Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam Pathology notes prepared by Agam Divide and Rule
2020 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pathology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Vignesh M, who took the responsibility of leading the
team. The following are the name list of the team who worked together, to bring out the material in
good form.

Neelavathi S
Prasanna Sri P
Projatna Chaudhuri
Shalika G
Shenbaga Praveen N
Vignesh J
Keerthana M
Advaitha Ashwath
Sarah
Shivangi Pal
Vishnu Harish
Muthamil Selvi E
Kaushik N R
Vignesh. M
 HEMODYNAMIC DISORDERS

ESSAY
1. Edema.
2. Thrombosis.
3. Shock.

SHORT NOTES
1. Morphology of infarct
2. Fat embolism
3. Amniotic fluid embolism
4. Decompression sickness
5. Thromboembolism

SHORT ANSWERS
1. Difference between thrombus and blood clot
2. Difference between transudate and exudate
3. Types of embolism
4. Heart failure cells
5. Hyperemia and congestion
6. Lines of Zahn
7. Gamna Gandy bodies

UPDATES

PATHOLOGY AGAM
ESSAY
1. EDEMA
• Accumulation of fluid in interstitial tissue space is called as oedema.
• Disorders that perturb cardiovascular, renal, or hepatic function are often marked by
oedema and effusions

↑ Hydrostatic pressure Edema ↓ Osmotic pressure

When,
Net rate of fluid movement >>> Rate of lymphatic drainage → Oedema or Effusion

Inflammatory Non- Inflammatory

Protein-rich exudates Protein-poor transudate
Due to increased vascular hydrostatic pressure
Due to increased vascular permeability
and decreased colloid osmotic pressure

CAUSES OF EDEMA
➢ Increased Hydrostatic Pressure
• Impaired venous return
o Localised
✓ Deep vein thrombosis in lower limb,
✓ External pressure,
✓ Venous obstruction
o Systemic
✓ Liver cirrhosis,
✓ Long heart failure
• Arteriolar dilatation
✓ Heat,
✓ Neuro-humoral dysregulation
➢ Reduced Plasma Osmotic Pressure
• Due to decreased secretion of albumin
✓ End stage cirrhosis
✓ protein energy malnutrition
• Due to increased loss of albumin
✓ Nephrotic Syndrome

AGAM PATHOLOGY
 Reduced plasma Oncotic pressure

Due to low albumin content SystemDecreased Intravascular

volume
Increased blood volume Renal hypo perfusion

Secondary hyperaldosteronism

➢ Sodium & Water retention

Heart Failure ↓ Renal Blood Flow

Activation of Renin Angiotensin

Renal Failure Retention of Sodium and Water

↑ Blood Volume Heart Failure

↓ Colloidal Osmotic Pressure Edema ↑ Hydrostatic Pressure

➢ Lymphatic obstruction
Lymphatic Obstruction

Trauma Invasive tumors Fibrosis Infectious agents

Disruption of Lymphatic Vessels

Impaired clearance of interstitial fluid

Lymphedema

PATHOLOGY AGAM
MORPHOLOGY AND CLINICAL FEATURES
• Edema is easily recognised grossly.
• Edema is most common in subcutaneous tissues, brain and the lungs.

➢ SUBCUTANEOUS EDEMA
• Influenced by gravity.
• Dependent edema.
• Pitting edema.
• Sign of underlying renal or cardiac disease.
• When significant, impairs wound healing.

➢ PERIORBITAL EDEMA
• Seen in renal dysfunction.

➢ PULMONARY EDEMA
• Lungs are 2-3 times their normal weight.
• Sectioning yields blood - tinged frothy fluid.
• Seen in left ventricular failure, renal failure, acute respiratory distress syndrome and
pulmonary inflammation.
• Impedes oxygen diffusion and creates a favourable environment for bacterial infection.

➢ BRAIN EDEMA
• Can be localised or generalised.
• Brain exhibits narrow sulci and distended gyri; compressed by skull.
• When severe, can injure medullary centres and cause death.

➢ PERITONEAL EFFUSION
• Mostly due to portal hypertension.
• Prone to seeding by bacteria.

