HAEMODYNAMIC DISORDERS,

THROMBOSIS & SHOCK

Dr Mbayah Etabalé
Anatomical Pathologist and Lecturer of Pathology
Maseno University
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Introduction
• The cardiovascular system, CVS, is composed of 3 major components:
• Blood
• Haemodynamics
• Haemostasis
• Embolism
• Blood vessels
• Heart
• Disorders affecting one component lead to adaptations and abnormalities
involving the others
• This discussion covers NOT the diseases of blood vessels, but what can go
wrong with the fluid inside them
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Definition of Terms
1. Oedema – increased fluid in the extracellular compartment
2. Hyperaemia – increased flow of blood
3. Congestion – stagnation of blood
4. Haemostasis – maintenance of fluid state of blood
5. Haemorrhage – extravasation of blood beyond the vessel
6. Thrombosis – in vivo clot formation
7. Embolism – downstream travel of a clot
8. Infarction – tissue death due to inadequate blood supply
9. Shock – inadequate perfusion of tissues with blood
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1. OEDEMA
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Oedema
• Can result from either disturbances
in Starling forces or from damage to
the capillary wall e.g. in inflammation
• Deranged Starling forces →
transudate
• Damaged capillary wall → exudate
• List 5 differences between a
transudate and an exudate

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Systemic Oedema

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Oedema
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More on Oedema
Manifestation of Oedema Clinical Consequences of Oedema

• Subcutaneous → pitting • Signal of potential underlying cardiac or

• Dependent renal disease
• Generalised = anasarca • Impairment of wound healing; clearing of
• Cardiac failure oedema infection
• LH • Pulmonary oedema
• Pulmonary • Impaired respiration
• RH • Fertile ground for infections
• Generalised • Brain oedema
• Periorbital → renal cause • Life-threatening
• Closed cavity, no expansion → herniation
• Tonsillar herniation
• Uncal herniation
• Subfalcine herniation
• Impaired cerebral perfusion
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2. HYPERAEMIA AND CONGESTION

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Hyperaemia Congestion
1. Local increase in blood volume due 1. Local increase in blood volume due
to arteriolar dilatation (active) which to reduced outflow of blood (passive)
leads to increased blood flow 2. Localised or Systemic
2. Localised • Localised – isolated venous obstruction
3. Results in erythema • Systemic – CCF
3. Results:
• Cyanosis
• Increased hydrostatic pressure
• Oedema
• Capillary rupture
• Chronic hypoxia
• Ischaemic tissue injury & scarring
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Acute Passive Congestion, Liver

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2. HAEMOSTASIS
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Haemostasis
• Formation of a haemostatic clot at sites of vascular injury
• 3 players:
1. Vascular wall
2. Platelets
3. Coagulation cascade
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1. Arteriolar Vasoconstriction
• Neurogenic reflex
• Endothelin

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2. Primary Haemostasis
• Platelet adherence
• vWF receptor Gp Ib
• Platelet activation
• Platelet aggregation

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The Granules
α-granules δ-granules

1. P-selectin 1. ADP
2. Fibrinogen 2. ATP
3. Fibronectin 3. Ca+2
4. Factor V 4. Histamine
5. PDGF 5. 5-HT
6. TGFβ 6. Adrenaline
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3. Secondary Haemostasis
• Tissue factor/thromboplastin
• Coagulation cascade

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4. Clot Stabilisation and Resorption

• Clot remodelling

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3. HAEMORRHAGE
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Patterns of Tissue Haemorrhage

1. Petechia: 1 – 2 mm haemorrhages • Increased vascular fragility
into skin, mucous membranes, 3. Ecchymosis: > 1cm
serosal surfaces 4. Haematoma
• Locally increased intravascular pressure
5. Serous cavity bleeding
• Thrombocytopenia
• Pleural cavity - haemothorax
• Defective platelet function
• Pericardial cavity - haemopericardium
2. Purpura: > 2 mm but less than 1 cm • Peritoneal cavity - haemoperitoneum
• Locally increased intravascular pressure
• Thrombocytopenia
• Defective platelet function
• Trauma
• Vasculitis
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Evolution of the Haemorrhage

RBCs > DeO2 > RBC

breakdown to biliverdin >
bilirubin > haemosiderin

Red > Purple > Green >

Brown
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Clinical Significance of Haemorrhage

• Volume of bleeding
• Large volume losses → haemorrhagic shock
• Rate of bleeding
• Slow bleeds more tolerable than rapid bleeds
• Location of bleeding
• Intracranial bleeding
• Intra-abdominal bleeding
• Internal vs external blood loss
• External haemorrhage → Fe deficiency
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4. THROMBOSIS
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The Triad
1. Endothelial injury
2. Abnormal blood flow
3. Hypercoagulability of blood
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Endothelial Injury
• Most important factor especially in the arterial circulation/cardiac chambers
• Examples:
1. Myocardial infarction
2. Ulcerated atherosclerotic plaques
3. Traumatic vascular injury
4. Vasculitis
• Ditto any circumstance that will lead to endothelial activation = endothelial
dysfunction
1. Hypertension
2. Diabetes mellitus
3. Cigarette smoking
4. Hypercholesterolaemia
5. Bacterial endotoxin
6. Radiation exposure
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Abnormal Blood Flow

