HEMODYNAMIC DISORDERS The normal composition of your body 60% of which is water, 2/3 of which is coming from the

intracellular component and the remainder is extracellular mostly in the interstitium

EDEMA Presence of fluid on the interstitial tissue spaces, normally edema should not be present because whatever amount of fluid that goes in the arterial end is the same amount of fluid that goes out on the venular end and the rest is drained via lyphatic system

When does edema form : y Increase in hydrostatic pressure Force that drives fluid out of the vessel types LOCALIZED : DVT disease precipitated by immobilization of lower extremities Thrombus increase hydrostatic pressure Unilateral swelling of the leg SYSTEMIC: congestive heart failure left side of heart fails edema will accumulate in the lungs; the right will compensate to pump against a greater pressure gradient because of resistance secondary to edema of the lungs backing of blood to systemic circulation one clinical significance of edema in patients with CHF manifestation of edema in systemic side particularly in dependent part of the body (lyinglumbosacral standing- extremities) Apply finger pressure will lead a depression (pitting edema) clue of possibility of CHF Accumulation of fluid in the subcutaneous tissue y Decrease in plasma colloid oncotic pressure Pushes water in Loose proteins Periorbital swelling Nephrotic Syndrome (glomerular bdisease in which proteins leak out ) Urinalysis peroteinuria Blood decreased protein Whenever you loose it in the urine one manifestation will be edema Problem in the synthesis liver cirrhosis can lead to manifestation of edema Nutritional deficiency kwashiorkor y Sodium and Water retention

common trigger of RAAS hypotension or decreased circulating blood volume decrease in GFR triggering macula densa to secrete Renin Angiotensinogen converted to Angiotensin II vasoconstriction hypotension vasodilation of vessel vasoconstriction decrease in blood volume together with angiotensin aldosterone absorb sodium together with water increasing blood volume patients with RAAS activation CHF edematous not because of sodium and water retention but because of increase hydrostatic pressure but automatically RAAS will be activated so that you have more edema with patient with CHF so they manifest congestion part of the treatment would be giving diuretics furosemide compensatory mechanism but with patients with CHF it adds up to the problem coupled with RAAS is secretion of ADH conserves water together with sodium to increase blood flow y Lymphatic obstruction Eau de orange orange-like discoloration with staining crest of patients with lymphatic obstruction, characteristic edema here is nonpitting unlike in CHF pitting edema Cause secondary to: Fibrosis in healing ex. Removing the breast secondary to malignancy One complication is unilateral swelling of the arm part of the regimen is to dissect the axillary lymph nodes chronic inflammation and necrosis which blocks the lymph flow Physical disruption, radiation, infection, wuchereriabancrofti When lungs is edematous and you dissect it frothy or bubbly The alveoli is expected to be filled up with fluid; congested blood vessels and few hemosiderin macrophage BRAIN tends to flatten the surface of gyri pushing the sulci narrowing the sulci but the problem in edema of the brain is that it can herniate pressing the respiratory center leading to the death of the patient

Accumulation of edema can be found within the body cavities, that s why it can actually be aspirated to know if its transudate(protein core fluid with low specific gravity) or exudate (inflammatory lesions) Edema in the cavities: Pleural , pericardial, peritoneal, generalized(anasarca) HYPEREMIA AND CONGESTION Similarity is you ll have increase in blood volume Hyperemia is brought about by arteriolar dilatation Oxygenated; tissues appear red or erythema Congestion is brought about by impaired outflow from the tissue Bluish red Pulmonary congestion pulmonary edema Long standing P.E. can eventually give rise to chronic passive congestion of the lungs

Rupture of the blood vessel wall leading to the release of the red cell

Petechiae -pinpoint Purpura Bigger

Hematoma ecchymosis There is a change in the coloration of the blood clot this is secondary to the change in the pigment or hemoglobin When your abput to heal you will have golden brown color Accumulation of fluid in thorax hemothorax In the joints hemearthrosis Hemopericardium Hemoperitoneum The problem is the development of hypovolemic shock When you lose more than 20% of your blood depending on the site of blood loss It can lead to hypovolemic shock especially in the heart Less than 20% the body can compensate; NSD 500ml blood donation- 500ml

Acute pulmonary congestion Exhibits engorged alveolar capillaries often with alveolar septal edema Focal intra-alveolar hemorrhage

Chronic pulmonary congestion Septa are thickened and fobrotic Alveolu contain numerous hemosiderin laden macrophages (heart failure cells)

HEMOSTASIS 1. 2. The blood should be fluid clot free Whenever you have endothelial injury, your body has inherent mechanism to stop the bleeding unnecessary clot formation (thrombosis )

Acute hepatic congestion Congestion best seen at the level of the sinusoids It is said that the farthest from the blood supply are cells near the hepatic vein the first one to degenerate there will be central hepatocyte degeneration

