An understanding of cells and cell behavior is a critically important component of disease diagnosis and treatment. But some diseases can be complex in nature, with a variety of factors and circumstances impacting their emergence and severity.

Effective disease analysis often requires an understanding that goes beyond isolated cell behavior. Genes, the environments in which cell processes operate, the impact of patient characteristics, and racial and ethnic variables all can have an important impact. ADVANCED PATHOPHYSIOLOGY

An understanding of the signals and symptoms of alterations in cellular processes is a critical step in the diagnosis and treatment of many diseases. For APRNs, this understanding can also help educate patients and guide them through their treatment plans.

Learning Objectives

Students will:

  • Evaluate cellular processes and alterations within cellular processes
  • Analyze alterations in the immune system that result in disease processes
  • Identify racial/ethnic variables that may impact physiological functioning
  • Evaluate the impact of patient characteristics on disorders and altered physiology ADVANCED PATHOPHYSIOLOGY

In this Assignment, you examine a case study and analyze the symptoms presented. You identify cell, gene, and/or process elements that may be factors in the diagnosis, and you explain the implications to patient health.

The Assignment (2-page case study analysis)

Develop a 1- to 2-page case study analysis in which you:

  • Explain why you think the patient presented the symptoms described.
  • Identify the genes that may be associated with the development of the disease.
  • Explain the process of immunosuppression and the effect it has on body systems.



McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). St. Louis, MO: Mosby/Elsevier.

  • Chapter 1: Cellular Biology; Summary Review
  • Chapter 2: Altered Cellular and Tissue Biology: Environmental Agents(pp. 46-61; begin again with Manifestations of Cellular Injury pp. 83-97); Summary Review ADVANCED PATHOPHYSIOLOGY
  • Chapter 3: The Cellular Environment: Fluids and Electrolytes, Acids, and Bases,
  • Chapter 4: Genes and Genetic Diseases (stop at Elements of formal genetics); Summary Review
  • Chapter 5: Genes, Environment-Lifestyle, and Common Diseases (stop at Genetics of common diseases); Summary Review
  • Chapter 7: Innate Immunity: Inflammation and Wound Healing
  • Chapter 8: Adaptive Immunity (stop at Generation of clonal diversity); Summary Review
  • Chapter 9: Alterations in Immunity and Inflammation (stop at Deficiencies in immunity); Summary Review
  • Chapter 10: Infection (stop at Infectious parasites and protozoans); (start at HIV); Summary Review
  • Chapter 11: Stress and Disease (stop at Stress, illness & coping)Summary Review
  • Chapter 12: Cancer Biology (stop at Resistance to destruction); Summary Review
  • Chapter 13: Cancer Epidemiology (stop at Environmental-Lifestyle factors); Summary Review

Introduction Hypersensitivity reactions (HR) are immune responses that are exaggerated or inappropriate against an antigen or allergen. Coombs and Gell classified hypersensitivity reactions into four forms. Type I, type II, and type III hypersensitivity reactions are known as immediate hypersensitivity reactions (IHR) because occur within 24 hours. Antibodies including IgE, IgM, and IgG mediate them.[1] ADVANCED PATHOPHYSIOLOGY

Type I or Anaphylactic Response

Anaphylactic Responseis mediated by IgE antibodies that are produced by the immune system in response to environmental proteins (allergens) such as pollens, animal danders or dust mites. These antibodies (IgE) bind to mast cells and basophils, which contain histamine granules that are released in the reaction and cause inflammation. Type I hypersensitivity reactions can be seen in bronchial asthma, allergic rhinitis, allergic dermatitis, food allergy, allergic conjunctivitis, and anaphylactic shock.[2][3]


Anaphylaxis is a medical emergency because can lead to an acute, life- threatening respiratory failure. It is an IgE-mediated process. It is the most severe form of an allergic reaction, where mast cells suddenly release a large amount of histamine and later on leukotrienes. In severe cases intense bronchospasm, laryngeal edema, cyanosis, hypotension, and shock are present.[4] ADVANCED PATHOPHYSIOLOGY

