Todays Quranic verse

And hold fast, all together, by the rope which God (stretches out for you), and be not divided among yourselves; and remember with gratitude God's favour on you; for ye were enemies and He joined your hearts in love, so that by His Grace, ye became brethren; and ye were on the brink of the pit of Fire, and He saved you from it. Thus doth God make His Signs clear to you: That ye may be guided. [003:103]

If one advances confidently in the direction of his dreams, he will meet with a success unexpected in common hours
"Shoot for the moon. Even if you miss it, you will land among the stars.!"

HEMODYNAMIC DISORDERS

THROMBOSIS

DEFINITION:

It is the process of formation of solid mass in circulation from the constituents of flowing blood (within a blood vessel or cardiac chamber, in a living organism-always formed ante-mortem). The mass itself is called Thrombus.
Blood clot: mass of coagulated blood formed in vitro Hematoma: extravasular accumulation of blood clot into tissues. Hemostatic plugs: simplest form of thrombus formed in healthy individuals at the site of bleeding

COMPOSITION OF THROMBUS
Fibrin, Platelets, RBC's
(Hemostatic plug formation: endothelial injury, platelet aggregation, fibrin meshwork )

LOCATION OF THROMBI
Arteries, veins, heart chambers, heart valves

TYPES OF THROMBI
Arterial vs. venous; bland vs. septic

PATHOGENESIS OF THROMBOSIS
(Predisposing Factors)

Virchows Triad
Endothelial injury Stasis or turbulence of blood flow Blood hypercoagulability

Endothelial Injury
Tissue Damage (Surgery, Fractures, Burns) Atherosclerosis Hypertension Toxic Products (cigarettes, homocysteine etc. )

Abnormal Blood Flow

Turbulence of Blood Flow
Swirls, Eddies and increased pressure are injurious These changes occur in arteries and the heart Atherosclerosis, Aneurysms, Myocardial Infarction, Cardiac Valve Lesions Hyperviscosity Syndromes e.g. Sickle Cell Anemia, Polycythemia

Stasis of Blood Flow

More commonly a problem on the venous side leading to Venous Thrombosis Can occur in the heart (Atrial Fibrillation or Infarction) Pregnancy, long plane ride, immobility after surgery

Turbulence and Stasis :

Disrupt normal laminar flow and bring platelets in contact with endothelium Prevent dilution of activated clotting factors Retard the inflow of clotting factor inhibitors and permit thrombi build-up Promote endothelial cell activation

Hypercoagulability
Any alterations of the coagulation pathways that predispose to Thrombosis
Primary (Genetic) or Secondary (Acquired) Disorders

Factor V Leiden mutation is the most common inherited cause of

hypercoagulability, it is resistant to the anti-coagulant effect of Activated Protein C Lack of Protein S, Protein C and Antithrombin III, patients present with venous thrombosis and recurrent thromboembolism in adolescence and early adulthood Lupus Anticoagulant with Lupus Erythematosus is associated with arterial and venous thrombosis & recurrent abortion Smoking, Obesity, Oral Contraceptives (BCP)

Lupus -Anticoagulant

Called an Anticoagulant because it interferes with a Coagulation Test, artificially prolonging It. But It Is Not an Anticoagulant. It Is a Procoagulant

HIT syndrome
3-5% population Un-fractionated heparin for therapeutic anticoagulation induces circulating antibodies resulting in platelet activation & endothelial cell injury ending up in prothrombotic state

HEMOSTASIS

Hemostasis & Thrombosis

Hemostasis is the normal, rapid formation of a localized plug at the site of vascular injury Thrombosis is the pathologic formation of a blood clot within the non-interrupted vascular system in a living person

Hypercoagulable States Inherited

A bnorm ality A pproxim ate Rate
15-30% 8-13% 5-6% 5 - 6% < 1% 3 - 5% Factor VLeiden - APCR (Caucasion) Prothrombin Gene Mutation Protein C Deficiency Protein S Deficiency Antithriombin Deficiency Hyperhomocysteinemia
Rogers: Am J Hem 41: 113, 1992

