Transcript Radiographs: Angulate

General Pathology (DENF 2701)
Fall, 2005
Topic: Hemodynamic Disorders, Thrombosis, Shock
Fall, 2005; Mondays & Wednesdays, 11:00-11:50 am; Room 132
Course Director: Dr. Jerry Bouquot
Room 3.094B; 713-500-4420; 713-745-2330 (cell)
Blood Flow Problems
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Hemorrhage (rupture of vessel)
Edema (excess interstitial fluid)
Hemophilia (diminished clotting capacity)
Thrombosis (vessel blockage from local clot)
Embolism (vessel blockage from something upstream)
Ischemia (diminished local blood flow)
Infarction (complete blockage of local blood flow)
Shock (generalized lack of tissue perfusion)
Hemorrhage
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Ruptured vessels, usually from trauma or infection or
atherosclerosis
– Can lose 20% of blood volume (more if slow lose) with little effect
on health
– Great blood loss >> hypovolemic shock (hemorrhagic shock)
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Hemorrhagic diathesis: tendency to bleed with minor injury
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Hematoma: localized pool of blood outside vessels (e.g. bruise)
– If severe: death from blood loss (e.g. dissecting aortic aneurysm)
Extravasation
Hemorrhage (Haemorrhage) Exsanguination
Rupture of Blood Vessels
Term
Description
Main Cause(s)
Hematoma
Blood in tissues
Trauma, vessel disease
Hemopericardium
Blood in pericardium
Rupture of aorta, heart
Hemothorax
Blood in pleural
cavity
Trauma, aortic rupture
Hemoperitoneum
Blood in peritoneal
cavity
Rupture of aorta, spleen, liver
Hemarthrosis
Blood in joint space
Bleeding disorder, trauma
Post-Anesthetic Hematoma
Hemopericardium
Hemorrhage (Haemorrhage)
Telangiectasia
Rupture of Blood Vessels
(Blood in Vessels)
Term
Purpura
(2-10mm)
Petechiae
(1-2 mm)
Ecchymosis
Description
Main Cause(s)
Focal hemorrhage
(submucosal, etc.)
Vessel fragility
Focal hemorrhage
(submucosal, etc.)
Increased pressure, small
vessel disease, abnormal
clotting disease
Widespread surface
petechiae
Same as above
Colonic Petechiae
Purpura
Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
Hemorrhage
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Petechiae: 1-2 mm bleeds in skin, mucous membranes or serosal
surfaces
– Usually from increased intravascular pressure, low platelet counts
(thrombocytopenia), defective platelet function, clotting factor
deficiencies
Purpuras: 3-5 mm bleeds beneath surfaces
– Same causes as petechiae, but also trauma, vessel inflammation
(vasculitis), increased vascular fragility
Ecchymosis: 1-2 cm subcutaneous or submucosal hemorrhages
(bruise)
– Color change: red/blue (hemoglobin) >> blue/green (bilirubin) >>
golden brown (hemosiderin)
Hemothorax (chest), hemopericardium (heart), hemoperitoneum
(gut), hemarthrosis (joints)
Problems: jaundice; iron deficiency anemia
Hematoma/Ecchymosis/Petechiae/Purpura
Submucosal Hemorrhage; Extravasation of Erythrocytes
Acute trauma from bite/Hematoma
Post-anesthetic hematoma
Cough (viral) hematoma
Fellatio trauma/Petechiae
© Photos: Dr. Jerry Bouquot, The Maxillofacial Center, Morgantown, West Virginia
Hereditary
Hemorrhagic
Telangiectasia
Osler-Weber-Rendu Syndrome
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Autosomal dominant
HHT1: mutation, endoglin gene, chromosome 9
HHT2: mutation, ALK-1 (activin receptor-like kinase-1), chromosome 9
Prevalence: 10/100,000 population
Poor protein production for endothelium
Numerous vascular 1-2 mm hamartomas, especially in mouth
(lips, tongue, buccal)
 Clinical: epistaxis; blanching of telangiectasias
 GI bleeds, urinary, ocular vessels
 Clinical: brain lesions tend to abscess; thromboemboli
 CREST syndrome (Acrosclerosis): Calcinosis cutis, Raynaud’s phenomenon,
Esophageal dysfunction, Sclerodactyly, Telangiectasia
Hemorrhage
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Ruptured vessels, usually from trauma or infection or
atherosclerosis
– Can lose 20% of blood volume (more if slow lose) with little effect
on health
– Great blood loss >> hypovolemic shock (hemorrhagic shock)
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Hemorrhagic diathesis: tendency to bleed with minor injury
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Hematoma: localized pool of blood outside vessels (e.g. bruise)
– If severe: death from blood loss (e.g. dissecting aortic aneurysm)
Fluid Balance Across Capillary Walls
Factors Involved
Edema
(Oedema):
accumulation of
excess fluid in
tissues
How?
