Haemostasis

Question 1

Describe the structure and function of the circulatory system, structure of veins/arteries/capillaries, function of blood

Answer 1

• Transport oxygen and nutrients to specialised tissues and organs
• Blood vessels
• Heart
• Blood
• Veins carry low-pressure, oxygen-poor blood
• Arteries carry high-pressure, oxygen-rich blood
• Large arteries and veins closer to heart
• Small arteries (arterioles) and small veins (venules) closer to capillary beds

> Transportation of:
- Gases oxygen (O2) and carbon dioxide (CO2)
- Chemical substances (hormones, nutrients, salts)
- Cells that defend the body

> Regulation of the body’s fluid and electrolyte balance, acid-base balance, and body temperature.

> Protection of the body from:
- Infection
- Loss of blood by the action of clotting

Arteries:
1. Large arteries
- Elastic fibres alternate between smooth muscle cells of the media
- Expansion and contraction to maintain pressure of the heartbeat

2. Medium arteries (muscular)
    Media primarily composed of smooth muscle cells with elastin found in internal and external elastic lamina
    Distribute blood to individual organs
    Regulate blood flow/resistance vessels
3. Small arteries
    Control/regulate blood flow
    Reduce pressure and velocity
    Vasoconstriction and vasodilation
    Media principally smooth muscle cells

Capillaries
- Diameter of a red blood cell (7-8µm)
- Endothelial layer
- No media
- Thin-walled and slow-volume flow
- Facilitate diffusion of oxygen and nutrients
- Permeability determined by endothelial cells

Veins
- Capillary  venule
- Venules
o Thin media (low intraluminal pressure)
o Vascular leakage and leukocyte emigration (inflammation)
- Venules  progressively larger veins
o Large diameter
o Large lumen
o Thin, unorganised walls
o Valves prevent reverse blood flow

Question 2

Describe the components and functions of blood and why normal blood flow is laminar

Answer 2

Transportation of:
- Gases oxygen (O2) and carbon dioxide (CO2)
- Chemical substances (hormones, nutrients, salts)
- Cells that defend the body

> Regulation of the body’s fluid and electrolyte balance, acid-base balance, and body temperature.

> Protection of the body from:
- Infection
- Loss of blood by the action of clotting

Blood composition
> Plasma
- Liquid part of blood (mostly water ~90%)
Contains:
- Proteins (albumin, antibodies, clotting factors)
- Nutrients (glucose, amino acids, vitamins)
- Hormones
- Waste products (urea, CO₂)
- Electrolytes (Na⁺, K⁺, Cl⁻)

> Platelets

> WBCS/Leukocytes
- Neutrophils (bacterial killers)
- Lymphocytes (B cells & T cells – immune memory)
- Monocytes (become macrophages)
- Eosinophils (allergies/parasites)
- Basophils (release histamine)

> RBCS/Erythrocytes

Blood flow in laminar:
- Normal blood flow is laminar (in lines, smooth (cars in lanes)
o Cellular elements (RBC’s) in the centre of the vessel lumen (fast-moving)
o Surrounded by a slower-moving layer of plasma near vessel walls

If this pattern is disrupted, it can lead to turbulent flow → which may damage vessels or contribute to clotting.

• Endothelium (inner lining of blood vessels)
  o Maintains normal flow of blood
   Anticoagulant/antithrombotic and
  o Controls coagulant at the site of injury
   Procoagulant/prothrombotic

Question 3

Describe the components and processes involved in haemostasis

Answer 3

1. Arteriolar vasoconstriction
   - Narrowing of small arteries (arterioles) right after vessel injury to reduces blood flow
   - It’s an immediate but short-lived response (transient)
   - Caused by:
   > Neurogenic signals → from pain or injury
   > Local vasoconstrictors like:
   - Endothelin (released by damaged endothelium) → powerful constrictor
2. Primary hemostasis
   > What are platelets?
   - Small cell fragments, not full cells (they have no nucleus/DNA)
   - Come from big bone marrow cells called megakaryocytes
   - Main job: form a quick plug at the injury site to prevent blood loss
   - Also help heal the vessel by releasing growth factors

Endothelium Damage
The inner lining of the blood vessel (endothelium) gets damaged

Underneath it, collagen and a sticky protein called vWF (von Willebrand factor) are exposed

🧲 b) Platelet Adhesion
Platelets stick to exposed collagen via vWF

This is the first step in plug formation

💥 c) Platelet Activation
Once they stick, platelets change shape

From smooth discs → they become spiky

This increases their surface area, so they can interact better with clotting factors

📣 d) Platelet Recruitment
Activated platelets release signals (like ADP, thromboxane A2)

