Pathology Final - Inflammation & Immunity

hydropic change –swelling of cytoplasm, influx of sodium and water

• Plasma membrane ruptures and nuclear changes
• 3 types:
• Pyknosis---condensation of chromatin
• Karyolysis—lysis of chromatin
• Karyorrhexis---fragmentation of nuclear material

• Necrosis: groups of cells; inflammation; non-energy dependent
• 1. Coagulative-most common—outline of tissue preserved—MI, kidney infarcts
• 2. Liquefactive---brain infarct, abscess, wet gangrene
• 3. Caseous---granulomas of tuberculosis/deep fungal
• 4. Fat necrosis—found with acute pancreatitis or trauma to fat
• 5. Fibrinoid necrosis—small blood vessels; Systemic lupus

programmed cell death-involves gene activation and enzyme action; no significant inflammation; single cell; requires energy

• 1. Hypertrophy—increase in tissue/organ size due to increase in cell
• size (weight lifter; left ventricle enlargement secondary to HBP)
• 2. Hyperplasia—increase in tissue/organ size due to increase numbers of
• cells (endometrium)
• 3. Metaplasia---replacement of one mature cell
• type by another—example: Barrett’s esophagus—reversible in most cases
• 4. Atrophy (pathologic or physiologic)
• 5. Dysplasia

wear and tear pigment of aging

found in areas of necrosis

a consequence of hypercalcemia

Neutrophils

• Hemodynamic changes (brief vasoconstriction, then vasodilatation), increased permeability of vessel walls, and emigration of leukocytes from blood vessels into the tissues.
• Transudate—clear, protein poor, relatively acellular liquid—seen in renal and heart failure (low protein; spec. gravity < 1.02)
• Exudate—viscous, protein rich, seen in pus (high protein; specific gravity > 1.02)
• Anasarca—severe generalized swelling of all subcutaneous tissues (cirrhosis or nephrotic syndrome)
• Ascites-- edema in peritoneal cavity (end stage liver disease)

• 1. margination
• 2. rolling
• 3. adhesion
• 4. transmigration

• 1. Clotting factors—Hageman, thrombin, fibrinogen
• 2. Anticoagulants—plasmin
• 3. Complement proteins
• 4. Kinins—bradykinin

• 1. Biogenic amines—histamine and serotonin—from mast cells and platelets
• 2. Arachidonic acid derivatives prostaglandins and leukotrienes
• 3. Cytokines
• 4. Platelet activating factors
• 5. Nitric acid from endothelial cells and macrophages

Prostaglandins & nitric oxides

• 1. histamine
• 2. bradykinin
• 3. platelet activating factor
• 4. leukotrienes

C5a, leukotriene B4, interleukins

prostaglandins and bradyinin

Neutrophils, eosinophils, macrophages

• Part of the innate immune system, it causes massive amplification of the response and activation of the cell-killing membrane attack complex (MAC).
• It is composed of more than 20 plasma enzymes.

• 1. Classical path—antigen antibody reactions
• 2. Alternative path---usually activated by fragment of fungi or bacteria, toxins, foreign substances.

• 1. opsonization of bacteria (coating with IgG and complement C3b)
• 2. anaphylatoxic action—stimulates release of histamine
• 3. chemotaxis—C5a attracts neutrophils
• 4. cytolysis—Membrane Attack Complex formed (MAC)

• 1. Bleeding and clot formation
• 2. Inflammation
• 3. Granulation tissue
• 4. Scarring
• 5. Restructuring (reorganization) of scar

• Primary intention---edges of wound approximated and held in place by sutures
• Secondary intention----edges of wound are not approximated or are missing (takes longer to heal).

Hypertrophic scar composed of type III collagen; results from defective remodeling of scar tissue

• Permanent: cannot regenerate—neurons, striated muscle of myocardium**(some debate about validity now)
• Labile: Can readily regenerate---skin, mucosa
• Stable: can also regenerate (if needed) such as liver or kidney

• Increased intravascular (hydrostatic) pressure
• Increased permeability of vessel wall
• Decreased osmotic pressure of plasma (reduced albumin)
• Sodium retention
• Obstruction of lymph flow

Reduced perfusion of kidneys (such as from heart failure) leads to rennin secretion. Renin activates the angiotensin system causing the increased secretion of aldosterone from the adrenal cortex. Aldosterone stimulates the tubules of the kidney to retain sodium. Retention of sodium is accompanied by retention of water which expands the intravascular volume leading to increased hydrostatic pressure and edema.

active process—blood influx into tissues—tissue is bright red, warm

passive process-stasis, tissue is dusky red to blue—tissues are cold and clammy

Chronic passive congestion results in pooling and necrosis of hepatocytes (red-brown). These hepatocytes are replaced by fibrous tissue—uncongested areas appear pale tan--- nutmeg appearance to cut surfaces.

