GENERAL PATHOLOGY (PART 1)

Dr Amos Tay
Consultant,
Department of Anatomical Pathology,
Singapore General Hospital

[email protected]
PATHOLOGY MODULE OVERVIEW
BS3104 - Pathology
• Module is divided into 2 main segments –
General Pathology and Systemic Pathology
• Delivered over 13 sessions - 2 hours 50 mins
each
• 2 exams:
– Mid term (50 CA MCQs in 1 hour)
– End of term (5 SA short questions in 2.5 hours)
 BS3104 - Pathology
Date Day Lecture Title Lecturer

18-Jan Thu General Pathology I Dr Amos Tay

25-Jan Thu Cardiovascular Pathology Dr Chow Chun Yuen

01-Feb Thu General Pathology II Dr Cheo Fan Foon 50 CA

MCQ
8-Feb Thu Breast & Skin Diseases Dr Tan Yongcheng

15-Feb Thu Endocrine including Pancreas Adj A/Prof Leow Wei Qiang

22-Feb Thu Bone & Joint & Soft Tissue Dr Sathiyamoorthy

29-Feb Thu CA paper (2:30-3:30 pm)/ Diseases of GI Tract Adj A/Prof Leow Wei Qiang

14-Mar Thu Liver & Pancreas Adj A/Prof Leow Wei Qiang

21-Mar Thu Respiratory Diseases Dr Sangeeta Mantoo

5 SA
28-Mar Thu Diseases of Kidney & Urinary Tract Dr Alwin Loh
short
4-Apr Thu Gynae & Reproductive Organs Dr Sangeeta Mantoo questions
11-Apr Thu Haematolymphoid Pathology Dr Amos Tay

18-Apr Thu Genetic basis of diseases and Genetic Diseases Dr Evelyn Heng

07- May Tues SA Paper Adj A/Prof Leow Wei Qiang

BS3104 - Pathology
• References:
– Powerpoint slides
– Robbins Basic
Pathology 10E by
Kumar, Abbas, Aster
(Saunders 2017)
GENERAL PATHOLOGY (PART 1)
What is Pathology?
• The study (logos) of disease (pathos)

• Serves as a bridge between basic science and clinical medicine

– Etiology (cause : Genetic vs Acquired)
– Pathogenesis (Mechanism of development) how to bring about the disease?
– Molecular and morphologic changes (biochemical and structural alterations in
cells and organs)
– Clinical manifestations (Functional consequences: Symptoms and Signs)
Pathology
• General pathology (Week 1 & 2)
– Reaction of cells and tissues to abnormal
stimuli and inherited defects -> Cause of
disease
– Adaptation, inflammation, repair, healing, cell
death, disordered growths

• Systemic pathology (Week 3 onwards)

– Alterations and disorders involving specialized
organs and tissues
 Pathology – How?
• To render diagnoses and guide therapy in
clinical setting -> pathologists identify
changes in gross and microscopic
appearance (morphology) of cells and
tissue

• To understand structural and functional

changes in cells tissues and organs ->
pathologists use molecular, microbiologic
and immunologic techniques etc
Pathology – General
• Approach to the pathological basis of
disease:
– Epidemiology – age, sex, race, location, season
– Aetiology – causes of disease
– Pathogenesis – process/mechanism of disease
– Morphology – appearances at the cellular, tissue
(microscopic) and organ (macroscopic) level
– Clinical manifestation – symptoms and clinical signs
– Treatment principles
Learning Objectives (Gen Path 1)

• Cell injury, cell death and adaptations

• Acute and chronic inflammation

• Haemodynamic Disorders
CELL INJURY, ADAPTATION AND DEATH
Cell injury, adaptation and death (1)

• Cell
– Basic structural, functional and biological
unit of all known living organism
– ‘building block of life’
– Maintain normal homeostasis
• Preserve their immediate environment and
intracellular milieu within a relatively narrow range
of physiologic parameters
• Changes in the cell’s environment causes cell stress
 Cell injury, adaptation and death (2)
• Cell undergoes physiologic stress or pathologic stimuli
– Undergo adaptation, to achieve new steady state and
preserving viability
• Reversible functional and structural responses
• Adaptative response includes: atrophy, hypertrophy,
hyperplasia and metaplasia
– If adaptive capability is exceeded -> cell injury develops
• Cell injury can be:
– Reversible -> if the injury is within a certain limit; cell
return to stable baseline
– Irreversible -> if severe or persistent stress -> cell death
• Two patterns of cell death:
– Necrosis
– Apoptosis
Robbins Basic Pathology 9th Edi, 2013
sudden and severe stress
Cellular adaptation to injury (1)
• Adaptation: Reversible changes in