Allergic bronchial asthma

Allergic bronchial asthma is an atopic disease, characterized by bronchospasm. It may also be a chronic inflammatory disease. In its etiology, and environmental factors along with a genetic background play an important role. The diagnosis is dependent on history and examination. In allergic bronchial asthma, IgE is elevated, and sputum eosinophilia is common. Epidemiologically, a positive skin prick test or specific IgE are risk factors for asthma.[5]

Allergic rhinitis

Allergic rhinitis is another atopic disease where histamine and leukotrienes are responsible for rhinorrhea, sneezing and nasal obstruction. Allergens are similar to those found in bronchial asthma. Nasal polyps may be seen in chronic rhinitis.[6]

Allergic conjunctivitis

Allergic conjunctivitis presents with rhinitis and is IgE-mediated. Itching and eye problems including watering, redness, and swelling always occur.[7]

Food allergy

One must differentiate food allergy (IgE-mediated) from food intolerance that can be cause for a variety of etiology including malabsorption and celiac disease. It is more frequent in children as seen in cow’s milk allergy. Food allergy symptoms mostly affect the respiratory tract, the skin, and the gut. Skin prick tests are helpful to test for food allergens that can trigger severe reactions, e.g., peanuts, eggs, fish, and milk.[3] ADVANCED PATHOPHYSIOLOGY

Atopic eczema

Atopic eczema is an IgE-mediated disease that affects the skin and has an immunopathogenesis very similar to that of allergic asthma and allergic rhinitis, which are present in more than half of the diseased. Radioallergosorbent (RAST) may reveal the specificity of the IgE antibody involved but has little help in management.[8]

Drug allergy

Drugs may cause allergic reactions by any mechanism of hypersensitivity. For example, penicillin may cause anaphylaxis, which is IgE-mediated but ADVANCED PATHOPHYSIOLOGY

must responses be trivial. Penicillin cross-reacts with other semisynthetic penicillins including monobactams and carbapenems and may also cross- react with other antibiotics such as cephalosporins.[9]

Type II or Cytotoxic-Mediated Response

IgG and IgM mediate cytotoxic-mediated response against cell surface and extracellular matrix proteins. The immunoglobulins involved in this type of reaction damages cells by activating the complement system or by phagocytosis. Type II hypersensitivity reactions can be seen in immune thrombocytopenia, autoimmune hemolytic anemia, and autoimmune neutropenia. ADVANCED PATHOPHYSIOLOGY

Immune thrombocytopenia (ITP)

ITP is an autoimmune disorder that occurs at any age. Phagocytes destroy sensitized platelets in the peripheral blood. Clinically, it manifests by thrombocytopenia with shortened platelet survival and increased marrow megakaryocytes. Sudden onset of petechiae and bleeding from the gums, nose, bowel, and urinary tract occurs. Bleeding can accompany infections, drug reactions, malignancy and other autoimmune disorders such as thyroid disease and SLE.[10]

Autoimmune hemolytic anemia (AIHA)

There are two types of immune hemolytic anemia: IgG-mediated (warm AIHA) and IgM-mediated (cold AIHA). The warm type may be idiopathic autoimmune or secondary to other diseases such as malignancy affecting the lymphoid tissues. The cold type may be idiopathic or secondary to infections such as Epstein-Barr virus. The primary clinical sign of the two is jaundice. The laboratory diagnosis is made by a positive Coombs test, which identifies immunoglobulins and C3 on red blood cells.[11]

Autoimmune neutropenia

Autoimmune neutropenia may be present with bacterial and fungal infections, or it may occur alone or with autoimmune diseases (SLE, RA, autoimmune hepatitis), infections and lymphoma. Bone marrow examination is needed if neutropenia is severe. For associated autoimmune disorders, an autoimmune antibody panel is necessary (ANA, ENA, and dsDNA).[12] ADVANCED PATHOPHYSIOLOGY

Hemolytic disease of the fetus and the newborn (erythroblastosis fetalis)