EFFECTS OF THROMBI
Stenosis or blockage of arterial lumen ischemia, infarction

Venous occlusion local congestion and edema and/or pulmonary embolism (travels)

Left heart valve & chamber thrombi systemic embolism

MORPHOLOGY OF THROMBI
THROMBI DEVELOP IN THE CARDIOVASCULAR SYSTEM

Lines of Zahn
Alternating Pale Layers of Platelets & Fibrin With Darker Layers of Rbcs (seen in areas with active blood flow like heart, aorta & large arteries not in veins) *Postmortem clots are gelatinous with a dark red dependent portion & yellow chicken fat supernatant, usually not attached to the underlying wall *Thrombi in heart chamber/aortic lumen are applied to the underlying structure, mural thrombi (non-occlusive)

Arterial thrombi are Occlusive/Non-occlusive, begin at site of endothelial injury and grow along flow of blood & typically are firmly adherent to the injured arterial wall (atherosclerotic plaque) Venous thrombi are almost always Occlusive- 85-90% of venous thrombi form in lower extremities

Atheroma with Thrombosis:

Thrombus
(Lines of Zahn)

Layering
(Lines of Zahn)

Cardiac Mural Thrombus

Notice underlying endocardial fibrosis

Right

Left

Cardiac Mural Thrombi

Mural Thrombus Aortic Aneurysm

CLINICAL SETTING FOR CARDIAC /ARTERIAL THROMBUS FORMATION

Myocardial Infarction (MI) Rheumatic Heart Disease Atherosclerosis

Rare large round thrombus obstructing mitral valve is called ball-valve thrombus Thrombi formed in ventricles just before death composed of mainly fibrin Agonal thrombi

VENOUS THROMBOSIS
Superficial Veins of the Lower Extremities
Cause Pain, Swelling - Rarely Embolize Associated With Varicosities Abnormally Dilated, Tortuous Veins Increased Risk of Infections Increased Risk of Varicose Ulcers

Deep Veins of the Lower Extremities

Thrombi in Deep Veins (Popliteal, Femoral, Iliac Veins) More Likely to Embolize About 50% Are Asymptomatic (Formation of Collaterals) May Produce Edema, Pain and Tenderness

 Phlebothrombosis
It is due to stasis of blood in un-inflamed veins, particularly the calf veins.

Thrombophlebitis
It is related to inflammation of the vein walls.

PHLEBOTHROMBOSIS
Main cause Primary thrombus Stasis Small

THROMBOPHLEBITIS
Inflammation Larger-depends on extent of phlebitis. Usually none-if present short and well-anchored Rare unless infective

Propagated clot

Long/poorly anchored

Emboli

Common, may be massive Sterile Usually calf veins Often silent

Site Clinical

Anywhere Pain Signs of inflammation

CLINCAL SETTING FOR VENOUS THROMBUS FORMATION

Cardiac Failure (CHF) Trauma Surgery Burns 3rd Term Pregnancy and Postpartum Cancer (migratory thrombophlebitis-Trousseaus Syndrome) Bed Rest Immobilization

Valvular Thrombi (vegetations)

Infective Endocarditis Non-bacterial Thrombotic Endocarditis (NBTE)
-Seen in patients dying of chronic debilitating diseases- advanced cancer (50% cases) & other end stage diseases (cachectic, marantic or terminal endocarditis)

Atypical Verrucous Endocarditis (Libman-sacks)

-Seen in 50% of acute SLE, Systemic sclerosis, TTP, Collagen diseases

Capillary thrombi
Minute thrombi composed mainly of packed red cells in vasculitis & DIC

FATE OF THROMBOSIS
Resolution (Dissolution)
Recent thrombi can undergo total lysis by activation of fibrinolytic system (mostly small venous thrombi). After the first 2-3 h, thrombi wont undergo lysis. Thus the use of tPA is only effective in the first 1-3 hours

Organization and recanalization

Replacement by granulation tissue followed by recanalaization or healing totally to leave only a small fibrousLump as evidence of a previous thrombus

Propagation
Accumulation of more platelet & fibrin and obstruction

Embolization
Early & infected thrombi may detache from site of origin and may block distal vesseles
Hyalinization & Calcification (Degraded thrombus with superadded bacterial infection may lead to mycotic aneurysm)

Thrombus Propagated into the Inferior Vena Cava

CLINICAL SIGNIFICANCE:
Obstruction of arteries or veins can cause ischemia, infarction, or may embolize
Venous thrombi may lead to congestion, poor wound healing, skin ulcers and painful thrombosed veins Microthrombi in microcirculation (capillaries) may cause DIC

DIAGNOSIS:
Clinical signs are unreliable. Phlebography using a contrast medium. Radioactive iodine-labelled fibrinogen test. Doppler ultrasound.