AGAM PATHOLOGY
2. THROMBOSIS
INTRODUCTION
• Thrombogenesis: Process of formation of solid mass in circulating blood from the
constituents of flowing blood
• Underlies the most serious and common forms of
cardiovascular disease.
• The primary abnormalities that lead to thrombosis are:
o Endothelial injury
o Stasis or turbulent flow
o Hypercoagulability of blood
(So called Virchow Triad)
CAUSES AND PATHOGENESIS
A. ENDOTHELIAL INJURY
• Endothelial damage can be caused by either:
▪ Physical Damage
▪ Endothelial Dysfunction

PHYSICAL ENDOTHELIAL INJURY

• It is important for formation of thrombus in the heart or the arterial circulation.
• The endothelial cell injury promotes adhesion of platelets at the site of injury
MECHANISM
Physical Loss of Endothelium

Exposed Thrombogenic Sub-endothelial ECM

Platelets adhere to the site of endothelial injury

Platelets release Pro-thrombotic Tissue Factor

Local depletion of Anti-thrombotic factors like PGI2

PATHOLOGY AGAM
 CAUSES:
• Chambers of heart: For example,
▪ Endocardial injury due to myocardial infarction
▪ Catheter trauma.
• Valves of heart: Small thrombi on the valves are called as vegetations.
▪ Infective endocarditis: Thrombi on valves (e.g. mitral, aortic valve) damaged by a
blood-borne bacteria or fungi.
▪ Damaged valves: Due to
✓ Rheumatic heart disease,
✓ Congenital heart disease
▪ Libman-Sacks endocarditis in systemic lupus erythematosus
▪ Nonbacterial thrombotic endocarditis: They are sterile vegetations on noninfected
valves with hypercoagulable states.
• Arteries:
▪ Ulcerated atherosclerotic plaques
▪ Traumatic or inflammatory vascular injury (vasculitis).
• Capillaries: Causes include
▪ Acute inflammatory lesions,
▪ Vasculitis and
▪ Disseminated intravascular coagulation (DIC).

ENDOTHELIAL DYSFUNCTION
• Endothelial Injury → Platelet activation → Thrombus Formation
(In the heart and arterial circulation, where the high rates of blood flow impede clot
formation).
• Inflammation and other noxious stimuli also promote thrombosis by ‘prothrombotic’
pattern of gene expression; also called endothelial activation or dysfunction.
CAUSES:
o Physical injury
o Infectious agents
o Hypertension
o Turbulent Blood Flow
o Inflammatory mediators
o Metabolic abnormalities (Hypercholesterolemia or Homocystinemia)
o Toxins absorbed from cigarette smoke
o Bacterial Endotoxins
o Radiation

AGAM PATHOLOGY
MECHANISM
• Endothelial dysfunction can disturb the balance between prothrombotic and
antithrombotic activities of endothelium
• Procoagulant changes: Producing more pro-coagulant factors. Eg:
▪ Platelet adhesion molecules
▪ Tissue factor
▪ PAI
Endothelial cells activated by cytokines

Downregulates the expression of thrombomodulin

Sustained activation of thrombin

Stimulates platelets and causes procoagulant changes

Procoagulant

Inflamed endothelium causes downregulation of

expression of other anticoagulants

• Anti-thrombotic activities: Synthesizing fewer anticoagulant effectors. Eg:

▪ Thrombomodulin
▪ PGI2
▪ t-PA

Activated Secrete plasminogen Limit Downregulate

endothelial cells activator inhibitors fibrinolysis expression of t-PA

PATHOLOGY AGAM
B. STASIS OR TURBULENT FLOW
• Turbulence: Causes endothelial injury or dysfunction; Forms counter currents that
contribute to local pockets of stasis.
• Stasis: Contributes to the development of venous thrombi.

MECHANISM:

Changes in expression of adhesion molecules and pro-inflammatory factors

Promote Endothelial Enhance Pro- Leucocyte

Activation coagulant activity Adhesion

Bring Platelets in contact with endothelium

Prevent washout and dilution of activated clotting factors by:

• Fresh flowing blood
• Inflow of clotting factor inhibitors

CLINICAL SETTINGS:
• Ulcerated atherosclerotic plaques → expose sub-endothelial vWF, TF → turbulence
• Aneurysms → Local stasis → Thrombosis
• Acute MI, cardiac aneurysms → areas of non-contractile myocardium → stasis
• Rheumatic mitral valve stenosis → Left arterial dilation → stasis and throbosis
• Hyper viscosity (Polycythaemia vera) → ↑ resistance to flow → small vessel stasis
• Sickle cell anaemia → Abnormally shaped RBC → impede blood flow → stasis

AGAM PATHOLOGY
C. HYPERCOAGULABILITY
• Hypercoagulability can be loosely defined as any disorder of the blood that predisposes to
thrombosis; also called thrombophilia.
• Has an important role in venous thrombosis.

• Primary disorders (Inherited causes of hypercoagulability)

A. Single nucleotide mutation in factor V that (factor V Leiden)

Glutamine to arginine substitution at amino acid residue 506

Factor V resistant to cleavage and inactivation by Protein C

Important antithrombotic counter- regulatory pathway lost

Venous thrombosis

▪ Increased risk in homozygotes.