Interstitial Fluid
 Hydrostatic pressure up:
-- venous obstruction
-- heart failure
 Osmotic pressure down:
-- hypoproteinemia
 Vascular permeability up:
-- allergy (histamine)
-- acute inflammation
Two major types of edema:
 Pulmonary edema
-- Left sided heart failure
 Subcutaneous edema
-- Right sided heart failure
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Edema
Increased Fluid in Interstitial Spaces
 60% of body weight is water: 1/3 = extracellular (interstitial fluid); 5% =
blood plasma
 With hemodynamic problems: transudate (protein-poor; specific gravity
below 1.012)
 With inflammation: exudate (protein-rich; specific gravity above 1.020)
 Clinical subtypes:
– Hydrothorax (chest dropsy)
– Hydropericardium
– Hydroperitoneum (Ascites)
– Anasarca (severe, generalized
edema with subcutaneous swelling)
Gingivitis
Edema
Increased Fluid in Interstitial Spaces
 Increased hydrostatic pressure:
– Impaired venous return
– Congestive heart failure (poor right ventricular function)
– Constrictive pericarditis
– Ascites (peritoneal dropsy; e.g. from liver cirrhosis)
– Venous obstruction or compression (thrombosis, external pressure,
dependency of lower limbs)
 Arteriolar dilation (heat; neurohumoral dysregulation)
 Reduced plasma osmotic pressure (hypoproteinemia)
– Nephrotic syndrome (protein-losing glomerulopathies)
– Liver cirrhosis (ascites)
– Malnutrition
– Protein-losing gastroenteropathy
Edema
Increased Fluid in Interstitial Spaces
 Lymphatic obstruction
– Interstitial fluids are removed via lymphatic drainage, to thoracic duct
and left subclavian vein
– Inflammation, neoplasm, surgery, irradiation
 Sodium retention (water follows sodium)
– Excess salt intake with renal insufficiency
– Increased tubular reabsorption of sodium (renal hypertension;
increased renin-angiotensin-aldosterone secretion)
 Inflammation (acute, chronic, angiogenesis)
Ludwig’s Angina
Cellulitis
Congestive Heart Failure
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Right ventricular malfunction >>
Reduced cardiac output >>
Reduced renal perfusion >>
Renin-angiotensin-aldosterone axis triggered >>
Sodium/water retention by kidneys (secondary aldosteronism) >>
Increased intravascular volume >>
Attempted increase in cardiac output, but heart can’t do it >>
Increased venous pressure >>
Edema
Help: salt restriction, diuretics, aldosterone antagonists
Right or left side
Usually from hypertension
Events Leading to Systemic Edema
Secondary to Primary Heart Failure
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Lymphatic Obstruction
Causes Edema
 Lymphedema (from inflammation or neoplasm, usually)
 Filariasis (parasite infection) >>
massive edema/fibrosis of genitals and legs (elephantiasis)
 Resected axillary nodes (breast cancer) >>
massive edema of arm and peau d-orange
(orange peel stippling, depressions at site of hair follicles)
Reduced Plasma Osmotic Pressure
Causes Edema
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Albumin = the protein most responsible for colloid osmotic pressure
Reduced albumin in blood >>
Decreased osmotic pressure >>
Not as much fluid reabsorbed across endothelium >>
More fluid outside vessels (edema) and less inside vessels >>
Less plasma volume >>
Renal hypoperfusion >> secondary aldosteronism, etc.
