Haemodynamic disorders

Formation of atheromatous plaque & consequences

What is atherosclerosis?

Chronic inflammatory disease, caused by the formation of ‘fibro-fatty’ lesions in the arterial wall

Which arteries does atherosclerosis occur in?

All arteries - including aorta, carotid, coronary, iliac, femoral …

What is atherosclerosis a major cause of?

• Heart attacks

• ischemic stroke

• PAD

What two conditions are major risk factors for atherosclerosis?

• hypercholesterolaemia

• inflammation

What are the 3 stages of atheroma?

1. Initiation (fatty streak)

2. Plaque progression (fibrous cap atheroma)

3. Plaque rupture (atherothrombosis)

What layer of artery structure does atherosclerosis occur in?

Intimal layer - specifically the tunica intima

Initiation (fatty streak)

• Endothelial dysfunction - lipids accumulate and modify in this area forming fatty streak

• Leukocyte recruitment - includes macrophages from tissue and monocytes from blood

• These cells phagocytise the lipids, before becoming foam cells

How are lipids modified by macrophages?

Macrophages oxidise LDL

How are foam cells formed?

Recruited monocytes differentiate into macrophages and engulf lipids trapped in subendothelial space = foam cells

Plaque progression (fibrous cap atheroma)

Has a lipid rich necrotic core comprised of dead foam cells, macrophages, smooth muscle cells, lymphocytes and ECM.

What separates the necrotic core of the atheroma from the vessel lumen?

Fibrous cap

What is atherothrombosis

Rupture of the fragile atheroma into the blood

What can atherosclerosis cause?

• acute narrowing of vessel lumen

• chronic occlusion of vessels (due to growing plaque)

• Thrombosis and embolism (rupture of plaque)

What is PAD?

Peripheral arterial disease - it is the presence of systemic atherosclerosis distal to the arch of the aorta

What is the primary symptom of PAD?

Intermittent claudication

Intermittent claudication

pain with walking

What are other symptoms of PAD?

• cold feet

• weak/absence of popliteal and pedal pulses

• blanching of limb colour with elevation

Non-modifiable risk factors of PAD

• Increasing age

• male gender

• Genetic disorders of lipid metabolism

• Family history of premature CAD

Modifiable risk factors of PAD

• Smoking

• Obesity

• Hypertension

• Hyperlipidaemia?

• Diabetes mellitus

What is ischemia?

Restriction in blood flow/ supply to tissues = shortage of oxygen and glucose needed for cellular metabolism.

Also the reduced ability to remove metabolites

Result of ischemia?

Tissue damage - by build up of metabolic waste, inability to maintain cell membranes, mitochondrial damage, and eventual leakage of autolyzing proteolytic enzymes into the cell and surrounding tissues.

What characterises hyperaemia & congestion of haemodynamic disorders?

• local increase in tissue blood volume

• focused on microcirculation (arterioles, capillaries, venules)

What is hyperaemia?

It is an adaptive local increase in blood volume in tissues due to a change in environment

What are 2 kinds of hyperaemia?

• reactive

• active

Reactive hyperaemia

Local vasodilation due to oxygen debt or accumulation of metabolic waste

eg: raynaud syndrome

Active hyperaemia

Increased blood flow/vasodilation due to period of activation (increase in blood in skeletal muscle during exercise)

What is congestion?

Its is a passive process caused by impaired venous return from affected area

Hyperaemia vs congestion - process

Hyperaemia = adaptive process

congestion = passive process

Hyperaemia vs congestion - MOA

Hyperaemia = increase in blood volume in tissues in response to change in environment

Congestion = due to impaired venous return from affected area

What causes congestion?

• failure of heart to pump blood away from affected area

• Physical obstruction in veins

What impact does congestion have on venous pressure?

increases VP

Types of congestion?

• Local

• Systemic

Cause of local congestion

Blood vessel compression due to venous obstruction (eg: tumour, VT)

Cause of systemic congestion

Often associated with heart failure = widespread oedema

Examples of congestion

• Chronic pulmonary congestion

• Centrilobular hepatic congestion

What is oedema?