• Size
• Number
• Phenotype
• Metabolic activity
• Function of cells

• In response to changes in the environment

• Can be physiological
• Functional demand, hormones, growth factors
• or pathological
• Causing cell injury. Some changes always pathological
 Cellular adaptation to injury (2)
• Adaptive response:
– Change in size of cells: -
---trophy

• Hypertrophy (‘hyper’ = increase)

• Atrophy (‘a’ = no)
– Change in numbers of cells:
• Hyperplasia (‘plasia’ = growth
in numbers)
• Hypoplasia
– Change in form and function:
• Metaplasia (‘meta’ = change)
– Others:
• Intracellular accumulation store in cytoplasm
• Leads to change in functional capacity
or function in itself
 Hypertrophy
- Increase in the size of cells, resulting in increase in the size of the organ
- Hypertrophy and hyperplasia, or just hypertrophy (In non-dividing cells)
- Synthesis of more structural components (cellular proteins) -> Larger cells

Stimulus:

- Mechanical sensors
- Growth factors
- Vasoactive agents
 Atrophy
- Reduced size of an organ or tissue from decrease in cell size and number
thymus

Stimulus:

- Decreased workload
(disuse)
- Loss of innervation
(denervation)
- Decreased blood supply
(Ischaemia)
- Inadequate nutrition
- Loss of hormonal
support
- Pressure
 Hyperplasia
Increase in number of cells in organ or tissue
(Cell population capable of dividing)

Stimulus:

- Compensatory
hyperplasia
- Hormones
- Some viral infections benign prostatic hyperplasia
 Metaplasia
One differentiated cell type replaced by another cell type
New cell type may be better able to withstand the adverse environment

squamous is to
better withstand
Stimulus: the change but
environment the cilia function
- Change of milieu is lost
- Physical irritation
- Chemical irritation
 Intracellular accumulation
Intracellular accumulation of abnormal amounts of various substances
A normal cellular constituent, eg. Lipid, protein, carbohydrate e.g. liver, kidneys
Abnormal substance, exogenous or endogenous

Endogenous:
- Inadequate rate of
metabolism to
remove
- Defective enzymes in
metabolism
- Abnormal
endogenous
substance because of
defects in folding,
transport, degradation
Exogenous:
- Cannot metabolise or
transport it away
Cell Injury
• Occurs when injurious stimulus is too
severe and overwhelms adaptative
mechanism
• Can be reversible or irreversible
• Irreversible -> cell death
Causes of cell injury (1)
• Internal factors
– Genetic Derangements
– Gene or chromosomal defects

• External sources
– Deprivation of oxygen (ischaemia, hypoxia)
– Physical agents - trauma, thermal, electric, radiation,
– Chemical agents – acid / alkali, solvents, hypertonic solutions,
drugs
– Infectious agents – bacteria, viruses, fungi, parasites etc
– Immunological reaction – reaction to endogenous antigens
(autoimmune) or external agents
– Nutritional imbalances – protein and caloric deficiency, vitamin
deficiency
– Aging
Causes of cell injury (2)
• VITAMIN D3
– Vascular (includes haematological) – systemic hypertension,
stroke, coronary artery disease, myocardial infarction
– Inflammation and infections
– Traumatic – physical, biological, chemical, environmental,
psychological
– Autoimmune – ie systemic lupus erythematosus
– Metabolic (endocrine) – ie diabetes mellitus, hyperlipidaemia,
osteoporosis, vitamin deficiencies
– Iatrogenic (caused by medical intervention)/Idiopathic
– Neoplastic (benign and malignant)
– Developmental – defect in formation, congenital diseases,
genetic diseases
– Degenerative – eg ageing, regressive
– Drugs (chemicals and toxins) – include medicines, drugs of
abuse, cigarette smoking and alcohol
 Cell Injury – Reversible (1)
ATP to keep the Na out, but no energy, the sodium
• Morphologic changes of come in , water come in

reversible cell injury:

1. Cellular swelling (aka
hydropic change, vacuolar
degeneration)
• Cells incapable of maintaining ionic
and fluid homeostasis (energy
dependent ion pumps in cell
membrane)
• Small clear vacuoles in cytoplasm

• Ultrastructurally:
• Plasma membrane blebbing, blunting
• Mitochondrial swelling and densities
Robbins Basic Pathology 7th Edi, 2003
• ER dilation
• Nuclear alterations
 Cell Injury – Reversible (2)
• Morphologic changes of
reversible cell injury:
2. Fatty change
• Seen mainly in cells active
in fat metabolism ie. liver
cells (hepatocytes) and
heart muscle cells
(myocardium)
• Often in hypoxic, toxic and
metabolic injury
• Microscopy -> lipid
vacuoles in cytoplasm

Fatty liver is due to the deposition of fat, seen here as

white droplets. Normal hepatocytes become vacuolated
and the difference between normal liver becomes very
obvious
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Cell Death (1)
• Cell injury becomes irreversible
• Also plays a central role in multicellular organisms
during their early development in sculpting body
parts and in adult life by controlling cell numbers
• Further protects the organism overall by removal
of cells damaged by disease, aging, infection,
genetic mutation and exposure to toxic agents
• Types:
1. Necrosis Did you know?
Cell death is not always bad
2. Apoptosis - Some tumours are caused by
inability of cells to die!
 Cell Death (2)
• Necrosis (always pathological)
– Lethally injured cell
– Unable to maintain membrane integrity, contents leak out.
– Organelles rupture
– Denaturation of intracellular proteins and enzymatic digestion
– Breakdown of nuclear DNA (pyknosis, karyolysis, karyorrhexis)
– Inflammation in response to leaking contents

– Different patterns : coagulative, liquefactive, fibrinoid,

caseation, fat, gangrene
– Often a large group of neighbouring cells
 Cell Death (2)
• Apoptosis
– Tightly regulated, Programmed cell death (cell suicide)
– Can be both pathological or physiological (embryonic
development, normal cell turnover)

– Cell shrinkage, Chromatin condensation

– Activation of Caspases (a family of cysteine proteases)
– Activate enzymes to degrade nuclear DNA, nuclear and
cytoplasmic proteins
– Plasma membrane intact, no inflammatory response
– Cytoplasmic blebs and apoptotic bodies
– Phagocytosis of apoptotic bodies
– Generally scattered individual cells undergo apoptosis.
the neighbours come and eat it
 Robbins and Cotran’s Pathological Basis of Disease 8th Edi, 2010

Nuclear changes include:

a. Pyknosis: irreversible
condensation of chromatin and
shrinkage of the nucleus.
b. Karyorrhexis: fragmentation of
the nucleus.
c. Karyolysis: dissolution
of the nucleus.
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Necrosis – 6 Patterns
must know

• Coagulative
• Liquefactive
• Gangrenous
• Fat necrosis
• Fibrinoid
• Caseous
Coagulative necrosis death caused by blood loss
• Seen in infarcts/ischaemia of any solid organ (except brain)
• Gross: tissue is firm and pale
• Micro:
• Preservation of the basic structural outline and architecture of
cells (Ghost outlines)
• Cytoplasmic eosinophilic
• Loss of nuclei (Chromatin clumping, pyknosis, karyorrhexis,
karyolysis)
 Liquefactive necrosis in patient who suffered from a stroke

Liquefactive necrosis
• Digestion of dead cells, tissue transforms into liquid viscous mass.
• Seen in infections (enzymes from leukocytes) and brain infarcts
• Gross: tissue is liquid-like and creamy yellow (pus)
• Micro: Mainly neutrophils and cell debris (abscess)
 https://en.wikipedia.org/wiki/Gangrene

Gangrenous necrosis
• More of a clinical term; seen in limbs with decreased blood
supply (ischaemic coagulative necrosis), necrosis involving
multiple tissue planes
• if with superimposed infection with liquefactive component =
wet gangrene and dry gangrene
• Gross: skin looks black and dead; underlying tissue in varying
stages of decomposition
Fat necrosis
• Seen in acute pancreatitis due to enzymatic
destruction
• Gross: chalky, white areas from combination of
newly formed free fatty acids with calcium (fat
saponification)
• Micro: shadowy outlines of dead fat cells; Normal fat cells
sometimes with basophilic (bluish) cast from
calcium deposits
Fibrinoid necrosis too much antigens