The maternal immune system suffers an initial sensitization to the fetal Rh+ red blood cells during birth, when the placenta tears away. The first child escapes disease but the mother, now sensitized, will be capable of causing a hemolytic reaction against a second Rh+ fetus, which develops anemia and jaundice once the maternal IgG crosses the placenta.[13]

[14]Myasthenia gravis is an autoimmune disorder caused by antibodies to post-synaptic acetylcholine receptors that interfere with the neuromuscular transmission. It is characterized by extreme muscular fatigue, double vision, bilateral ptosis, deconjugate eye movements, difficulty swallowing, and weakness in upper arms. Babies born to myasthenic mothers can have transient muscle weakness due to pathogenic IgG antibodies that cross the placenta. ADVANCED PATHOPHYSIOLOGY


Goodpasture syndrome

Goodpasture syndrome is a type II hypersensitivity reaction characterized by the presence of nephritis in association with lung hemorrhage. In most patients, it is caused by cross-reactive autoantigens that are present in the basement membranes of the lung and kidney. A number of patients with this problem exhibit antibodies to collagen type IV, which is an important component of basement membranes.[15]


Pemphigus causes a severe blistering disease that affects the skin and mucous membranes. The sera of patients with pemphigus have antibodies against desmoglein-1 and desmoglein-3, which are components of desmosomes, which form junctions between epidermal cells. Pemphigus is strongly linked to HLA-DR4 (DRB1*0402), which is a molecule that presents one of the autoantigens involved in the immunopathogenesis of this disease (desmoglein-3).[16][17]

Type III or Immunocomplex Reactions

These are also mediated by IgM and IgG antibodies that react with soluble antigens forming antigen-antibody complexes. The complement system becomes activated and releases chemotactic agents that attract neutrophils and cause inflammation and tissue damage as seen in vasculitis and glomerulonephritis. Type III hypersensitivity reactions can classically be seen in serum sickness and Arthus reaction. ADVANCED PATHOPHYSIOLOGY


Serum sickness

Serum sickness can be induced with massive injections of foreign antigen. Circulating immune complexes infiltrate the blood vessel walls and tissues, causing an increased vascular permeability and leading to inflammatory processes such as vasculitis and arthritis. It was a complication of anti-serum prepared in animals to which some individuals produced antibodies to the foreign protein. It was also experienced in the treatment with antibiotics such as penicillin.[18] ADVANCED PATHOPHYSIOLOGY

Arthus reaction

Arthus reaction is a local reaction seen when a small quantity of antigens is injected into the skin repeatedly until detectable levels of antibodies (IgG) are present. If the same antigen is inoculated, immune complexes develop at the mentioned local site and in the endothelium of small vessels. This reaction is characterized by the presence of marked edema and hemorrhage, depending on the administered dose of the foreign antigen.[19][20]

Etiology Multiple causes of IHR depend on the type of antigen or allergen that trigger this inappropriate immune reactivity. In type I hypersensitivity reactions, the allergens are proteins with a molecular weight ranging from 10 to 40 kDa. These include cats, dust mite, German cockroaches, grass, rats, fungi, plants, and drugs. They stimulate the IgE production. Bee and wasp venoms, tree nuts (e.g., almond, hazelnut, walnut, and cashew), eggs, milk, latex, antibiotics (e.g., cephalosporins), heterologous antisera, hormones (e.g., insulin) and others including shellfish and anesthetics can trigger anaphylaxis.[21]

In type II hypersensitivity reactions, the antigens can be found in the membrane of erythrocytes (e.g., A, B, O, C, c, D, d, E, e, K, k, Fy, M, and N). In transfusion reactions, all blood groups are not equally antigenic, e.g., A or B evoke stronger hypersensitivity reactions in an incompatible recipient than other antigens such as Fy.[22] ADVANCED PATHOPHYSIOLOGY

In type III hypersensitivity reactions, the persistence of antigen from chronic infection or autoimmune diseases can develop complex immune diseases, including vasculitis and glomerulonephritis. Penicillin as an antigen can


produce any hypersensitivity reactions, e.g., anaphylactic shock, hemolytic anemia, and serum sickness.[23]