EMBOLISM

EMBOLISM
It is the process of carrying an abnormal mass (embolus) in the blood stream to a point distant from its origin.
*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

TYPES OF EMBOLI
Gas
(air, nitrogen , other gases)

Liquid
(amniotic fluid, radiographic contrast material, fat after soft tissue trauma / fracture, bone marrow )

Solid
(thrombus-- most common, foreign body- bullet, catheter; also atheroematous material, tumor cell clumps, tissue fragments, parasites, bacterial clumps etc.

99% are dislodged thrombus

Rarely: Bullets, Fat, Air, Atherosclerotic Fragments, Tumor Fragments, Bone Marrow Emboli can be Bland (sterile) or Septic (infected)

 ORIGIN & SITES OF EMBOLIZATION:

Venous: Arterial: Paradoxic: Systemic veins Heart or aorta Pulmonary arteries Systemic circulation

Systemic veins (through septal defect in heart or AV shunts in lungs) systemic circulation

*Retrograde: Embolus traveling against the flow of blood (metastatic deposits in spine from
carcinoma prostate due to retrograde embolism through intraspinal veins from large thoracic & abdominal veins due to increased pressure in body cavities: during coughing or straining)

EFFECTS OF EMBOLISM
Ischemia Infarction Sepsis if infected (example: pulmonary embolism with pulmonary infarction)

Thromboembolism
A detached thrombus or part of thrombus constitutes the most common type of embolism *Arterial (systemic) thromboembolism
(from within heart & arteries)

*Venous thromboembolism

Pulmonary thromboembolism

(from veins of lower legs & upper limbs, pelvic vein, cavernous sinus of brain, right side of heart)

Systemic Thromboembolism
Emboli traveling within the arterial circulation 80% arise from intra-cardiac mural thrombi (myocardial infarction) Vegetations on the heart valves (mitral/aortic) & prosthetic heart valves may embolize to the systemic circulation Infective endocarditis, Cardiomyopathy & CHD may be cause Emboli developing in relation to atherosclerotic plaques, aortic aneurysms, pulmonary veins and paradoxic emboli Major site of embolization are lower extremities (75%), brain (10%), intestine, kidney & spleen Leads to infarction of the affected organs, gangrene, arteritis & mycotic aneurysm, myocardial infarction and sudden death.

Emboli can arise from--

Pulmonary Thromboembolism
Generally originate from deep leg veins (popliteal, femoral & iliac) Usually pass through the right heart Into pulmonary vasculature 60% Pulmonary Arterial obstruction usually leads to sudden death, RVF Most pulmonary emboli (60-80%) are clinically silent because of small size May occlude main pulmonary artery, across the bifurcation (Saddle Embolus) or pass into the smaller branching arterioles Embolic obstruction of medium-sized arteries may result in hemorrhage without infarction because of intact bronchial circulation. If bronchial circulation is compromised as in left heart failure it results in infarction Emboli obstructing small end-arteriolar pulmonary branches usually result in associated infarction Multiple pulmonary emboli over time may cause pulmonary hypertension and right heart failure

Thromboembolism

Pulmonary Embolus

Saddle Pulmonary Embolus

Fat embolism syndrome

Microscopic fat globules derived from long bone fractures (fatty marrow) or rarely from soft tissue trauma and burns 10% of cases show clinical findings Clinically characterized by Pulmonary insufficiency, neurologic symptoms, anemia & thrombocytopenia Symptoms appear 1-3 days after injury Pathogenesis Mechanical obstruction in pulmonary & cerebral microcirculation and chemical injury to endothelium by free fatty acids resulting in skin rash

