Vascular Connective Tissue

Body Fluids

1) Blood 2)Lymph

Blood • Red colored fluid connective tissue

• Contains - Plasma and Blood cells

• Specific gravity : 1.04- 1.07

• Ph: 7.3 – 7.5

• Volume :

• Males – 5 -6 ltr

• Females – 4 -5 ltr

• 7 – 8% of total body weight

• Viscosity: 4.2 – 5.2 times

more thicker than water.

Composition of Blood

• Liquid part - Plasma – 55%

• Solid part – Blood cells – 45%

Blood Plasma

• Plasma is yellow transparent fluid part of blood.

• 55% of whole blood.

• Composition:

1) Water – 90 – 92%

2) Inorganic salts – 0.9%

- Na+, K+, Mg+, Ca+, HCO3-, Cl-

3) Organic substances – 7 – 8%

•Includes plasma proteins – Albumin, globulin, prothrombin and fibrinogen• Glucose, amino acids, lipids •Clotting factors and anticoagulants

Composition of plasma

Prothrombi

n

Ammonia

Anticoagulants – Heparin, Hirudin

- Coumarin/ Dicumarol

Plasma Proteins

1.Albumin

2.Globulin

3.Fibrinogen

4.Prothrombin

Plasma Proteins

• Types• Albumin: Synthesized by liver

- 4- 7% of total plasma proteins

- Maximum among plasma proteins

• Function:

- Maintains colloid osmotic pressure

- Helps in tissue filtration

- Helps in taking back water from tissues

- Maintains blood volume and pressure

Plasma Proteins

• Globulin : - Synthesized by Plasma cells (B-lymphocytes)

- 1.3 – 2.5% of total plasma proteins

Types -

Transport of

various Proteins

& Hormones

Transport of

Lipids, Vitamins

& iron

Immunoglobulin

(Ig A, Ig M, Ig D,

Ig E, Ig G) fights

against pathogens

Plasma Proteins

• Fibrinogen - Synthesized by Liver

- It is a clotting factor

- Involved in clot formation

• Prothrombin - Synthesized by Liver

- It is a clotting factor

- Involved in clot formation

Blood Cells/ Formed elements

• Cells forms 45% of total blood

• RBC – Red Blood Cells - 4.5 – 6 million / mm3 of blood

• WBC – White Blood Cells - 5,000 - 11,000 cells/mm3 of blood

• Platelets – Thrombocytes – 2 - 5 lakh cells/mm3 of blood

Red Bone marrow

12

Is the site of production of all blood cells

13

ProerythroblastPPSC

Early Intermediate Late

Reticulocyte RBCNormoblast

Erythropoiesis

• Process of RBC formation

• Haemopoiesis , Haematopoiesis

• Sites of RBC production

• Fetus : Liver , spleen , Bone marrow

• After Birth : only bone marrow

• 5 yrs – 25 yrs – Bone marrow of long bones

• Later - from red bone marrow of

flar bones - Skull, Vertebrae, Ribs, Sternum, Pelvis

RBC / Erythrocytes

• Discovered by Leeuvenhoek in 1674.

• No nucleus , Biconcave / Disc shaped

• Provides more surface area for diffusion of

O2 & CO2

• Cell membrane of RBC is Donnan’s membrane

RBC / Erythrocytes

• Donnan’s membrane is highly

permeable to HCO3- ions and

impermeable to Na+ & K+ ions.

• Mitochondria & golgi complex are

absent in RBC.

• Thus anaerobic respiration occurs

in RBC.

• Enzymes of glycolysis – absent

Enzymes of Kreb’s cycle - present

Doesn't utilize O2 that it carries

• RBC cytoplasm has numerous red colored pigment ----

Haemoglobin

• Oxygen & carbondioxide binds to Hb

• RBC cell size :

• Diameter – 6.5 – 8 µ

• Thickness – 1.2 µ

• Molecular weight - 67,200 Dalton

• Normal RBC count

• Males : 5.5 – 6 million / mm3 of blood

• Females : 4.5 – 5 million / mm3 of blood

• Composition : 64% water, 20% Hb, 7% lipids

• Erythrocytes of different

size & shape are called

Poikilocytes.

Shape of RBC

• Normal – Biconcave shape

• Sickle cell anemia – Sickle shape

• Iron deficiency anemia – RBC small

• Pernicious anemia/ Megaloblastic anemia –

RBC big

Lack of Hb – Microcytic cells

Immaturity of RBC – Macrocytic / megaloblastic cells

Haemoglobin

• Red colored Protein pigment inside

RBC .

