Cell Pathology 1- Haemodynamic disorders

Question 1

What is Oedema

Answer 1

An abnormal increase in interstitial fluid.

Question 2

What are the aetiologies of oedema

Answer 2

1. Increased hydrostatic pressure
2. Salt and H20 retention
3. Reduced plasma oncotic pressure
4. Inflammation
5. Lymphatic obstruction

Question 3

What percentage of the body weight does water constitute in both sexes

Answer 3

• 60% of total body weight for men

- 50% total body weight for women

Question 4

What are the two opposing forces acting on blood in the capillaries, describe the transport of substances in the capillaries

Answer 4

Opposing forces ; hydrostatic pressure and plasma oncotic pressure keep interstitial fluid in balance in the microcirculation.
Fluid leaves the circulation at the arterial end ( hydrostatic pressure> oncotic pressure)
Fluid enters the circulation at the venous end ( oncotic pressure > hydrostatic pressure)

Question 5

What is the flow of interstitial fluid governed by

Answer 5

Flow of interstitial fluid is governed by 1) hydrostatic and oncotic pressures and 2) endothelial permeability

Question 6

What is generalised oedema

Answer 6

Fluid in serous cavities (pleural , pericardial, peritoneal) and subcutaneous tissues.
>5L
Causes:
Left heart failure
Inflammation
Venous hypertension
Lymphatic obstruction.

Question 7

What is localised oedema

Answer 7

Cerebral and pulmonary oedema
Causes:
Congestive heart failure
Hypoproteinaemia (low protein content)
 Nutritional oedema

Question 8

Describe generalised pitting oedema

Answer 8

Widespread accumulation of fluid in subcutaneous tissues and serous cavities.

Question 9

Describe how increased hydrostatic pressure can cause oedema

Answer 9

Heart failure results in increase in hydrostatic pressure (generalised oedema).

Question 10

Describe how reduced plasma oncotic pressure (reduced albumin) can lead to oedema

Answer 10

Plasma oncotic pressure is governed by [albumin]
When [albumin] <25g/L fluid leaves the microcirculation
Cause of generalised oedema
Loss of protein ( nephrotic syndrome, protein loss enteropathy)

Question 11

Describe how lymphatic obstruction can cause oedema

Answer 11

Localised oedema
Non pitting protein rich oedema
Obstruction by tumour, lymph node dissection, chronic inflammation

Question 12

Describe how sodium retention can cause oedema

Answer 12

Reduced cardiac output ( volume of blood pumped out of the heart per unit time) stimulates the renin-angiotensin system which leads to sodium retention (generalised oedema).

Question 13

Describe how inflammation can cause oedema

Answer 13

Loss of protein rich fluid locally

Question 14

Describe the link between heart failure and systematic oedema

Answer 14

Reduced renal blood flow- activation of renal-angiotensin system to increase blood pressure again- can cause oedema due high hydrostatic blood pressure in patients with heart failure.

Question 15

How does the renin-angiotensin system increase blood pressure

Answer 15

Drop in blood pressure and fluid volume
Renin release from kidney
Renin acts on angiotensinogen released from the liver, to form angiotensin 1
ACE (Angiotensin converting enzyme) is released from the lungs and converts angiotensin 1 into angiotensin 2.
Angiotensin 2 acts directly on blood vessels to stimulate vasoconstriction, as well as acting on the adrenal gland to stimulate the release of aldosterone, which increases the resorption of salt and water in the kidneys to increase blood pressure.

Question 16

What are the causes of pulmonary oedema

Answer 16

Normally due to raised pulmonary capillary hydrostatic pressure, due to pulmonary venous congestion, of which a common cause is left ventricular failure,Fluid accumulates first in the interstitial space and then eventually spills into the alveolar spaces.
The consequences include breathlessness and pneumonia.

Question 17

Explain the consequences of pulmonary oedema

Answer 17

Breathlessness (dyspnoea) is the main symptom.

Breathlessness is typically worse on lying flat (orthopnoea).