Air embolism
Gas bubbles within the circulation can obstruct vascular flow to cause distal ischemic injury Air can enter the circulation during
Chest wall injury, Operation on neck & head, Obstetrical operation & trauma, Intravenous infusion, Sudden atmospheric pressure changes in scuba & deep sea divers, underwater construction workers and in individual in unpressurized aircraft in rapid ascent (Decompression sickness- Caisson disease)

Clinically characterized by
Bends due to rapid gas bubble formation within skeletal muscle & about joint Chokes due to respiratory distress caused by edema, hemorrhage, focal atelectasis, emphysema CNS & CV effects due to focal ischemia Multiple foci of ischemic necrosis specially in heads of femur, tibia, humerus etc Clinical effects observed with air in excess of 100 ml

Amniotic Fluid Embolism

Torn placental membrane- amniotic fluid release Rupture of uterine veins Infusion of amniotic fluid into maternal venous circulation Morphologically characterized by
Lungs show squamous cells, lanugo hair, fat from vernix caseosa & mucin from GIT & RS pulmonary edema, diffuse alveolar damage, systemic fibrin thrombi

Clinically characterized by
Severe dyspnea, cyanosis, hypotensive shock, seizures, coma & DIC

Mortality rate> 80%

Disseminated Intravascular Coagulation (DIC)

Sudden widespread fibrin deposition in microcirculation Rapid consumption of platelets and coagulation proteins Secondary massive fibrinolysis, all the little thrombi dissolve Clotting Disorder Turns Into a Bleeding Disaster

Sepsis is common cause of DIC (30-50% of patients with gram negative sepsis)

Disseminated Intravascular Coagulation

Schistocytes Microthrombi

Clinical Consequences of DIC

Tumor Embolism
Tumor Embolism
Lymphatics (Carcinoma) Blood vesseles (Sarcoma)

Common sites
Liver (Carcinoma) Lung (Carcinoma & Sarcoma) Bone (Prostate, Thyroid, Breast, Kidney, Lung

INFARCTION

INFARCTION
An infarct is a localized area of ischemic necrosis caused by occlusion of either the arterial supply or venous drainage in a particular tissue
90-99% of all infarcts due to arterial thrombotic or embolic events
Less common causes of infarction are vasospasm, hemorrhage in atheromatous plaque, twisting of vessel, extrinsic compression or traumatic rupture of blood supply

Coagulative necrosis is characteristic of hypoxic death in all tissues except CNS All infarcts tend to be wedge-shaped, with the occluded vessel at the apex

TYPES OF INFARCTS:
Bland vs. Septic (assumed to be bland unless specified as septic) Arterial (usually white/pale) vs. Venous (red/hemorrhagic);

Bland and arterial most common

Organs with a single venous outflow channel (testis & ovary) are predisposed to infarction caused by venous thrombosis

MORPHOLOGY OF INFARCTS
White/Pale:
Occur with arterial occlusion or in solid organs with single blood supply (ex: kidneys, spleen)

Red/Hemorrhagic:
Occur with venous occlusion, in loose tissues, tissues with dual circulation, in tissues previously congested and when flow is re-established to a site of arterial occlusion & necrosis. All infarcts are wedge shaped, poorly defined & hemorrhagic in initial stage, later margins are better defined revealing hyperemia, become pale & sharply defined in solid organs and firmer & browner in spongy organs Microscopic evidence is visible after (12-18) hours if patient survives Characterized by coagulative / liquefactive necrosis surrounded by inflammatory zone, later there is evidence of regeneration & repair. Most infarcts are ultimately replaced by scars tissue. Septic infarction results from embolization of infected vegetation from heart valve or if microbes seed area of necrosis abscess organization

FACTORS AFFECTING INFARCTS:

Nature of the vascular supply (dual arterial supply) Collateral circulation Rate of development of occlusion Duration of occlusion Metabolic needs of the tissue/organ Vulnerability of the tissue to hypoxia
Brain - < 3 minutes Heart 0.5-2 hours Kidney 2-3 hours Skin fibroblasts - < 24 hours

Oxygen content of blood

Hemorrhagic Lung Infarct

Pale Splenic Infarct

Myocardial Infarction

MYOCARDIAL INFARCTION

RENAL INFARCTION

Lung Infarct Wedge Shape...