• Heamoglobin

Haem Globin

Iron Protein

Major (normal) Types of Hemoglobin

Type Composition

HbAα2β2

HbA2 α2δ2

HbF α2γ2

• HbA – Adult Hemoglobin • HbA2 – Variant of Adult Hemoglobin • HbF - Fetal Hemoglobin

carbonic anhydrase

Hemoglobin – Normal Value

• Adult Males : 15 gm/dl

• Adult Females: 13 gm/dl

• Life span of RBC - 120 Days

- stored blood – 60 days

- RBC in fetus – 180 days

• after the life span

RBC are destroyed

in spleen (Grave yard of RBC )

By Macrophages

A variety of WBC

Fate of Hemoglobin Heamoglobin

Heam Globin

Amino Acids

Reutilized in Bone marrow

Iron Porphyrin

ring

Reused

in bone

marrow

Biliveridin

Yellow

pigment

Bilirubin

• Haemoglobin count

- Heamometer

• RBC count

- Haemocytometer

Normocytic

Normochromic

Anemia

Microcytic

Hypochromic

Anemia

Macrocytic

Normochromic

Anemia

Ex: Acute blood loss

Accidents, surgery

Chronic blood loss Iron Deficiency Worm infestationExcess menstrual bleeding

Vitamin B12 deficiency Folic Acid deficiency

Anemia - Decrease in RBC count ( less than the normal range )

microcytes or small RBC’s

macrocytes or large RBC’s

Functions of RBC

• Provides more surface area for diffusion of

O2 & CO2

• Antigens present on its membrane determines

blood group

Erythrocyte Sedimentation Rate

( ESR)

• Defn of E S R :

The rate at which the erythrocytes sediment to

bottom when blood mixed with anticoagulant is

held in a vertical tube.

• Reason for sedimentation

- Erythrocytes are heavier than plasma

- Piling of RBC

( Rouleaux Formation)

Rouleax Formation

• In circulation

• Negative charges due to sialic acid on RBC membrane .

• Repels the neighboring cells

Rouleax Formation

• Blood in the pipette is constant

• Fibrinogen in plasma neutralizes the negative charges.

RBC surface becomes sticky

adheres to one another

forming a pile of RBC’s

• Normal values :

• Males – 0 -10mm/hr

• Females – 0 – 20 mm/hr

• Significance of ESR

• To diagnose various diseases.

• High – infections, arthritis, TB,

Anemia

• Low - Polycythemia ,

sickle cell anemia

Due to less RBC count

Ghost Cells

• RBC post haemolysis

• RBC’s loose their inner contents and have only

cell membrane

• Empty RBC covers are called Ghost cells

Difference in RBC size

• Amphibians have Largest RBC

• RBC of Proteus & Amphiuma

is largest in animal kingdom.

• Mammalian RBC are smallest among vertebrates

• Smallest in Musk deer – 1.5 microns

• Largest in elephant – 9.4 microns

WBC / Leucocytes

• Colorless, nucleated cells

• Larger than RBC

• Count : 5,000 - 11,000 cells/mm3 of blood

WBC

Granulocytes Agranulocytes

•Neutrophils

• Eosinophils

• Basophils

• Lymphocytes

• Monocytes

Neutrophil Eosinophil Basophil Lymphocyte Monocyte

60- 65 % 2 -3 % 0-1% 20-25 % 2-10 %

Multilobed

nucleus

Bilobed

Nucleus

Tri lobed Round nucleus Horse – shoe

shaped

Site of production

bone marrow

bone marrow bone marrow

bone marrow,

lymph nodes,

Thymus gland,

spleen, payers

patches

bone marrow

blood – 4-8 hrs

Tissue –4-5days

blood – 4-8 hrs

Tissue –4-5days

blood – 4-8 hrs

Tissue –4-5days

blood – 4-8 hrs

Tissue –months

blood – 4-8 hrs

Tissue –

120days

MacrophagesMast cells

Origin : Bone

marrow Origin : Bone

marrow

Development :

- Liver

-Bone marrow

Development :

-Thymus gland

Produce

antibodies

Do not produce

antibodies

Defense against

bacteria/virus

Defense against

fungus, cancer &

transplant cells

2 types of

Lymphocytes

Neutrophil Eosinophil Basophil Lymphocyte Monocyte

60- 65 % 2 -3 % 0-1% 20-25 % 2-10 %

Multilobed

nucleus

Bilobed

Nucleus

Tri lobed Round nucleus Horse – shoe

shaped

FunctionAgainst

Pathogens

Against allergens

Release heparin, Histamine

Immunity Against

Pathogens

Bacterial

infection

Allergy chicken pox viral infection Tuberculosis

Macrophage

s

Mast cells

Phagocytosis Phagocytosis

Origin : Bone

marrow Origin : Bone

marrow

Development :

