(From Path, 8-12 Sept 2000, by Brian Buschman)
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Edema is an abnormal accumulation of fluid in body cavities. It can be:
1) Inflammatory
2) Hemodynamic (non-inflammatory) meaning it is related to an imbalance in Starling’s forces.
3) Lymphoedema (because of lymph node blockage).
· Anasarca is a severe systemic edema.
· Hydrothorax is edema of the thorax.
· Hydropericardium is edema of the pericardium.
· Hydroperitoneum is edema of the peritoneum.
Edema has a variety of causes. Often times these causes are related to Starling’s law imbalances. The four categories are:
1) Increased hydrostatic pressure which obviously works by either arteriolar dilation or venous impairment. Arteriolar dilation comes from heat and neurohumoral excess. Impaired venous return comes from:
a. CHF
b. Constrictive pericarditis
c. Cirrhosis of the liver (ascites)
d. Obstruction of veins from thrombosis, pressure and problems with the L.L.
Increased hydrostatic pressure can also be secondary to aldesteronism as it causes reuptake of H2O and hence increased blood volume.
2) Reduced plasma oncotic pressure (hypoproteinemia) that comes from conditions like:
a. Protein-loosing glomerulopathies like nephrotic syndrome.
b. Ascites (cirrhosis of the liver)
c. Malnutrition
d. Protein-loosing gastroenteropathy.
3) Sodium retention from excess salt intake or increased tubular reabsorption.
4) Lymphatic obstruction from neoplasty, inflammation, post surgical or post-irradiation. Lymphatics can lead to filariasis (elephantiasis) and is seen in breast cancer.
CHF is the most common cause of systemic edema. Left heart failure is the most common cause of pulmonary edema.
Subcutaneous edema is most often seen in the L.L of patients with right heart failure. If the patient is confined to bed it will probably result in anasarca. This is referred to as dependent edema since this form depends of gravity to work differently then it is while constantly in bed.
Renal dysfunction causes anasarca edema affecting most all solid organs. One place it is specifically prominent is the periorbital area (eyelids). It is also the cause of pitting edema. That is if you push on the skin to move the fluid it leaves a temporary pit before reforming.
Pulmonary edema is usually mostly in low lobes (gravity) but will effect all lobes. If you puncture the edeminous lung it will ooze a white froth which is fluid mixed with air.
Cerebral edema is caused by an increased CSF pressure and is just bad. If can kill the patient from brainstem herniation. Brain tumors tent to cause an area of edema all around themselves.
One mini question that Dr. T gave away was that we need to know what Prussian Blue stains for. It is iron.
Both hyperemia and congestion are ways of saying that excess volume of blood is in a particular tissue.
Hyperemia is an excess of active blood in the tissue because of excess input. In this cause the problem is usually increased arteriolar dilation. This causes more blood to move in then is able to move out but the tissue is still getting plenty of supply. It is an excess of active blood flow in a tissue as the blood is still moving.
Congestion is an excess of blood in the tissue resulting from a blockage of the drainage pathway. The excess comes from having a normal input of blood but there is a greatly reduced outflow causing the backpressure. It is an increase in passive blood volume in a tissue because the blood is not moving.
Acute pulmonary congestion is a backup of blood into the lungs usually from left heart failure. Chronic pulmonary congestion is similar to acute pulmonary congestion but results in rupture of small vessels. It also has an increase of hemosiderin laden macrophages. These macrophages are called heart failure cells because they can be seen when the patient has heart failure.
Note the difference is that in chronic pulmonary congestion there is rupture of small vessels. The increase of internal bleeding and heart failure cells will cause the slide to have more area that stains with Prussian Blue.
Acute hepatic congestion results from right heart failure. It could possibly result from a IVC occlusion but usually from the heart failure.
In chronic passive congestion (CPC) of the liver. The hepatocytes near the central vein become swollen and are killed because of the backpressure. The outer hepatocytes are hardly effected. The description is called “Nutmeg liver.” It has centrilobular necrosis and is called cardiac cirrhosis due to original cause (right heart failure).
