PathoAna - Lecture 2

Describe what can be seen microscopically in chronic liver congestion

"nutmeg" liver (brown = congestion, white = steatosis (due to hypoxia)) Centrolobular congestion (the centrolobular regions are grossly red-brown and depressed on section) Possible steatosis in the periphery of the lobule Possible fibrosis

State factors that influence the development of infarction.

- Anatomy of blood supply - The rate of thrombosis - Tissue sensitivity to hypoxia - The blood oxygenation

State possible blood vessel endothelial injuries (Virchow's triad).

- Atherosclerosis - Myocardial infarction - Trauma - Vasculitis - Inflammation - Arterial hypertension - Turbulent blood flow - Bacterial endotoxins in sepsis - Hypercholesterolemia - Smoking - Radiation

State some clinical consequences of thrombosis.

- obstruction of arteries (more dangerous, e.g. coronary artery occlusion --> myocardial infarction) and veins (causing distal congestion and oedema) - source of emboli (most dangerous in veins) - phlebothrombosis, arterial thrombosis

Describe the "fate" of thrombus.

1. propogation = the growth of thrombi 2. dissolution = the restoration of blood vessel walls 3. embolisation = detachment from blood vessel walls 4. organisation of thrombus = CT replaces thrombus which may block more of the blood vessel.

Define embolus.

A detached intravascular solid/liquid/gaseous mass carried by blood to distant sites from the origin. Embolisms can be classified by site (systemic vs pulmonary) and by cause (fat, air, amniotic fluid).

Describe what can be seen microscopically in acute pulmonary congestion.

Alveolar capillaries are enlarged with blood Alveolar septal and intraalveolar oedema Intraalveolar hemorrhage due to an increase in hydrostatic pressure (RBC located outside of blood vessels)

Define hemorrhage.

An extravasation of blood due to blood vessel rupture.

Define oedema.

An increase in volume of extravascular fluid.

Define hyperemia and congestion.

An increased volume of intravascular fluid.

Describe how fluid circulation is maintained using different pressures.

At the venous end, fluid is reabsorbed from the interstitial space due to: ↑ interstitial fluid pressure ↑ plasma colloid osmotic pressure ↓ hydrostatic pressure At the arterial end, fluid is diffused out into the interstitial space due to: ↓ interstitial fluid pressure ↓ plasma colloid osmotic pressure ↑ hydrostatic pressure There is a larger pressure difference at the arterial end than the venous due to fluid at the venous end also entering the lymphatic vessels.

Describe what is necessary for normal blood fluid homeostasis.

Blood vessel wall integrity Preserved intravascular pressure and osmolarity Maintenance of blood as liquid until injury

Explain the classifications of infarction and state the 3 types of infarction.

By "colour" = indicates the amount of hemorrhage By type of necrosis (coagulative vs liquifactive) By presence/absence of infection (septic vs bland) White infarction Red infarction Septic infarction

Describe what can be seen microscopically in chronic pulmonary congestion

Capillaries and veins filled with blood Interstitial fibrosis Numerous intraalveolar haemosiderin-labeled m/ph (clearly visible in Perls' stain)

Describe amniotic fluid embolism.

Causes: amniotic fluid/fetal tissue enters the maternal circulation via placental membrane tears or uterine vein ruptures which activates thrombosis. First symptoms: severe dyspnea, cyanosis, hypotensive shock, siezures, coma. Late on-set symptoms: pulmonary oedema and DIC syndrome. This embolism is rare but the death rate is high (20-40%).

How are congestion and oedema related?

Congestion facilitates transudation (oedema due to decreased colloid osmotic pressure).

Describe DIC syndrome.

Disseminated intravascular coagulation It is triggered by general endothelial cell activation leading to thrombosis. Small fibrin thrombi are formed on endothelial cells, in various parts of the body and can lead to organ hypoxia. This leads to an imbalance of more fibrin thrombi formation than fibrinolysis, and the depletion of clotting factors due to the high rate of fibrin formation. The depletion of clotting factors causes the inability to perform haemostasis when hemorrhages do occur.

Describe what can be seen microscopically in acute liver congestion

Engorged central veins and sinusoids Centrolobular necrosis is possible

Characterize hemorrhage by location.

External Internal - hemotoma = blood accumulation in soft tissue - accumulation in body cavity →haemothorax →haemopericardium →haemoperitoneum →haemoathrosis

Describe the morphology of oedema.

Grossly: swelling (if inflammation = red) Microscopically: widening/separation of ECM (especially clear in loose CT)

State the difference between hyperemia and congestion.

Hyperemia is the active process of volume increase in blood vessels due to arterial dilation, whilst congestion is a passive process (usually occurring in veins). Hyperemia is either physiological or pathological, but congestion is always pathological.

State some consequences of chronic congestion.

Hypoxia, parenchymal cell death and fibrosis (replacement of cells with connective tissue), capillary rupture.

State the clinical consequences of subcutaneous oedemas.

Impaired wound healing and clearance of infection.

Define thrombosis.

Inappropriate (pathological) activation of hemostasis leading to clot formation with intact vessels that may obstruct blood flow.

Describe infarction and its causes.

Ischemic necrosis caused by occlusion of arterial blood supply (most often) or venous drainage in a particular tissue. 99% of causes are thrombosis or embolism. Other causes are vasospasm, hemorrhages within an arterial atheromatous plaque, compression of blood vessels (by sutures, tumors, connective tissue, oedema), twisting of vessels, trauma.

State the clinical consequences of brain oedemas.

Life-threatening condition

State the clinical outcomes of hemorrhages.