- Liver

-Bone marrow

Development :

-Thymus gland

Produce

antibodies

Do not produce

antibodies

Defense against

bacteria/virus

Defense against

fungus, cancer &

transplant cells

2 types of

Lymphocytes

Phagocytosis

The process of engulfment of microrganisms by

neutrophils and monocyte cells

Variations of WBC

• Leucocytosis – Increased WBC count

- more than 11,000 cells/mm3

• Leucopenia

– Reduced WBC count

- less than 3,500 cells/mm3

• Leukemia

- Abnormal increase in WBC

- more than 100,000cells/mm3

Platelets / Thrombocytes

• Named by Bizzozero

• Count : 2 – 5 lakhs /mm3 of blood

• Size : 2 – 4 micron

• Shape : round , oval , biconcave ( Anucleated)

• Cytoplasm contains – Thrombosthenin (contractile protein)

& basophilic granules.

Platelets

• Production : Megakaryocytes of bone marrow

• Cytoplasm of Megakaryocytes pinches off to form

platelets.

• Life span: 7 – 10 days

• Thrombocytopenia – Reduced platelet count

• Critical Platelet count - 40,000 cells/mm3

• Below this leads to spontaneous bleeding and red

spots on the skin called Purpura

Platelet Function

• Helps in Haemostasis /blood clotting

• By forming platelet plug

fully activated

Following injury to a blood vessel – platelets attach to injured site get activated ----- There is a

change in its shape – spicules develop around platelets -----

surface become sticky ---- attract thousands of platelets to

site ---- platelet plug – temporarily stops bleeding

Platelet activation

Platelet Plug

1. Presence of specific antigen

on the surface of RBC.

2. It depends on what you have

inherited from your parents .

Blood Groups

dependent on

• Antigen/Agglutinogen

- On RBC membrane

• Antibody/ Agglutinin

- Present in plasma

• Agglutination

- reaction between antigen and antibody

Blood Group Classification

Major Blood Groups

Minor Blood Groups

• ABO system

• Rh system

• MNS system

• Kell system

•Lewis System

• Duffy system

• Kidd system

KARL LANDSTEINER

Discovered ABO

blood groups in

1900

Land-Steiner’s law of blood grouping

Can receive

blood fromA , O B, O A, B, AB, O O only

Can donate

blood to A , AB B, AB AB only A, B, AB, O

2 types - BLOOD GROUPING SYSTEM

21

Rh antigen

First identified in RBC’S of rhesus monkeys

Land-Steiner & Wiener in 1940

by

Rh Blood Group system

In India

Rh positive ---- 97%

Rh negative ----- 3%

Globally

Rh positive ---- 80%

Rh negative ----- 20%

Universal Donor is O-veUniversal Recipient is AB+ve

Rh ANTIBODIES

Ig G immunoglobulins

do not occur naturally

produced when Rh – ve person infused Rh+ve blood

OR

Rh-ve mother carries a Rh+ve fetus

Erythroblastosis FoetalisRh incompatibility

One parent + ve One parent - ve

Progeny will

be + ve

Rh + ve is a

dominant gene

• Rh negative Mother carries Rh positive fetus

Small amount of fetal blood enters into

maternal circulation at the time of delivery

Erythroblastosis fetalis

Mothers blood develops antibodies against

Rh + antigens of the fetus and that remains in

maternal circulation for years

In second pregnancy -- If fetus is again Rh+

Erythroblastosis fetalis

• Rh antibodies can cross the placenta & reach fetus

• These antibodies bring about the agglutination of fetal

RBC cause hemolysis.

• This results in hemolytic disease of newborn

( Erythroblastosis Fetalis).

Mother’s immune system is not activated

Rhogam – Rh antibody injection is given to mother within 72 hours of delivery, to destroy the fetal RBC that has entered her blood stream so that Rh antibody formation is prevented in the mother .

Hydrops Fetalis

• Edematous appearance with enlarged spleen and

liver .

• Features of Erythroblastosis Fetalis

Severe anemia with huge immature RBC , Jaundice , enlarged spleen.

Bombay Blood Group• Also known as hh /Oh group

• A rare blood group

• Without H antigen on RBC membrane

• But have anti – H in the plasma

• First discovered in 1952

• By Dr. Bhende etal

• Can donate blood to any group but can receive only from Bombay group.

Blood clotting

• When bleeding occurs from an injured blood vessel.

• In few minutes blood gets converted to semisolid jelly like

mass .

