HUMAN PATHOLOGY EXAM

• Body Fluid Compartments


  • Water = ~60% of body weight
  • Changes as you age
  • Differences based on sex - men typically have more than women

  
• Fluid Compartment Exchange


  1. Plasma volume can expand and reduce but only within narrow physiological limits

  2. Dehydration: hemorrhage, sweating and diarrhea

  3. Overhydration: inadequate renal excretion, edema

  4. Redistribution: shock

  5. Circulatory disruption: atherosclerosis, embolism, thrombosis
• Edema


  Excessive fluid in interstitial space and/or body cavities
• Types of edema


  • Localized edema
  • Generalized edema: anasarca
• Localized edema


  • Cerebral edema
  • Pulmonary edema
  • Periorbital (facial) edema
  • Ascites or hydroperitoneum: abdominal cavity
  • Hydrothorax: pleural cavity
  • Hydropericardium: pericardial cavity

  
• Exudate


  Rich in protein and blood cells, typical of inflammation
• Transudate


  Contains less proteins and fewer cells (ultrafiltrate of plasma fluid)
• Pathogenesis of edema


  • Increased hydrostatic pressure
  • Increased permeability
  • Decreased oncotic pressure
  • Obstruction of lymphatic vessels

  
• Forms of edema


  • Inflammatory edema
  • Hydrostatic edema
  • Oncotic edema
  • Lymphedema
  • Hypervolemic edema
• Inflammatory edema


  • Vessel permeability and hyperemia
  • Permeable due to mediators of inflammation and increased blood flow (dilation)
  • Fluid is initially transudate
  • Transforms into exudate containing inflammatory cells
• Hydrostatic edema


  • Increased arterial pressure inside blood vessels (ex// arterial hypertension)
  • Increased intravascular pressure promotes trans membranous passage of fluids
  • Increased venous backpressure
  • Venous stagnation
  • Right sided heart failure: increased blood volume in the periphery causes venous congestion, peripheral edema and ascites
  • Left sided heart failure: pooling in the lungs causes pulmonary hypertension, pleural effusion and chronic congestion of the lungs

  
• Oncotic edema


  • Reduced oncotic pressure of the plasma
  • Albumin = most active oncotic protein
  • Hypoalbuminemia - Loss of protein in the urine (proteinuria): nephrotic syndrome
  • Decreased protein synthesis: end stage liver disease (cirrhosis)
  • Usually generalized but prominent in the face
• Lymphedema


  • Obstruction of lymphatic vessels
  • Decreased drainage of interstitial
  • Rare but caused by tumour cells or chronic inflammation
  • Can be caused by worms - filarial nematodes - "elephantiasis"

  
• Hypervolemic edema


  • Due to retention of Na and H2O in the kidneys
  • Kidney disease promotes renin -> angiotensin -> adrenal cortex -> aldosterone -> renal Na retention

  
• Hyperemia


  Accumulation of blood in peripheral circulation
• Types of hyperemia


  • Active hyperemia
  • Passive hyperemia
  • Chronic passive congestion in the lungs
• Active hyperemia


  • Dilation of arterioles and influx of blood
  • Blushing, exercise
  • Mediated by neural signals to relax arteriolar smooth muscle
  • Acute inflammation (swelling)
• Passive hyperemia


  • Congestion
  • Caused by venous backpressure/impaired venous drainage
  • Typically due to heart failure (chronic)
  • Associated with hydrostatic edema
  • Cyanosis: stagnation of deoxygenated blood, bluish discolouration

  
• Chronic passive congestion in the lungs

  • Increased venous pressure -> edema
  • Leakage of fluid and RBC into alveoli
  • RBCs fall apart
  • Macrophages
  • Hemoglobin is degraded into a brown pigment (hemosiderin)
  • Accumulates in macrophages
• Hemorrhage


  Passage of blood outside the cardiovascular system

  
• Clinically, hemorrhage can be

  • Sudden onset (acute)
  • Long standing (chronic)
  • Recurrent and marked by repeated episodes of blood loss

  
• Classification of hemorrhages


  • Cardiac
  • Aortic
  • Arterial
  • Capillary
  • Venous

  
• Arterial hemorrhage


  Characterized by bright red pulsating blood (oxygenated)

  
• Venous hemorrhage


  Dark red (deoxygenated), blood flows freely and slow

  
• Hemorrhages classification


  • External
  • Internal

  
• External hemorrhage


  • Exsanguination and death
  • Hypovolemia

  
• Internal hemorrhage


  • Fills body cavities
  • Hematomas: blood filled swelling

  
• Hemorrhages of the skin

  • Petechiae: small <1 mm into skin and mucosa
  • Purpura: 1mm-1cm
  • Ecchymoses: larger blotchy bruises
• Clinically important forms of hemorrhages

  • Hematemesis: vomiting
  • Hemoptysis: respiratory bleeding
  • Metrorrhagia: uterovaginal bleeding
  • Hematuria: blood in urine
  • Hematochezia: anorectal bleeding
  • Melena: black blood in stool

  
• Consequences of hemorrhage


  • Massive acute hemorrhage: increased blood loss, hypovolemic shock, exsanguination and eventual death
  • Hematoma: compression of tissues
  • Intracerebral hemorrhage: stroke
  • Chronic hemorrhage: slow blood loss, usually results in iron deficiency anemia (bleeding gastric ulcer)

  
• Thrombosis


  Transformation of fluid of blood into solid made of blood cells and fibrin -> thrombus
• Pathogenesis of thrombosis


  • Thrombi: end product of coagulation
  • Activated to prevent blood loss in disrupted vessels
  • Clotting factors and platelets promote thrombosis
  • Endothelial cells and plasmin counteract thrombosis
• Factors involved in intravascular coagulation

  • Coagulation proteins
  • Endothelial cells
  • Platelets
• Coagulation proteins


  • Circulate in inactive form
  • Coagulation factors work to form thrombin
  • Thrombin: the catalyst promoting polymerization of fibrinogen to fibrin
  • Mesh of fibrin: framework for the clot, includes blood cells and plasma proteins
• Endothelial cells


  • Secrete substances to prevent coagulation (prostacyclin and nitric oxide)
  • Injured vessels switch from anticoagulant to procoagulant state - promote thrombus formation
  • Mediators of inflammation (IL-1, TNF) activate endothelial cells to become initiators of thrombosis
• Platelets


  • Neutralize heparin and other anticoagulation factors
  • Activated platelets secrete thromboxane -> stimulates coagulation process
• Formation of thrombi


  • Endothelial defect is covered with fibrin and platelets
  • Fibrin forms a meshwork that anchors blood cells into the nascent thrombus
  • Fully formed thrombus consists of layers of fibrin and blood cells

  
• Pathological thrombi


  • Mural thrombi -> wall of vessel of cardiac chamber
  • Valvular thrombi of the heart -> heart valve
  • Arterial thrombi (athersclerotic aorta, aortic aneurysm)
  • Venous thrombi
  • Microvascular thrombi

  
• Virchow's triad (predisposing conditions for pathological thrombi)

  • Endothelial cell injury (severe)
  • Hemodynamic changes (turbulence, slow flow, sedimentation of cells)
  • Hypercoagulability (platelets and coagulation factors)
• Gross features of thrombi

  • Red (conglutination) thrombi
  • Layered (sedimentation) thrombi