These signals attract more platelets to the site

🧷 e) Platelet Aggregation
The new and old platelets stick together

They link up using fibrinogen, like molecular glue

This forms the platelet plug — a temporary patch

3. Secondary hemostasis - coagulation cascade
   > Initiation
   - TF (tissue factor) is exposed
   - TF activates FVII into FVIIa
   - FVIIa starts clotting factors (coagulation cascade) on the exposed phopholipids on activated platelets in initial platelet plug
   - FVIIa eventually converts FX to FXa (activated)
   - FXa and FVa form a complex (generate little thrombin initially)

> Amplification
- FXa and FVa complex generates thrombin
- Thrombin loops back to amplify clotting factor activity and generates more thrombin

> Propagation
- FVIIIa and FIXa complex strengthens
- This strengthens FXa and FVa complex creating a thrombin burst
- Thrombin converts fibrinogen to fibrin
- Thrombin also activates platelets to help hold everything together.
- Fibrin polymerisation stabilises the fibrin clot

4. Clot stabilisation
   - Platelet contraction strengthens the clot.
   - Trapped neutrophils help fight infection at the site of injury.
   - Trapped red cells contribute to the red color of the clot and help seal the wound.
   - Factor XIIIa activates to stabilize the clot by linking fibrin threads together.
   - Covalent crosslinking of fibrin makes the clot stronger and more durable.

• Polymerised fibrin and platelet aggregates undergo contraction to form a solid plug that prevents further haemorrhage

5. Clot resorption
   - Counterregulatory mechanisms kick in
   These are the body’s natural ways of stopping clotting and clearing the clot.
   - Blood flow helps
   As blood flows through the vessel again, it washes away clotting factors (like thrombin, etc.) so the clot doesn’t keep growing.
   - Plasminogen is activated to plasmin
   Plasminogen is an inactive protein floating in blood.
   - It gets converted into plasmin, the main enzyme that breaks down clots.
   - What activates plasminogen?
   Tissue plasminogen activator (t-PA) — released by healthy endothelial cells.
   - Also helped by some clotting factors like factor VII.
   - Plasmin breaks down fibrin
   Fibrin is the “glue” of the clot. Plasmin chops it up into pieces.
   - This dissolves the clot, clearing the vessel and allowing blood to flow normally again.

Question 4

What is hemophilia?

Answer 4

Hemophilia
- Due to deficiency in factor VIII or Factor IX
- Easy bruising and severe hemorrhage after trauma
- prone to spontaneous hemorhages in joints

Question 5

Describe composition of blood vessels

Answer 5

Blood vessels are all composed of:
> Cell
o Endothelial cells (ECs)
o Smooth muscle cells (SMC)
> Extracellular matrix (ECM)
o Elastin
o Collagen
o Glycosaminoglycans
> Organisation
- Three layers
 Intima, media, adventitia
o Present to varying degrees in each blood vessel type

1. Intima:
   - Endothelial monolayer
   - Thin ECM sheet
   - Bordered by internal elastic lamina (a dense elastic membrane)
2. Media:
   - Smooth muscle cells
   - Extracellular matrix
   - Bordered by external elastic lamina (in some blood vessels)
3. Adventitia:
   - Loose connective tissue
   - Nerve fibres
   - Small blood vessels

> The blood supply of the blood supply:
- Fenestrations in internal elastic lamina provide oxygen and nutrients to the innermost smooth muscle cells of the media
- Vaso vasorum of adventitia provide oxygen and nutrients to outer smooth muscle cells
- Coronary arteries supply oxygen and nutrients to heart

Question 6

Distinguish between antithrombotic and prothrombotic factors.

Answer 6

1. Antithrombotic
   - Antiplatlet: PGI2, NO, Adenosine diphosphate
   - Anticoagulant: Heparin molecules, thrombomodulin
   - fibrinolytic: Tissue plasminogen activator (tpa)
2. Prothrombotic
   - platelet adhesion: vWF
   - procoagulent: cytokines
   - antifibrinolytic: plasminogen activator inhibitors

Question 7

What happens when hemostasis goes wrong?

Answer 7

> Inadequate haemostasis (inability to form a clot)
1. haemorrhage (which can compromise regional tissue perfusion)
2. Too much blood loss (severe hemorrhage) then leads to hypotension, shock, and death

> Extreme hemostasis
1. clotting (thrombosis)
2. migration of clots (embolism) can obstruct blood vessels, potentially causing ischemic cell death (infarction)

Question 8

What is shock and explain types of shock

Answer 8

Shock:
- Shock is a state of circulatory failure that impairs tissue perfusion and leads to cellular hypoxia

1. Hypovolemic shock (blood loss/fluid loss)
   - burns
   - severe hemorrhage
   - dehydration
2. Cardiogenic shock (pump failure)
   - mycardinal infarction
   - arrythiamus
3. Distributive shock (vasodilation)
   - Septic: inflection causing inflammation and vasodilation
   - Anaphylactic: allergy releases histamine causes vasodilation