▪ Factor V Leiden heterozygosity may trigger DVT when combined with enforced inactivity.

B. Single nucleotide change Elevated Increased risk

(G20210A) in the 3’-untranslated prothrombin of venous
regions of the prothrombin gene levels thrombosis

C. Elevated Thioester linkages between Arterial and

levels of homocysteine metabolites and a variety venous
homocysteine of proteins, including fibrinogen Limit
fibrinolysis

• Rare inherited causes of primary hypercoagulability: Deficiencies of anticoagulants such as

anti-thrombin III, protein C, or protein S.
o Inherited causes of hypercoagulability must be considered in patients younger than 50
years of age when they present with thrombosis – even when acquired risk factors are
present.

PATHOLOGY AGAM
• Secondary disorders (Acquired thrombophilia)
o Pathogenesis is frequently multifactorial.
o High risk:
▪ Prolonged Bed Rest
▪ MI, Atrial Fibrillation
▪ Cancer
o Low Risk:
▪ Cardiomyopathy
▪ Nephrotic Syndrome
o Among the acquired thrombophilic states, the anti-phospholipid antibody syndrome and
heparin-induced thrombocytopenia are important.
• Antiphospholipid Antibody Syndrome (can be asked separately as 4m)
o APLA reacts with plasma proteins, which are to phospholipids
o Important antibodies:
▪ Anti-β 2 glycoprotein antibodies (binds to cardiolipin antigen used in syphilis test)
▪ Thrombin
o Has protean clinical manifestations: Recurrent thromboses, repeated miscarriages,
cardiac valve vegetations and immune thrombocytopenia.
o Depending on the vascular bed involved, clinical presentations: Pulmonary embolism,
pulmonary hypertension, stroke, bowel infarction, or renovascular hypertension.
o Also causes renal microangiopathy → renal failure.
o Types:
▪ Primary form: Only manifestations of a hypercoagulable state.
▪ Secondary form: Patients also have a well-defined auto-immune disease like SLE.
(earlier called Lupus Anticoagulant syndrome)
o Laboratory Tests:
▪ Coagulation tests: APTT: prolonged, factor 8, prothrombin, thrombin time,
fibrinogen level is normal.
▪ Confirmatory test: test for lupus anticoagulant, Antibodies against the
phospholipid beta 2 glycoprotein complex
o Treatment: Anticoagulation and Immunosuppression.
• Heparin-Induced Thrombocytopenia
o Administration of unfractionated heparin
o Appearance of antibodies that recognize heparin-platelet factor 4 complexes on platelets
and complexes of heparin-like molecules and platelet factor 4-likeproteins on endothelial
cells
o Binding of antibodies to platelets
o Activation, aggregation and consumption of platelets (along with endothelial damage)
o Thrombocytopenia, pro-thrombic state

AGAM PATHOLOGY
MORPHOLOGY
• Thrombi are focally attached to the underlying vascular surface, at the point of initiation.
• All thrombi propagate towards the heart. The propagating portion is prone to fragmentation
and embolization.
• Thrombi often have grossly and microscopically apparent laminations called lines of Zahn,
which are pale platelet and fibrin deposits alternating with darker red cell-rich layers;
indicates that a thrombus has formed in flowing blood; distinguishes antemortem clots from
non-laminated post mortem clots.
• Mural thrombi
o Occurs in heart chambers due to abnormal myocardial contraction or endomyocardial
injury.
o Occurs in aortic lumen due to ulcerated atherosclerotic plaque or aneurysmal dilation.
• Arterial thrombi
o Frequently occlusive.
o Frequency: Coronary arteries > Cerebral arteries > Femoral arteries
• Venous thrombi (phlebothrombosis)
o Almost invariably occlusive, with the thrombus forming a luminal cast.
o Contain more enmeshed red cells and are called red or stasis thrombi.
o Veins of lower extremities are mostly involved.
o Other sites: Upper extremities, periprostatic plexus, ovarian veins or peri-uterine veins,
portal vein, hepatic vein, dural venous sinuses.
• Post-mortem clots
o Gelatinous; have a red dependent portion and yellow “chicken fat” upper portion.
o Not attached to underlying vessel wall.
• Vegetations
o Thrombi on heart valves.
o Can be due to bloodborne bacteria or fungi that adhere to damaged valves or cause
direct valve damage (Infective endocarditis, Rheumatic heart disease).
o Can be sterile vegetations (Non-bacterial thrombotic endocarditis).