Abnormally increased fluid in interstitial tissue spaces

Causes of oedema?

• Increased hydrostatic pressure

• Decreased colloidal osmotic pressure

• Lymphatic obstruction

• Sodium retention

• Inflammation

Causes of increased hydrostatic pressure

• Can be generalised (termed anasarca)
  e.g. in heart failure

• Can be localised as in limbs
  e.g. deep vein thrombosis (DVT)

Causes of decreased colloidal osmotic pressure

• Reduction in the generation of plasma proteins
  e.g. liver cirrhosis, malnutrition

• Loss of protein
  e.g. via skin (burns), urine (nephrotic syndrome),
  faeces (bowel disease)
  
  

How can lymphatic obstruction cause oedema?

Lymph no longer circulates and drains into tissues

• Obstruction by malignancy, radiation therapy, surgery, parasites

How can sodium retention cause oedema?

As in excessive salt intake in renal insufficiency, or increased RAAS activation

• Increases hydrostatic pressure

How can inflammation cause oedema?

• Blood vessel dilation increases blood flow to the area = redness

• increased blood vessel permeability = increased movement of fluid, proteins and leukocytes from blood into interstitial space

Haemorrhage

Extravasation of blood due to vessel rupture

What % of blood volume loss can cause hypovolemic shock?

>15%

Petechiae

Minute haemorrhage (1-2mm diameter) of skin and
mucosa.
• Due to thrombocytopenia, clotting factor deficiency, or
increased pressure in capillaries

Purpura

Small haemorrhage (3-10mm diameter)
• Due to trauma or vasculitis

Ecchymosis - haematoma/ bruise

Subcutaneous haematoma (>1cm)
• Trauma, platelet or clotting factor deficiencies
• Colour change (red–blue green–yellow brown) due to
metabolism of haemoglobin to bilirubin and hemosiderin

What is a thrombus?

Blood clot that has formed within the blood vessel AND which remains attached to the vessel wall

• resulting from inappropriate activation of the haemostatic system

What 3 factors are the main cause of thrombi?

• endothelial injury

• abnormal blood flow

• hypercoagulability

Thromboembolism

Thrombi that has detached from the blood vessel wall

Composition of thrombi?

• platelets

• RBCs

• Neutrophils

• Lymphocytes

All held together by fibrin mesh

2 types of arterial thrombi

• mural thrombi - doesn’t occlude vessel

• occlusive thrombi - occludes vessel

Are arterial thrombi platelet of fibrin driven?

platelet driven

Are venous thrombi platelet or fibrin driven?

Fibrin driven - due to hypercoagulation

Embolism

Solid, liquid or gaseous mass carried in blood to site distant from its point of origin - lodging in smaller vessels = occlusion and infarction

Pulmonary embolism

Blockage of an artery in the lungs, may cause sudden death

• 90% result from DVT

Infarct

An area of ischemic necrosis caused by occlusion of either arterial supply or venous drainage in a tissue

• 99% result from thrombosis or embolism

What is the most common kind of occlusion?

Arterial occlusion

List common clinical conditions caused by infarctions

• MI

• Cerebral infarction (ischemic stroke)

• PI

• Intestinal infarction

• Ischemic necrosis of extremities (gangrene)

Aneurysm

Blood vessel enlargement caused by vessel weakness

Main causes of aneurysm?

• Hereditary conditions or birth defect

• Acquired disease - high BP, atherosclerosis, trauma

Aneurysm classification by morphology?

Fusiform: bulge all sides of the vessel

Saccular: bulge on one side

What is a true aneurysm?

It involves all three layers of the wall of an artery
(intima, media and adventitia)

What is a false/pseudoaneurysm?

Does not contain any layer of the vessel wall.
• Result of trauma that punctures the artery (needle, knife, bullets), percutaneous surgical procedures (coronary
angiography, arterial grafting)

Shock

Clinical state characterised by systemic hypoperfusion (lack of blood flow) leading to reduced delivery of oxygen and nutrients

What does shock ultimately lead to?

Cellular injury, inadequate tissue function, multi-organ dysfunction syndrome