CH3 Patho D&R Agam
CH3 Patho D&R Agam
CH3 Patho D&R Agam
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
When,
Net rate of fluid movement >>> Rate of lymphatic drainage → Oedema or Effusion
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
Secondary hyperaldosteronism
➢ Lymphatic obstruction
Lymphatic Obstruction
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
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
Procoagulant
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:
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.
Venous thrombosis
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.
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
PATHOLOGY AGAM
MAJOR PATHOGENIC PATHWAYS OF SEPTIC SHOCK
Microbial Products
PAMPs (Pathogen Associated Molecular Patterns)
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)
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
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
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.
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
3. TYPES OF EMBOLISM
Types of embolism depending upon
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
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
PATHOLOGY AGAM
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).
AGAM PATHOLOGY
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
Formation of neo-antigen
PATHOLOGY AGAM
COMPLICATIONS
▪ Necrosis of the skin
▪ Gangrene of the limbs
▪ Myocardial infarction
▪ Stroke
3. DEFINITION OF SEPSIS:
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host
response to infection.
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.
PATHOLOGY AGAM