FATE OF THROMBUS
• Propagation: Thrombi accumulate additional platelets and fibrin.
• Embolization: Thrombi dislodge and travel to other sites in the vasculature.
• Dissolution: Rapid shrinkage and total disappearance of recent thrombi due to fibrinolysis.
• Organization and Recanalization: Eventually, only a fibrous lump may remain to mark the
original thrombus.

PATHOLOGY AGAM
CLINICAL FEATURES
• Thrombi come to clinical attention when they obstruct arteries or veins, or give rise to
emboli.
• Clinical presentation depends on the involved site.

• Phlebothrombosis:
o Mostly occur in superficial or deep veins of leg.
o Superficial venous thrombi cause local congestion, swelling, pain and tenderness, but
rarely embolize. Overlying skin is predisposed to infections and ulcers (varicose ulcers).
o Deep vein thrombosis is more serious because such thrombi can embolize to the lungs
and cause pulmonary infarction.
o DVTs are asymptomatic in 50% of patients. If symptomatic, local pain and edema are
seen.
o Lower extremities DVTs are often associated with hypercoagulable states.
o Common predisposing factors for lower extremities DVT: Bed rest and immobilization,
congestive cardiac failure, trauma, surgery, burns, pregnancy.
o There is increased risk of thromboembolism in disseminated cancers; called migratory
thrombophlebitis or Trousseau syndrome.

• Arterial and Cardiac Thrombosis

o Atherosclerosis is a major cause of arterial thromboses.
o MI can predispose to cardiac mural thrombi.
o Both cardiac and mural thrombi are prone to embolization.
o Brain, kidneys and spleen are likely targets because of their rich blood supply.

AGAM PATHOLOGY
3. SHOCK
INTRODUCTION
• Shock is a state in which diminished cardiac output or reduced effective circulating blood
volume impairs tissue perfusion and leads to cellular hypoxia.
• Prolonged shock → Irreversible tissue injury.

CAUSES OF SHOCK:
• Cardiogenic shock: Low cardiac output due to myocardial pump failure. (MI, ventricular
arrhythmia, cardiac tamponade, pulmonary embolism).
• Hypovolemic shock: Low cardiac output due to low blood volume. (Massive haemorrhage,
severe burns).
• Shock associated with systemic inflammation:
Inflammatory mediators from innate and adaptive immune cells

Arterial vasodilation, vascular leakage, venous blood pooling

Tissue hypo Cellular Organ Organ

Death
perfusion hypoxia Dysfunction failure

▪ Microbial and non-microbial triggers associated with inflammation produce a similar

set of clinical findings, referred to as the systemic inflammatory response syndrome.
▪ Septic shock: Shock caused by microbial infection.
• Neurogenic shock: Shock due to an anaesthetic accident or spinal cord injury.
• Anaphylactic shock: Shock due to IgE-mediated hypersensitivity reaction.
PATHOGENESIS OF SEPTIC SHOCK
• Most frequently triggered by gram-positive bacterial infections, followed by gram-
negative bacteria and fungi.
• Factors that play a major role in the pathophysiology of septic shock include:
o Inflammatory and counter-inflammatory responses
o Endothelial activation and injury
o Induction of a procoagulant state
o Metabolic abnormalities
o Organ dysfunction

PATHOLOGY AGAM
MAJOR PATHOGENIC PATHWAYS OF SEPTIC SHOCK

Microbial Products
PAMPs (Pathogen Associated Molecular Patterns)

Factor XII Complement Activation Neutrophil and

Macrophage Activation
Direct and Indirect

TNF, IL-1, HMGB1

Cytokine and Cytokine-

Endothelial Activation like mediators

Procoagulant Anti-fibrinolytic IL-6, IL-8, IL-10, apoptosis,

PAF, ROS sTNFR
↑ Tissue Factor ↑ PAI-1
↓ TFPI Secondary
↓ Thrombmodulin anti-inflammatory
↓ Protein C Systemic mediators
Effects

• Vasodilation • Fever Immuno-

• Increased • ↓ Myocardial suppression
Microvascular
permeability contractibility
Thrombosis (DIC)
• Decreased • Metabolic
perfusion abnormalities
Tissue Ischemia

Adrenal Insufficiency
Multi-Organ Failure

AGAM PATHOLOGY
STAGES OF SHOCK
• Shock is a progressive disorder that, if uncorrected, leads to death.
• Unless the insult is massive and rapidly lethal, shock in those settings tends to evolve
through 3 general phases:
o An initial non-progressive phase – reflex compensatory mechanisms are activated;
perfusion of vital organs maintained.
o A progressive phase – tissue hypoperfusion; onset of worsening circulatory and
metabolic imbalances, including lactic acidosis.
o An irreversible stage – severe cellular and tissue injury; survival is not possible even if
hemodynamic defects are corrected.