Fluid in the alveolar spaces predisposes to bacterial infection in the lung (pneumonia).

Question 18

Describe the typical causes of cerebral oedema

Answer 18

Breakdown of normal capillary barrier and typically occurs in brain tissue surrounding lesions such as haemorrhages, infarcts, contusions and tumours. Cerebral oedema contributes to a rise in intracranial pressure, which can be fatal.
Vasogenic
Increased permeability of capillaries and venules
Cytotoxic
derangement of sodium-potassium membrane pump e.g. ischaemic strokes

Question 19

Where can thromboses form

Answer 19

Veins, arteries and heart.

Question 20

What is a thrombosis

Answer 20

Pathological clot formation in blood vessels (circulatory system) caused by abnormal activation of the haemostatic system.

Question 21

Describe Vichow’s triad (the three factors that predispose thrombosis)

Answer 21

1) Endothelial injury
2) Stasis or turbulent blood flow
3) Blood hypercoagulability

Question 22

How can endothelial injury lead to thrombosis

Answer 22

Endothelial injury leads to platelet activation

Arteries have high rates of blood flow and hence are under high shear stress; this leads to endothelial injury

Question 23

How can a stasis or turbulent blood flow lead to thrombosis

Answer 23

Stasis and turbulent blood flow leads to endothelial injury
Stasis; disruption of laminar blood flow and development of venous thrombi
Turbulent blood; endothelial injury and formation of local pockets of stasis
Turbulent blood ;arterial and cardiac thrombi

Question 24

How can blood hypercoagulability lead to thrombosis

Answer 24

Blood disorder that leads to thrombi formation
Can be primary or secondary
Primary; Factor V mutation, Protein C deficiency
Secondary; Multifactorial, obesity, cancer, stasis, advancing age, use of oral contraceptive pill

Question 25

Describe venous thrombosis

Answer 25

Usually related to stasis of blood and hypercoagulability. Most form in deep leg veins (deep venous thrombosis or DVT). Pulmonary embolism is the most important potential complication Occlusive thrombi; due to sluggish blood flow Composed of red blood cells >platelets Can develop in healthy individuals with no risk factors Veins of lower extremities mostly commonly affected Venous thrombi have characteristic appearances with lines of Zahn (alternating layers of platelets and red blood cells)

Question 26

Describe arterial thrombosis

Answer 26

Almost always related to vessel wall injury caused by atherosclerotic plaques. Narrowing (stenosis) of the artery by thrombus causes ischaemia of the tissue supplied by the artery. Complete blockage (occlusion) of the artery by thrombus causes infarction of the tissue supplied by the artery. Occlusive thrombi composed of platelets, fibrin, red blood cells and leucocytes Mostly in coronary > cerebral > femoral arteries Most commonly superimposed on ruptured atherosclerotic plaques Atherosclerosis leads to endothelial injury and abnormal blood flow

Question 27

Describe cardiac thrombi

Answer 27

Stasis of blood in cardiac chamber-left atrium is associated with atrial fibrillation, left ventricle- myocardial infarct.

Question 28

What are the fates of thrombi

Answer 28

Propagation Accumulation of further platelets and fibrin in a semi-occlusive thrombus Embolisation Thrombi can dislodge and travel through the circulation Dissolution Fibrinolysis in early thrombi; fibrinolytic agents ie t-PA Organisation and recanalization Older thrombi enveloped by fibroblasts, endothelial cells and smooth muscle cells Capillary channels develop within the thrombus These remain clinically silent, and can become significant if they occlude a vessel or embolize.

Question 29

What is meant by an embolus

Answer 29

An embolus is an abnormal detached mass within the circulatory system that is carried within the blood to a site distant from its point of origin. Most emboli (90%)are fragments of a dislodged thrombus (thrombo-emboli). Other types of emboli: Vegetations ( from valves) Gas ( interventional procedures, divers) Fat ( fractures) Tumour Amniotic fluid ( childbirth) Foreign material ( intravenous drug users)

Question 30

What can emboli cause

Answer 30

They can lodge in small vessels and occlude them.