 Albumin loss from leaky glomerular capillary walls: nephrotic syndrome
 Reduced albumin synthesis: liver diseases (e.g. cirrhosis); malnutrition
 Problem: salt and water retention don’t help; salt isn’t large molecule
-- It exacerbates the edema
Extra Credit Question
Ascites refers to severe edema of:
A.
B.
C.
D.
E.
Brain
Pericardium
Peritoneum
Lungs
Lower extremities
Edema: Clinical Problems
 Subcutaneous edema: mostly a annoyance, but points to
underlying cardiac failure (right sided) or renal failure
– Dependent edema (pitting edema): gravity draws fluids downward
 Impaired wound healing or clearance of infection
 Brain edema: Swollen brain is painful, may be fatal, may force brain
substance out through foramina (herniated)
-- May compress vascular supply in brain stem
-- Trauma, brain abscess, viral infections, etc.
 Pulmonary edema: fluid fills lungs >> less oxygen diffusion,
maybe infection; can be fatal
– Especially in left ventricular heart failure
– Also: pneumonia, hypersensitivity reactions, adult respiratory
distress syndrome (ARDS)
Pulmonary Edema
Excess Blood
Hyperemia:
 Local increase in blood volume from active process
– E.g.: arterial dilation during exercise, etc.
 Tissue is more red than normal (excess oxygenated blood;
erythema)
Congestion:
 Local increase in blood volume from passive process
– E.g.: cardiac failure, venous obstruction
 Tissue is blue-red (poorly oxygenated blood; cyanosis)
 Congestion of capillary beds >> edema
 Chronic passive congestion: long-standing stasis and hypoxia; may
rupture vessel walls (hemorrhage and hemosiderin deposits)
Organ Congestion
Lungs:
 Acute pulmonary congestion: engorged alveolar capillaries and
pulmonary edema
 Chronic pulmonary congestion: fibrotic, thick septa
-- Heart failure cells (macrophages filled with hemosiderin)
Liver:
 Acute hepatic congestion: distended central vein and sinusoids;
peripheral cells better oxygenated
– Chronic passive hepatic congestion: Central regions of lobules are
red/brown and less cellular, perhaps necrotic (nutmeg liver)
– Can also be from shock
Congested Liver (Passive) = Nutmeg Liver
Right Heart Failure
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.; Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Types of Shock
Generalized Failure of Tissue Perfusion
 From profound hypotension (low blood pressure)
 Cardiogenic shock
-- failure of heart to pump
 Hypovolemic shock
-- lack of blood to pump (hemorrhage, fluid loss)
 Septicemic/Septic/Endotoxic shock
-- bacterial infections (dilated veins, no blood return)
 Obstructive shock
-- blockage of major artery
 Anaphylactic shock
-- allergic reaction (dilated veins, no blood return)
 Neurogenic shock
-- dilated veins, no blood return
Persistence of shock:
 Systemic acidosis >> dilation of previously constricted vessels >> hypotension
 Blood diverted from gut and kidneys to maintain perfusion of heart & brain
 Kidney damage; urine output falls
 Gut stasis, then necrosis
Shock
Tissue
Early Change
Late Change
Skin
Pale, cold
Cyanosis
Kidneys
Low urine output
Necrosis of tubular epithelium
Gut
Bowel stasis
Necrosis of lining epithelium
Lungs
Tachypnoea
Necrosis of alveolar epithelium
Liver
Fatty change
Necrosis of neurons
Brain
Reduced consciousness Necrosis of neurons, coma
Heart
Tachycardia
Myocardial necrosis
Effects of
Lipopolysaccharide
LPS = lipopolysaccharide
TNF = tumor necrosis factor
IL = interleukin
NO = nitric oxide
PAF = platelet-activating factor
Protection from Shock
 Renin-angiotensin-aldosterone system
-- retention of sodium, fluids; expanded blood volume
 Increased catecholamines from adrenals
 Increased sympathetic activity
-- tachycardia
-- vasoconstriction
 Increased ADH
-- increased sodium and water retention
Thrombosis
Three Primary Influences
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Endothelial injury (the dominant influence); does not need to be
physically disrupted to do this
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Abnormal blood flow (turbulence; stasis)
– Platelets contact endothelium and each other
– Less flow: less dilution of clotting factors
– Less flow: less ingress of clotting inhibitors
– Activates endothelium
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Hypercoagulability (hypercoagulation state)