MORPHOLOGY
• Cellular and tissue damage induced by cardiogenic and hypovolemic shock – hypoxic injury
in brain, heart, adrenals, kidneys and GIT.
o Adrenal changes: Cortical cell lipid depletion (conversion of relatively inactive vacuolated
cells to metabolically active cells that utilize lipids to synthesize steroids).
o Kidneys: Acute tubular necrosis.
• Changes in septic shock:
o Lungs: Diffuse alveolar damage is seen (shock lung).
o Disseminated intravascular coagulation → Fibrin-rich microthrombi in brain, kidney,
lungs, adrenal glands and GIT.
o Serosal surface and skin: Petechial haemorrhages.
• With the exception of neuronal and myocyte ischaemic loss, all other tissues may revert to
normal if the individual survives.

CLINICAL FEATURES
• Hypovolemic and Cardiogenic Shock: Hypotension, weak and rapid pulse, tachypnoea and
cool, clammy, cyanotic skin.
• Septic Shock: Initially, skin may be warm and flushed due to peripheral vasodilation.
• Initial Phase
o Rapidly, cerebral, cardiac and pulmonary dysfunction sets in.
o Metabolic acidosis and electrolyte disturbances worsen the condition
• Second Phase: If the patient survives,
o Renal insufficiency → Progressive fall in urine output
o Severe fluid and electrolyte imbalances
• Prognosis
o Hypovolemic shock: 90% of young, otherwise healthy patients survive with
appropriate management.
o Septic shock and Cardiogenic shock associated with extensive MI: High mortality
rates even with state-of-the-art care.

PATHOLOGY AGAM
SHORT NOTES:
1. MORPHOLOGY OF INFARCT
RED INFARCTS (haemorrhagic) occurs in
• venous occlusions (e.g., testicular torsion)
• loose, spongy tissues (e.g., lung) - blood collects in the infarcted zone
• tissues with dual circulations (e.g., lung and small intestine) t-allow blood to flow from
an unobstructed parallel supply into a necrotic zone
• tissues previously congested by sluggish venous flow
• site of previous arterial occlusion and necrosis (e.g., following angioplasty of an arterial
obstruction)

WHITE INFARCTS occur in

• Arterial occlusion in solid organs with end arterial circulation (spleen, heart, kidney)
• Tissues where increased density prevents seepage of blood from capillary beds into
necrotic area

MORPHOLOGY
• Wedge shaped
• Occluded vessel at the apex and periphery of organ as the base
• Fresh infarcts-poorly defined, haemorrhagic
• After 1-2 days, it becomes soft, sharply demarcated and light yellow in colour
• As time passes, the infarct becomes paler and more sharply defined if it doesn’t have a
dual blood supply

HISTOLOGY
• Ischemic coagulative necrosis seen
• Mins-hrs: no histology change
• 4-12 hrs: frank necrosis
• Few hrs- 1-2days: acute inflammation present along margins of infarcts and becomes
prominent
• Reparative process- macrophages phagocytose necrotic cells- begins at the preserved
margin
• Infarcts replaced by scar

Except brain- liquefactive necrosis occurs

AGAM PATHOLOGY
2. FAT EMBOLISM
Obstruction of arterioles and capillaries by fat globules constitutes fat embolism. If the
obstruction in the circulation is by fragments of adipose tissue, it is called fat-tissue embolism.
CAUSES:
• Traumatic causes:
o Trauma to bones (leading to passage of fatty marrow into circulation)
o Trauma to soft tissue e.g. laceration of adipose tissue and in puerperium due to injury
to pelvic fatty tissue.
• Non-traumatic causes:
o Extensive burns
o Diabetes mellitus
o Fatty liver
o Pancreatitis
o Inflammation of bones and soft tissues
o Extrinsic fat or oils introduced into the body
o Hyperlipidaemia
PATHOGENESIS
• Mechanical theory -
o Mobilization of fluid fat may occur following trauma to the bone or soft tissues and
may enter venous circulation and finally gets arrested in the small vessels in the lungs.
o Some of the fat globules may further pass through lungs and enter into the systemic
circulation to lodge in other organs.
• Emulsion instability theory –
o According to this theory, fat emboli are formed by aggregation of plasma lipids due to
disturbance in natural emulsification of fat.
• Intravascular coagulation theory –
o In stress, release of some factor activates disseminated intravascular coagulation
(DIC) and aggregation of fat emboli.

