Haemodynamic disorders

Question 1

Explain how fluid balance is maintained in the body?

Answer 1

• Interplay between hydrostatic pressure and colloid osmotic pressure
• Arteriole –> capillary –> venule
• At the arteriole end, the HP > COP, so fluid tends to escape into the tissue = filtration
• As blood continues across the microvessel, at the venule end the COP>HP due to the increasing concentration of albumin, which returns fluid from the tissues into the vessel!

Question 2

6 causes of oedema?

Answer 2

1. Increased hydrostatic pressure: Heart failure, can be localised in the limbs (DVT)
2. Decreased colloid osmotic pressure: Reduction in generation of plasma proteins (albumin). Liver cirrhosis and malnutrition. Also loss of protein via skin (burns), urine (nephrotic syndrome), faeces (bowel disease)
3. Lymphatic obstruction: lymph nodes blocked by parasitic worm (lymphatic filariasis) - lymph no longer circulates and drains into leg –> lymphoedema/elephantiasis
4. Sodium retention: Xs salt intake or increased RAAS. This increases the hydrostatic pressure (favours fluid leaking into tissues)
5. Inflammation: septic shock

Question 3

Causes of the redness and oedema associated with inflammation?

Answer 3

Redness: blood vessels dilate to allow more blood flow to the tissue

Oedema: blood vessels are more permeable, allowing more fluid to migrate to the area, with proteins and leukocytes

Question 4

Definition of hyperaemia and congestion?

Answer 4

Hyperaemia: increased blood flow in a particular tissue, in response to change in environment - adaptive change

Congestion: reduced blood flow out, caused by impaired venous return from the affected area - PASSIVE process

• Both based on microcirculation

Question 5

Reactive vs active hyperaemia?

Answer 5

Reactive: Local vasodilatation in response to O2 debt or accumulation of metabolic waste. Always follows a period of ischaemia. Compensatory mechanism after a period of nutrient and O2 deprivation.

Active: Increased blood flow/vasodilatation in response to period of activation. More related to exercise, the tissue requires more blood in response to increased activity such as lifting weight

Question 6

Causes & types of congestion?

Answer 6

• Physical obstruction of veins
• Failure of heart to pump blood away from the affected area
• Results in increased venous pressure
  1. Local congestion - compression of blood vessels… tumour, venous thrombosis etc
  2. Systemic congestion: associated with heart failure and can lead to widespread oedema
• CONGESTION AND OEDEMA GO TOGETHER VERY COMMONLY

Question 7

What is the haemostatic strategy & 3 phases?

Answer 7

Strategy used by the body to prevent bleeding and stop bleeding while keeping the blood within a damaged vessel

1. Haemorrhage: process of bleeding
2. Thrombosis: process of clotting
3. Fibrinolysis: process of clot dissolution

Question 8

What is a haemorrhage? Causes & consequences?

Answer 8

The extravasation of blood due to rupture of a blood vessel

• Caused by trauma, atherosclerosis, inflammation
• Loss of 15% blood volume = little effect
• Loss of >15% blood volume = hypovolemic shock
• Recurrent blood loss causes iron deficiency

Question 9

What is the difference between a thrombus and an embolus?

Answer 9

A thrombus is a blood clot formed within the blood vessel that remains attached to the vessel wall. If this detaches from the vessel wall it is now called an embolus

Question 10

3 main factors causing pathological thrombosis?

Answer 10

• Endothelial injury
• Abnormal blood flow
• Hypercoagulability

Question 11

What makes up a thrombus?

Answer 11

• Platelets
• RBCs
• Neutrophils
• Lymphocytes
• ^ Held together by a fibrin derived from the coagulation cascade

Question 12

Difference between arterial and venous thrombosis?

Answer 12

Arterial thrombosis:
- Platelet driven/rich
- Formed under high shear flow
- Around ruptured atherosclerotic plaques and/or damaged endothelium
Mural thrombi = do not occlude vessel. Minor clinical events e.g taking meds
Occlusive thrombi = occludes vessel. Major adverse clinical events

Venous thrombosis:

• Not mainly related to platelet function, MORE to do with stasis i.e changes in blood flow
• Formed under low shear flow (around veins)
• Fibrin and erythrocyte rich
• E.g sitting on a flight for a long period of time
• Fibrin driven response to hypercoagulation, around the valves of the veins

Question 13

What is atherosclerosis? How does it progress?

Answer 13

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

• Develops progressively through continuous evolution of arterial wall lesions centred on the accumulation of cholesterol-rich lipids and the accompanying inflammatory response

Question 14

What is an atheroma? Describe the stages of atheroma development (atherogenesis)

Answer 14

Atheroma is an accumulation of degenerative material in the tunica intima of artery walls. Material = macrophages, debris containing lipids, calcium and fibrous connective tissue

Stages:

1. Initiation - fatty streak formation
   - Endothelial dysfunction
   - Lipid entry and modification. Formation of lipid layer ‘fatty streak’ within the intima layer
   - Leukocyte recruitment
   - Foam cell formation (monocytes/macrophages that have phagocytosed lipids)
2. Plaque progression - fibrous cap atheroma
   - Lipid-rich necrotic core, dead foam cells, macrophages, smooth muscle cells, ECM
   - Necrotic core is encapsulated by a fibrous cap that separates the necrotic core and vessel
   - This causes the artery to become narrower, restricting and reducing blood flow through the artery
3. Plaque rupture
   - Mature plaques are vulnerable to rupturing, exposing thrombogenic material to the blood, this is what causes atherothrombosis/blood clot formation over the atheroma which will completely block blood flow

• The plaques can cause arteries to harden and narrow, restricting blood flow and O2 supply to vital organs (atherosclerosis), increasing risk of blood clots blocking flow to the heart (CHD) or brain

Question 15

Clinical complications of atherosclerosis?