– Primary (genetic)
– Secondary (acquired)
Predisposition to Thrombosis
Site
Predisposition to Thrombosis
Artery
Atheroma
Aneurysm
Heart valve
Inflammation caused by infection
Ventricle
Inflammation following infarction
Ventricular aneurysm
Atrium
Atrial fibrillation (leads to stasis)
Mitral valve stenosis
Vein
Slow flow; stagnation
Hypercoagulation state
Cerebral venous sinus
Inflammation following infection
Hypercoagulability state
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Factor V Leiden mutation
Prothrombin mutation
Antithrombin III deficiency
Protein C deficiency
Thrombosis Risk
Protein S deficiency
Genetic and Acquired
Prolonged bed rest; immobilization
Myocardial infarction
Factor
V Leiden mutation
Tissue
damage
The most common of the hypercoagulation mutations
Cancer
– 2-15%
population
Prosthetic
cardiacofvalves
– 60% of patients with deep vein thrombosis
Disseminated
coagulation
– 75%intravascular
of patients with
ischemic (DIC)
osteonecrosis
Lupus anticoagulant (anticardiolipin antibody)
Corticosteroid
use Va: in the 3' untranslated region of prothrombin
Mutant factor
 geneelevated
(G20210A
mutation)
Congenitally
levels
of homocysteine
Atrial fibrillation/Cardiomyopathy
Mutation cannot be inactivated by protein C >>
Nephrotic
sydnrome
less
antithrombotic activity
Hyperestrogenic states/Oral contraceptive use
Sickle cell anemia
Smoking
Effects of Vascular Injury
Coagulation Cascade
Photos: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Factor X > Factor Xa > Factor II Conversion
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Normal Platelet Thrombus Inhibition
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995; Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Thrombus Formation
Virchow
Triad in
Thrombosis
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995; Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003
☺
Coagulation Activity of Endothelial Cells
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Fibrinolytic System
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Thrombus
Laminated Pattern of Platelets and Fibrin RBCs
 Elements from activated
coagulation cascade
 Aggregated platelets
 Insoluble fibrin
-- from soluble plasma fibrinogen
 Entrapped erythrocytes (RBCs)
 Tiger stripes (RBCs layered
between platelets, heart)
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Mural Thrombi
In Ventricles (Left) and Aortic Aneurysm (Right)
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Embolization (Embolus)
Thromboembolism of Pulmonary Artery
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003; . Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Thrombotic Vegetations
Mitral Valve
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Fate of the Thrombus
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Propagation (obstruction)
Embolization (dislodged and transported elsewhere)
Dissolution
Organization
Venous Thrombosis
Outcomes
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Bone Marrow Embolus
In Pulmonary Vessel
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Infarction (Infarct)
Lung (Left); Spleen (Right)
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Intracerebral Hemorrhage
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Myocardial Infarction
Regional Full-Thickness (Left); Circumferential Subendocardial (Right)
Left Ventricle
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Myocardial Infarction
Chronological Appearance
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Mural Thrombus
Over Myocardial Infarction
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Kidney Infarction
Replaced by Fibrotic Scar (Left)
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Myocardial Infarction
Rupture
Ventricle
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Myocardial Infarction
Chronological Appearance
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Myocardial Infarction
Chronological Appearance
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Myocardial Infarction
Chronological Appearance
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Myocardial Infarction
Chronological Appearance
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.