Question 31

What may arise from a venous embolism

Answer 31

Venous emboli travel via the heart into the pulmonary arteries causing pulmonary embolism.

Question 32

What are the potential consequences of an arterial emboli

Answer 32

They may impact in cerebral arteries (causing stroke), the mesenteric arteries (causing small bowel infarction) or the lower limbs (causing acute lower limb ischaemia).

Question 33

Describe pulmonary embolism

Answer 33

Occlusion of pulmonary artery by embolus, which can cause instantaneous death if it occurs in a major pulmonary artery.Emboli lodging in medium sized arteries present with breathlessness. Emboli lodging in small arteries cause subtle symptoms of breathlessness, chest pain, and dizziness – these are the hardest to diagnose- 'silent'. 30% of patients with pulmonary embolism will die from it. The risk of death increases the longer it takes to make the diagnosis.

Question 34

Describe systemic emboli

Answer 34

Arise in the arterial system Originate from 1) dislodged atheromatous or 2)thrombi from within heart Thrombi within the heart: -due to cardiomyocyte death and thus no contractility- left ventricle -due to atrial fibrillation- left atrium Arterial emboli: TIA (transient ischaemic attack), stroke, bowel infarction, limb ischaemia

Question 35

What is meant by an infarct

Answer 35

Tissue necrosis due to ischaemia Most commonly caused by thrombotic or embolic vascular occlusion, though other causes need to be excluded In occlusion of an artery either by thrombosis overlying a complicated atherosclerotic plaque or a thromboembolism (acute MI and cerebral infarction). In venous obstruction the tissue becomes massively suffused with blood and appears dark purple or black (testicular torsion, sigmoid volvulus).

Question 36

Do infarcts normally heal

Answer 36

Infarcts heal by repair. Although structural integrity is maintained, there is permanent loss of functional tissue

Question 37

What are red infarcts

Answer 37

Occur as a result of venous occlusion Occur in loose tissue; lungs Occur in organs with dual circulation ; lung, bowel Can reperfuse a site of previous arterial occlusion

Question 38

What are white infarcts

Answer 38

Occurs as a result of arterial occlusion | In dense/solid organs

Question 39

How can infarcts evolve over time and how are they shaped

Answer 39

Infarcts can be subtle initially and become more prominent with time. They are wedge shaped.

Question 40

How does an infarcted segment of the small bowel appear

Answer 40

dark/dusky

Question 41

Describe myocardial infarction

Answer 41

Most commonly due to coronary artery occlusion Occlusive thrombus in coronary artery Acute plaque change/ rupture Can also be due to : Coronary artery vasospasm Emboli (from left atrium-atrial fibrillation) Vasculitis Haematological abnormalities ( sickle cell disease) There is cardiomyocyte death

Question 42

Why is the diagnosis of myocardial infarction important

Answer 42

Myocardial Infarction can be reversible if treated early in most instances

Question 43

Describe the appearance of a myocardial infarction

Answer 43

Mottled areas ; acute Myocardial Infarction | White areas ; past Myocardial Infarction/ myocardial scarring

Question 44

Where do most pulmonary emboli originate from

Answer 44

DVT (lower extremities).

Question 45

What is meant by a haemorrhage

Answer 45

Extravasation of blood due to tissue rupture.

Question 46

What are the typical causes of a haemorrhage

Answer 46

May be due to trauma or an intrinsic disease of a vessel Amyloid Collagen vascular diseases Rupture of a major vessel causes acute haemorrhage with risk of hypovolaemia, shock and death. Examples include: Abdominal Aortic Aneurysm Brain stem haemorrhage Extravasation of blood due to vessel rupture Even a small bleed at a vital site can be fatal- brainstem.

Question 47

What is hypovolaemia

Answer 47

Low volume of fluid in the blood.

Question 48

What are the typical symptoms of a ruptured abdominal aortic aneurysm.

