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MICROBIOLOGY /PATHOLOGY

Terms in this set (364)

Virion
In contrast to bacteria, fungi, and parasites, viruses are not cells; i.e., they are not capable of reproducing independently, do not have a nucleus, and do not have organelles such as ribosomes, mitochondria, and lysosomes. Viruses are smaller than cells and cannot be seen in the light microscope.
Note: Almost all viruses are haploid (contain a single copy of their genome; the exception is the retrovirus family, whose members are diploid).
The viral particles, or virions, contain either single- or double-stranded DNA or RNA (never both) that is encased in a protein coat called a capsid. The combination of the nucleic acid and the protein capsid is called the nucleocapsid. They are either naked or enveloped, depending on whether the capsid is surrounded by a lipoprotein envelope. The capsid is composed of polypeptide units called capsomeres. Some viruses (orthomyxoviruses and paramyxoviruses) have envelopes that are covered with spikes, which contain either hemagglutinin, neuraminidase, or a fusion protein that causes cell fusion and, in some cases, hemolysis.
Viroids consist solely of a single molecule of circular RNA without a protein coat or envelope. They cause several plant diseases but are not implicated in any human disease.
Prions are infectious protein particles (atypical virus-like agents) that are composed solely of protein. They cause certain "slow" diseases such as Creutzfeldt-Jakob disease, a severe degenerative brain disease caused by the ingestion of beef from a cow infected with mad cow disease.
Note: Prions do not elicit inflammatory or antibody responses.
Can be treated prophylactically by a vaccine
*** This is false; it cannot be treated prophylactically by a vaccine.
The inactive HSV-virus resides in sensory nerve ganglia (most commonly, the trigeminal ganglion), but will often reappear later as the familiar "cold sore" (herpes labialis), most often along the vermillion border of the lips. This disease is referred to as "recurrent herpes labialis." Emotional stress, trauma, and excessive exposure to sunlight have been implicated as factors for the appearance of the recurrent herpetic lesions on the lip. Note: Zovirax is the brand name for acyclovir, a synthetic nucleoside analogue active against herpesviruses. It acts as a competitive inhibitor of viral DNA polymerase.
Remember: Typically, HSV-1 infects ABOVE the Other nucleoside analogues: waist: eye and mouth lesions. HSV-2 infects
• Penciclovir (Denavir) BELOW the waist: genital lesions.
• Valacyclovir (Valtrex) Note: Oral-genital sex can lead to HSV-1 below
the waist and HSV-2 above the waist.
Remember:
• The primary infection can range from subclinical (asymptomatic) to severe systemic infections.
• HSV-1 can also cause the following recurrent infections: keratoconjunctivitis and encephalitis.
• A tzanck smear is a diagnostic test that reveals intranuclear inclusions in herpes virus infections.
Genital herpes (caused by HSV-2) may have serious consequences in pregnant women because the virus can be transmitted to the infant during vaginal delivery. The virus can cause damage to the infant's central nervous system and/or eyes.
Respiratory tract
Adenoviruses are naked (non-enveloped) medium-sized viruses composed of an icosahedral nucleocapsid and a double-stranded linear DNA genome. They have spikes (glycoprotein¬aceous projections that in this case are hemagglutinin proteins) protruding from their surfaces that are involved in the absorption or attachment of the virus to the host cell. These viruses frequently cause subclinical infections. Infection is usually transmitted in droplets of respiratory or ocular secretions. Diseases include respiratory illnesses (especially in children), conjunctivitis, and pharyngitis.
Virus Structure
• Virion: infectious, complete virus particle: RNA or DNA and proteins. Note: Enveloped viruses have carbohydrates and lipids
• Capsid: composed of repeating protein subunits (protomers)
— protect viral genome from extracellular nucleases
— impart structural symmetry to virion (icosahedral or helical)
— essential for the infectivity of virion
— in naked (non-enveloped) virus, the capsid serves as the attachment protein that binds to the
host cell receptor
— antigenic and provoke host immune response
— most viruses have one capsid, an exception is Reoviridae that has two capsid layers
• Nucleocapsid: composed of capsid and nucleic acid
• Envelope: viral membrane, lipid bilayer carrying viral glycoproteins
• Matrix protein: welds the capsid or nucleocapsid to the envelope
1. The ability of pathogenic microorganisms, including viruses, to attach to and invade particular cells and tissues establishes specific tissue affinities for pathogenic microorganisms.
2. Most viral antigens of diagnostic value are proteins.
Infectious mononucleosis
The Epstein-Barr virus (EBV) is a member of the herpes virus group. It causes infec-tious mononucleosis and has been associated with the subsequent development of two forms of cancer: Burkitt's lymphoma and nasopharyngeal carcinoma. EBV is also associated with hairy leukoplakia, a whitish, nonmalignant lesion on the tongue seen especially in AIDS patients. The virus specifically infects B lymphocytes and can remain latent in them after symptoms have resolved.
Laboratory findings include lymphocytosis, the presence of atypical lymphocytes and IgM heterophile antibodies identified by the heterophile test (also called the mononucleosis spot test). This antibody eventually appears in the serum of more than 80% of the patients with infectious mononucleosis; hence, it is highly diagnostic of the disease.
1. Rubella viruses cause German measles (rubella), which present with a characteristic rash (flat, pink spots on the face and then spreads to other body parts).
2. Paramyxoviruses can cause measles (rubeola) and mumps. Rubeola is character ized by the formation of Koplik's spots in the oral cavity. These spots are small, bluish-white lesions surrounded by a red ring. They cannot be wiped off and occur opposite the molars. Mumps cause enlargement of the parotid glands. Serious complications include deafness in children and orchi¬tis (inflammation of the testis) in males past puberty.
3. The MMR vaccine is a mixture of three live attenuated viruses, adminis¬tered via injection for immunization against measles, mumps and rubella. It is generally administered to children around the age of one year, with a booster dose before starting school (i.e., age 4/5).
Retroviruses
Retroviruses are RNA viruses that have their genome surrounded by an inner protein envelope and an outer envelope that contains lipid and glycoprotein spikes, which serve to attach the virus to the host cells. The word "retro" refers to the possession of the enzyme reverse transcriptase (an RNA-directed DNA polymerase), which transcribes RNA to DNA during the process of viral nucleic acid synthesis.