• Normal flow is laminar flow
• Blood cells including platelets are
central
• Plasma more peripheral
• Abnormal flow can be turbulent
or static
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Abnormal Blood Flow

Turbulent Flow Stasis

1. Injures the endothelium → 1. Brings platelets into contact with

endothelial dysfunction the endothelium
(procoagulant shift) 2. Prevents dilution of activated
2. Brings platelets into contact with clotting factors by fresh blood
the endothelium 3. Slow the inflow of clotting factor
3. Causes eddies and local pockets inhibitors
of stasis 4. Allows clot to grow
4. Significant in arterial circulation 5. Significant in venous circulation
and cardiac chambers
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Abnormal Blood Flow

Turbulent Flow Stasis

• Causes • Causes
1. Atherosclerotic plaques 1. Aneurysms
2. Intravascular clots 2. MI
3. Valvular stenosis 3. Dilatation of a heart chamber
4. Atrial fibrillation
5. Cardiac failure
6. Hyperviscosity syndromes
7. Vascular occlusion
8. Prolonged bed rest/immobilisation
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Hypercoagulability
• An alteration in the coagulation • Secondary/acquired thrombophilia
pathway that predisposes to • High risk
thrombosis 1. Tissue damage (burns, trauma, surgery)
2. Cancer
• Primary/genetic thrombophilia
3. DIC
• Mutation in factor V gene
4. Heparin-induced thrombocytopenia (HIT)
• Resistant to degradation by Protein C syndrome
• Mutation in prothrombin gene 5. Antiphospholipid syndrome
• Increased prothrombin transcription • Low risk
• Homocysteinaemia 1. Hyperoestrogenic states
• Crosslinking with fibrinogen 2. OCPs
• Antithrombin II deficiency 3. Smoking
• Protein C deficiency 4. Obesity
• Protein S deficiency 5. Advancing age
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Morphology
• Focal attachment to endothelium • Septic vegetations
• Sterile vegetations
• Laminations – Lines of Zahn
• Antemortem clots vs postmortem clots
• Arterial thrombi vs Venous thrombi
• Arterial thrombi
• Heart/aorta = mural thrombi • List 4 differences between arterial and
• Occlusive venous thrombi
• Retrograde propagation • List 4 differences between
• Venous thrombi antemortem and postmortem clots
• Aka phlebothrombosis
• Red/stasis thrombi
• Anterograde propagation
• Thrombi on heart valves = vegetations
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Occlusive Arterial Thrombus Occlusive Venous Thrombus

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Fate of a Thrombus
1. Dissolution
2. Organisation
3. Recanalisation
4. Propagation
5. Embolisation
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6. EMBOLISM
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Embolus
• A detached solid, liquid or gaseous intravascular mass that is carried by blood
from one point to a distant site
• Examples:
• Thrombus → thromboembolism
• Fat droplets
• Bone marrow
• Air bubbles e.g. N2 in dysbarism
• Atherosclerotic debris
• Foreign bodies
• Amniotic fluid
• Lodge in downstream vessels that are too small to allow further passage →
occlusion → infarction
• Can be pulmonary or systemic
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Pulmonary Thromboembolism (PTE)

• Risk factors: • Most are silent (small arteries). They
• Immobilisation eventually organise
• Trauma • Complications occur when ≥ 60% of
• Surgery the circulation is obstructed:
• Pregnancy • Sudden death (cardiovascular collapse)
• OCP use • Cor pulmonale
• Malignancies
• Multiple emboli over time cause
• Previous PTE
pulmonary hypertension and eventual
• 95% originate from DVT RVF
• Pelvic / lower limb veins > vena cava >
heart chambers > main pulmonary artery >
bifurcation of pulmonary artery > small
branches of pulmonary artery
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Systemic Thromboembolism
• Sources: 4. Kidneys
1. Intracardiac thrombi – commonest, 80% 5. Spleen
1. Left ventricular wall infarct 6. Upper extremities
2. Left atrial dilatation and left AF • Generally, systemic emboli cause
2. Aortic aneurysms infarction
3. Thrombosed atheromas
• Whether infarction occurs depends
4. Valvular vegetations
on:
5. Paradoxical embolism
• Calibre of the vessel
6. Unknown origin
• Availability of collateral circulation
• Sites: • Susceptibility to ischaemia
1. Lower limbs
2. Brain
3. Intestines
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Fat and Marrow Embolism