• Seen in immune reactions involving blood vessels

• Gross: changes too small to see grossly
• Micro: vessel walls are thickened and ‘fibrinoid’ (Bright
pink and amorphous)
Caseous necrosis
• Seen in tuberculosis
• Gross: white, soft, cheesy-looking (‘caseous’) material
• Micro: fragmented cells and amorphous debris surrounded by
a collar of lymphocytes and macrophages (granuloma)
Summary
- Cellular swelling
- Fatty change

- Hyper/Atrophy
- Hyper/Hypoplasia
- Metaplasia

- Coagulative necrosis
- Liquefactive necrosis
- Gangrenous necrosis
- Fat necrosis
- Fibrinoid necrosis
- Caseous necrosis
 Normal cell is in
H___________ Irreversible injury leads
to C____ D_____

A cell that is stressed will

try undergo Two types of Cell death are
A___________ N_______ (a messy disorganized
death) and
Types of adaptation A_______ (a silent and tidy death)
include
Differences between necrosis
H________ and apoptosis include
A________
- Loss of M_______ integrity

H________ - Presence of I________

H________
- Necrosis is always
P______ but apoptosis can
M________ be P______ or P______

Stresses beyond the Types of necrosis:

inability to adapt leads to C________
I_____ L________
G________
C________
Injury can be
F___
R____ or I______
F________
ACUTE AND CHRONIC INFLAMMATION
 Inflammation – General (1)
• INFLAMMATION – Protective response:
• Aims:
• Eliminate cause of cell injury
• Eliminate consequences of injury (necrotic
cells and tissues)
• Bring about healing and repair (Gen path 2)

• The same stimuli that causes cell injury also

elicit a complex reaction in vascularized
connective tissues called inflammation
Inflammation – General (2)
• Divided into 2 patterns:
– Acute
• Relatively short duration (few minutes to few days)
• Characterized by fluid and plasma protein exudation and
neutrophilic accumulation
white blood cells
– Chronic
• Longer duration (days to years)
• Characterized by influx of lymphocytes and
macrophages with associated vascular proliferation and
scarring
Inflammation – General (3)
• Initiators of inflammation

• Infections
• Trauma (physical / chemical)
• Tissue necrosis (from any cause)
• Foreign body
• Immune reaction (Hypersensitivity, autoimmune)
Components of acute and chronic
inflammatory response

Robbins Basic Pathology 7th Edi, 2002

Acute inflammation (1)
• Immediate and early response to injury
– Innate (non-selective but rapid)

– 2 major components (occur at same time):

1. Vascular changes
– Vasodilation: Changes in vascular caliber and flow
– Increase vascular permeability (allow plasma protein and
fluid move out of blood vessels) more leaky now
2. Cellular events
– Emigration of neutrophils (polymorphonuclear
leukocytes) from microcirculation and accumulation in
the focus of injury
– Activation of leukocytes
– Chemical mediators = cellular and plasma proteins
Acute inflammation (2)
• 5 classic local signs of acute inflammation:
– Heat (calor)
– Redness (rubor)
– Swelling/oedema (tumor)
– Pain (dolor)
– Loss of function (function laesa)
Acute inflammation (3)
• Vascular changes
1. Changes in vascular caliber and flow
• After transient (seconds) vasoconstriction, arteriolar
first thing to occur
VASODILATION occurs (induced by chemical mediators such as
histamine and NO) -> increased blood flow and engorgement of
the down-stream capillary beds -> Redness (erythema) and
warmth
• As microvasculature becomes more permeable -> movement of
protein rich fluid into extravascular tissue (causing edema) -> red
blood cells more concentrated, therefore increase blood viscosity
and slowing circulation (stasis)
• As stasis develops, neutrophils start to settle out of flowing blood
and accumulate along the vascular endothelial cells
(margination)
Robbins and Cotran’s Pathological Basis of Disease 8th Edi,
2010
Acute inflammation (4)
• Vascular changes
2. Increased vascular permeability
• Contraction of endothelial cells, Endothelial injury, Increased
transcytosis (transport of fluid and protein through the cell)
• Movement of protein-rich fluid and even blood cells into the
extravascular tissues -> increased osmotic pressure of the
interstitial fluid, which lead to more outflow of water from the
blood into the tissue (exudate)

