins & Fats
• Tissue fluid in liver GIT contains more protein & lipid.
• Thus, large quantities of proteins & lipids enter lymph vessels of liver & GIT.
 FUNCTIONS OF LYMPH
• Redistribution of Protein [Tissue spaces  blood]
• Redistribution of fluid in the body.
• Removal of Bacteria, toxins from tissues.
• Responsible for maintenance of structural & functional integrity of tissue.
• Lymph flow serves as an important route for intestinal fat absorption.
• It plays an important role in immunity by transport of lymphocytes.