• Setting
• Fractures of long bones
• Soft tissue trauma/burns
• Venular/bone marrow sinusoidal rupture with entry of fat globules into the
circulation
• Usually insignificant; only about 10% of patients develop symptoms (fat
embolism syndrome):
• Pulmonary insufficiency: tachypnoea, dyspnoea; tachycardia
• Neurologic symptoms: irritability, restlessness, delirium, coma
• Thrombocytopenia
• Anaemia
• Death
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Air Embolism
• Entry of gas bubbles into circulation
• At least 100 mL is needed before clinical manifestations
• Sources
• Accidental during invasive surgical procedures
• Traumatic chest wall injuries
• Dysbarism
• Consequences:
• Bends: pain in skeletal muscle and soft tissue within and around joints
• Chokes (respiratory distress)
• Caissons disease: ischaemic necrosis of bones due to chronic decompression sickness
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Amniotic Fluid Embolism (AFE)

• Peripartum obstetric complication
• Rare: 1 in 40 000 deliveries
• Generally bad outcome: 80% mortality
• Survivors have long-term neurologic defects
• Amniotic fluid enters maternal circulation through venous sinuses in the
placental bed, uterine tears, cervical tears or rupture of uterine vein
• Amniotic fluid impacts in the pulmonary circulation leading to respiratory
distress
• Amniotic fluid is highly thrombogenic leading to DIC
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Disseminated Intravascular Coagulopathy (DIC)

• Widespread thrombosis within
the microcirculation
• Consumptive coagulopathy
duet due to depletion of
platelets, coagulation factors
• Subsequent activation of
fibrinolytic system

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7. INFARCTION
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Infarct
• An area of ischaemic necrosis
• Can be arterial or venous
• Causes
1. Thrombotic events
2. Embolic events
3. Vasospasm
4. Haemorrhage into an atheroma
5. Extrinsic vessel occlusion
6. Torsion of a vessel
7. Traumatic rupture
8. Compartment syndromes
9. Entrapments
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Classification
• Red infarct (haemorrhagic) • Septic infarct
1. Venous occlusion • Causes
2. Loose tissue where blood collects (lungs) • Embolisation of infected material e.g., vegetation
in infective endocarditis
3. Dual circulations (lungs, intestines)
• Secondary infection of an infarcted tissue
4. Previously congested tissue
• Subsequent abscess formation
5. Reperfusion of infarcted areas
• Repair by organization and fibrosis
• White infarct (anaemic / pale infarct)
• Arteries of solid organs with end-arteries
(heart, kidney, spleen) • Bland infarct
• Wedge-shaped
• Occluded vessel at the apex, infarcted
tissue forming the base
• Acutely, they are ill-defined; better
delineated with time
• Pale infarcts become even paler with time
• Red infarcts become firmer and browner with
time e.g. lung
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Source: Grant’s Dissector, 13e

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Factors Influencing Infarct Formation

1. End-arterial blood supply vs dual blood supply
2. Rate of development of occlusion
3. Vulnerability of affected tissue to hypoxia
4. Oxygen content in blood
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8. SHOCK
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Shock
• Inadequate tissue perfusion with inadequate cardiac output, whether relative
or absolute
• This leads to an initial reversible injury; sustained shock eventually leads to
irreversible tissue injury
• Classification
• Cardiogenic shock
• Hypovolaemic shock
• Distributive shock
• Anaphylactic shock
• Septic shock
• Neurogenic shock
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Sepsis / Septic Shock

• Definitions
• Sepsis – Systemic response to infection (Systemic Inflammatory Response Syndrome –
SIRS)
• Septic Shock – Hypotension secondary to sepsis
• Severe Sepsis – Organ dysfunction due to sepsis
• Septic shock has mortality rates of ≥ 20%
• Increasing rates due to:
• Improved life-support-management of critically ill patients
• Increased population of immunocompromised individuals (HIV, chemotherapy, radiotherapy,
increased number of ageing people, immunosuppressed individuals)
• Increasing use of invasive techniques
• Increase in MDR organisms
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Pathogenesis of Septic Shock

1. Recognition of microbial products
by host cells (Mø, Nø, EC) with
subsequent activation of the cells

2. Production of inflammatory 3. Triggering of anti-inflammatory

cytokines (TNF, IL-1, IL-6, IFN-γ, IL-8, (IL-10, TGF-β, STNFR, IL-1
IL-12, IL-18), mediators of antagonist),
inflammation (PGs, LTE, histamine, anticoagulant/fibrinolytic system
PAF), ROS, CAMs; triggering of
coagulation-complement-kallikrein
pathways

a) Acute-phase reaction – ↑WBCs, ↑ESR, fever, ↑CRP

b) DIC
c) Metabolic derangements – lactic acidosis, hyperglycaemia, electrolyte imbalance
d) Immune suppression
e) Organ dysfunction – renal, cardiac, pulmonary, adrenocortical
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Stages of Shock
1. Non-Progressive / Compensatory Phase
• Reflex compensatory mechanisms are activated
thereby maintaining organ perfusion
• Examples:
• Baroreceptor reflexes
• Catecholamine release
• Renin-angiotensin aldosterone system
• Sympathetic nervous system activation
2. Progressive Phase
• Tissue hypoperfusion persists despite reflex
compensatory mechanisms
• Injury due to hypoxic insult
3. Irreversible Phase
• Widespread irreversible cellular and tissue injury
due to persistent hypoperfusion
• Despite corrective efforts, survival is not possible
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The End