The nucleocapsid of HIV consists of two single strands of RNA along with the enzymes reverse transcriptase, protease, and integrase, all encased in an outer lipid envelope derived from a host cell via budding. This envelope has 72 surface projections containing an antigen, gp120, that aids in the binding of the virus to the target cells with CD4 receptors. A second glycoprotein, gp41, binds gp120 to the lipid envelope. The genome of HIV, similar to retroviruses in general, contains three major genes:
• env gene - codes for its two envelope glycoproteins
• pol gene - codes for its three enzymes
• gag gene - codes for core proteins
The transmission of HIV occurs primarily by sexual contact and by transfer of infected blood. The virus infects and kills helper (CD4) T-cells, resulting in the depression of both humoral and cell-mediated immunity. It travels throughout the body, particularly in macrophages, which are the first cells infected by HIV. It induces a distinctive CPE (cytopathic effect) called giant-cell (syncytial) formation. In addition to the CD4 receptor, a core receptor known as a chemokine is required for HIV to infect cells. Important: The rapid emergence of new strains of HIV is pri¬marily the result of frequent errors introduced by viral reverse transcriptase.
1. Acute HIV-1 primary infection can present as a mononucleosis-like syndrome
Notes with fever, fatigue, sore throat, and skin rash.
2. HIV differs from the RNA tumor viruses in that it lyses the host cells. RNA tumor viruses transform the cells that they invade but do not possess cytolytic activity.
Varicella-Zoster virus, a member of the herpes virus family
The varicella-zoster virus is a member of the herpes virus group. It causes the diseases chickenpox (varicella) and shingles (herpes zoster). The virus is very contagious and may be spread by direct contact or droplets. 90% of all cases of chickenpox occur in children under 9 years of age. Local lesions (vesicles) occur in the skin after dissemination of the virus through the body. These lesions become encrusted and fall off in about one week. Important: The administration of aspirin is contraindicated in this and in other childhood viral infections. Aspirin given to infected children increases the incidence of Reye's syn-drome, which can cause encephalitis and liver impairment.
Shingles (herpes zoster) is the result of reactivation of a latent varicella-zoster virus that may have remained within the body from a childhood case of chickenpox. The virus reaches the sensory ganglia of the spinal or cranial nerves (most frequently the trigeminal nerve), produc¬ing an inflammatory response. It is characterized by painful vesicles that occur on the skin or mucosal surfaces along the distribution of a sensory nerve. It is usually localized to a sin¬gle dermatome, and is more common in individuals who are immunocompromised.
Note: Adenosine arabinoside (vidarabine) suppresses the synthesis of varicella-zoster and herpes simplex viruses, and it tends to diminish new lesion formation and the duration of fever and to prevent the spread of the virus through the viscera.
Remember: Poxviruses are DNA viruses that are the largest and most complex animal viruses. This group includes the variola viruses that cause smallpox. Smallpox is an acute, highly infectious, often fatal disease that is characterized by high fever, prostration, and a vesicular, pustular rash. Fortunately, man is the only reservoir for the virus and vaccination with vaccinia, a related poxvirus, has been effective in eradicating smallpox.
They can be observed with a light microscope
*** This is false; viruses cannot be observed with a light microscope.
The replication of a virus within a host cell depends on the ability of the viral genome to enter the host cell, to remain functional, and to direct the host cell to produce viral macromole¬cules. Within the host cell, the viral genome achieves control of the cell's metabolic activi¬ties. The virus then uses the metabolic capacity of the host cell for production of new virus¬es. Often the replication of a virus causes changes in the host cell, usually causing the death of that cell. Note: For viruses, the burst size is the average number of progeny viruses released per infected cell.
Remember:
• The capsid has three functions:
1. It protects the nucleic acid from digestion by enzymes.
2. It contains special sites on its surface that allow the virion to attach to a host cell.
3. It provides proteins that enable the virion to penetrate the host cell membrane and, in some cases, to inject the infectious nucleic acid into the cell's cytoplasm.
• Many types of virus have a glycoprotein envelope surrounding the nucleocapsid. The enve¬lope is composed of two lipid layers interspersed with protein molecules (lipoprotein bilay¬er) and may contain material from the membrane of a host cell as well as that of viral origin. The virus obtains the lipid molecules from the cell membrane during the viral budding process. However, the virus replaces the proteins in the cell membrane with its own proteins, creating a hybrid structure of cell-derived lipids and virus-derived proteins. Many viruses also develop spikes made of glycoprotein on their envelopes that help them to attach to spe¬cific cell surfaces.
Note: The most generally accepted laboratory method for the diagnosis of most common viral infections is whether or not specific antisera neutralize the virus (cell culture tech-niques).
They are DNA enveloped viruses
*** This is false; influenza viruses are RNA enveloped viruses.
Influenza viruses are the only members of the orthomyxovirus family. The influenza virus is composed of a unique segmented, negative, single-stranded, RNA genome, a helical nucleocapsid, and an outer lipoprotein envelope. The envelope is covered with two different types of spikes (which are glycoproteinaceous projections or peplomers), that contain either hemagglutinin (which causes the agglutination of RBCs) or neu¬raminidase (which aids in the attachment to the host cell via specific receptors). Influenza viruses are classified as type A, B, or C, depending on a nucleocapsid antigen.
The ability of the influenza virus to cause epidemics is dependent on antigenic changes in the hemagglutinin and neuraminidase. There are two types of changes: antigenic shifts, which are major changes based on reassortment of genome pieces, and anti¬genic drifts, which are minor changes based on mutations.
Important: Reye's syndrome includes vomiting, lethargy and may result in coma. It is rare, but approximately 40% of cases are fatal. The origin of Reye's syndrome is unclear but seems to follow certain viral infections such as influenza or chickenpox (varicella zoster / herpes zoster), especially if they are in the young and especially if they have been treated with aspirin. Aspirin is contraindicated for childhood or adolescent fevers because it is a risk factor in the development Reye's syndrome. Acetaminophen and Ibuprofen are apparently not associated with Reye's syndrome.
Rhinoviruses
The common cold is most frequently caused by rhinoviruses (there are over 110 different stereotypes; this is why development of a vaccine is so difficult). Rhinoviruses are members of the picornavirus family, which have single-stranded positive sense RNA genome, with an icosahedral capsid. No envelope is present.
Note: The common cold is also caused by coronaviruses in adults.
1. Mumps is caused by an RNA paramyxovirus and is transmitted via respirato-
Notes ry droplets. The most noticeable symptom of mumps is the painful swelling of the parotid glands, either unilateral or bilateral. Note: Two complications are of signif-icance: orchitis with painful swelling of the testicles in postpubertal males, which can result in sterility, and deafness in children.
2. Influenza is caused by influenza viruses A, B, and C (orthomyxoviruses). Complications include Reye's syndrome in children. Amantadine and rimanta-dine act to prevent viral replication and are only effective against influenza A.
3. Measles (Rubeola) is caused by rubeola virus (RNA paramyxovirus). It charac¬terized by skin rash with Koplik's spots, and is transmitted via respiratory droplets.
4. German measles (Rubella) is caused by the rubella virus (RNA virus). Transmitted via respiratory droplets. Flu-like symptoms and lymphadenopathy, followed by a rash on the entire body.