Epidemiology Hypersensitivity reactions are very common. Fifteen percent of the world population will be affected by any type of allergic reaction during their lives. In the second half of this century, allergic diseases have increased. The cause of the increase is unknown, but it may reflect lifestyle changes, decreased breastfeeding, and air pollution. The hygiene hypothesis proposes that since IgE is no longer needed to protect against parasites in the Western world, the IgE-mast cell axis has evolved in type I hypersensitivity reaction.[24][25] ADVANCED PATHOPHYSIOLOGY

European data estimate that 0.3% of the population will be troubled by anaphylaxis at some point in their lives. In addition, 1 out of 3000 inpatients in the United States experiences a severe allergic reaction every year. However, the prevalence of bronchial asthma was 1.5% in Korea. Fernández- Soto et al., 2018 reported that fungal infections could be as high as 50% in inner cities and constitute a risk factor predisposed to the development of allergic bronchial asthma.[26] Worldwide epidemiological data of anaphylaxis are scanty and remain unavailable in many countries.

Pathophysiology In type I hypersensitivity reactions after a previous sensitization, the immunoglobulin (Ig) E is produced and binds to Fc receptors on mast cells and basophils. On encountering the allergen, it triggered cross-linking of mast-cell cytophilic IgE, causing the activation of mast cells and their degranulation of mediators that cause an allergic reaction. The mediators that participate in this type of hypersensitivity reaction include histamine and lipid mediators such as PAF, LTC4, and PGD2 that cause a vascular leak, bronchoconstriction, inflammation, and intestinal hypermotility. Enzymes (e.g., tryptase causes tissue damage) and TNF causes inflammation. Eosinophils release cationic granule proteins, e.g., major basic protein (causes killing of host cells and parasites) and enzymes (e.g., eosinophil peroxidase, which participates in tissue remodeling).[27]

In type II hypersensitivity reaction antibodies against basement membranes produce nephritis in Goodpasture’s syndrome. Myasthenia gravis and ADVANCED PATHOPHYSIOLOGY

Lambert-Eaton syndrome are caused by antibodies that reduce the amount of acetylcholine at motor endplates, and autoantibodies to an intercellular adhesion molecule cause pemphigus.

In type III hypersensitivity reactions immune-complex deposition (ICD) causes autoimmune diseases, which is often a complication. As the disease progresses a more accumulation of immune-complexes occurs, and when the body becomes overloaded the complexes are deposited in the tissues and cause inflammation as the mononuclear phagocytes, erythrocytes, and complement system fail to remove immune complexes from the blood.

Histopathology Human basophils present multi-lobed nuclei and distinctive granules. They can be found in local tissues including the nose, lungs, skin or gut in response to allergic and immune responses. The two populations of mast cells are mucosal and connective tissue. They have morphological and pharmacological differences. The mucosal mast cells can associate with a parasitic infestation, and connective tissue mast cells are smaller and live shorter. Both contain histamine and serotonin in their granules. Skin biopsy of patients with allergic dermatitis shows inflammatory infiltrate with few eosinophils, but their degranulation in the skin demonstrated in the biopsy stained with antibodies against eosinophil major basic protein (MBP). In the nasal smear of a patient with acute bronchial asthma, an infiltrate consistent of eosinophils, and polymorphonuclear cells with a normal cytoplasm stained with hematoxylin and eosin were shown.[28][29] ADVANCED PATHOPHYSIOLOGY

In type II hypersensitivity reactions, autoantibodies bind to desmosome involved in cell adhesion, and autoantibodies in diabetes mellitus bind to islet cells. They can be demonstrated in tissues by immunofluorescence. The method that uses fluorescent antibodies has also been used in type III hypersensitivity reactions to demonstrate the presence of immune complexes in the intima and media of the arterial wall, as well as IgG and C3 deposits in kidney, joints, arteries, and skin. In Goodpasture syndrome, the antibodies involved are IgG and have the capacity to fix complement. Necrosis of the glomerulus, with fibrin deposition, is a major feature of this syndrome ADVANCED PATHOPHYSIOLOGY

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