CLINICAL FEATURES
• Asymptomatic
• It is characterised by
o Tachypnoea, Dyspnoea and Tachycardia (sudden onset after injury)
o Pulmonary insufficiency
o Anaemia
o Thrombocytopenia
o Neurological symptoms
o Irritability & Restlessness
o Finally, coma

PATHOLOGY AGAM
3. AMNIOTIC FLUID EMBOLISM

• Amniotic fluid embolism is the 5th most common cause of maternal mortality worldwide
• It may result in permanent brain damage in 85% of survivors
• During labour and in the immediate postpartum period, the contents of amniotic fluid
may enter the uterine veins and reach right side of the heart resulting in fatal
complications

MORPHOLOGY FEATURES
Notable changes are seen in the lungs such as
• Haemorrhages
• Congestion
• Oedema
• Changes of ARDS
• Dilatation of right side of the heart

CONTENTS WITHIN PULMONARY VASCULATURE:

Amniotic fluid emboli are composed of:
• Squamous cells shed from foetal skin
• Lanugo hair
• Fat from vernix caseosa
• Mucin derived from the foetal respiratory or gastrointestinal tract.

CLINICAL FEATURES
• Dyspnoea
• Cyanosis
• Shock
• Neurologic impairment ranging from seizures and coma
• Later pulmonary edema may develop
• Death may occur due to
o Mechanical blockage of the pulmonary circulation in extensive embolism
o Anaphylactoid reaction to amniotic fluid components
o Disseminated intravascular coagulation (DIC) due to liberation of thromboplastin by
amniotic fluid
o Haemorrhagic manifestations due to thrombocytopenia and afibrinogenemia

AGAM PATHOLOGY
4. DECOMPRESSION SICKNESS
Decompression sickness also known as Caisson’s disease is a form of air embolism
PATHOGENESIS:
• It is produced when an individual decompresses suddenly either from high pressure to
normal pressure or normal pressure to low pressure
• In divers and mine workers, who descend to high ATM pressure, gases in body gets
dissolved in tissues. When this person ascends back to ground, the dissolved gases come out
as bubbles and form a large embolus.
• In those who ascend to low pressure altitudes in unpressurised cabins, decompression
occurs similarly.

CLINICAL EFFECTS of decompression sickness are of two types,

Acute form
• Occurs due to acute obstruction of small blood vessels in the vicinity of joints and skeletal
muscles.
• Clinical features:
o ‘The bends’, as the patient doubles up in bed due to acute pain in joints, ligaments and
tendons.
o ‘The chokes’ occur due to accumulation of bubbles in the lungs, resulting in acute
respiratory distress.
o Cerebral effects may manifest in the form of vertigo, coma, and sometimes death.

Chronic form
• It is due to foci of necrosis throughout body, especially the skeletal system.
• Ischemic necrosis may be due to
o Embolism per se (main)
o Platelet activation,
o Intravascular coagulation
o Hypoxia
• Clinical features:
o Avascular necrosis of bones
o Neurological symptoms paraesthesia and paraplegia.
o Lung involvement - Haemorrhage, oedema, emphysema and atelectasis may be seen.
These result in dyspnoea, non-productive cough and chest pain.
o Skin manifestations include itching, patchy erythema, cyanosis and oedema.
o Other organs like parenchymal cells of the liver and pancreas may show lipid vacuoles

PATHOLOGY AGAM
5. THROMBOEMBOLISM
Thromboembolism is an embolism arising from a detached thrombus from either arterial or
venous circulation

SYSTEMIC THROMBOEMBOLISM:
• Systemic thromboembolism also known as arterial thromboembolism arises from:
o Mural thrombi from LA/LV
o Vegetation on mitral/aortic valves
o Atherosclerotic plaques
o Aortic aneurism
• Effects: The effects of arterial emboli depend upon their size, site of lodgement, and
adequacy of collateral circulation
o Infarction
o Gangrene
o Arteritis and mycotic aneurysm
o Myocardial infarction
o Sudden death

PULMONARY THROMBOEMBOLISM:
• It is the most common form of venous thromboembolism
• There is occlusion of pulmonary arterial tree
• Pathogenesis:
o The emboli can originate from
▪ Thrombus originating from DVT (90%)
▪ Thrombus from varicosities of superficial veins of legs and pelvic veins
o The detached embolus
▪ If large, lodges in the bifurcation site of pulmonary artery or in the right ventricle
▪ If gets fragmented into multiple small fragments, they may block multiple small
pulmonary arterioles affecting the lower lobes of lung
o May enter the systemic circulation by passing through a defect in the AV septum (if
present) and may block arteries of other organs (Paradoxical embolism)
• Consequences:
o Acute Cor pulmonale
o Pulmonary infarction
o Pulmonary haemorrhage
o Pulmonary hypertension
o Sudden death