5. Pharyngitis is an inflammation of the pharynx. The main symptom is a sore throat. It is caused by a variety of viruses (adenoviruses and coxsackieviruses).
6. Arthopod-borne viruses (Arboviruses) are viruses which can be transmitted to via an insect (arthropod) vector. In general, arboviruses belong to 3 families: Togaviruses (i.e., rubella virus), bunyaviruses (i.e., Rift valley fever), and fla-viviruses (i.e., yellow fever virus).
One-step growth curve



A typical one-step growth analysis can be divided into several phases:
1. Adsorption of virus (initial phase)
2. Eclipse phase: This lasts for 10-12 hours, and it corresponds to the period during which the input virus becomes uncoated. As a result, no infectious virus can detected during this time
3. Synthetic phase: This starts around 12 hours post-infection and corresponds to the time during which new virus particles are assembled.
4. Latent period: During this period, no extracellular virus can be detected. After a certain time period, extracellular virus is detected. Ultimately, production will reach a maximum plateau level.

Steps in the Replicative Cycle of Viruses
1. Attachment: Through a receptor. Specific: • CD4 on T-cells for HIV
• ICAM on upper respiratory epithelial cells - Rhinoviruses (common cold)
• Immunoglobulin-like receptors - polio virus
2. Entry - receptor-mediated endocytosis, e.g. influenza and adenovirus - membrane fusion, e.g., herpesviruses and paramyxoviruses
3. Uncoating - triggered by pH changes in endosomes, e.g. Influenza A virus
4. Replication and viral protein production: Transcription and translation
** All DNA viruses (except poxviruses) replicate in the nucleus using host cell RNA polymerase. ** All RNA viruses (except retroviruses and orthomyxoviruses) replicate in the cytoplasm using their own RNA polymerase.
5. Assembly: The new viral nucleic acid and capsid proteins are packaged.
6. Release: Either by budding through the host plasma membrane or by host plasma membrane rupture.
Rubella virus
Rubella virus is the sole member of the genus Rubivirus in the family Togaviridae. Only one serotype has been identified. It contains three major structural polypeptides.
The disease is transmitted via direct or droplet contact with respiratory secretions. Rubella virus multiplies in cells of the respiratory system; this is followed by viremic spread to target organs. It causes German measles and is a teratogen (causes malfor-mation of an embryo or a fetus).
The typical picture of rubella includes a maculopapular rash that appears first on the face and neck and quickly spreads to the trunk and upper extremities and then to the legs. It often fades on the face while progressing downwards. The lesions tend to be dis¬crete at first, but rapidly coalesce to produce a flushed appearance. The onset of rash is often accompanied by low-grade fever. Although the rash usually lasts 3 to 5 days (hence the term "3-day measles"), the associated fever rarely persists for more than 24 hours. The earliest and perhaps the most prominent and characteristic symptom of rubella infection is lymphadenopathy of the postauricular, occipital, and posterior cer¬vical lymph nodes; this is usually most severe during the rash but may occur even in the absence of rash.
Rubella infection acquired during pregnancy can result in stillbirth, spontaneous abor-tion, or several anomalies associated with the congenital rubella syndrome. The clas-sic triad of congenital rubella syndrome includes cataracts, heart defects, and deaf-ness.
1.The virus particles are generally spherical with spiky hemagglutinin-containing surface projections.
2.The rubella vaccine in current use is prepared from attenuated rubella virus.
It is coagulase negative whereas other Staphylococci are coagulase positive
*** This is false; it is coagulase positive whereas other Staphylococci are coagulase negative.
Staphylococcus aureus cannot invade through intact skin or mucous membranes, and infection usually begins with traumatic inoculation of the organism. Once inside the body, it secretes a number of enzymes and toxins that harm most tissues. Note: The cell wall of S. aureus contains ribitol phosphate teichoic acid.
S. aureus infection usually produces suppuration and abscess formation. It most commonly causes skin infections. It it responsible for the following: scalded skin syndrome, toxic shock syndrome; osteomyelitis; infections of burns or surgical wounds; respiratory tract infections; septicemia; bacterial endocarditis; and staphylococcal food poisoning.
Coagulase-negative staphylococci (less virulent than S. aureus):
• S. epidermis: the most frequent cause of infections associated with medical devices.
• S. saprophyticus: the frequent culprit of acute urinary tract infections in young women.
Remember: Staphylococci are facultative anaerobes that grow by aerobic respiration or by fermentation that yields principally lactic acid. The bacteria are catalase-positive and oxidase-negative. S. aureus can grow at a temperature range of 15 to 45 degrees and at NaCI concentrations as high as 15%. Note: Nearly all strains of S. aureus produce the enzyme coagulase.
Note: Major virulence factors include: protein A, beta-lactamase, enterotoxin, hyaluroni-hyaluronidase and staphylokinase.
Cause incomplete lysis of red blood cells
Some streptococcal species produce toxins, called hemolysins, that cause lysis of erythrocytes. Note: Streptoccal species are cocci-shaped, gram-positive and are facultative anaerobes.
Alpha-hemolytic streptococci produce a zone of incomplete hemolysis and green discoloration adjacent to the colony. Beta-hemolytic streptococci produce a clear zone of hemolysis around the colony. Gamma-Streptococci produce no hemolysis.
Beta-hemolytic forms are classified into Lancefield groups (A thru U) according to the C carbohydrate composition of the cell wall.
• Group A strains are pathogenic for humans. They are further subdivided by Arabic
numerals into specific antigenic types based on the cell wall M protein. This M
protein seems to be closely associated with the virulence of the bacteria. The
prototype is S. pyogenes (causes rheumatic fever, scarlet fever, and sore throat). Remember: Toxins produced by Group A beta-hemolytic streptococci include pyrogenic (erythrogenic) toxin, DNAse, hemolysins (streptolysins 0 & S), hyaluronidase, strepto-kinase, and exotoxin A.
Important:
:Notes 1. Streptococcal Exotoxin A (SpeA) is a superantigen (as is Exotoxin B) produced by Streptococcus pyogenes and is associated with severe infections characterized by rash, hypotension, multiorgan failure and a high mortality rate.
2. Oral Streptococci are usually alpha-hemolytic (i.e., S. viridans, S. mutans, S. sanguis and S. salivarius). These bacteria are the most common organisms causing subacute endocarditis.
LPS
The function of the outer membrane of gram-negative bacteria is to act as a protective permeability barrier. The outer membrane is impermeable to large molecules and hydrophobic compounds from the environment. LPS is essential to the function of the outer membrane.
Important:
1. Endotoxins are not secreted by bacterial cells. The bacterial cell must die and the outer membrane be broken down for the endotoxin to be released into the bloodstream. The host's responses to endo¬toxins include chills, fever, weakness, generalized aches, and, in severe cases, shock and death.
