week 6

what is oedema?

• an abnormal accumulation of fluid in intercellular spaces or within body cavities

• leads to tissue swelling

• accumulation of fluid between cells - oedema

what pressures cause oedema?

• due to disruption of normal Starling forces acting across blood vessel walls

  • hydrostatic pressure

  • plasma osmotic pressure

  • when balanced, no net loss or gain of fluid across capillaries

  • if hydrostatic pressure increases, or plasma osmotic pressure decreases, can lead to oedema

where can oedema be located, and what is it termed? (2)

1. localised - one specific area

2. generalised - throughout whole body

what are examples of localised oedema? (4)

Ascites

• oedema in peritoneum

Hydrothorax

• oedema in thoracic cavity

Hydropericardium

• oedema in pericardium

Hydrocoele

• oedema in tunica vaginalis

what are examples of generalised oedema? (2)

Anasarca

• extreme generalised oedema

Hydrops or hydrops foetalis

• foetus

• baby with haemolytic disease may have hydrops foetalis

what are the fluid types found in oedema? (2)

• nature of fluid relates to oedema aetiology

• transudate

  • non inflammatory tissue fluid, little protein content

• exudate

  • inflammatory fluid, high protein content

  • serous

  • fibrinous

  • haemorrhagic

  • suppurative

what are the 4 causes of localised oedema?

1. acute inflammation

2. type 1 hypersensitivity reaction

3. lymphatic obstruction

4. impaired venous drainage

how can acute inflammation cause localised oedema?

• due to increased vascular permeability

• protein rich exudate (usually quickly resorbed)

• ie. ankle sprain, hydropericardium (in pericarditis)

how can type 1 hypersensitivity reaction cause localised oedema?

• acute inflammatory mechanism (effects of histamine)

• inflammatory exudate seen

• ie. bee stings, allergic rhinitis

how can lymphatic obstruction cause localised oedema?

• prevention of normal drainage of tissue fluid (ie. transudate)

• ie. fibrosis of tissue, tumour invasion in tissue, radiotherapy, parasitic infections

  • especially microfilariae Wuchereria bancroftii

    • parasitic worm

    • larvae are transmitted by female mosquitoes

• can lead to elephantiasis - trophic changes

  • reactive changes in cells

    • decreased oxygen and nutrients

  • worm blocks lymphatic vessels

how can impaired venous drainage cause localised oedema?

• if blood flow back to right side of heart is hindered and blood pools in venous system

  • increase in venous hydrostatic pressure

• increased venous hydrostatic pressure

  • increased pressure within lumen of vein, so fluid moves into tissue space

• ie. tumour invasion, fibrosis, varicose veins, thrombosis, pregnancy, immobility, long periods of standing

• sluggish blood flow back to right side of heart

what is generalised oedema?

• classified as generalised when there is >5 litres of fluid retention

• fluid is found in entire body

  • more noticeable in lower limbs because of effects of gravity

• usually called ‘pitting oedema’

  • pit remains when touching it

  • skin doesn’t bounce back

• fluid balance is disrupted and pathogenesis involves hormonal mechanisms

what is the pathogenesis of generalised oedema?

• liver disease - not enough albumin produced

• hypoproteinaemia disrupts Starling forces

  • decreases plasma osmotic pressure

  • causes oedema

  • reduced blood volume

    • reduced blood flow in kidney

    • activates RAAS

      • sets off another pathway

• increased sodium retention can also be caused by increased oestrogen

  • tumours secreting too much oestrogen

  • menstrual cycle

what are the causes of generalised oedema?

1. right heart failure

2. renal disorders

3. liver disease

4. malnutrition

5. other clinical states

how can right heart failure cause generalised oedema?

• reduces blood flow through kidney, stimulates RAAS

• ie. with obstructive lung diseases where much scarring found in lungs

  • chronic obstructive airways diseases

  • right ventricle fails

  • blood pools in venous system → increased hydrostatic pressure

• emphysema, anthracosis, scarring (smoking)

how can renal disorders cause generalised oedema?

• ie. glomerulonephritis, renal failure

• as kidneys fail, there is loss of plasma protein from kidney glomeruli

  • hypoproteinaemia

  • disruption of Starling forces

  • plasma volume decreases

  • reduced blood flow through kidney stimulates renin aldosterone system

• due to chronic autoimmune damage

how can liver disease cause generalised oedema?