Answer 48

back pain, hypotension and pulsatile mass

Question 49

What is meant by shock

Answer 49

Generalised failure of tissue perfusion. Systemic hypotension due to 1) reduced circulatory volume or 2)reduced cardiac output

Question 50

What are the typical causes of shock

Answer 50

Pump failure (acute MI) or peripheral circulation failure (hypovolaemia, sepsis, anaphylaxis) leading to circulatory collapse.

Question 51

List the different types of shock

Answer 51

``` Hypovolaemic shock Cardiogenic shock Anaphylactic shock Septic shock Neurogenic shock ```

Question 52

Describe hypovolaemic shock

Answer 52

Loss of blood or plasma due to haemorrhage or fluid loss >1L of blood (20%) Most perfused organs: kidney, brain & skin

Question 53

Describe cardiogenic shock

Answer 53

Effectively the heart isn’t working properly ; numerous causes such as acute MI, arrhythmias, cardiac tamponade (compression of heart due to accumulation of fluid in pericardium). etc Heart cannot pump enough blood to meet body’s demands Caused by acute myocardial infarction High mortality rate

Question 54

Describe septic shock

Answer 54

``` An infection activates immune system ; resultant vasodilatation and pooling of blood Systemic inflammatory response syndrome >2 or more Temperature >38 C or < 36 C Tachycardia >90 bpm Respiratory rare >20 breaths/min or PaCO2 <4.3KPa WBC >12 x109/ L or >10% immature blasts Sepsis SIRS + infection Severe sepsis Sepsis + organ hypoperfusion ``` Septic shock Severe sepsis + hypoperfusion despite adequate fluid resuscitation , or the use of vasopressors/inotropes to maintain blood pressure

Question 55

Describe neurogenic shock

Answer 55

Loss of vascular tone; cord injury, anaesthetic medication

Question 56

Describe the pathogens that may cause septic shock and the mechanisms that these pathogens use

Answer 56

``` Pathogen: Gram positive > Gram negative bacteria > fungi Endotoxins released by pathogens Activate complement pathway Damage endothelial cells Tumour necrosis factor ```

Question 57

What are the complications of septic shock

Answer 57

Organ dysfunction and multi-organ failure Ischemic tissue- Lactic acidosis Acute tubular necrosis

Question 58

What are the typical signs of shock

Answer 58

The patient may look grey and clammy. There it tachycardia (rapid heart rate) and hypotension.

Question 59

What can untreated shocks lead to

Answer 59

Ischaemia of the heart, lungs, gut, kidneys and brain. Rapid treatment is necessary to prevent multiple organ failure and death.

Question 60

What is meant by atherosclerosis

Answer 60

An inflammatory disease of large and medium sized arteries characterised by the formation of lipid-rich plaques in the vessel wall.

Question 61

Describe the causes of atherosclerosis

Answer 61

Risk factors include: older age, male gender, obesity, diabetes mellitus, hypertension and smoking. Endothelial injury leads to an inflammatory and fibroproliferative response culminating in atherosclerosis. Oxidised LDL is a potent driver. Very common, particularly in developed countries.

Question 62

Describe the difference between stable and unstable plaques

Answer 62

Stable plaques cause symptoms of reversible ischaemia of the supplied organ- angina pectoris, chronic lower limb ischaemia. Unstable (vulnerable) plaques can cause acute ischaemic events due to thrombosis overlaying them- acute coronary syndromes and cerebral infarction.

Question 63

How can fluid in the lungs be detected

Answer 63

Fine crackling

Question 64

Why do patients with pulmonary oedema need to lie down

Answer 64

Unable to breath lying flat- need an incline

Question 65

In which tissues does red infarct occur

Answer 65

Tissues with dual circulation such as the lungs.

Question 66

What are the risk factors of DVT

Answer 66

``` Immobility Surgery ( orthopaedic/ pelvic) Trauma Contraceptive pill; oestrogen Thrombophilia Malignancy Obesity Past DVT Increased age Pregnancy ```