2. Endotoxins are highly potent lipopolysaccharides released from the cell walls of gram-negative bacteria. Minute amounts in the oral mucosa cause inflammation and resorption of adjacent bone. Endotoxin has a chemotactic effect on neutrophilic granulocytes and induces phagocytosis by these cells.
1. In addition to endotoxin, plaque bacteria also produce enzymes (hyaluronidase, colla¬genase, chondroitin sulfatase, elastase, and proteases) that may initiate periodontal disease. Free endotoxin is present in dental plaque and in inflamed gingiva. Remember: The most likely source of bacteria found in diseased periodontal tissue is subgingival plaque.
2. Collagenase is the protease which degrades collagen, one of the body's primary connec-tive tissues. In patients with periodontal disease, the collagen which forms the structural basis of the periodontium is broken down by collagenase. This protease has been demon¬strated to be a part of the component system in the following bacteria: Porphyromonas species, Clostridium species, Bacteroides species, and AA.
3. Although most bacterial exotoxins are proteinaceous in nature, endotoxin is a lipopolysaccharide complex composed of a lipid A (portion most responsible for toxic activ¬ity) core polysaccharide, and an "0" antigenic side chain.
4. Endotoxin can activate the complement system via the alternative pathway. C3 can be activated by endotoxin in the absence of preceding activation of C 1 , 4, and 2. As a result, the various complement components (C3, 5-9) are consumed and then their activity disap-pears or is reduced from serum.
Staphylococci
Staphylococcus aureus causes a variety of suppurative (pus-forming) infections and toxinoses in humans. It causes superficial skin lesions such as boils, styes and furunculosis; more serious infections such as pneumonia, mastitis, phlebitis, meningitis, and urinary tract infections; and deep-seated infections, such as osteomyelitis and endocarditis. S. aureus is a major cause of hos¬pital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices. S. aureus causes food poisoning by releasing enterotoxins into food, and toxic shock syndrome by release of superantigens into the blood stream. Important: Protein A is a surface protein of S. aureus which binds IgG molecules by their Fc region; it may be respon¬sible for its virulence.
The genus Neisseria contains two important human pathogens, N. gonorrhoeae and N. meningi¬tidis. N. gonorrhoeae causes gonorrhea, and N. meningitidis causes meningococcal meningitis. N. gonorrhoeae infections have a high prevalence and low mortality, whereas N. meningitidis infec¬tions have a low prevalence and high mortality.
Salmonella is a gram-negative facultative rod-shaped bacterium in the same proteobacterial fam¬ily as Escherichia coli, the family Enterobacteriaceae, trivially known as "enteric" bacteria. In humans, Salmonella is the cause of two diseases called salmonellosis: enteric fever (typhoid), resulting from bacterial invasion of the bloodstream, and acute gastroenteritis, resulting from a foodbome infection /intoxication.
1. Streptococci are aerobic to facultatively anaerobic gram-positive cocci that grow in pairs or chains in culture. They are the most numerous group of microorganisms that occur in the oral cavity, where they can grow and cause dental caries (mainly S. mutans). Other more serious infections caused by Streptococcus include pneumonia (S. pneumoniae), rheumatic fever (S. pyogenes), and heart valve infections (S. viri¬dans).
2. Staphylokinase (produced by S. aureus), Streptokinase (produced by hemolytic streptococci), and Urokinase are enzymes that cleave plasminogen, producing plas¬min, which causes the liquefaction of fibrin. They are used clinically in the removal of blood clots.
Acid-fast bacteria
Mycobacterium tuberculosis is not classified as either gram-positive or gram-negative because it does not have the chemical characteristics of either, although the bacteria do contain peptidoglycan (murein) in their cell wall.
Important: Mycobacterium tuberculosis is a fairly large non-motile rod-shaped, acid-fast, niacin-producing bacterium. It produces neither exotoxins or endotoxins. Many non-patho-genic mycobacteria are part of the normal flora of humans, found most often in dry and oily locales. Mycobacterium tuberculosis is an obligate aerobe. For this reason, in the classic case of tuberculosis, the M.TB complexes are always found in the well aerated upper lobes of the lungs. The bacterium is a facultative intracellular parasite, usually of macrophages, and has a slow generation time of 15-20 hours, a physiological characteristic that may cotribute to its virulence.
1. Acid-fast staining is one of the methods used to diagnose active tuberculosis. It
Notes is a method of staining used in bacteriology in which a smear on a slide is flooded with carbol-fuchsin stain, decolorized with acid alcohol, and counterstained with methylene blue. Acid-fast organisms resist decolorization and appear red against a blue background when viewed under a microscope. This property of being acid-fast is attributable to the presence of lipids and waxes (mycolic acids) in the cell wall of certain bacteria.
2. The classic skin test (PPD skin test) is another method of testing for tuberculosis. It may indicate an infection, but not whether the infection is active. A purified pro¬tein derivative (PPD) extract from mycobacterium tuberculosis is injected subcuta¬neously, and the area near the injection is observed for evidence of a delayed hyper¬sensitivity reaction. A positive test indicates a hypersensitivity to tuberculoproteins.
3. Common acid-fast bacteria of medical importance include the Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium avium-intracellulare com¬plees.
Capsule
The capsule is a gelatinous coat which surrounds the cell wall of certain bacteria and is especially important in protecting these cells against phagocytosis by eukaryotic cells. The presence of a capsule can be a major factor in determining the pathogenicity of a bacterium; that is, the ability of a bacterium to cause disease in the organism that it infects. Other important functions include mediate adherence of cells to surfaces (i.e., caries on the tooth surfaces) and for identification purposes. When the polysac-charide capsules are treated with antiserum, they swell, allowing them to be identified.
These antiphagocytic polysaccharide capsules surrounding the cells of strains of strep¬tococcus pneumoniae, for example, permit these bacteria to invade the normal defense mechanisms of the host, allowing them to reproduce and cause the symptoms of pneu¬monia. The virulence of other bacteria, including Haemophilus influenzae, Klebsiella pneumoniae, and Cryptococcus neoformans is also enhanced by capsule production.
1. The cell membrane (cytoplasmic membrane) is a selectively permeable Note, membrane that is involved in energy transformations (i.e., oxidative phospho¬rylation). It is bordered externally by the cell wall in most bacteria.
2. The cell wall surrounds the plasma membrane and serves to protect the cell from changes in osmotic pressure. Then it also anchors flagella, maintains cell shape, and control the transport of molecules into and out of the cell.
3. The plasma membrane is a dynamic, selectively permeable membrane enclosing the cytoplasm. It is located between the cell wall and the cytoplasm, and it regulates the movement of substances, including water, into and out of the cell.