Robbins Basic Pathology 9th Edi, 2013

Robbins and Cotran’s Pathological Basis of Disease 8th Edi,
2010
Acute inflammation (4)
• Cellular events (inflammatory cells)

• Recruitment selectins
WBC roll along the blood vessel wall
1. MARGINATION and ROLLING
2. ADHESION and TRANSMIGRATION (DIAPEDESIS)
between endothelial cells
3. MIGRATION (CHEMOTAXIS) in interstitial tissues
towards a chemotactic stimulus down the conc. gradient
• Activation reach liao do what?

1. Phagocytosis
2. Killing and degradation (ROS, NO, enzymes)
3. Mediators (cytokines) – amplify inflammation and
systemic effects.
Margination Rolling Adhesion Transmigration

L-selectin

Chemotaxis

The multistep process of leukocyte migration through blood vessels, shown here for neutrophils. The leukocytes first roll, then
become activated and adhere to endothelium, then transmigrate across the endothelium, pierce the basement membrane, and
migrate toward chemoattractants emanating from the source of injury. Different molecules play predominant roles in different
steps of this process—selectins in rolling; chemokines (usually displayed bound to proteoglycans) in activating the neutrophils to
increase avidity of integrins; integrins in firm adhesion; and CD31 (PECAM-1) in transmigration. Neutrophils express low levels of
L-selectin; they bind to endothelial cells predominantly via P- and E-selectins. ICAM-1, intercellular adhesion molecule 1; TNF,
tumor necrosis factor. th
Robbins and Cotran’s Pathological Basis of Disease 8 Edi, 2010
 Robbins and Cotran’s Pathological Basis of Disease 8th Edi, 2010

• Although the process is similar for all other leukocytes, note

that neutrophils, monocytes, eosinophils and various types of
lymphocytes use different (but overlapping) molecules for
rolling and adhesions
• The type of recruited leukocytes depends on nature of
inciting stimulus as well as age of the inflammatory site
• Neutrophils for first 6-24 hours
• Monocytes in subsequent 24-48 hours
Chemical mediators of inflammation
fever and pain COX enzyme!!!

Antihistamines

anti-inflammatory
Aspirin, NSAIDs

Robbins Basic Pathology 9th Edi, 2013

Systemic Effects of Inflammation
• Constitutional symptoms eg fever
• Multi-organ dysfunction and sepsis
(septicaemia)
• Septic shock
• Disseminated intravascular coagulation
(DIC/DIVC)
– Aka consumption coagulopathy – bleeding
tendency
• Death (in the most severe cases)
liquefactive!
 Chronic inflammation (1)
• Inflammation of prolonged duration (weeks to
months to years) in which inflammation, tissue
injury and healing proceed simultaneously
• Characterized by the following:
– Infiltration with mononuclear (‘chronic inflammatory’)
cells including macrophages, lymphocytes and plasma
cells
– Tissue destruction, largely
directed by the inflammatory cells
– Repair, involving new vessel
proliferation (angiogenesis) and fibrosis
collagen
Chronic inflammation (2)
• Chronic inflammation arises in the following
settings:
– Viral infections
– Persistent microbial infections – especially
mycobacteria (tubercle bacilli), Treponema
pallidum (syphilis), and fungi
– Prolonged exposure to potentially toxic agents (ie
silica -> silicosis in lung; lipid -> atherosclerosis in
vessels)
– Autoimmune disease (immune response to self-
antigens and tissues)
must know TB