OK Colon

Infarcted Colon

CLINICAL SIGNIFICANCE OF INFARCTION

Usually cause pain; May cause loss of function (example: myocardial infarct may cause heart failure); May cause hemorrhage or sepsis (examples: lung infarct causes hemoptysis, bowel infarct causes GI bleeding or sepsis).

DIAGNOSIS OF INFARCTION
Depends on the organ involved MI (ECG, Serum markers) Common serum markers used to detect AMI
Marker
Myoglobin CK-MB MB-isoform cTnI cTnT Initial elevation after AMI 1-4h 3 - 12 h 1-6h 3 - 12 h 3 - 12 h Mean time to peak elevation after AMI 6h 10 - 24 h 4 - 12 h 10 - 24 h 12 - 24 h Time to return to baseline after AMI 18 - 24 h 48 - 72 h 38 h 5 - 10 days 5 - 14 days

SHOCK

SHOCK
It is defined as systemic hypo-perfusion due to reduction either in Cardiac Output or Effective Circulating Blood Volume.

The End Results are: Hypotension, followed by Impaired Tissue Perfusion and Cellular Hypoxia Reversible Cellular Injury Irreversible Tissue Injury Death Non-Progressive Stage, Progressive Stage, Irreversible Stage

TYPES OF SHOCK
Three Main Categories: Cardiogenic, Hypovolemic, and Septic Others:
Neurogenic Shock (anesthetic and spinal cord injury) & Anaphylactic Shock

CARDIOGENIC SHOCK
Results From Severe Myocardial Failure Due to:
Intrinsic myocardial damage (myocardial infarction, ventricular rupture, arrhythmia) Extrinsic Compression (cardiac tamponade) Outflow Obstruction (pulmonary embolism)

HYPOVOLEMIC SHOCK
Results From Loss of Blood or Plasma Volume: - Hemorrhage - Fluid Loss (severe burns, trauma, vomiting, diarrhea etc.)

SEPTIC (ENDOTOXIC) SHOCK

Most common cause of death in ICUs in the US Dissemination of infection into the vasculature Caused by overwhelming systemic microbial infection, most often by Gram-negative infection (Endo-toxic Shock) but can also occur with Gram-positive and fungal infections Spread & expansion of localized infection (abscess, peritonitis, pneumonia) into the blood stream.

Pathogenesis Of Septic Shock

Endotoxins are bacterial wall lipopolysaccharides (LPS) which consists of a toxic fatty acid (Lipid A) core and a complex polysaccharide coat (unique to each species). Gram-positive bacteria and fungi have analogus molecules. High quantities of LPS p (TNF & IL-1 IL6 & IL8)

-Systemic vasodilation (hypotension), -Diminished cardiac contractility, -Widespread endothelial injury and activation (SLA, ARDS, DAD), -Activation of coagulation system (DIC)

Multi-organ system failure and death

Effects of Shock on Tissues

Brain -- ischemic encephalopathy --> confusion, obtundation; Heart -- subendocardial ischemia, infarction; contraction band necrosis --> decreased output Kidneys -- acute tubular necrosis --> oliguria, anuria and electrolyte disturbances Lungs -- diffuse alveolar damage (DAD) --> adult respiratory distress syndrome (ARDS) --> hypoxia GI tract -- mucosal necrosis, hemorrhages Liver -- central necrosis, fatty change Coagulation system -- disseminated intravascular coagulation (DIC)

Morphology of Shock

Clinical Course of Shock

Hypotension Weak, rapid pulse, tachycardia Rapid shallow respiration Drowsiness, confusion & irritability Cool, clammy skin
In septic shock the skin is initially warm and flushed secondary to peripheral vasodilation

Multi-organ failure ensues if shock continues

EDEMA

EDEMA
Excess accumulation of fluid in the interstitial tissue spaces.
Increased intracellular accumulation (edema) is generally termed as hydropic change.