AGAM PATHOLOGY
SHORT ANSWERS
1. DIFFERENCE BETWEEN THROMBUS AND BLOOD CLOT

THROMBUS BLOOD CLOT

Occurs in circulating blood when alive Occurs in stagnant blood- when alive or after death
Firmly attached Loosely attached
Friable and dry Soft and moist
Pale, red or mixed Red or yellow
Formed of fibrin, platelets Formed of fibrin and other blood elements
Lines of Zahn seen No lines of Zahn

2. DIFFERENCE BETWEEN TRANSUDATE AND EXUDATE

TRANSUDATE EXUDATE
Non inflammatory Inflammation related
Ultra-filtrate of plasma Increase in vascular permeability
Protein poor <2 g/dl Protein rich >2g/dl
Clear, serous Cloudy, purulent
Specific gravity <1.018 Specific gravity >1.018
Doesn’t clot Clots spontaneously due to presence of fibrinogen
Few lymphocytes Neutrophils in acute and
Lymphocytes seen in chronic inflammation
Bacteria-not seen Bacteria growth seen
Ex. Heart failure, liver failure, Ex. Pus
severe nutritional disorders
Pitting edema No pitting seen

3. TYPES OF EMBOLISM
Types of embolism depending upon

Matter in emboli Infected / Not Source of emboli Flow of Blood

• Solid • Bland (sterile) • Cardiac emboli • Paradoxical
• Liquid • Septic (infected) • Arterial emboli embolus
• Gaseous • Venous emboli • Retrograde
• Lymphatic emboli embolus

PATHOLOGY AGAM
4. HEART FAILURE CELLS:
• Pulmonary congestion with dilated capillaries and
leakage of blood into alveolar spaces leads to an
increase in hemosiderin-laden macrophages
• Brown granules of hemosiderin from break down of
RBC's appear in the macrophage cytoplasm.
• These macrophages are sometimes called "heart
failure cells" because of their association with
pulmonary congestion with CHF

5. HYPEREMIA AND CONGESTION:

● Both refer to locally increased blood volume

HYPERMEIA:
• Active process
• Arterial dilatation leads to increased blood flow
• Area turns red (erythema) due to oxygenated blood pooling.

CONGESTION:
• Passive process
• Reduced outflow from tissue
• Systemic (cardiac failure) or local (isolated vein)
• Reddish – blue coloured due to RBC stasis and deoxy Hb
• Usually leads to edema
• Chronic hypoxia causing injury and scarring
• Congested tissue usually discoloured to deoxy blood
• Morphological Features:
▪ Acute Pulmonary congestion- bigger alveolar capillary, alveolar edema, intra alveolar
haemorrhage
▪ Chronic Pulmonary congestion- septa thickened, alveoli form hemosiderin laden
macrophages – HEART FAILURE CELLS
▪ Acute hepatic congestion - dental vein and sinusoids distended ,ischemic hepatocytes
▪ Chronic hepatic congestion –centrilobular region red brown and prominent against
uncongested parts.

AGAM PATHOLOGY
6. LINES OF ZAHN
• These are gross and microscopic lamination seen in thrombus
• It is composed of alternating areas of:
▪ Pale area : Platelets admixed in fibrin meshwork
▪ Darker area : Red cell-rich layer
• The laminations signify that the thrombus is formed in the flowing blood
• It is used to differentiate between ante-mortem and post-mortem clots (bland non-
laminated)

7. GAMNA-GANDY BODIES:
• In CVC-Spleen, there may be fibrous thickening of the capsule and the trabeculae
• In some cases, the haemorrhages overlying the fibrous tissue gets deposits of hemosiderin
pigment and calcium salts
• These organized structures are called Gamna-Gandy bodies or Sidero-fibrotic nodules

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UPDATES FROM ROBBINS: 10TH EDITION
1. INITIATORS OF INFLAMMATION IN SEPSIS
• Initiators of inflammation in sepsis are:
▪ Signalling pathways downstream of Toll-like receptors (TLRs) , which recognize a host
of microbe-derived substances containing
✓ Pathogen associated molecular patterns (PAMPs)
✓ Damage-associated molecular patterns (DAMPs)
▪ G-protein–coupled receptors that detect
✓ Bacterial peptides
✓ C-type lectin receptors such as Dectins.
• Ligation of these receptors leads to ↑ expression of the genes encoding inflammatory
mediators via activation and nuclear translocation of the transcription factor nuclear
factor-κB (NF-κB).