Gram-positive usually non-motile, non-spore-forming rods and cocci
Most species of this non-sporeforming bacterium ferment glucose into lactose, hence the name Lactobacillus. The most common application of Lactobacillus is industrial, specifically for dairy production. This genus also contains several bacteria that make up part of the natural flora of the human vagina. Because of their ability to derive lactic acid from glucose, these bacteria create an acidic environment which inhibits growth of many bacterial species which can lead to urogenital infections.
Although Lactobacillus species are normally present in low numbers in the oral cavity, they are frequently found in association with dental caries (especially Lactobacillus casei), most probably as secondary microbial invaders.
Lactobacillus acidophilus is added to commercial milk products to assist lactose intolerant individuals in digesting lactose sugars. The enzymes produced by these bacteria convert milk sugars to products that do not cause GI problems.
Lactic acid bacteria include Lactobacillus and Streptococcus. These bacteria use the lactic acid fermentation pathway in which pyruvate is reduced to lactic acid. These two bacteria are also referred to as aciduric, meaning that they can tolerate an acid environ¬ment, and acidogenic, meaning acid forming.
1. Lactobacillus is generally harmless to humans, rarely inciting harmful
Notes infections or diseases. Treatment of this vancomycin-resistant microbe usual-
ly consists of high doses of penicillin in combination with gentamicin.
2. Streptococcus mutans is the main culprit in dental caries (especially smooth surface caries).
3. Actinomyces has been found to be a causative agent of root surface caries.
Actinobacillus actinomycetemcomitans (Aa) Capnocytophaga ochraceus
Important: The new classification system for periodontitis is more descriptive and not as temporal as was the previous system. The terms adult, juvenile, early onset, and pre-pubertal have been replaced with various forms of chronic and aggressive disease. The term refractory periodontitis has been removed as a distinct disease entity, as the cur¬rent thinking is that any type of periodontitis may be refractory.
Aggressive periodontitis (formerly called Juvenile periodontitis) occurs in two forms:
1. Generalized form (formerly known as rapidly progressive periodontitis): Prevotella intermedia and Eikenella corrodens predominate. It occurs between the ages of 12-25 and is characterized by rapid, severe periodontal destruction around most teeth. It is characterized by episodic, rapid, and severe attachment loss.
2. Localized form: Gram-negative anaerobes Actinobacillus Actinomycetemcom-itans (Aa) and Capnocyto-phaga species (ochraceus) predominate. Prevotella inter-rmedia and Eikenella corrodens may also be present to a lesser extent. It occurs in an otherwise healthy adolescent (12-19). It is characterized by rapid and severe attach¬ment loss confined to the incisors and first molars. The one outstanding negative feature is the relative absence of local factors (plaque) to explain the severe periodon¬tal destruction which is present. Possible etiologic factors include a genetic predispo¬sition or a dysfunction of neutrophils (a chemotactic defect).
Note: Aa and Capnocytophaga species (specifically C. Ochraceus) are also associated with periodontitis in juvenile diabetes.
Conjugation
Conjugation is a form of sexual reproduction in which DNA is transferred from one live bacterium to another through direct contact. This physical contact is established through the presence of pili.
• The ability to transfer DNA by conjugation is dependent on the presence of a cytoplasmic entity termed the fertility factor, or F
• Cells carrying F are termed F+; cells without F are F. F is a small, circular DNA element that acts like a minichromosome. It is an example of a class of elements termed plasmids, which are self-replicating extrachromosomal DNA molecules
1. In conjugation, the greatest amount of genetic information is transferred from Notes one cell to another (compared to transduction and transformation).
2. Conjugation occurs more frequently than transformation; it takes place within members of different genera (e.g. Escherichia-Shigella, Salmonella-Serratia).
3. Can result in passage of genes for antibiotic resistance from one bacterium to another; bacterium potential for pathogenicity can increase.
4. F factors are plasmids transferred from a donor cell (an F+ cell) to a recipient
cell (an F- cell) during conjugation.
5. An Hfr (high frequency of recombination) is a cell with an F plasmid incorporat¬ed into the chromosome.
6. During conjugation, portions of the Hfr chromosome are transferred from the
Hfr bacterium to the F- bacterium.
7. Transfer of DNA within bacterial cell occurs via transposons, which are por¬tions of DNA that move from one site on the chromosome to another (or to a plas¬mid).
Cytoplasm of prokaryotes, while it occurs in the nucleus of eukaryotes
Transcription is the transfer of the genetic information from the archival copy of DNA to the short-lived messenger RNA. The enzyme RNA polymerase binds to a particular region of the DNA and starts to make a strand of mRNA with a base sequence complementary to the DNA template that is "downstream" of the RNA polymerase binding site. When this tran¬scription is finished, the portion of the DNA that coded for a protein (i.e., a gene) is now rep¬resented by a messenger RNA molecule that can be used as a template for translation.
The steps in transcription are:
1. DNA unzips (by DNA gyrase) and RNA polymerase enzyme binds to one strand of DNA.
2. RNA polymerase makes an elongating chain of RNA nucleotides; each new RNA nucleotide complimentary to the DNA nucleotide is hydrogen bonded to it.
3. The completed mRNA molecule is released from RNA polymerase - DNA complex, and can begin translation. In eukaryotic cells this means first moving from the nucleus into the cytoplasm. In prokaryotic cells (bacteria), ribosomes can bind and begin translation before polymerase has completed the new mRNA strand.
1. Translation is the process wherein information in the form of nitrogenous bases Notes along an mRNA is translated into the amino acid sequence of a protein.
2. Transduction is the transfer of DNA via a phage particle. Does not require cell-to-cell contact.
3. Reverse transcription is the formation of DNA from an RNA template. Retroviruses (e.g., HIV, tumor viruses), which are enveloped and contain a linear, single-stranded, positive-sense RNA genome, utilize this process. They use their RNA genome as a template for an RNA-directed DNA polymerase. These viruses have a virion-associated reverse transcriptase, which makes DNA copies from RNA. This DNA is then integrated into the host genome. Important: This RNA-directed synthesis of DNA is the reversal of normal informational flow within the cell.
Much more efficient
Respiration refers to the method of obtaining metabolic energy that involves an oxidative phosphorylation. It involves the formation of ATP during electron transfer. It can be aerobic (with molecular oxygen as the terminal hydrogen acceptor) or anaerobic (with nitrate or sulfate as the terminal hydrogen acceptor). Respiration is much more efficient than fermentation, thus respiring organisms, including us, have come to dominate the earth. Fermenting organisms are restricted to niches where oxygen is lacking and suitable carbon
Aerobic respiration involves a cell membrane respiratory (electron transport) chain. The electron transport chain is present in the inner mitochondrial membrane and is the final common pathway by which electrons derived from different fuels of the body flow to oxygen. It has four stages:
1. Glycolysis 3. The citric acid cycle
2. Formation of acetyl coenzyme A 4. Electron transport chain and chemiosmosis
Fermentation is defined as an energy yielding process whereby organic molecules serve as both electron donors and electron accepters. The molecule being metabolized does not have all its potential energy extracted from it. In other words, it is not completely oxidized.