• ie. cirrhosis, liver failure

• as the liver fails, there is decreased albumin production

  • hypoalbuminaemia

  • disrupted Starling forces

  • plasma volume decreases

  • reduced blood flow through kidney stimulates renin-aldosterone system

• also, with impaired lymphatic drainage in liver

  • portal hypertension, ascites

• liver also catabolises oestrogen

  • increased oestrogen levels if liver is diseased (unable to catabolise)

  • can increase sodium retention → increased ADH → increased water retention → increased generalised oedema

how can malnutrition cause generalised oedema?

• ie. Kwashiorkor - severe dietary protein deficiency

• decreased plasma protein levels

  • hypoalbuminaemia

  • disrupted Starling forces

  • plasma volume decreases

  • reduced blood flow through kidney stimulates renin aldosterone system

  • ascites often seen as well

how can other clinical states cause generalised oedema?

• generally relate to increased oestrogen in body

• pregnancy, contraceptive pill

• oestrogen increases angiotensin secretion by liver, stimulating sodium and water retention

what are the life threatening forms of oedema, and what occurs? (2)

1. Pulmonary oedema

• ie. due to left ventricular failure, infections

• exudate and infiltrate forms within lungs

2. Cerebral oedema

• ie. due to head trauma, infections

what is haemorrhage, and what are its causes?

• due to loss of blood from circulation

  • intercellular tissue spaces

  • body cavities

  • exterior of body

• causes

  • trauma damaging vessels, vascular disease, destruction of vessels in cancer, high blood pressure, aneurysms

  • all cause damage to vessels - blood escapes

what is haemostasis?

• the physiological process preventing blood loss from circulation

• if blood is lost too quickly/too much, haemostasis fails and haemorrhage continues

• involves a blood coagulation cascade

  • interaction of proteins, coagulation factors, co factors

what occurs following injury of a blood vessel?

1. Vasoconstriction

• spasm → decreased blood volume flowing in injured vessel

2. Blood coagulation cascade activated

• fibrinogen (soluble blood protein) forms fibrin (insoluble protein) via thrombin

• fibrin and platelets form haemostatic plug sealing defect in blood vessel wall

3a. Fibrinolytic mechanism

• once defect is plugged effectively and vessel wall repaired, haemostatic plug is removed by fibrinolysis

• plasminogen (inactive form in blood) converts to plasmin (active enzyme which dissolves fibrin)

3b. Clot retraction, organisation, recanalisation

• shrinkage of clotted blood partially unblocks vessel

• fibrous tissue replace clots → new channels form

what is hypovolaemia?

decreased blood volume

• main effect of haemorrhage

• decreased cardiac output and blood pressure

• may cause brain and heart damage, death

• may lose ~20% of blood with no adverse effects

  • rate and volume of blood loss are important, as well as the situation in body

  • ie. small cerebral haemorrhage may cause fatal rise in intracranial pressure

  • ie. blood loss in pericardium

what are the two types of haemorrhage, and what occurs?

External haemorrhage

• blood lost to exterior of body

• ie. bleeding into GI tract

• body loses haemoglobin/iron

Internal haemorrhage

• blood lost into tissues or internal body cavities

• ie. bleeding into pleura

• body does not lose iron

what are the different types of internal haemorrhages based on size? (3)

Petechiae

• very small spots of haemorrhage

• from microvasculature - capillaries

Haematoma

• large haemorrhage, bruise

• from larger vessels

Ecchymosis

• very large haematoma

• patient on anticoagulants

what occurs when there is an internal haemorrhage, when there is blood in tissue spaces or cavities?

• incites inflammatory response

• extravasated blood excites inflammatory response

• haemoglobin is removed, broken down, recycled

• colour changes in tissue reflect breakdown of Hb

• blood from veins - unoxygenated

• blood from arteries - oxygenated

• depends on how long it has been and where the blood has been lost

what is haemorrhagic diatheses, and what occurs?

• diathesis = predisposition or tendency to suffer from a disease

  • caused by abnormalities in blood coagulation or anticoagulant administration

• haemophilia A = more common in men, women are carriers

• melaena - dark stool

• haematemesis - vomiting blood

• deficiency in vitamin K affects factors - more prone to haemorrhaging

what is purpura?