Chronic passive hepatic congestion Nutmeg liver Centrolobular necrosis Abundance of hemosiderin macrophages Degeneration of hepatocytes

HEMORRHAGE

3 components y Endothelium Whenever you have endothelial injury the blood sometimes you don t know unless the blood starts to drip after a few seconds- reflex of body is vasoconstriction Endothelial cells secretes endothelin mediator which facilitates vasoconstriction the trigger is collagen exposure of subendothelial collagen vasoconstriction and release of endothelin Reflex, endothelin, collagen y Platelets

You have toform a primary hemostatic plug Facilitated by platelets going to the site of injury Platelets bind to the site of injury through a receptor found in endothelium vWF (deficiency prolonged bleeding) Platelets have to adhere unfergo a shape change to fill up the gap, secrete granules particularly ADP and TXA2 to recruit platelets on the site and form an aggregate that serve as primary hemostatic plug Code : ASSRA = primary hemostasis y Adhesion y Shape change y Secretion y Recruitment y Aggregation Secondary hemostasis Tissue factor has to be activated and leads to formation of fibrin Fibrin will be entangled with the platelets because the purpose is to stabilize the clot Process goes in and on until you fill the gap and stop the bleeding However when healing is complete the clot must be lysed ,go back to normal (blood should be in fluid clot-free state) Inherent mechanism which lyse the clot; tPA which acts on activation of plasmin and thrombomodulin which blocks the coagulation cascade Vasoconstriction mediator>>endothelin Trigger?? Exposure of collagen Primary hemostasis?? ASSRA Particular mediators important for recruitment?? ADP TXA2 1. Your body has inherent mechanisms so that your blood is kept on a fluid clot-free state; anti-platelet mechanism platelet bind only to injured endothelium ; your body secretes mediators like prostacyclin and nitric oxide so that in normal endothelial lining they are not supposed to be activated You have ADPase which further inhibit platelet aggregation anticoagulant mechanisms in the form of heparin like molecules which acts on certain factors thrombin factor Xathrombomodulin which act on inhibition of coagulation cascade through protein c activation protein c 5A and 8A

protein s tissue factor pathway inhibitor factor 7a 10a tPA formation of plasmin- degrades clot and form fibrin degradation products endothelial injury promote clot formation vWF facilitates binding of platelets; initiation of formation of primary hemostatis tissue factor secondary hemostasis; formation of fibrin; stabilize the clot PAI(plasminogen activator inhibitor)- counteract the effect of tPA when healing is not yet complete Non activated platelets should be inhibited from binding to injured endothelium PGI2 , nitric oxide , ADPase mediators when you have endothelial injury it will result in procoagulant mechanism to facilitate thrombus formation Platelets contain 2 types of granules ; Degranulation : alpha and dense bodies On the side of platelets glycoprotein Ib one that binds to vWF (deficiency adhesion will not happen) For adhesion you need vWF(deficiency : von Willebrand disease ) on endothelium and GpIb(deficiency : Bernard Soulier syndrome) on the platelet For fibrin to attach to platelet GpIIb-IIIa (deficiency ; Glanzmannthrombasthenia no aggregation bleeding); where platelets and fibrinogen binds to each other Main mediators facilitate recruitment : ADP and TXa2 Once plasmin acts on clot it will form the so called fibrin split products fibrin degradation products in lab assayed D-dimer in DIC
y Coagulation cascade Leads to formation of fibrin Active in secondary hemostasis

2.

Inherent anticoagulants like anti-thrombin protein c and s and PAI Injury to endothelium activate mechanism for clot to be formed Whenever the healing is complete you will have anti-platelets anti-coagulant mechanism and plasmin activation to actually lyse the clot Plasmin Plasminogen to plasmin -lyse clot via 1. Factor 12 dependent pathway 2. plasminogen activators particularly uPA and tPA 3. bacterial end product called streptokinase - lyse the clot to produce fibrin degradation products d-dimer - in case something is missed out, free plasmin will be acted upon by your alpha 2 plasmin inhibitor - once plasmin is formed it will be cleaved and lead to the formation of FDP FSP can be assayed d-dimer THROMBUS 1. Endothelial injury most important Single most important The endothelium need not be denuded for clot to be formed Pathologic the endothelium does not have to be denuded even tough it is intact the platelets will adhere to the site that is why it will lead to thrombosis or unnecessary clot formation 2. Disturbance in blood flow - stasis; turbulence Normal blood flow is laminar Turbulent blood flow- you don t want it, because it allows the platelets to come in contact with endothelium It allows your procoagulant to win over your anticoagulant mechanism so that you end up with thrombin The disruption of the laminar flow will lead to turbulence 3. Hypercoagulability of blood Can be inherited or acquired Inherited Factor 5 Most common type Caused by substitution of glutamine to arginine at position 506 and prothrombin gene mutation Caused by glutamine to arginine transition to 3 prieuntranslated region DVT