•

Process is called Clotting

Clotting starts after platelet plug formation

Clotting factors

• Group of plasma proteins

• Site of production : Liver

• Co Factor : Vitamin K

• 12 clotting factors in blood .

• But maintained in inactive state

Vitamin Kdependent

Calcium is cofactor in each step of blood clotting

Laki Lorand Factor

Hagman Factor

or Proaccelerin

Accelerin but rejected

Platelet Plug & Clot

Clot is a meshwork of fibrin threads

Mechanism of coagulation

Prothrombin activator

complex

Enzyme cascade theory - by Macfarlane &

coworkers

Thrombokinase

Trauma stimulates platelets to release thromboplastinsthat activates coagulatiion

mechanism

FACTOR XIII OR FIBRIN STABILIZING FACTOR

Fibrin stabilizing factor

83

Blood Clot

• Blood clot is meshwork of fibrin threads entrapping blood cells, platelets and plasma.

fibrin threads in clot

Clotting

Mechanism of coagulation (source ALLEN)

• There are Three steps in coagulation

1)Releasing of Thromboplastin

- Injured tissues release exothromboplastin and platelets release

endothromboplastin.

- Both these react with clotting factors along with calcium ions to

form Thrombokinase / Prothrombinase enzyme.

- This enzyme inactivates anticoagulant heparin.

2) Conversion of Prothrombin to Thrombin

- Prothrombinase enzyme converts inactive Factor 2 ( Prothrombin )

to active factor Thrombin. In the presence of ca2+.

3) Conversion of Fibrinogen to Fibrin

- Thrombin converts inactive Factor 1 ( Fibrinogen ) to active factor

Fibrin and forms a mesh work

• Blood minus blood cells = Plasma

• Plasma minus Fibrinogen and = Serum

large plasma proteins

• Bleeding time – from onset of bleeding till platelet plug

formation. Time: 1- 3 minutes

• Clotting time - from onset of bleeding till clot formation.

Time: 2- 8 minutes

• Clot can be formed in intact blood vessels

1)Thrombus – static clot, grows bigger and can block the vessel.

2) Embolus - Moving clot, flows in the blood vessels and finally

dissolves.

• Anticoagulants are substances that prevent clotting of blood.

• Heparin , Antithrombin III, Protein C – natural anticoagulants

• Sodium citrate, Double oxalate, EDTA – used in lab

• Significance :

Has an important role in maintaining the fluidity of blood in circulation.

Anticoagulants

Heparin

• Released from basophils , mast cells

Mechanism of action :

• Inhibits conversion of Prothrombin ---- thrombin

• Combines with Antithrombin III and it

neutralizes the action of thrombin, inactivates

Factors 9,10,11 & 12

Actions of Heparin

XII

XI

IX

XaVIII

Prothrombin

(II)

thrombin

fibrinogen fibrin

STABILISED FIBRIN

V, Ca, P/L

VII

Intrinsic pathway

Extrinsic pathway

XIII

Golden Key points

• PCV (Packed Cell Volume)- total number of blood

corpuscles.

• Haematocrit Volume : total number of RBC in blood.

• PCV is almost equal to Haematocrit

• 1gm Haemoglobin carries – 1.34 ml of oxygen

• 100ml of blood transports – 20 ml of oxygen.

• Increase in RBC count --- Polycythemia – occurs

in hill station due to reduced PO2 at high altitude.

99% of PCV is by RBC and 1% is by WBC and platelets

• Barr body:

• Formed by modification of one X chromosome

• Drum stick like appendage attached to the nucleus of

neutrophils.

• Found only in the neutrophils of females.

• Significance – Helps in sex detection

• AB blood group was discovered by Decastello and Sturli

in 1902

What is Lymph ?

In tissue filtration

20 ltr filtered – 17 ltr

reabsorbed

3ltr remains in interstitium

Enters Lymphatic capillaries

Lymph

Composition of Lymph

• Plasma

• Cellular debris

• Lymphocytes

• Macrophages

• Bacteria

Lymph node

Lymph nodes

Functions of Lymphatic System

1. Returns excess filtered fluid back into circulation.

3. Returns filtered proteins

Proteins leaked in filtration

Not reabsorbed by capillaries

Enters lymphatic capillaries

2. Defense against diseases

Phagocytes (Lymphocytes)

in Lymph Nodes

Destroys pathogens in lymph

3. Transports absorbed fat from GIT

Digested fat & fat soluble vitamins

from small intestine

into Lymph capillaries

Chyle

Lymphadenopathy

• Enlargement of lymph nodes

• swollen, painful node responding to

foreign antigen

Indicates infection in that area

• Ex :Tonsillitis

Swelling Elephantiasis