9.3 Hemodynamic Disorders: Edema, Hemorrhage, Thrombosis, Embolism, Infarction, DIC & Shock

Why this area matters

The TOS basic area names "hemodynamic disorders; thromboembolic disease; shock". These underlie heart failure, stroke, pulmonary embolism, dengue shock, burns and trauma throughout the clinical subjects. Questions often give a postmortem finding (lines of Zahn, saddle embolus, nutmeg liver) or a hemodynamic profile and ask for the mechanism.

Hemodynamic Disorders: Edema, Thrombosis, Embolism & Shock

Starling Forces and Pathophysiology of Edema

Fluid movement across microvascular walls is governed by the Starling equation:

$J_v = K_f \cdot [(P_c - P_i) - \sigma (\pi_c - \pi_i)]$

Where $P_c$ is capillary hydrostatic pressure, $P_i$ is interstitial hydrostatic pressure, $\pi_c$ is capillary plasma oncotic pressure, $\pi_i$ is interstitial oncotic pressure, and $\sigma$ is the reflection coefficient. Pathologic fluid accumulation in interstitial spaces occurs via four mechanisms:

1. Increased Capillary Hydrostatic Pressure ($P_c$): Impaired venous outflow seen in congestive heart failure, deep vein thrombosis, and constrictive pericarditis.
2. Decreased Capillary Oncotic Pressure ($\pi_c$): Loss of serum albumin ($< 3.0\text{ g/dL}$) secondary to renal protein wasting (nephrotic syndrome), decreased liver synthesis (cirrhosis), or protein-energy malnutrition (kwashiorkor).
3. Lymphatic Obstruction (Lymphedema): Disruption of lymphatic drainage due to filariasis (Wuchereria bancrofti), axillary lymph node dissection in breast surgery, or radiation-induced lymphatic sclerosis.
4. Increased Vascular Permeability: Mediated by inflammatory mediators (histamine, bradykinin, leukotrienes), forming a protein-rich exudate (specific gravity $> 1.020$, protein $> 3\text{ g/dL}$) rather than a protein-poor transudate (specific gravity $< 1.012$, protein $< 3\text{ g/dL}$). Fluid accumulation in body cavities is termed effusion (hydrothorax, hydropericardium, ascites).

Hyperemia vs. Congestion

• Hyperemia: An active process resulting from arteriolar dilation with increased arterial inflow (e.g., exercising skeletal muscle, cutaneous flush, site of acute inflammation); tissues turn bright red due to oxygenated blood.
• Congestion: A passive process resulting from impaired venous outflow (e.g., heart failure, venous thrombosis); tissues turn dusky blue-red (cyanotic) from deoxygenated hemoglobin. Chronic passive congestion of the liver produces a mottled gross appearance termed "nutmeg liver", characterized by centrilobular congestion and necrosis surrounded by uncongested, pale periportal hepatocytes.

Thrombogenesis & Virchow's Triad

Thrombosis is the pathological formation of an intravascular solid mass (thrombus) in non-interrupted blood vessels, governed by Virchow's Triad:

1. Endothelial Injury: The most critical factor in arterial and cardiac thrombosis. Denudation of endothelium exposes subendothelial von Willebrand factor (vWF) and tissue factor, initiating platelet aggregation and coagulation cascade activation.
2. Abnormal Blood Flow (Stasis or Turbulence): Turbulence causes endothelial injury and countercurrent pockets, while stasis permits platelets to contact endothelium and prevents dilution of activated clotting factors. Common in venous beds of immobilized patients, ventricular aneurysms, and fibrillating atria.
3. Hypercoagulability (Thrombophilia): Primary (Factor V Leiden mutation causing activated protein C resistance; Prothrombin G20210A mutation; Antithrombin III, Protein C, or Protein S deficiency) or Secondary (antiphospholipid syndrome, oral contraceptive use, advanced malignancy, nephrotic syndrome).

Lines of Zahn: Gross and microscopic laminations consisting of alternating pale layers of platelets and fibrin and darker layers of red blood cells. Lines of Zahn are diagnostic of a thrombus formed in flowing blood, definitively distinguishing an ante-mortem thrombus from a post-mortem "currant jelly" / "chicken fat" clot.