Edema Fluid can be A transudate (protein-poor fluid -specific gravity <1.012) or An exudate (protein-rich fluid -specific gravity >1.020)

SPECIAL TYPES OF EDEMA

Pleural effusion (hydro-thorax) Pericardial effusion (hydro-pericardium) Ascites (edema in peritoneal cavity) Anasarca (widespread edema) Cerebral edema (in brain, intra- and extracellular)

Normal Microcirculation

Capillary Arterial Hydrostatic Pressure + 36 Oncotic Pressure - 26 Net filtration Pressure + 10 mmHg (leak-out)

Venous + 16 - 26 - 9 mm Hg (Reabsorb)

Homeostasis is maintained by the opposing effects of vascular hydrostatic pressure and plasma colloid osmotic pressure

Pathophysiologic Categories of Edema

I. II. III. IV. V.

Increased Hydrostatic Pressure Reduced Plasma Osmotic Pressure Lymphatic Obstruction Sodium Retention Inflammation

Increased Hydrostatic Pressure

A. Congestive Heart Failure B. Portal Hypertension C. Venous Thrombosis

Congestive Heart Failure

Inability of Heart to Pump blood in systemic circulation Blood backing up into the lungs Blood backing up into the venous circulation Increasing Central Venous Pressure (CVP) Increased capillary pressure (Hydrostatic Pressure)

Edema
Cardiac Output Decreased Arterial blood volume Decrease Renal perfusion

Activates the Renal Defense Mechanisms Renin-Angiotensin-Aldosterone Axis, Renal Vasoconstriction, Increased ADH

Congestive Heart Failure

Renin-Angiotensin-Aldosterone Axis

Decreased Renal Perfusion

Renin Aldosterone Renal Na reabsorption

Plasma volume Transudation

Renal retention of Na + H2O

EDEMA

Congestive Heart Failure

Renal Vasoconstriction

Decreased Renal Perfusion

Renal Vasoconstriction Tubular reabsorption of Na + H2O Plasma volume Transudation Glomerular Filtration Rate (GFR)

Renal retention of Na + H2O

EDEMA

Congestive Heart Failure

Anti-Diuretic Hormone

Decreased Renal Perfusion

Anti-Diuretic Hormone (ADH) Renal retention of H2O

Plasma volume Transudation

Renal retention of Na + H2O

EDEMA

Congestive Heart Failure

Central Venous Pressure

Renin

Renal Perfusion
ADH Renal Vasoconstriction

Clinically initially cardiac edema can be demonstrated in legs or sacrum

Portal Hypertension
Portal Hypertension is Increased resistance to portal blood flow The most common cause of Portal Hypertension is CIRRHOSIS Results in Ascites Pathogenesis of Ascites is complex
Increased Portal Pressure (hydrostatic pressure) leads to increased liver sinusoidal hypertension. Fluid moves into the Space of Disse then into lymphatics

The hepatic lymph percolates into the peritoneal cavity

Normal thoracic duct lymph = 1 Liter/d In cirrhosis, hepatic lymph flow far exceeds Thoracic duct capacity Cirrhosis hypoalbuminemia decrease in plasma osmotic pressure ascites decrease in blood volume decreased renal perfusion secondary hyperaldosteronism (increased renin etc.)

Ascites

Portal Hypertension
Sinusoidal Hypertension
Hepatic Lymph Overwhelms Thoracic Duct

Cirrhosis

Serum Albumin

Renal Perfusion
Aldosterone

ASCITES

Venous Thrombosis
Impaired venous outflow increases hydrostatic pressure

Reduced Plasma Osmotic Pressure

Albumin is the serum protein MOST responsible for the maintenance of colloid osmotic pressure. A decrease in osmotic pressure can result from increased protein loss or decreased protein synthesis

Increased albumin Loss:

Nephrotic Syndrome
Increased protein permeability of the glomerular basement membrane

Protein losing gastroentropathy

Reduced albumin synthesis

Cirrhosis Protein malnutrition

Inflammation
Both Acute and Chronic Inflammation are associated with Edema Generalized edema in systemic infections, poisoning, certain drugs & chemicals, anaphylactic reactions and anoxia Localized edema in infections, allergic reactions, insect bite, irritant drugs & chemical and Angioneurotic edema*
*It involves skin of face & trunk and may involve lips, larynx, pharynx, lung etc