• disorder in which multiple small purplish bruises develop on the skin or mucosal surfaces

  • ie. petechiae/petechial haemorrhages

what are the different types of purpura, and what occurs? (3)

a. Thrombocytopenia

• platelet counts <100,000 platelets/microlitre blood

• ie. decreased platelet production from bone marrow

  • ie. cytotoxic drugs

• ie. antibodies against platelets as seen in SLE

b. Non-thrombocytopenic purpura

• vascular defects, normal platelet numbers

• small, fragile blood vessels

c. Thrombasthenia

• platelets are abnormal in function

• ie. cytotoxic drugs, rare bone marrow conditions

what is shock?

• not a distinct pathological entity but rather a clinical syndrome

• a collection of symptoms and signs

  • pallor, nausea, hypotension, confusion

• defined as

  • low perfusion circulatory insufficiency leading to an imbalance between the metabolic needs of the tissues and the blood available to perfuse them

what is primary shock?

• redistribution of blood volume

• seen after

  1. injury (usually traumatic)

  2. great pain

  3. strong emotion

• low blood pressure mediated by a transient neurovascular reaction

• fluid balance is not affected

• frequently results in syncope (fainting)

• recovery soon occurs

what is secondary shock?

• more serious

• disturbance of fluid balance

  • ie. low blood volume

• peripheral circulatory deficiency

• manifested by decreased volume of blood and renal functional deficiency

• sweating, diarrhoea

• less blood flow through kidney

• oedema

what are the different types of secondary shock, and what occurs? (3)

1. Hypovolaemic shock

• due to haemorrhage, plasma loss (burns), fluid/electrolyte loss (sweating, diarrhoea)

2. Cardiogenic shock

• due to cardiac diseases (heart attack), respiratory disorders affecting heart (respiratory failure)

3. Septic shock

• due to septicaemia (gram negative bacteria)

  • production of endotoxin as bacteria are destroyed in body - can cause damage to blood components

what is thrombosis?

• process resulting in the formation of a solid or semi solid mass composed of blood constituents, within the circulation during life

• the resulting mass is called a thrombus

• different to haemostatic plug, coagulum (outside circulation), post mortem clot (dead)

what are the ways thrombi can be categorised? (2)

1. based on composition

2. based on behaviour

what are the composition-based thrombi categories? (3)

1. pale (white)

2. dark (red)

3. mixed (laminated)

what are pale thrombi?

• platelets, fibrin

• form in fast flowing blood (arteries)

• associated with atherosclerosis (damage to wall)

what are dark thrombi?

• fibrin, red and white blood cells

• form in static blood (typically in veins)

• slower blood flow

• associated with obstruction

• compressed veins

what are mixed thrombi?

• regions of platelet/fibrin and RBC/WBC/fibrin

• laminations are called lines of Xahn

• form in slow flowing blood (arteries or veins)

• associated with narrowed lumen

what are the behaviour-based thrombi categories? (7)

1. mural

2. occlusive

3. corraline

4. propagating

5. ball

6. septic

7. vegetations

what are mural thrombi?

• adherent to one side of vessel wall

• lumen not completely obstructed

what are occlusive thrombi?

lumen totally obstructed

what are corraline thrombi?

irregular, can become occlusive

what are propagating thrombi?

progressive involvement of thrombus into other vessel branches

what are ball thrombi?

unattached spherical thrombus

what are septic thrombi?

presence of infection

what are vegetation thrombi?

thrombi on heart valves

what is the aetiology of thrombosis? (3)

virchow’s triad

1. changes in the vessel wall

2. change in blood flow

3. changes in blood constituents

how can changes to the vessel wall be a factor that predisposes to thrombosis?

• damage to endothelium that lines vessel

  • atherosclerosis

  • infection

  • toxic injury

    • potentially could include smoking

  • immune mechanisms

how can changes in blood flow be a factor that predisposes to thrombosis?

• flow is laminar in normal vessels

• blood flow is central

  • edges are free of cells

• plasma should surround vessel wall

• stasis or turbulence has more cells colliding with wall

• stasis, tumours, slowing, disruption of heart function

• may damage the intima of vessels (direct trauma)

• bring platelets in prolonged contact with endothelium

• prevent clearance of clotting factors

• promote fibrin and thrombus formation, and prevent their removal

how can changes in blood constituents be a factor that predisposes to thrombosis?

thrombocythemia: increased platelets

polycythaemia: increased RBCs, WBCs

hyperproteinaemia: increased plasma proteins

hyperlipidaemia: increased cholesterol

hypercoagulability of blood: increased clotting factors

hyperoestrinism: increased endogenous/exogenous oestrogen

what are the clinical risk factors for thrombosis? (6)

• increased age

  • can develop atherosclerosis

• medical history

  • heart condition

  • blood disorder

• immobility

  • especially when post operative

• hormonal, pregnancy, childbirth

• cigarette smoking

• septicaemia

what are the fates of thrombi?

