FIBRINOLYTIC SYSTEM

Dr.G.Sandeep
Balancebetween clotting
and anticlotting
mechanisms
1)physiological vascular stress

a)low level of coagulation factors

activity is seen normally (due to
normal vascular stress)
b)high level seen only during
significant vascular injury

2)basal anticoagulation balances basal

coagulation.
Low protein c and tissue plasminogen
activator presence is seen normally
 FIBRINOLYTIC
SYSTEM(ANTICOAGULANTMECHANISM)(clot lysis)

Factors that initiate clotting mechanism also stimulate

breakup of blood clot called fibrinolysis
a)It is due to proteolytic enzyme fibrinolysin or plasmin
b)Thrombin and TPA convert inactive plasminogen into
plasmin.
c)Plasmin lyses fibrin and fibrinogen into FDP
FDP again inhibits thrombin
d)Human TPA,urokinase and streptokinase are
fibrinolytic ,so used in early MI .
fibrinolysis
 PHYSIOLOGICAL ROLE

• Clearing the small minute clots in the vessels

• Promotes normal healing process
• Destruction of menstrual clots in the vagina
• Liquifies semen coagulum to facilitate sperm
motility in female genital tract
• Sperm distruction in epidydimis
 MECHANISM OF FIBRINOLYSIS
• Three steps
• 1)activation of protein c
• Thrombin and thrombomodulin(endothelial
cells of vessel) activates protein c
2)activation of plasmin

Activated protein c inactivates inhibitors of plasmin

activator which activates plasminogen activator

plasminogen activator promotes plasminogen

conversion into plasmin

5a and 8a are inactivated by protein c and protein s

to prevent coagulation
3)fibrinolysis
• Plasmin degrades fibrin into FDP and causes
clot lysis known as fibrinolysis
• Thrombin and tissue and urokinase
Plasaminogen Activator facilitate clot lysis
Functions of plasmin
• 1)Fibrinolytic
• Converts fibrin in to FDP
• 2)Non fibrinolytic
• Involve in tissue remodelling
• Role in inflammation and tumour cell invasion
• Control ovulation and embryogenesis
• Regulates neural devolopment
• Activates growth factors and blood vessel
growth
Inhibitors of fibrinolysis

• 1)Plasmin inhibitors
• alpha 2 antiplasmin and alpha two
macroglobulin
• 2)Plasminogen activator inhibitors
• PAI-1 AND PAI-2
PLASMIN GENERATION DEFECTS
• FIBRINOLYTIC DEFICIENCY
• Due to plasminogen deficiency
• Type 1 –both conc and function reduced
• Type 2-only function is reduced
• The patient presents with thrombophlebitis
attacks,intracranial and mesenteric venous
thrombosis and pulmonary embolism
• Pregnancy is a hypofibrinolytic state-increase fibrin
and PAI levels predispose to intravascular
thrombosis
Enhanced fibrinolysis
due to congenital or acquired loss of
fibrinolytic inhibitor activity
1)deficiency of alpha 2 antiplasmin –bleeding
diathesis
2)acquired alpha 2 antiplasmin deficiency
 Factors affecting fibrinolytic system
• Promoted by
• Stress,strain
• After administration of
epinephrine,corticosteroidsa and phenformin
• Tissue activators like plasminogen activator
and urokinase
• Inhibited by
• E-amino caproic acid
• Aprotinin or trasylol(trypsin inhibitor)
 Physiological significance of
fibrinolytic system
• Prevents excessive fibrin formation on
vascular endothelium
• If clotting system predominates it leads
to intravascular thrombosis
• If fibrinolytic system predominates it
leads to tendency of bleeding
• Plasmin forms kinins(bradykinin,kallidin that
help in inflammatory responses to injury
• Has role in cell movement and in ovulation
 LYMPHOID ORGANS AND LYMPH

• tissue responsible for immunity consists of

network of lymphoid organs ,tissues and their
products
• A)primary lymphoid organs-1)thymus2)bursa
equivalent in humans

• B)secondary or peripheral lymphoid organs

• 1)lymph nodes ,2)SPLEEN,3)MUCOSA
ASSOCIATED LYMPHOID TISSUE(malt)
Thymus
weight-40grams ,in mediastinum

Function-Pre T cells proliferate and develop into

mature T cells
thymopoietin from epithelial cells of thymus aids
in maturation of T cells.

Thymus reaches maximum size by 12 years and

later degenerates later.
T cells enter sec. lymphoid organs and function as
immune cells
Bursa equivalent in human
Fetal liver and bone marrow That act as
equivalent of avian bursa fabricius produce B
lymphocytes in fetal stage
these migrate to lymph nodes and spleen
b cells get activated by antigens into plasma cells
to produce antibodies
Lymph nodes
present along lymphatic vessels.
Mammary glands,axilla and groin has high lymph
nodes
cortex - T cells,macrophages and dendritic cells
(activate T cells),bcells proliferate into plasma
cells in cortex
medulla –both T and B lymphocytes ,macrophages
and plasma cells are present.
The lymph flow is unidirectional in nodes
Spleen
Largest single mass of lymphatic tissue in body,12
cm length

Has white pulp-contain lymphatic tissue mostly B

cells(acts in immunity)

Red pulp-RBC,macrophages ,lymphocytes ,plasma

cells and granulocytes(acts in phagocytosis)

Spleen has no afferent lymphatic vessels so it does

not filter lymph.
FUNCTIONS OF SPLEEN
1)RES-it is a part of RES. Macrophages store iron as
ferritin,
destroy senile RBC,Hb,Platelets and WBC Phagocytose
foreign organisms ,concentrates antigens and help in
immunity

severe infections are common in spleen absence

2)production of RBCs in 2nd and 3rd trimesters storage of

RBCs and release during exercise and after adrenaline
injections and during stress in adults
3)production of wbc in fetal stages
produce B and T lymphocytes
increase fragility of rbc and other cells
regulates portal blood flow

Applied-
Splenomegaly patients suffer from haemolytic
anaemia.