2. ANTI-PHOSPHOLIPID ANTIBODY SYNDROME:

• The aPL antibodies are directed against anionic membrane phospholipids or proteins
associated with phospholipids.
• Proteins that are recognized by these antibodies include cardiolipin and β2-glycoprotein I.
• β2-glycoprotein I is found in plasma, but it has strong avidity for phospholipids expressed
on the surfaces of endothelial cells, monocytes, platelets, thrombin, and trophoblasts.
• Patients with APS also show evidence of:
▪ Complement activation
▪ Inhibition of fibrinolytic processes favor prothrombotic state
• Miscarriage
▪ The foetal loss is not caused by thrombosis
▪ It is due to antibody-mediated interference with the growth and differentiation of
trophoblasts→ failure of placentation.
• Second-hit theory:
▪ Antiphospholipid antibodies are identified in 5% to 15% of normal individuals
▪ Hence the presence of antibodies is not sufficient to cause the full-blown syndrome.
▪ It is postulated that a “second hit” is required that may be provided by:
✓ Infection
✓ Smoking
✓ Pregnancy
• The antibodies induce a hypercoagulable state in vivo, but interfere with phospholipids
and thus inhibit coagulation in vitro, thereby prolonging the PTT.
• Diagnosis: Based on clinical features and demonstration of aPL antibodies in the serum.

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3. HEPARIN-INDUCED THROMBOCYTOPENIA
TARGET OF ANTI-BODIES:
• Antibodies are formed that recognize complexes of
▪ Heparin
on surface of platelets
▪ PF4
▪ Heparin-like molecules
on endothelial cells
▪ PF4-like proteins.

MECHANISM

Activation of Platelets

Release of PF4 protein from platelet α-granules

PF4 binds to heparin and undergoes conformational change

Formation of neo-antigen

IgG antibody formed against neo-antigen

PF4-IgG immune complex attaches the Fc receptors on platelet surface

Platelet activation and aggregation

Removal of platelets by macrophages Pro-thrombotic state

Thrombocytopenia Thrombosis Activation of endothelium

Most common • Most serious complication Binding of HIT antibodies

manifestation • Occurs in 50% cases to PF4-like proteins on
• Affects arteries and veins surface of endothelium

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COMPLICATIONS
▪ Necrosis of the skin
▪ Gangrene of the limbs
▪ Myocardial infarction
▪ Stroke

DIAGNOSIS: Demonstration of anti–PF4-heparin antibodies

3. DEFINITION OF SEPSIS:
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host
response to infection.

4. DEFINITION OF SEPTIC SHOCK:

Septic shock is defined as a subset of sepsis in which particularly profound circulatory,
cellular, and metabolic abnormalities are associated with a greater risk of mortality than with
sepsis alone.

5. SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS)

• It is a sepsis-like condition associated with systemic inflammation triggered by a variety
of non-microbial insults, such as burns, trauma, and/or pancreatitis.
• Pathogenic feature common to SIRS and septic shock is a massive outpouring of
inflammatory mediators from innate and adaptive immune cells that produce:
▪ Arterial vasodilation
▪ Vascular leakage
▪ Venous blood pooling.
• With the advent of chimeric antigen receptor T-cell (CAR-T) therapy, a similar iatrogenic
syndrome called cytokine release syndrome is observed in cancer patients.
• The cardiovascular abnormalities associated with SIRS result in:
▪ Tissue hypo perfusion
▪ Cellular hypoxia
▪ Metabolic derangements
that lead to organ dysfunction, organ failure and death.

AGAM PATHOLOGY
6. ENDOTHELIAL DYSFUNCTION IN SEPSIS:
• Apart from loosening of endothelial tight junctions, another feature of sepsis is
microvascular dysfunction.
• There is an:
▪ Increase in capillaries with intermittent flow
▪ Heterogeneity of flow in various capillary beds
▪ Normal autoregulation of flow based on tissue metabolic environment is lost.
• These changes cause a mismatch in oxygen needs and oxygen delivery.

7. ONE LINERS
• Thrombin activates platelets through a special G-protein–coupled receptor referred to as
protease-activated receptor-1 (PAR-1)
• ADP acts by binding two G-protein–coupled receptors: P2Y1 and P2Y12.
• Platelets also adhere to exposed collagen via the platelet collagen receptor Gp1a/IIa.
• Markers of acute inflammation such as C-reactive protein and procalcitonin are elevated
in sepsis
• Role of NET in sepsis
▪ Neutrophil extracellular traps in promotes pro-coagulant state by stimulating both
intrinsic and extrinsic pathways of coagulation.

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