Purpara is a type of hemorrhage that is greater then 3mm.
Ecchymoses are hematomas that are 1-2 cm.
Thrombosis is from an inappropriate clot that can break loose and is then called the thrombus.
The normal hemostatic process has four stages:
1) Neurogenic vasoconstriction that is quick to help prevent blood loss.
2) Subendothelial collages is exposed which causes platelet activation. It includes the release of ADP, TxA2 and seretonin. This is the primary hemostatic response. A temporary plug is formed.
3) Tissue factors and platelet factors are released so coagulation happens. The fibrin plug that is formed is what is known as secondary hemostasis.
4) A permanent plug of fibrin and platelets if formed.
Platelets are activated and adhesion is stimulated by platelet activating factor, tissue factor and vonWillebrand’s factor.
Platelet aggregation is also inhibited by PgI2, NO, ADPase, heparin and antithrombin III.
Fibrinolysis (antithrombic) is mediated by tissue plasminogen activator (t-PA) while the prothrombic effects are mediated by t-PA inhibitor.
Platelet aggregation is mediated by TxA2 and ADPase followed by thrombin and fibrin.
Platelets adhere to each other by binding fibrinogen molecules between each other. They bind them using GpIIb-IIIa receptors. They join to the subendothelial collagen by binding vonWillebrand’s factor (vWF) with GpIb receptors. (The Gp in the receptor names are for glycoprotein). The vWF is already bound to the subendothelial layer.
Platelet aggregation can go bad with a number of diseases including the genetic deficiencies of many of the above molecules including:
1) vonWillebrand’s disease which is a shortage of vWF. It will obviously cause a lack of platelet binding to the subendothelial layer.
2) Bernard-Soülier syndromes is a shortage of the GpIb receptor. Like the vonWillebrand’s disease this causes a lack of platelet binding to the subendothelial layer.
3) Glanzmann thrombasthenia is a defective GpIIb-IIIa receptor. This prevents platelets from binding fibrin and hence makes platelet aggregation impossible.
The sequence of platelet events is:
1) Adherence to ECM and activation.
2) Secretion of ADP and synthesis of TxA2 to activate the platelets.
3) Phospholipid complexes are exposed to the intrinsic coagulation pathway.
4) Endothelial cell factors trigger extrinsic coagulation pathway.
5) ADP stimulates the primary plug. TxA2 stimulates the secondary plug.
6) Fibrin is deposited which stabilizes the plug and anchors the platelets.
Coagulation proceeded by the extrinsic and intrinsic pathways. The intrinsic pathway is activated by factor XII and the extrinsic pathway by tissue factor. The cascade is controlled and restricted by:
1) Antithrombin III binds to heparin and inactivates thrombin, Xa and IXa.
2) Proteins C and S inactivate factors Va and VIIIa.
3) Urokinase and tissue plasminogen activators (u-PA, t-PA) convert plasminogen to plasmin. The endothelial cells make the plasmin inhibitor.
4) Plasminogen lyses clots and results in fibrin degradation products.
You can test the serum for fibrin degradation products and if you find them but also see a lot platelet count then you can deduce that the presenting clotting failure is due to both the clotting and the plasmin pathways working together. This condition is a result of defective control on the plasmin pathway.
Thrombosis is caused by one of three influences:
1) Endothelial injury. This is the biggest cause. What happens is that a clot builds up on the vessel’s wall and then the injury causes it to break loose.
2) Alterations in normal blood flow. Such as when the blood flow through a given vessel is normally laminar but becomes turbulent.
3) Hypercoagulability.
Hypercoagulability is the least common cause of thrombosis but of course, it’s the one that we need to spend the most time studying. It may be inherited or acquired. If found early in life it is probably inherited as a(an):
1) Antithrombic deficiency.
2) Protein C deficiency.
3) Protein S deficiency.
4) Fibrinolysis defect.