Angioedema

Angioedema

Lymphatic Obstruction
Impaired lymphatic drainage with resultant lymphedema, usually localized Commonly due to inflammation or neoplastic obstruction, may be post-surgical & post-radiation in patient undergoing treatment for Breast Cancer Both Acute and Chronic Inflammation are associated with EDEMA
Filariasis: A parasitic infection causing massive lymphatic & lymph nodes fibrosis in inguinal region resulting in edema of external genetalia & lower limbs called elephantiasis

Carcinoma of breast with obstruction of superficial lymphatics can lead to an unusual appearance of the breast- peau dorange (orange peel) Resection and/or radiation to axillary lymphatics can lead to arm edema
Milroys disease or hereditary edema due to abnormal development of lymphatic channels

Elephantiasis

Elephantiasis (filariasis)

peau dorange appearance in breast cancer

Sodium & Water Retention

Contributory factors in several forms of edema Salt retention may be primary cause of edema Post-streptococcal glomerulonephritis & Acute Renal failure Increased salt with accompanying water cause increase hydrostatic pressure and decreased vascular colloid osmotic pressure leading to edema

EDEMA
INCREASED HYDROSTATIC PRESSURE
Congestive Heart Failure Portal hypertension (Ascites) Venous Obstruction

HEART LIVER KIDNEY

DECREASED ONCOTIC PRESSURE

Nephrotic Syndrome Cirrhosis (Ascites) Protein Malnutrition

INFLAMMATION Increased permeability SALT & WATER RETENTION

LYMPHATIC OBSTRUCTION Inflammatory Neoplastic

GENERALIZED EDEMA

HEART LIVER KIDNEY

Edema Morphology
Edema of the Subcutaneous Tissue is most easily detected Grossly (not microscopically) Push your finger into it and a depression remains (pitting) Swelling and wetness of the tissues Subtle cell swelling with clearing and separation of extracellular elements

Dependent Edema is a prominent feature of Congestive Heart Failure (legs in standing & sacrum in recumbent position) Periorbital edema is often the initial manifestation of Nephrotic Syndrome, later affecting all parts of body

Pitting edema

Pulmonary Edema
Pulmonary Edema is most frequently seen in Congestive Heart Failure (LVF) May also be present in Mitral Stenosis, Cardiac Surgery, Renal failure, Adult Respiratory Distress Syndrome (ARDS), Pulmonary Infections, Inhalation of toxic substances, Aspiration, Radiation injury, Shock, Uremia, High altitude edema and Hypersensitivity reactions. The Lungs are typically 2-3 times normal weight Cross sectioning causes an outpouring of frothy, sometimes blood-tinged fluid representing mixture of air, edema fluid & extravasated red cells Microscopically alveolar capillaries are congested and there is collection of eosinophilic, granular and pink proteinaceous material (edematous fluid) in interstitial and alveolar spaces

Pulmonary Edema

Normal Lung

Pulmonary Edema

Pulmonary Congestion and Edema

Edema of the Brain

Localized: Abscess, Neoplasm Generalized: Encephalitis, Hypertensive crises, Obstruction of venous outflow, Trauma In Generalized edema brain is grossly swollen with narrowed sulci and distended gyri showing flattening against skull Vasogenic & Cytotoxic edema

Brain edema

Clinical Correlation
Subcutaneous Edema-Annoying but Points to Underlying Disease
However, it can impair wound healing or clearance of Infection

Pulmonary Edema-May cause death by interfering with Oxygen and Carbon Dioxide exchange & Creates a favorable environment for infection

Edema of Brain-The big problem is: There is no place for the fluid to go! Herniation into the foramen magnum will kill or brain stem vascular supply can be compressed and damage vital centers

Hyperemia & Congestion

Increased volume of blood in an area compared to normal

Hyperemia
Hyperemia is an active process resulting from augmented tissue inflow due to arteriolar dilation (e.g. Acute inflammation, Exercising muscles, Blushing, Sexual arousal)

