HAEMATOLOGY , EXPLANATION OF CONCEPTS AND DISEASES, Study notes of Biology

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HEMATOL&GY

PHYSIOLOGY

Table of Contents

• Blood Components & Function
• Blood Components
• Platelet Plug Formation (Primary Hemostasis)
• Coagulation (Secondary Hemostasis)
• Role of Vitamin K in Coagulation
• Anticoagulation, Clot Retraction & Fibrinolysis
• Blood Groups & Transfusion

LUMEN

----- SMOOTH MUSGLE C.£.LLS

'- CONTRACTION8. RELAXATION

E.NDOTHE.LIUM

'- ENDOTHELIALC.ELLS

5. Aggregation - GPIIB/IIIA binds to fibrinogen, links platelets - platelet plug 4. Activation

• Platelet changes shape (forms arms to grab other platelets). releases more von Willebrand factor. serotonin, calcium, ADP. thromboxane A2 (positive feedback loop)
• ADP, thromboxane A2 result in GPIIB/IIIA expression 3. Adhesion
• GPlB surface proteins on platelets bind to Von Willebrand factor

Figure 43.2 Layers of an arterial wall.

C,ONNECTIVE TISSUE

'- COLLAGEN

P~OTEIN LAYER

'- ELASTIC.ABERS

2. Exposure - Damage to endothelial cells exposes collagen - Damaged cells release Von Willebrand factor (binds to collagen) 1. Endothelial injury - Nerves, smooth muscle cells detect injury - Trigger reflexive contraction of vessel (vascular spasm) -! blood flow, loss - Secretion of nitric oxide, prostaglandins stop; secretion of endothelin begins - further contraction

PLATELET PLUG FORMATION

STEPS

• Hemostasis: blood-loss prevention
• First two hemostasis steps: platelets clump, form plug around injury site in five steps

osms.tl/ plo.-lele-1:-plug-f0Tmo.-lion-primo.r14-hemos-lo.sis

PLATELET PLUG FORMATION

(PRIMARY HEMOSTASIS)

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Figure 43.3 Platelet plug formation steps.

PLATELET PLUG

UNBOUND PLATELETS

o.t INJ"URY SITE

S> A66RE6ATION

3) ADHESION

CONTRACTION

VON WILLE.BRAND'S

DAMAGED FAC.TOP.

E.NDOTHE.LIAL C.E.LLS /

~ v---J

C.OLLAGE.N

2) E. XPOSUR£

SMOOTH MUSCLE CELLS

ENDOTHEUN,

VASCULAR SPASM

-----') ... ---=--:s.,:--=;:,'

STEPS oJ PRIMARY HEMOSTASIS

U £NDOTH£LIAL INJ'URY

Figure 43.4 Coagulation steps, including the intrinsic, extrinsic, and common pathways.

(b~@

i i i

@JW~

~I J =r: 7 C.01'\l'\ON INTRINSIC PATHWAV PATHWAY

1. ACTIVATES II. ACTIVATES 3 COfl\CTORS

:!..CLEAVES !.PROTEOLVTICALLV CLEAVES FIBRINO<.EN ... FIBRIN STABILIZINC:. FACTOP.

~~~~ IEEJ-+~

«:" /Q2·

• PP.ECIPITATES _ ~ _ .J _ ••lof PLASMA ~ ~-,. I FORM CROSS XII I PROTEIN ~i'~LINKS- Q. C,HAINS ~

~ f'I

( {

ENDOTHELIAL LAYER

EXTRINSIC PATHWAY

COMMON

PATHWAY

e~~

~~p

'[) w g+

r

• tQ2+

<> VIII Q.

I! __' ----l--,

~o'^ '

~ , ............

(b $} -------------·

+¥Q2+

~} PROTHROM81NASE C,01'\PLE.X.

PROTHROMBIN fiil) fii) THROMBIN FACTORII ~ '-'{;) FACTORlb (Q2+

{J)

t

INTRINSIC PATHWAY

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Figure 43.6 Proteins involved in

anticoagulation. Thrombomodulin is found on the surface of intact epithelial cells lining blood vessels.

THROMSOMODVLIN

PROTEIN C.

ANTITHROMSIN 111

(ANTITHROMSIN)

• Occurs during primary, secondary hemostasis; regulates clot formation
• Prevents clots from growing too large - block blood flow, form emboli
• Regulation starts with thrombin (factor II) O (^) Multiple pro-coagulative functions O (^) Proteins C, S bind thrombomodulin- thrombin - cleaves, inactivates factors V,VIII O (^) Antithrombin Ill binds thrombin/factor X - inactivates both (plus factors VII, IX, XI, XII with lower affinity)
• Other factors prevent platelets adhering during primary hemostasis O (^) Nitric oxide, prostacyclin -! thromboxane A

ANTICOAGULATION

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ANTICOAGULATION, CLOT

RETRACTION & FIBRINOLYSIS

Figure 43.5 Vitamin K cycle. A single molecule of Vitamin K can be reused many times.

~ FUNGTIONAL

FORM

II VII IX X

r-uLUTAM't'L CARBO~VLASE

R-NH to 1-o-R' 0 , 0

R-iH^ °'t[°' 0-R' 0

1. VITAMIN K.

QUI NONE "~• i

0~ ~QUl 1 NO~ REDUC.TASE

M· \ :>..VITAMIN K ~c;,., HYDRO QUI NONE.

R/5'-H @

£POX.ID£ ~£DUC.TAS£

Figure 43.7 Blood types are reported as ABO group and Rh+ or -. When both classification systems are combined, there are eight possible blood types: A+, A-, B+, B-, AB+, AB-, O+, 0-.

A g^ AB 0

Rh+ (^) WTYPEA+ e

TYPE 8+

TYPE AB+ ~ TYPEO+

Rh- (^) ~ TYPE A- $

TYPE 8-

$

TYPE AB-

B

• TYPE 0-

:c

w I- C/)

>- Cl)

.s::. ct:

ABO SYSTEM

9 TYPE A ANTIGEN 'j' TYPE 8 ANTIGEN

9 Rh ANTIGEN

BLOOD TYPING