Key points of fermentation:
• NAD+ is almost always reduced to NADH • Oxygen is not involved
• Fermentation results in a excess of NADH • Energy yields are low
• Pyruvate is often an important intermediate
• Energy is derived from Substrate-Level Phosphorylation
Fermentation can involve any molecule that can undergo oxidation. Typical substrates include sugars (such as glucose) and amino acids. Typical products depend upon the substrate but can include organic acids (lactic acid, acetic acid), alcohols (ethanol, methanol, butanol), ketones (acetone) and gases (H2 and CO2).
Gram-positive, nonmotile, facultative anaerobes
In the healthy mouth, more than 350 species of microorganisms have been found. Periodontal infections are linked to fewer than 5% of these species.
• Periodontal health is characterized by the presence of the following bacteria: Gram-positive bacteria such as Streptococcus sanguis, Streptococcus mitis, Actinomyces visco-sus, Actinomyces naeslundii and a few gram-negative species such as Veillonella parvula and Capnocytophaga ochracea.
• In periodontal disease, the bacterial balance shifts over to gram-negative, motile, strictly anaerobic bacteria. Inflammatory disease and injury cannot develop without these bacteria.
Among the bacteria most implicated in periodontal disease and bone loss are the following:
• Actinobacillus actinomycetemcomitans (Aa): associated with aggressive periodontal disease (formerly called early onset periodontitis) and localized aggressive periodontitis (formerly called localized juvenile periodontitis).
• Porphyromonas gingivalis: associated with chronic and aggressive periodontitis.
• Tanerella forsythensus (formerly Bacteroides forsythus): strongly linked to periodont¬al disease.
• Treponema denticola, sokranskii: associated with deep periodontal pockets, chronic periodontitis and ANUG.
• Prevotella intermedia: associated with deep periodontal pockets, chronic periodontitis and ANUG
Note: Eikenella corrodens, Campylobacter rectus, Fusobacterium nucleatum, Peptostrepto-coccus, Prevotella nigrescens, Enteric rods / Pseudomonas species and Eubacterium species have also been implicated as periodontal pathogens.
Superoxide dismutase (-), Catalase (-), and Peroxidase (-)
Two toxic molecules arise as a byproduct of aerobic metabolism, hydrogen peroxide and free superoxide radicals. Cells possess an elaborate defense system to destroy these toxic molecules, including enzymes such as catalase and superoxide dismutase. Superoxide dismutase catalyzes the decomposition of free superoxide radicals into water and hydrogen peroxide, which is subsequently degraded by catalase. Catalase catalyzes the decomposition of hydrogen peroxide to water and oxygen. Peroxidase catalyzes the oxidation of various substances by peroxides.
Obligate aerobes require 02 for growth; they use 02 as a final electron acceptor in aerobic respira¬tion.
Obligate anaerobes (occasionally called aerophobes) do not need or use 02 as a nutrient. In fact, 02 is a toxic substance, which either kills or inhibits their growth. Obligate anaerobic procaryotes may live by fermentation, anaerobic respiration, bacterial photosynthesis, or the novel process of methanogene¬sis.
Facultative anaerobes (or facultative aerobes) are organisms that can switch between aerobic and anaerobic types of metabolism. Under anaerobic conditions (no 02) they grow by fermentation or anaerobic respiration, but in the presence of 02 they switch to aerobic respiration.
Aerotolerant anaerobes are bacteria with an exclusively anaerobic (fermentative) type of metabolism but they are insensitive to the presence of 02. They live by fermentation alone whether or not 02 is present in their environment.
Bacillus and Clostridium
Spores (or endospores) are the most resistant biological form known to exist. Only gram-positive cells form spores, specifically members of the genera Bacillus and Clostridium. Spores are formed by bacteria that survive during periods of deprivation, such as the loss of a food or water supply. When a spore-forming bacterium (SFB) sens¬es that tough times are coming, a series of complex events are triggered that lead to the formation of a spore. Basically a spore is a structure that contains the absolute minimum of genetic information and associated materials required to produce the vegetative form once times become good again.
Example: Bacterial endospore is a heat-resistant spore formed within the cell. The endospore is a complex, multilayered structure containing peptidoglycan within its com¬plex spore coat and calcium dipicolinate within its core. This bacterial endospore is very difficult to destroy (more so than HIV, HBK and TB viruses). To destroy the bacteria it must autoclaved at the proper temperature (1210C for 20 minutes).
1. Spores contain dipicolinic acid and other components imparting high res-
Notes istance.
2. By means of a process called asexual reproduction, spores are able to grow into new organisms without uniting with another reproductive cell.
3. Active spores have thin cell walls; dormant spores have thick, strong cell walls.
4. Anthrax is caused by Bacillus anthracis. Botulism, gas gangrene, and tetanus are caused by Clostridium botulinum, C. perfringens, and C. tetani, respectively.
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a gram-negative, aerobic rod belonging to the bacterial family Pseudomonadaceae. Most strains are obligate anaerobes.
Pseudomonas aeruginosa is an opportunistic pathogen, meaning that it exploits some break in the host defenses to initiate an infection. It causes urinary tract infections, respiratory sys¬tem infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections, gas¬trointestinal infections and a variety of systemic infections, particularly in patients with severe burns, cancer and in AIDS patients who are immunosuppressed. Pseudomonas aerug¬inosa infection is a serious problem in patients hospitalized with cancer, cystic fibrosis, and burns.
1. P. aeruginosa strains produce fluorescent pigments contained in metachromat¬Notes= ic granules. Wounds infected with P. aeruginosa, therefore, display a bluish-green color.
2. P. aeruginosa is notorious for its resistance to antibiotics and is, therefore, a particularly dangerous and dreaded pathogen.
3. Only a few antibiotics are effective against Pseudomonas, including fluoro¬quinolones, gentamicin and imipenem, and even these antibiotics are not effective against all strains. The futility of treating Pseudomonas infections with antibiotics is most dramatically illustrated in cystic fibrosis patients, virtually all of whom eventually become infected with a strain that is so resistant that it cannot be treat¬ed.
4. P. aeruginosa produces two extracellular protein toxins, Exoenzyme S and Exotoxin A. It has been suggested that exoenzyme S may act to impair the func¬tion of phagocytic cells in the bloodstream and internal organs to prepare for inva¬sion by P. aeruginosa. Exotoxin A has exactly the same mechanism of action as the diphtheria toxin; it causes the ADP ribosylation of eukaryotic elongation fac¬tor 2.