Answer 15

N.B acute narrowing of the vessel lumen, chronic occlusion, embolism

Can cause:

• Coronary heart disease: angina, MI, heart failure
• Carotid artery disease: brain TIA, stroke (necrosis)
• PAD: when it narrows arteries in arms or legs
• CKD
• Aneurysm

Question 16

How can atheroma formation be controlled?

Answer 16

• Statins: Inhibit HMG-CoA reductase, which reduces the production of cholesterol
• Fibrates: Activates PPAR, induces transcription of genes facilitating lipid metabolism. Increases HDL levels
• High BP medicines
• Anti-coagulants
• Dietary changes
• Procedures to widen or bypass an affected artery
• Stop smoking
• Exercise and maintain healthy body weight

Question 17

Risk factors for atherogenesis?

Answer 17

• Smoking: chemicals damage lining of coronary arteries.
• Hypertension: Over time, >pressure can damage the arteries, making them vulnerable to narrowing and plaque buildup associated with atherosclerosis
• Hyperlipidaemia: LDL cholesterol builds up on the walls of coronary arteries
• Diabetes
• Sedentary lifestyle
• Obesity
• Family history of CHD
• South Asian, African or Afro-Caribbean descent
• Drinking Xs alcohol
• Age
• Bad diet

Question 18

What is an infarct? Clinical implications?

Answer 18

• An infarct is an area of ischaemic necrosis caused by occlusion of either the arterial supply or venous drainage
• Nearly 99% of all infarcts result from thrombosis or embolism
• Arterial occlusion is most common, obstruction of venous drainage is rare!

Clinical implications:

• MI
• Cerebral infarction (ischaemic stroke)
• Pulmonary infarction
• Intestinal infarction
• Ischaemic necrosis of extremeties: gangrene

Question 19

Definition of ischaemia?

Answer 19

Inadequate BLOOD supply to an organ or tissue, leading to insufficient supply of oxygen and nutrients & inadequate removal of metabolic waste

Question 20

What is an embolism? Pulmonary embolism?

Answer 20

Embolism: solid, liquid or gaseous mass carried in the blood to a site distant from the point of origin, nearly all of them are a result of a dislodged thrombus (thromboembolism)

• Pulmonary embolism is the blockage of an artery in the lungs. 90% of PE originate in the deep veins of the leg (DVT)

Question 21

Pathophysiology of an infarction

Answer 21

• Death of tissue resulting from lack of blood supply
• Thrombosis –> embolism –> Ischaemia (occlusion of blood supply) –> Tissue necrosis INFARCTION –> Inflammatory response –> Scar formation

Question 22

What is an aneurysm? Causes? Complications?

Answer 22

• Aneurysm: enlargement of a blood vessel caused by weakness in the vessel wall
• Can be arterial and venous, with arterial being more common

Causes:

• Hereditary or defect from birth
• Acquired disease, high BP, atherosclerosis, trauma

Complications:

• Most are asymptomatic
• Rupture: life-threatening, internal bleeding
• Clot formation (thrombosis) and embolisation

Question 23

Classification of aneurysms, by morphology and type.

Answer 23

Morphology:

• Fusiform: bulge all sides of a blood vessel
• Saccular: bulge only on one side

Type:

• True aneurysm: Involves all 3 layers of the wall of an artery (intima, media and adventitia). The artery weakens, forming a blood-filled sac
• False aneurysm: Locally contained haematoma. Result of trauma that punctures the artery and blood leaks into the surrounding tissue

Question 24

What is shock? Causes? Associated factors?

Answer 24

A clinical state characterised by systemic hypoperfusion (lack of blood flow), leading to reduced delivery of oxygen and nutrients
–> cellular injury, inadequate tissue function

• Associated with: HYPOtension, HYPOperfusion, and cellular HYPOxia

Question 25

3 different types of shock?

Answer 25

1. Neurogenic shock: Caused by severe damage to the CNS. Loss of systemic stimulation of blood vessels leads to wide spread vasodilatation, pooling of blood in extremities and HYPOtension. E.g spinal cord injury 2. Septic shock: Systemic infection, commonly bacterial. Bacteraemia as a result of infection. Mortality rate of 40-55% 3. Anaphylactic shock: Severe allergic reaction (often to bee stings), causes release of inflammatory mediators and cytokines. Triggers widespread vasodilatation and HYPOperfusion

Question 26

Pathophysiology of septic shock

Answer 26

1. Bacterial components activate macrophages and neutrophils 2. Systemic release of cytokines 3. Activation of endothelial cells leading to systemic vasodilatation and HYPOtension 4. Activation of complement system 5. Dysregulation of the immune system and haemostatic systems (coagulation system and thrombosis) 6. Abnormal blood gases, respiratory distress and multiple organ failure