Granulomatous inflammation
• Specific form of chronic inflammation
• Due to prolonged inflammation related to infectious
agents or foreign materials difficult to remove or degrade
– Infective agents -> mycobacterium tuberculosis,
mycobacterium leprae, fungi
– Foreign materials – foreign bodies introduced via
trauma or iatrogenic ie suture, splinter, breast implant
• Distinctive morphology
• Aggregate of epithelioid macrophages (pink granular
cytoplasm) very activated histiocytes same as macrophages
• Surrounded by mononuclear cells (especially
lymphocytes)
• Often Multinucleated giant cells
• Older granulomas with surrounding fibrosis
lymphocytes
 Summary - INFLAMMATION
Cardinal signs
Minutes to days
1. H _ _ _ (Calor) Days to years
2. R_ _ _ _ _ _ (Rubor)
A_ _ _ _ inflammation C _ _ _ _ _ _ inflammation
3. S_ _ _ _ _ _ _ (Tumor)
4. P_ _ _ (Dolor)
5. Loss of F_ _ _ _ _ _ _
1. Infiltration with
M_ _ _ _ _ _ _ _ _ _ cells
Mediators
V_ _ _ _ _ _ _ C_ _ _ _ _ _
events Can be 2. Tissue D_ _ _ _ _ _ _ _ _ _
changes
C_ _ _ -derived
Eg. Prostaglandins, 3. Ongoing R_ _ _ _ _
Type of white blood cell: Histamine, Nitric Oxide
N_ _ _ _ _ _ _ _ _ A special type of chronic
1. V_ _ _ _ _ _ _ _ _ _ _ _ _ Or P_ _ _ _ _ protein derived inflammation (eg. In TB, foreign
Changes in vessel caliber Eg. Complement body) is
and flow and stasis

2. Increased vascular RECRUITMENT G_ _ _ _ _ _ _ _ _ _ _ _

P_ _ _ _ _ _ _ _ _ _ _ 1. Margination Inflammation.
Leads to exudate of protein 2. R_ _ _ _ _ _ ACTIVATION
rich fluid 3. Ad_ _ _ _ _ _ 1. P_ _ _ _ _ _ _ _ _ _ _ Accumulation of
4. Di_ _ _ _ _ _ _ 2. K_ _ _ _ _ _
Ep _ _ _ _ _ _ _ _ macrophages
(Transmigration through 3. Amplify inflammation by
the vessel wall) producing mediators
5. Ch_ _ _ _ _ _ _ _ (Cy_ _ _ _ _ _ _ ) Sometimes
towards stimulus along Multinucleated
a gradient G_ _ _ _
cells
HEMODYNAMIC DISORDERS
Haemodynamic disorders
• Health of cells and tissue depend not only on
intact circulation to deliver oxygen and remove
wastes, but also on normal fluid homeostasis
• Normal homeostasis encompasses maintenance
of vessel wall integrity as well as intravascular
pressure and osmolarity within certain physiologic
ranges
• Normal fluid homeostasis also mean maintaining
blood as liquid until such a time as injury
necessitates clot formation
impt

forces that
governs
the fluid
movement
s
outgoing blood pressure

pull water back into the blood

Haemodynamic disorders
• Oedema
• Hyperemia and congestion
• Coagulation disorders
– Normal clotting pathway
– Virchow’s triad
– Example of clotting disorders
• Embolism
• Shock
 Oedema Tumor-- swelling

• Increased fluid in the interstitial tissue spaces

– In pleural cavity = hydrothorax
– Around the heart = hydropericardium
– In abdominal cavity = hydroperitoneum / ascites
– Subcutaneous tissue (severe, generalized) =
anasarca
• Factors that can cause oedema
net movement – Increased hydrostatic pressure
to interstitial space
– Reduced plasma osmotic pressure
– Lymphatic obstruction
– Inflammation dilation and permeability
– Sodium and water retention
 3

2
Hyperemia and Congestion
• Hyperemia and congestion both refer to an
increase in blood volume within a tissue, but they
have different underlying mechanism
– Hyperemia
• active process resulting from arteriolar dilation and
increased blood flow (ie sites of inflammation, exercising
skeletal muscle)
• Looks redder than normal due to engorgement with
oxygenated blood
– Congestion
• passive process resulting from impaired outflow of venous
blood from a tissue
• Can occur systemically (cardiac failure) or locally
• Looks blue-red colour (cyanosis) due to accumulation of
deoxygenated hemoglobin in affected area
Hyperemia and Congestion

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Coagulation Disorder
• Normal clotting pathway

• Virchow’s triad

• Example of clotting disorders

 (Platelet plug formation)

(Coagulation)