Mutualism
Mutualism, along with commmensalism and parasitism describe three different kinds of symbiotic relationships.
The term symbiosis describes a close physical association between the individuals of two (or more) different species. It results in a stable condition in which the two organ¬isms live together in close physical proximity.
Symbiotic relationships are categorized as follows:
• Mutualism: An interaction that is beneficial to both species. Mutualistic relation¬ships can be obligate (necessary to the survival of at least one of the organisms involved), or facultative (beneficial but not essential to the survival of the organisms involved).
• Commensalism: Literally means "at table together;" this type of interaction bene¬fits one species while leaving the other one unaffected. Often, the host species pro¬vides a home and/or transportation for the other species. A common example would be the removal of oxygen from a habitat, as a result of the metabolic activities of a population of facultative anaerobic populations. This creates an environment favor¬able for the growth of obligately anaerobic populations.
• Parasitism: This is a symbiotic relationship between two organisms in which one species (parasite) benefits in terms of growth and reproduction to the harm of the other species (host). It must be emphasized that the parasite and host interact and that excessive harm is done to a host, which makes it less competitive, and also endangers the survival of the parasite species. Parasites can be differentiated into ectoparasites and endoparasites, depending, respectively, on whether they live on or in the host. Lice, flea, ticks, etc. are examples of ectoparasites. Tape-worms, schistosomiasis (bil¬harzias) and the malaria parasite are examples of endoparasites.
Frameshift mutation
In the living cell, DNA undergoes frequent chemical change, especially when it is being replicated (in S phase of the eukaryotic cell cycle). Most of these changes are quickly repaired. Those that are not result in a mutation. Thus, mutation is a failure of DNA repair. Mutations may be caused by various mutagens, including UV light, radiation, chemicals, and certain viruses.
Point mutations:
• Silent mutation: results in no detectable change at the level of the protein synthesized. Example of a silent mutation: the "A" and "T" at position 43 have been changed to "C" and "G" in a mutation event. Their sultant sequence will still encode mRNA that is translated into the amino acid threonine, because of redundancy in the genetic code (both "ACC" and "ACA" encode threonine).
• Missense mutation: the change in DNA base sequence results in a change in the mRNA that translates into a difference in the amino acid added to the growing polypeptide chain (e.g., valine replaces glutamate causing sickle cell anemia).
• Nonsense mutation: the change in DNA base sequence results in a change in the mRNA (results in a stop codon) that translates into premature chain termination. Protein function is usually profoundly affected.
• Transverse mutation: a point mutation involving base substitution in which the orientation of purine and pyrimidine is reversed (a purine is replaced by a pyrimidine or a pyrimidine by a purine).
• Transition mutation: a point mutation involving substitution of one base pair for another by replacement of one purine by another purine and of one pyrimidine by another pyrimidine but without change in the purine-pyrimidine orientation.
• Frameshift mutation: a mutation that inserts or deletes a number of nucleotides not divisible by three and thus disrupts the reading frame. Most codons after the mutation will code for different amino acids. Most of the time the resulting protein is not functional.
Atrophy
Causes of Cell Injury:
• Hypoxia (oxygen deficiency) and ischemia (blood flow deficiency)
• Chemical agents: including poisons (toxins), pollutants, insecticides, carbon monoxide, drugs and alcohol
• Physical agents: including mechanical trauma, burns, frostbite, sudden changes in pressure (barotrau¬ma), electric shock and radiation
• Infectious agents: bacteria, fungi, parasites, rickettsiae, viruses and prions
• Immunological reactions: including anaphylaxis and loss of immune tolerance that results in autoim¬mune disease
• Genetic defects: hemoglobinopathies (hemoglobin S in sickle cell disease), storage diseases (My-Sachs), inborn errors of metabolism (maple syrup urine disease)
• Nutritional defects: including vitamin deficiencies, obesity leading to type II DM, fat leading to athero¬sclerosis
• Aging
Cellular adaptive changes to injury:
• Atrophy (decrease in cell size): is the shrinkage in cell size by loss of cellular substance. Causes of atrophy include decreased workload, pressure, diminished blood supply or nutrition, loss of endocrine stimulation, and aging.
• Hypertrophy (increase in cell size): is an increase in cell size by gain of cellular substance. Hypertrophy is caused either by increased functional demand or by specific endocrine stimulations. With increasing demand, hypertrophy can reach a limit beyond which degenerative changes and organ failure can occur.
• Hyperplasia (increase in cell number): constitutes an increase in the number of indigenous cells in an organ or tissue. Pathological hyperplasia is typically the result of excessive endocrine stimulation. Important: Hyperplasia is often a predisposing condition to neoplasia.
• Metaplasia (change in cell type): is a "reversible" change in which one adult cell type is replaced by another adult cell type. It is a cellular adaptation in which indigenous cells are replaced by cells that are better suited to tolerate a specific abnormal environment. Note: The most common type of epithelial metaplasia involves replacement of columnar cells by stratified squamous epithelium.
1. Aplasia is a failure of cell production. During fetal development, aplasia results in agenesis (the Notes absence of an organ).
2. Hypoplasia is a decrease in cell production less extreme than aplasia.
Tissues transferred between genetically different members of the same species
Types of grafts:
• Autologous graft — self tissue transferred from one body site to another in the same individual (often for burns)
• Syngeneic graft — tissue transferred between genetically identical individuals
• Allogeneic graft — tissue transferred between genetically different members of the same species
• Xenogeneic graft — tissue transferred between different species Clinical Manifestations of Graft Rejection:
• Hyperacute rejection: minutes to hours tissue never becomes vascularized, because there is preexisting host serum Ab (IgG) specific for Ag in the graft.
• Acute rejection (cell-mediated allograft rejection): days to weeks later, this occurs when there are memory CD4 and CD8 T cells from previous exposures to graft.
• Chronic rejection: months or years after acute rejection has subsided. Both humoral and cell mediated. Antibody-mediated necrosis of graft vasculature.
1. The most feared consequence of graft therapy in a patient with an immun¬Notes odeficiency is a graft versus host reaction (GVHD). It occurs when trans¬planted immunogenic cells from the donor attack the host. Occurs most com¬monly after bone marrow transplants and can be fatal.
2. When a graft is rejected the first time and is tried again from the same donor, it will be rejected more rapidly than the first. This second set rejection occurs because the individual has been previously sensitized to the graft.
3. CD4 and CD8 T cells elicit most of the destruction in graft rejection.
4. The most common types of hyperacute rejection are ABO blood mis-matches.
Heterolysis
The morphologic appearance of dead cells vary depending on which of the two processes -enzymatic digestion or protein denaturation -- is dominant. Some degree of enzymatic diges¬tion is nearly always present, and is manifested by various nuclear and cytoplasmic changes.