• 1. Vascular wall
• 2. Platelets
• 3. Coagulation cascade

• 1. Platelet adhesion and shape change (adhesion mediated by VonWillebrand factor)
• 2. Secretion and release of granules by platelets—ADP, TxA2
• 3. Recruitment and aggregation to form hemostatic plug

Activation of the coagulation cascade

• (factors predisposing to thrombosis)
• 1. Endothelial injury
• 2. Alteration of blood flow (stasis or turbulence)
• 3. Hypercoagulability

• 1. Resolution
• 2. Propagation and eventual occlusion
• 3. Organization
• 4. Recanalization
• 5. Embolization

• An emboli is a dislodged thrombus.
• 1. Venous- originate in deep leg veins—carried to lungs
• 2. Arterial-originate in heart, aorta, or large arteries—carried to various organs
• 3. Fat emboli—fracture of long bones
• 4. Paradoxical embolism: goes through a defect in inner ventricular heart wall to bypass pulmonary—behaves as an arterial embolism

Clotting disorder---Microthrombi in small blood vessels consumes platelets and depletes fibrin. Can be triggered by obstetric complication, shock, gram negative sepsis (whole body inflammation), extensive trauma.

• 1. Cardiogenic (pump failure)
• 2. Hypovolemic (wounds, burns, vomiting)
• 3. Hypotensive (peripheral vasodilation)—bacterial toxins, anaphylactic, neural injury)

A lipid storage disease showing deficiency of hexosaminadase A.

a lipid storage disease showing deficiency of beta glucosidase.

Lipid storage disease showing deficiency of sphingomyelinase.

Lipid storage disease showing deficiency of alpha galactosidase.

• Mucopolysaccharidoses
• deficiency of alpha-L-iduronidase—results in buildup of heparin sulfate and dermatan sulfate

• abnormality in amino acid metabolism
• Deficiency of phenylalanine deaminase blocking conversion of phenyalanine to tyrosine.
• If untreated, mental and neurologic deterioration

• Intercellular deposition of a proteinaceous material in beta-pleated sheets; many different amyloid proteins.
• If deposited in sufficient amounts it can interfere with cell functions, most notably in the heart, adrenal, liver, and kidney (deposits in the glomeruli--nephrotic syndrome).

Homogenous pink material on H&E sections; green birefringence when stained with Congo red and subjected to polarized light.

• Seen in multiple myeloma (AL), medullary carcinoma of the thyroid (A cal—derived from calcitonin molecules), Alzheimer’s disease (AB2); AA amyloid—seen in areas of chronic inflammation)
• Not currently curable

Oncogenes are cancer-inducing genes; normal genes that may become oncogenes are called proto-oncogenes

• Epstein-Barr virus is a herpes virus.
• It is associated with: Nasopharygeal carcinoma, Burkitt’s lymphoma, Infectious mononucleosis, Oral hairy leukoplakia.

• HPV (human papilloma virus) subtypes 16, 18, 33 associated with cervical cancer.
• Subtypes 6 & 11

Prostate

Breast

Lung cancer (in both men and women)

Cancer is the second most common cause of death in the US, following cardiovascular disease.

Metatstasis

• hematogenous
• lymphatic
• Direct seeding of body cavities

• p53, Rb-1 (retinoblastoma)
• Loss or mutation of these genes can lead to cancer.

WT1 & WT2

APC

BRCA-1

two mutagenic events are required to initiate alterations on both chromosomes

gene amplification (N-myc oncogene)

• Familial polyposis coli
• Wilms tumor

Neurofibromatosis Type 1 - linked to a defective or missing NF1 gene.

Monoclonal

• Type 1 Anaphylactic (IgE Mast cell degranulation - Hay fever, hives, anaphylaxis)
• Type 2 Cytotoxic (IgG, IgM complement cell lysis - Goodpastures; Graves disease; hemolytic anemia)
• Type 3 Immune complex--(IgM +complement---antigen-antibody complexes - Serum sickness; Arthus rx; SLE)
• Type 4 Cell-mediated (delayed) Cellular—lymphokines; cell-mediated toxicity;Tuberculin reaction; contact dermatitis; poison ivy; granulomatous disease

Primary immunodeficiency

Poor response to viruses typically

Poor response to bacteria typically

• A primary/congenital T cell immunodeficiency.
• Thymus hypolplasia/ aplasia—no cell-mediated (t-cell) immunity; hypocalcemia

• Primary B cell immunodeficiency
• no plasma cells

Most common Primary B cell deficiency

• failure of B cell maturation
• primary B cell immunodeficiency

• Combined Immunodeficiency ("severe")
• Deficiency of B and T cells
• Severe infections/ failure to thrive

X-linked; characterized by eczema, thrombocytopenia, recurrent infections

• Acquired Immunodeficiency
• Virion has gp 120 surface protein which binds to CD4 lymphocyte
• Virus found in blood, semen, vaginal secretions, breast milk, saliva
• Increased opportunistic infections in late stage: Pneumocystis, Mucor, deep fungal