Splenectomy done in haemolytic anemia and

thrombocytopenia
MUCOSA ASSOCIATED LYMPHOID TISSUE(MALT)

Associated with mucosal surfaces of body

Consists of gut associated lymphoid tissue (Galt)and

bronchus associated lymphoid tissue(BALT)

Functions-act in regional defence barrier that filter

and destroy bacteria and virus

Participate in immunological reactions

 LYMPHATIC SYSTEM
• An accessory route by which the fluids can flow
from the interstitial space into the
blood(SUBCLAVIAN VEINS)

• All the tissues in the body have lymph channels

except cns ,Cornea,bones and alveoli of lungs

• Right lymph duct opens into rt subclavian vein

• Thoracic duct into left subclavian vein

 CHEMISTRY OF LYMPH
• Modified tissue fluid
• Transparent,yellowish,
• Alkaline in reaction,clots slowly,
• Its colloidal osmotic pressure is less than that of
plasma
• Protein content less than plasma protein
• Big lipid molecules-chylomicrons from intestine are
present.
• PROTEIN CONCENTRATION OF LYMPH
FROM
• LIVER —6Gms%
• INTESTINE,HEART,LUNGS & THORACIC
DUCT ---4Gms%
• SKIN & SKELETAL
• MUSCLES ---2 Gms%
• LEGS —1-1.5 Gms%
• AVERAGE CONC —3- 5 Gms%
COMPOSTION OF LYMPH
• Protein
• LIPIDS-IN INTESTINAL REGION FROM LACTEALS OF
INTESTINAL VILLI –chyle
Milky colour to the lymph
• Carbohydrates-than plasma
• Coagulation factors-produced more from the liver
region
• Cellular components--no of lymphocytes, rarely
monocytes & macrophages,few rbcs & platelets
• OTHERS- na, K, cl, SO4, ca, PHOSPHORUS,
UREA,CREATININE
 FORMATION OF LYMPH
• From tissue fluid through transcapillary exchange
• Flow rate-0.5—1 ml/ min [2—4 litres seeps back
into the blood stream]
• 9/10th Of fluid from the interstitial fluid flows into
the venous capillaries
• 1/10th of Fluid containing large proteins with
the high molecular weight flows into the
lymphatic capillaries
ENDOTHELIAL
LINING
 FORMATION OF LYMPH
INTERSTITIAL
FLUID
LYMPHATIC VESSEL

INTERSTITIAL FLUID
 FACTORS MAINTAINING FLOW OF LYMPH
TOWARDS THE HEART

1. Contractile valves-prevent retrograde flow

2. Muscle pump
3. Peristalsis of git
4. Rhythmic contraction of large lymphatic vessel wall
5.  Icsf pressure 1.9cm OF H2O [lymphatic pressure-
1.3 cm OF H2O]
6. Negative intrathoracic pressure
7. Suction effect of velocity of blood flow in veins
LYMPHOGOGUES[FACTORS WHICH INCREASE FLOW
OF LYMPH]

• INCREASED CAPILLARY PRESSURE AT THE

VENOUS END eg : OBSTRUCTION
• INCREASED CAPILLARY PERMEABILITY eg:
BACTERIAL TOXINS,
LOCAL TEMPERATURE
• DECREASED OSMOTIC PRESSURE OF PLASMA
• INCREASED MUSCLE PUMP ACTIVITY
 FUNCTIONS OF LYMPH
• TRANSPORT OF PROTEINS- 95 % Of proteins
from the interstitial fluid flows back into
blood [200 gms]
• Transports fatty acids & cholesterol from git
• Transports rbcs, wbcs, & bacteria to lymph
nodes
• Transports antibiotics
• Formation of highly conc urine in counter
current system
• Carrying big lipid molecules chylomicrons into the
blood
• Transport histamine, & lipase
• Supplies oxygen & nutrition to the parts where the
blood cannot flow eg:cartilage
• Enhances the efficiency of immune system by
-transporting antigen
-Continual movement of lymphocytes & exposes an
antigen to large no of them
-Disperses the memory lymphocytes for an encounter
with an antigen
 STARLING’S HYPOTHESIS

CAPILLARY
ARTERIAL END OP-25 mmHg VENOUS END

HP-35
HP-37mm of Hg
mmHg HP-17 mm Hg

INTERSTITIAL FLUID
HP-2-3 mmHg 25-17=8
37-25=12
OP-3-4mmHg

OP-ONCOTIC PRESSURE-- ABSORPTION

HP-HYDROSTATIC PRESSURE--FILTRATION
 OEDEMA
DEFINITION:
Abnormal accumulation of fluid in the interstitial
spaces- [ extra cellular oedema]
Mechanism & causes:
1.  Filtration pressure due to
A. Arteriolar dilatation
B. Venular constriction
C. Venous pressure due to heart failure; incompetent
valves; venous obstruction;  total ecfv; prolonged
standing
2.Decreased osmotic pressure gradient across the
capillary wall due to
a. Accumulation of osmotically active substances in the
interstitial space. [After injury, exercise ]
b. Decreased plasma protein level [hypoproteinemia]
3. Capillary permeability due to allergy-
histamine, kinins etc
4.Inadequate lymph flow :
filariasis- obstruction due to parasitic worm,
Obstruction by cancerous cells