Little/no impact on general health status Hemorrhagic/hypovolemic shock Death due to shock Significant local effect (e.g. brain) Iron-deficiency anaemia due to chronic bleeding The outcome is dependent on the volume, rate, and location of bleeding.

State some possible causes of pulmonary oedema.

Liver/renal failure, pulmonary infection, acute respiratory distress syndrome (ARDS).

State the causes of air embolism.

Medical manipulations, chest trauma, decompression

Describe the different types of thrombi.

Mural vs occlusive Mural: close to the wall, leaving some space for blood flow. They are mostly located in the heart and arteries. Occlusive: they close the lumen completely and they grow in arteries and veins. Arterial vs venous Arterial: usually occlusive, most often in coronary, brain or femoral arteries. Caused by atherosclerosis, trauma, vasculitis, etc. Composition: thrombocytes, fibrin, RBC, WBC Venous: usually occlusive, they are red, long and most often in veins of the lower extremities (90%), periprostatic/periuterine venous plexus.

Describe white infarction.

Occurs in solid organs with end-arterial circulation: typically in heart, spleen, kidney Necrosis is marked and heamorrhage is absent or limited.

Describe red infarction.

Occurs in tissues and organs with anastomosing blood vessels or dual blood supply. All venous infarction and infarctions on the background of congestion are red. In the attempt to restore tissue by revascularisation, white infarction can become red infarction. Examples: - intestinal infarction (anastomosing blood vessels) - pulmonary infarction (dual blood supply)

State some haemodynamic disorders.

Oedema Hyperemia Congestion Haemorrhage Thrombosis Embolism Infarction

Describe different hypercoagulability risk factors (Virchow's triad).

Primary = genetic - mutation of factor V/prothrombin gene - inherited hyperhomocysteinemia - inherited anticoagulant deficiency Secondary = acquired - hyper estrogen due to pregnancy/oral contraceptive - obesity - smoking - disseminated cancers - aging - heparin-induced thrombocytopenia syndrome - antiphospholipid antibody syndrome

Describe pulmonary embolism.

Pulmonary arteries are affected by embolisms. The most common source is deep vein thrombosis above the knee (95%). The possible outcomes are sudden death due to occlusion/hitting of the bifurcation of arteries leading to vasovagal reaction, lung infarction, or clinically silent chronic pulmonary hypertension.

Ecchymoses

Subcutaneous hemorrhage known as a bruse (1-2 cm).

Define purpura

Subcutaneous hemorrhage visible as larger (>3 mm) purple, red, brown spots in comparison to petechiae.

Define petechiae

Subcutaneous hemorrhage visible as tiny (1-2 mm) purple, red, brown spots.

Describe systemic embolism.

Systemic arteries are affected. Targeted sites are lower extremity arteries (75%), brain arteries (10%), and intestines/kidney/spleen/upper extremity (less frequently). Possible sources are intracardiac mural thrombi (80%), aortic atherosclerosis/aneurysm, heart valve vegetations, paradoxical emboli (if there is a pathological opening in the cardiac septum, embolism from systemic vein to the systemic artery may occur). The outcome depends on compensatory collateral circulation (anastomoses), the sensitivity of tissue to hypoxia, size of the embolism vessel. Usually, the outcome is infarction.

Describe fat embolism.

The causes are long bone fractures or soft tissue trauma. 90% have severe trauma and only 10% of these patients have clinical manifications (tachycardia, neuromanifestations, thrombocytopenia) which will occur within a few days after trauma. Pathogenesis: a mechanical obstruction in small vessels of the lungs and brain leading to aggregation of RBC and Thr on the fat globules, haemolysis, thrombocytopenia, anaemia and endothelial damage.

Describe how thrombi grow.

They grow attached to blood vessel walls and in the direction towards the heart. Arterial thrombi grow in the retrograde direction of blood flow. Venous thrombi grow in the direction of blood flow.

Describe the virchow's triad.

Three factors that increase the risk of thrombosis. 1. endothelial injury 2. normal blood flow alterations 3. hypercoagulability → primary: genetic → secondary: acquired

Describe how blood flow may be altered and how it may lead to thrombosis (Virchow's triad).

Turbulence in arteries because of ulcerated atherosclerotic plaque, aneurysms (localized enlargement of an artery caused by a weakening of the wall), myocardial infarction, and arterial dilation. Stasis/slow blood flow in veins. Stasis and turbulence promote endothelial activation by disrupting laminar blood flow and bringing platelets into contact with the endothelium. This prevents washout/dilution of activated clotting factors.

State a possible consequence of bacterial endocarditis.

Vegetations - large thrombotic masses of heart valves.

Define anasarca

general severe subcutaneous oedema within entire body

Define transudate oedema

oedema caused by a decrease in colloid osmotic pressure (low in protein) leading to insufficient reabsorption of fluid into blood vessels.

Define exudate oedema

oedema caused by a leakage of fluid (high in protein) from blood vessels due to increased permeability.

Define hydropericardium

oedema in the pericardiac cavity

Define ascites

oedema in the peritoneal cavity

Define hydrothorax

oedema in the pleural cavity

State some causes of oedema and explain how they can occur.

↑ hydrostatic pressure in blood vessels (by arterial dilation (e.g. due to heat), impaired venous drainage) ↓ colloid osmotic pressure of plasma (hypoproteinemia) (increase in protein loss due to kidney disease, decreased protein synthesis due to liver cirrhosis/amino acid malnutrition) lymphatic obstruction (inflammation, neoplastic, postsurgical, postirradiation) Sodium retention (increased salt intake, increased renal tubular reabsorption) Inflammation (acute/chronic inflammation, angiogenesis (new blood vessels are leaky at first)