Embolism Varieties

An embolus is a detached intravascular solid, liquid, or gaseous mass carried by the circulation to a distant site:

• Pulmonary Thromboembolism (PTE): Over 95% originate from deep vein thrombosis (DVT) of the lower extremities above the knee (popliteal, femoral, and iliac veins). A large saddle embolus lodged at the bifurcation of the pulmonary artery produces acute right heart failure (cor pulmonale) and electromechanical dissociation.
• Systemic Thromboembolism: Approximately 80% originate from left ventricular mural thrombi following myocardial infarction or left atrial thrombi in atrial fibrillation; commonly lodge in lower extremities (75%) and brain (10%).
• Fat Embolism Syndrome: Occurs 24 to 72 hours after fractures of long bones (femur, tibia) or orthopedic surgery. Characterized by the classic clinical triad: acute respiratory distress/hypoxemia, neurological deficits (confusion, delirium), and a petechial skin rash (conjunctival, neck, axillary).
• Amniotic Fluid Embolism: Entry of amniotic fluid containing fetal squamous cells and lanugo hair into the maternal circulation via uterine tears. Triggers sudden catastrophic dyspnea, cyanosis, cardiovascular collapse, and disseminated intravascular coagulation (DIC).
• Air Embolism: Entry of gas into circulation via surgical neck trauma, central venous line placement, or deep-sea diving (decompression sickness / "the bends" where dissolved nitrogen forms bubbles in tissues and joints; Caisson disease produces aseptic osteonecrosis).

Infarction: White vs. Red

• White (Pale / Anemic) Infarcts: Occur in solid organs with end-arterial circulation and high tissue density that limits hemorrhage (heart, spleen, kidney).
• Red (Hemorrhagic) Infarcts: Occur in loose, spongy tissues (lungs); organs with dual circulations (lungs, liver, intestine); tissues subjected to venous occlusion (ovarian or testicular torsion); or sites of reperfusion following arterial recanalization.

Circulatory Shock Classification & Hemodynamics

Shock is systemic hypoperfusion resulting from impaired cardiac output or reduced effective circulating volume, leading to cellular hypoxia and multi-organ failure.

Hemorrhage

Rapid loss of more than about 20% of blood volume can cause hypovolemic shock. Chronic loss causes iron-deficiency anemia. Bleeding into the brain or pericardium can kill even when the volume is small.

Fate of a thrombus

A thrombus can:

• propagate and occlude the vessel;
• embolize;
• dissolve through fibrinolysis, most likely when it is recent, which is the basis of early thrombolytic therapy;
• undergo organization and recanalization: granulation tissue grows in and new channels may restore some flow.

Arterial thrombi are pale, rich in platelets and fibrin, and occlusive at sites of atherosclerosis. Venous thrombi (phlebothrombosis) are red, rich in cells, form during stasis, and occur mostly in the deep veins of the legs. Postmortem clots are gelatinous, with a dark red "currant jelly" part and a yellow "chicken fat" part. They are not attached to the vessel wall and lack lines of Zahn.

Disseminated intravascular coagulation

DIC is not a disease but a complication. It follows:

• obstetric emergencies such as placental abruption, retained dead fetus, amniotic fluid embolism and septic abortion;
• sepsis, especially gram-negative and meningococcal;
• malignancy, such as mucin-secreting adenocarcinoma and acute promyelocytic leukemia;
• major trauma and burns;
• snake envenomation and severe dengue.

Tissue factor release or widespread endothelial injury triggers coagulation throughout the microcirculation. Microthrombi cause ischemic organ damage (kidney, brain, lungs). Platelets and clotting factors are consumed, and secondary fibrinolysis follows, so the patient bleeds. Laboratory findings are:

• thrombocytopenia;
• prolonged PT and aPTT;
• low fibrinogen;
• high D-dimer;
• schistocytes on the blood smear.

Stages and morphology of shock

1. Non-progressive (compensated): baroreceptor reflexes, catecholamines and the renin-angiotensin system cause tachycardia and vasoconstriction. Perfusion of vital organs is maintained.
2. Progressive: tissue hypoperfusion leads to anaerobic glycolysis, lactic acidosis, arteriolar dilation and pooling, and worsening cardiac output. Oliguria and confusion appear.
3. Irreversible: severe cell and tissue injury. Lysosomal enzyme leak, myocardial depression and ischemic gut injury that lets bacteria translocate into the blood all mean that correcting the hemodynamics no longer saves the patient.

Morphologic changes come from hypoxic injury in many organs:

• brain: ischemic encephalopathy;
• heart: subendocardial hemorrhage and contraction band necrosis;
• kidney: acute tubular necrosis, the cause of oliguria;
• lungs: diffuse alveolar damage with hyaline membranes, termed shock lung (acute respiratory distress syndrome);
• adrenals: lipid depletion; in fulminant meningococcemia, adrenal hemorrhage (Waterhouse-Friderichsen syndrome);
• gut: patchy mucosal hemorrhage and necrosis;
• liver: central (zone 3) necrosis.