All are deficiencies that would obviously cause clot formation or decreased clot degradation, as the term hypercoagulability would imply.
Acquired hypercoagulability is usually secondary to another state such as:
1) Prolonged bed rest.
2) Leukemia
3) Smoking
4) Thrombocytosis
Other can be found on P. 106 (Table 4-2).
Heparin syndrome causes thrombi because the heparin in the system is an impure heparin. You treat by administration of a pure heparin.
Antiphospholipid syndrome is an Ab to the phospholipid complexes. It may be seen in SLE.
Thrombi can form in the vessels pre or post-mortem and in an autopsy it’s important to distinguish. God gave us a good clue in that when the clot forms before the patient dies there are Lines of Zhan which are alternating red and white lines when viewing it’s cross-section.
Mural thrombi are thrombi that are only on one wall of the vessel. There is still plenty of room for blood to flow past them. The biggest problem is if they become too large or of they break loose.
Venous thrombi occur most often in the lower veins where there is the most stasis. In veins the post-mortem clot is not attached to the wall. The pre-mortem clot would be. You may remember seeing venous clots not attached to the walls when you took anatomy lab.
When a vein is thrombosed it can ultimately become:
1) Completely resolved with no remaining obstruction.
2) Organized and incorporated into a wall where blood can still pass.
3) Recanalize so a little blood can flow through the middle of it (but not very much).
4) It can break loose and will embolise into the lung.
Trousseau syndromes is venous thrombi associated with a cancer.
An embolism is a solid, liquid or gas carried in the blood away from it’s origin. An embolism is any substance carried somewhere that is should not. A thrombi is one form of embolism.
If the embolus comes into the venous circulation then it will lodge in the lungs. If it enters via the arterial circulation it will lodge in a capillary bed somewhere in systemic circulation. In either case it will cause an infarct in the given tissue.
Pulmonary emboli may become a saddle emboli of stuck at the bifurcation of the pulmonary artery. Large emboli can cause sudden death. Small emboli can be undetected indefinitely if there is sufficient collateral circulation.
Paradoxical emboli are ones that may sneak from the pulmonary to systemic circulation. This usually occurs through a channel like a semi-patient foramen ovale if the right heart pressure exceeds the left.
Cor pulmonale is sudden death from an embolism.
Fat embolism is an emboli of fat from extensive trauma to fatty tissue or fracture of long bones.
Air embolism is when air enters the blood supply. Some causes are SCUBA accidents, pneumothorax with a vessel rupture and surgical mistakes. It probably takes at least 100cc of air to cause a problem.
Ammonic fluid emboli can occur in the mother. It comes when there are lots of foreign material in the fluid such as squamous cells that cause blockages. Remember that ammonic fluid is full of cells and particles.
The severity of an infarct is affected by four factors:
1) Dual blood supply. If the tissue has collateral circulation or a dual blood supply it may be able to deal with the infarct without any problems.
2) Rate at which the occlusion develops. If it develops slowly other channels can become enlarges over time. If sudden the tissue is more likely to have ischemic problems.
3) Some tissues are better able to deal with temporary ischema. Muscles do fine for a time but the brain does not.
4) Conditions like anemia make the condition worse. It’s one of those states where having that decreased O2 carrying capacity is already a strike against you.
Hemorrhagic infarcts are from venous occlusion such as torsion. When the veins become blocked there is still the blood supply to the tissue which causes the buildup of pressure which makes a venous infarct more likely to have hemorrhage. The tissue does get a blood supply.
White infarcts are when the arteries are what is blocked and the tissue does not get a blood supply because there is no other collateral circulation like in the spleen or kidneys.
As we know shock can be cardiogenic, hypovolemic, anaphylactic or septic. Septic shock is all we need to discuss here.
With septic shock the infection leads to the immure response and the mediators produced/released can cause a variety of problems such at:
1) Myocardial dysfunction.
2) ARDS
3) Acute renal failure
4) Hepatic failure
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