1. propagation

2. lysis and resolution (most favourable)

3. calcification

4. infection

5. retraction, organisation, recanalization

6. thromboembolism

7. infarction

what is propagation as a fate of thrombi?

thrombus enlarges along a vessel, involving more branches

what is lysis and resolution as a fate of thrombi?

• thrombus undergoes lysis by fibrinolytic system

  • enzymatic action of plasmin

• also by therapeutic drug administration

what is calcification as a fate of thrombi?

• dystrophic calcification of thrombus

• thrombus can undergo necrosis

• Phlebolith = vein stone

• hard on palpation

what is infection as a fate of thrombi?

may give rise to septicaemia, gangrene or abscesses

what is retraction, organisation, recanalization as a fate of thrombi?

• granulation tissue forms (ie. organisation) and granulation tissue persist (recanalization)

• re establishment of blood flow through scar tissue

what is thromboembolism as a fate of thrombi?

• detachment of thrombus or small fragment (thromboembolus), travelling to distant location

• may lodge at distant site and interrupt blood flow

• may be fatal

  • ie. saddle thromboembolus of pulmonary artery from leg veins

what is infarction as a fate of thrombi?

• if thrombus interrupts blood flow, anoxia and necrosis of tissue will result

• ie. myocardial infarct (heart attack)

• ie. cerebral infarct (stroke)

  • autolytic necrosis of tissue

what is embolism?

• occlusion of a vessel by a mass of material that is transported in the bloodstream

• ie. a thrombus, becoming a thromboembolus

• mass of material is termed an embolus

  • may be solid, liquid or gas

  • nitrate, oxygen, catheter tip

• can lead to infarction

what are the types of emboli? (6)

1. thromboembolism

2. fat embolism

3. gas embolism

4. foreign body embolism

5. tumour embolism

6. amniotic fluid embolism

what are the types of venous thromboembolism? (2)

1. venous emboli

2. arterial emboli

what is a venous emboli?

• most commonly arise in deep leg or pelvis vein

• lodge in pulmonary vessel

• may cause death

what is an arterial emboli?

• most commonly arise in aorta, coronary, cerebral arteries due to atherosclerosis complicated by thrombosis

• may lodge in any organ

what are the types of fat emboli? (2)

1. bone fracture fat embolism

2. atherosclerotic plaque fat emboli

what is a bone fracture fat embolism?

• severe bone fracture trauma may tear thin walled veins and allow marrow fat to enter bloodstream

• may lodge in lungs and brain

what is an atherosclerotic plaque fat emboli?

lipids form atheromatous plaques may enter bloodstream

what are the types of gas embolism? (2)

1. air emboli

2. nitrogen emboli

what is an air emboli?

• most commonly arise in veins

• accidental introduction of air in veins

• faulty IV therapy technique

• complicated childbirth

• open heart surgery

what is a nitrogen emboli?

• arise throughout circulation

• due to deep sea divers ascending too quickly to the surface

  • as deep sea divers go deeper, more nitrogen is dissolved in their blood

  • increased atmospheric pressure → more gas can be dissolved in liquid

  • should ascend slowly to exhale nitrogen from lungs safely

  • if ascending too quickly, nitrogen comes out as bubbles → emboli

• aka Caisson disease, the bends

  • bend over with excruciating pain

• can lodge in joint spaces causing pain

• potentially fatal

what is a foreign body embolism?

• needles, wood splinters, talc grains, tubing, catheter tips, acrylic bone cement (after vertebral body treatment)

• due to IV drug use, faulty therapy techniques

what is a tumour embolism?

• metastasising tumours

• usually arise in venules or veins due to malignant tumour infiltrating through wall of blood vessel

what is an amniotic fluid embolism?

• occurs during childbirth

• amniotic fluid containing foetal cells from skin surface may enter maternal circulation via bleeding placental bed and travels to lung capillaries

• complications

  • acute alveolar wall damage

  • disseminated intravascular coagulation

• can cause adult respiratory distress syndrome

• high mortality rate for mothers if this occurs