Normal hemostasis:
3 processes:
1. Vasoconstriction – causing reduced blood flow to the site of injury
2. Platelet plug formation – platelets aggregate to the site of injury. They stick together acting as a ‘plug’
(temporary). Platelets also activate coagulation (for formation of fibrin clot)
3. Coagulation - Platelets alone are not enough to secure the damage in the vessel wall. A clot must form at the
site of injury. The formation of a clot depends upon several substances called clotting factors which activates
clotting cascade. The end result of this cascade is that fibrinogen, a soluble plasma protein, is cleaved into
fibrin, a nonsoluble plasma protein. The fibrin proteins stick together forming a clot.
Robbins and Cotran’s Pathological Basis of Disease 8th Edi, 2010
Vasoconstriction
Reflex neurogenic mechanisms
Local secretion of factors

But transient effect

Platelets AAA

ADHESION to extracellular matrix

ACTIVATION
-Change of shape
-- Release of granules

-AGGREGATION to form a
haemostatic plug
 Coagulation cascade proteins by the liver
converge at thrombin
Extrinsic Pathway
The extrinsic pathway is activated by tissue
factor (Factor III) expressed at sites of
injury

Intrinsic Pathway
The intrinsic pathway is activated by
trauma inside the vascular system
Activated by platelets, exposed
endothelium, chemicals, or collagen
(exposure of factor XII to thrombogenic
surface)

Common Pathway
Both pathways converge on activation of
factor X -> Activation of thrombin ->
Convert fibrinogen to FIBRIN
Fibrin protein sticks together to form a
clot. soluble to insolube mess clog

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 very impt

Virchow’s triad
• Three primary influences predispose to
thrombus formation (Virchow’s triad)
1. Endothelial injury
2. Blood hypercoagulability
3. Alteration in normal blood flow (to stasis or
turbulence)
anti-clotting to clotting phenotype increase the clotting factors

very rare more common

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Example of clotting disorders
• Hypocoagulability states
– X-linked recessive genetic disorders
• Hemophilia A – Factor VIII deficiency
• Hemophilia B – Factor IX deficiency
– Sepsis – DIVC

• Hypercoagulable states
– Primary
• Rare – factor V mutation, protein C and protein S deficiency
– Secondary causes
• More common – prolonged bed rest and immobilisation; atrial fibrillation; prosthetic cardiac
valve
 Embolism (aka things that block blood vessels)
• An embolus is a detached intravascular solid, liquid or
gaseous mass that is carried by the blood to a site
distant from its point of origin
• 99% of all emboli represent some part of a dislodged blood
thrombus, hence commonly termed thromboembolism
• Rare forms of emboli include: fat (after long bone
fracture), bubbles of air or nitrogen, bits of bone
marrow, atherosclerotic debris (cholesterol emboli)
amniotic fluid or foreign bodies such as bullets
• Inevitably, emboli lodge in vessels too small to permit
further passage -> lead to partial or complete vascular
occlusion -> ischaemic necrosis of downstream tissue
(infarction)
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https://www.drugs.com/cg/deep-venous-thrombosis.html
originated from the leg
terminology definition
Infarct = area of ischemic necrosis caused by
Red infarct = haemorrhagic
occlusion of either the arterial supply or the
White infarct = anaemic
venous drainage in a particular tissue
 Shock
• Fall in blood pressure (systemic hypotension) due to
various reasons – usually final common pathway for a
number of potentially lethal clinical events
• Example of causes
– Loss of blood volume (severe haemorrhage)
– Infections
– Heart (pump) failure (large myocardial infarction)
– Anaphylaxis (type 1 hypersensitivity)
– Trauma (eg brain)
• Shock leads to hypoperfusion -> decreased oxygen
supply, tissue ischaemia and local anaerobic respiration
to the peripheral organs
 important causes of shock

same volume but filling bigger

space
myocardial infarction Filling a larger container =
heart failure Distributive shock
- sepsis, anaphylaxis,
neurogenic
huge infection,blood vessel
Pump failure =
Cardiogenic shock dilation, allergies, loss of fluid to
peripheral, sudden loss of
spinal???

Block in the pipe = Water leak = Hypovolemic shock

pulmonary embolism Obstructive shock
can be caused by dehydration
Other types of shock: Robbins and Cotran’s Pathological Basis of Disease 8th Edi, 2010

- Obstructive shock (embolism)

- Neurogenic shock (anesthetic accident or spinal cord injury -> loss of vascular tone
and peripheral pooling of blood)
- Anaphylactic shock (associated with systemic vasodilation and increased vascular
permeability)
- (Note: Distributive = septic, neurogenic and/or anaphylactic shock)
Summary (1)
Summary (2)