Immobilization of the legs Endotheium need not be denuded Their adherence will facilitate formation of clot The problem with DVT is that fragments of the thrombi detach and travel in the blood(emboli) it usually lodges in the lungs in the case of DVT

Homocysteine deficiency of enzyme Homocysteinuria promotes hypercoagulable states or inherited deficiency of thrombin 3 protein c or s Pills above 35 should not take it because it can lead to thrombosis Smoking and obesity

HEPARIN INDUCED THROMBOCYTOPENIA SYNDROME Heparin(anticoagulant) is given to patients with thrombosis To maintain fluid on clot-free state The problem is heparin when given to patient acts or binds to platelets forming a complex, the bad thing about it is that this complex can actually be recognized by your splenic macrophages and be engulfed so that you end up with destruction of platelet leading to decreased platelet count - platelet for hemostatic mechanism This complex leads to the activation of platelets ASSRA + thrombin and eventually lead to thrombosis APAS -are auto antibodies that can cause direct platelet aggregation, inhibition of prostacyclin and interference with protein c synthesis 2 main types of thrombi 1. Arterial Result of endothelial injury or turbulence Lines of Zahn are more prominent in arterial thrombosis Alternating layers of platelets and fibrin - when thrombus is occurring in chambers of the heart Mural thrombi It can lead to arrhythmias, cardiomyopathy and MI Normally seen in heart, coronaries, cerebral and femoral Left anterior descending branch

2. Venous Is more of result of stasis In lower extremities Fates of thrombus Coming from the leg to heart (propagation) Detached fragments that travel in the blood (embolization) Incorporated in the wall (organization) Slits may be formed (recanalization) When treatment is successful (resolution) Thrombus on valves vegetation The clot fills up the vessel lumen it can promote ischemia or infarction on organ it supplies the thrombus is classically attached to the vessel wall or endothelium Differentiation on thrombus and post mortem clot Postmortem clot not firmly adherent Has an upper layer of yellow or chicken fat DIC Widespread fibrin in the circulation Not a primary disease; arising from another problem -

Diagnosis is finding the adipocytes within blood vessels Usually presenting difficulty of breathing, anemia and thrombocytopenia

Air embolism Problem for rapid ascend among scuba divers Nitrogen bubbles begins to form in circulation and can lead to embolism Bends and chokes ; difficulty in bending the joints and difficulty of breathing Caisson s disease Inject something to vessels more than 100ml can cause air embolism

Amniotic Fluid Embolism High mortality rate When you give birth and the placenta separates from the uterus fragments of the fetal components may be thrown in the circulation of the mother and usually it lodges in the lungs Diagnosis rest on doing an autopsy ; section of the lungs you will find keratin, lanugo hairs, vernixcaseosa embedded on the lungs

EMBOLISM Almost always came from thrombus

INFARCTION when you occlude a blood supply of an organ Almost always either thrombotic or embolic 99% Compression or traumatic injury Depends on type of tissue; one with dual circulation compensates better like lungs kidneys arteriole and liver General categories of infarction Hemorrhagic (red ) Usually occurs in ovarian or venous, tissue with dual circulation, tissue previously congested, Anemic (white) Arterial Solid (heart kidney spleen) Usual coagulation necrosis With microorganism Septic infarction

Pulmonary thromboembolism Systemic Comes from chamber of the heart (mural thrombus) The usual site of attachment will be lower extremities and the brain Almost always comes from DVT -trigger prolonged immobilization promoting stasis and hypercoagulability Detached lodges in the lungs causing total occlusion If occlusion is more than 60% may lead to death, biventricular failure cardiovascular collapse Is multiple- clinically silent

SHOCK

Fat Fracture of long bones lead to the release of marrow of long bones Systemic hypoperfusion can lead to decrease BP Pump failure Plasma or blood diarrhea

Septic microorganism Neurogenic accident spinal cord injury Anaphylactic IgE; gram positive Systemic vasodilation Factors predisposing to shock 1. Inflammatory mediators PLR production of ROS 2. Endothelial activation and injury insulin resistanc 3. Shift from pro anti-inflammatory apoptosis 4. Organ dysfunction characteristic 5. ARDS in lungs 3 phases 1. non progressive increase HR; RAAS; vasoconstriction 2. Necrosis aerobis to anaerobic 3. Irreversible multi organ; vital organs like kidney renal shutdown 4. Acutetubular necrosis 5. Oliguria and anuria difficulty f breathing ARDS 6. Ischemia other organ involvement

Hepatic failutre- cardiogenic shock Septic shock vasodilation Hypotension Body will compensate initially activation of RAAS tachycardia and conservation of fluid as well as vasoconstriction if not controlled irreversible anaerobic glycolysis DIC- usually lower; patient will bleed; no urine output; failing lung oliguria Patient starts to bleed 6. l 7. Cardiogenic Hypovolemic septic