Congestion
Congestion is a passive process resulting from impaired outflows from a tissue (cardiac failure-systemic or venous obstruction-local) Both can be Local or Diffuse

MORPHOLOGY OF HYPEREMIA & CONGESTION

Hyperemia: tissue is red or purple, engorged with oxygenated blood, swollen, often edematous. Examples- Lungs. Congestion: tissue is blue-red in color due to accumulation of deoxygenated hemoglobin in the affected tissues. Later on tissue becomes brownish (iron deposition) & indurated (fibrosis). Examples Liver, Legs, Lungs

PULMONARY CONGESTION
Acute Pulmonary Congestion: engorged alveolar capillaries, alveolar septal edema, focal minute intra-alveolar hemorrhage Chronic Pulmonary Congestion: thickened & fibrotic septa along with presence of numerous hemosidrinladen macrophages (Heart Failure Cells)

HEPATIC CONGESTION
Acute Hepatic Congestion: central vein and sinusoids are distended with blood, central hepatocytes may show degeneration & peripheral hepatocytes may develop fatty change Chronic Passive Congestion of Liver: central regions of hepatic lobules are grossly redbrown, slightly depressed & surrounding uncongested zones reveal fatty change (nutmeg liver). Microscopically there is centrilobular necrosis with hepatocyte drop out and hemorrhage & hemosidrin containing macrophages. Hepatic fibrosis (cardiac cirrhosis) may be seen in heart failure.

Hyperemia in Pneumonia Infection

(Pneumonia)

Hyperemia

Liver - Chronic Passive Congestion

Nutmeg Liver
Nutmeg Liver Cross Section of a Nutmeg

Chronic Passive Congestion

SIGNIFICANCE OF CONGESTION
If diffuse, usually indicates Heart failure; If local, usually indicates a blockage upstream toward the heart; Cirrhosis can cause Varices in esophagus

HEMORRHAGE
Extravasation of blood due to rupture of blood vessels
Rupture of a large vessel: Trauma, Atherosclerosis, Inflammatory or Neoplastic Erosion Rupture of small vessels: hemorrhagic diathesis
Hematoma is blood enclosed within tissue (red-blue blue-green golden brown) Petechiae are minute (1-2 mm) hemorrhages into skin, mucous membranes or serosal surfaces Purpuras are larger (3-5 mm) hemorrhages Ecchymoses are larger (1-2 cm) subcutaneous hematomas (bruises) Hemothorax, Hemopericardium, Hemoperitonium and Hemoarthrosis are bleeding in one or other body cavities. Hematochezia- bright red blood per rectum, Melena - dark black blood per rectum Hematuria - blood, gross or microscopic in urine Hemoptysis - coughing up of blood , Hematemesis - vomiting up of blood

CAUSES OF HEMORRHAGE
Trauma Vascular diseases with rupture (atherosclerosis, arteritis, aneurysms, etc.). Low platelets (below 10-15,000/cu mm) Coagulopathy (factors less than 10% activity) Ulcers, tumors, coagulation factors, infarcts,

MORPHOLOGY OF HEMORRHAGE

Acute
Red or purple collection of blood in tissue

Chronic or old
Brown or maroon pasty material

EFFECTS OF HEMORRHAGE

Effects of hemorrhage depends on following factors: Location Rate Duration Co-morbid diseases (emphysema, anemia, heart disease)

Hemorrhage
Why do bruises change color as they Resolve? The RBCs in a hemorrhage are broken down:
hemoglobin (red) p bilirubin (blue-green) p hemosiderin (golden-brown)

Clinical Effects of Hemorrhage

<20% blood loss, little health effect in otherwise healthy individuals
Thats why donating blood is OK But suppose you have heart or lung disease - mild blood loss could decrease critical oxygen carrying capacity and p heart attack

>20% blood loss hemorrhagic shock Bleeding into the brainstem is fatal while same blood loss from a finger cut is trivial Chronic recurrent bleeding can lead iron deficiency anemia!

Anemia from Blood Loss

This may be the only hint of Occult Cancer
Carcinoma of the Colon Gastric Carcinoma (less common)