If enzymatic digestion dominates, then dead cells are likely to be removed completely. This process is accomplished by activation of enzymes normally present within affected cells. The process of self digestion is known as autolysis.
If enzymatic digestion is accomplished "from outside," the process is termed heterolysis. Here the enzymes are derived from the lysosomes of cells such as neutrophils or macrophages.
Irreversible damage to the nucleus shows itself in one of three patterns:
1. Karyolysis: there is a gradual fading away of the basophilic (blue staining from the hematoxilin dye) nuclear material, presumably as a result of the activity of DNAses.
2. Pyknosis: the nucleus shrinks and becomes intensely basophilic; the DNA is packed into a solid shrunken mass.
3. Karyorrhexis: the pyknotic nucleus undergoes fragmentation and completely disap-pears in 1 to 2 days.
1. Apoptosis (also known as programmed cell death) plays a role opposing that of Notes mitosis in regulating the size of cell populations.
2. Necrosis is death of one or more cells, or a portion of tissue or organ. It is the result of irreversible exogenous injury that results in an insufficient blood supply to the tissue, whether from injury, radiation, or chemicals.
3. In Apoptosis, in contrast with necrosis, there is no:
• breakdown in the mechanisms supplying cellular energy
• failure in the maintenance of normal cell volume
• rupture of plasma membranes
• acute inflammatory reaction elicited by death
Are not virus specific but host specific
Interferons are species-specific proteins, which induce antiviral and antiproliferative responses in animal cells. They are a major defense against viral infections and abnormal growths (neoplasms). Interferons are produced in response to penetration of animal cells by viral (or synthetic) nucleic acid and then leave the infected cell to confer resistance on other cells of the organism. In contrast to antibodies, interferons are not virus specific but host specific. Thus, viral infections of human cells are inhibited only by human interferon.
Interferons are members of a larger class of proteins called cytokines (proteins that carry signals between cells). Most interferons are classified as alpha, beta, or gamma interferons, depending on their molecular structure.
Therapeutic uses of interferons:
Notes 1. Interferons-alpha and -beta have been used to treat various viral infections. One currently approved use for various types of interferon-alpha is in the treatment of certain cases of acute and chronic hepatitis C and chronic hepatitis B.
2. Interferon-gamma has been used to treat a variety of diseases in which macrophage activation might play an important role in recovery (e.g., lepromatous leprosy, leishmaniasis, toxoplasmosis).
3. Since interferons have anti-proliferative effects, they have also been used to treat certain tumors such as melanoma and Kaposi's sarcoma.
4. Interferons play an important role in the first line of defense against viral infections. They are part of the non-specific immune system (as are lysozyme, complement, etc.) and are induced at an early stage in viral infection — before the specific immune system has had time to respond.
5. Interferons themselves are not antiviral antibodies. They interfere with virus replication.
It is synthesized from the amino acid arginine
*** This is false; it is synthesized from the amino acid tryptophan.
Serotonin is synthesized by serotonergic neurons in the central nervous system (CNS) and by enterochromaffin cells (EC) in the gastrointestinal tract. It is synthesized from the amino acid tryptophan in a 2-step metabolic pathway: a hydroxylation reaction (rate lim¬iting step) and a decarboxylation reaction. The average adult human possesses only 5 to 10 mg of serotonin, 90 % of which is in the intestine and the rest in blood platelets and the brain.
Serotonin is widely considered to be a neurotransmitter. It is believed to play a role in temperature regulation, in sensory perception, and in the onset of sleep.
1. The chemical name for serotonin is 5-hydoxytryptamine which is Notes often abbreviated to 5-HT.
2. Enterochromaffin cells (EC) are a type of enteroendocrine cell. Entero-endocrine cells produce histamine and gastrin as well as serotonin.
3. In the pineal gland, which lies deep at the center of the human brain, sero¬tonin is produced as a precursor to melatonin.
4. Serotonin is a powerful vasoconstrictor.
5. The function of serotonin in blood platelets is not clear; it seems to have no important role in the clotting mechanism.
6. Serotonin is secreted in tremendous quantities by carcinoid tumors (tumors composed of chromaffin tissue).
7. Serotonin acts as an inhibitor of pain pathways in the spinal cord.
8. Lysergic acid diethylamide interferes with the action of serotonin in the brain.
Mast cells and basophils
Histamine is synthesized by the decarboxylation of the amino acid histidine. This reaction is catalyzed by the enzyme L-histidine decarboxylase. Once synthesized, histidine is stored in the coarse cytoplasmic granules of mast cells and/or basophils. In the early stages of acute inflammation, histamine mediates the contraction of endothelial cells, increasing vascular permeability. Histamine is liberated by degranulation triggered by the following stimuli:
1. The binding of specific antigen to basophil and mast cell membrane-bound IgE.
2. The binding of anaphylatoxins (C3a and C5a) to specific cell-surface recept-ors on basophils and mast cells.
1. Histamine is responsible for the principal symptoms of anaphylaxis. Notes 2. Histamine causes vascular dilation and increases the permeability of blood vessels during inflammation.
3. Mast cells are found in connective tissue and in extracellular spaces near blood vessels, particularly in the lungs.
4. Histamine is chemically similar to serotonin, epinephrine, and norepine-phrine.
5. Serotonin is synthesized from the amino acid tryptophan. Its actions are similar to histamine.
6. Bradykinin is a vasoactive kinin that mediates vascular permeability, arteriolar dilation, and pain (pain from inflamed tissues is associated with the release of bradykinin). It is a potent vasodilator and is produced by the action of kallikrein (generated by activated Hageman factor, factor XIIa) on an alpha 2 globulin (kininogen). It may be involved in blood pressure regulation
Microbodies
Microbodies are roughly spherical in shape, bound by a single membrane, and are usually 0.5 to 1 micrometer in diameter. There are several types, by far the most common of which is the peroxisome.
Two important families of microbodies are:
1. Peroxisomes: participate in the metabolism of fatty acids and other metabolites.
Peroxisomes have enzymes that rid the cell of toxic peroxides. These include oxidative enzymes, such as catalase, D-amino acid oxidase, and uric acid oxidase.
2. Glyoxysomes: are common in the fat-storing tissues of the germinating seeds of plants. They contain enzymes that initiate the conversion of fats to sugar, a process that provides seedlings with the carbohydrates they need until they can produce them on its own via photosynthesis.
1. Catalases are enzymes that catalyze the decomposition of hydrogen peroxide Notes into water and oxygen. Aerobic bacteria which possess this catalase are able to resist the effects of H202.
2. Superoxide dismutase catalyzes the destruction of 02 free radicals. It protects oxygen metabolizing cells against harmful effects of superoxide free radicals.
3. Anaerobic bacteria lack either superoxide dismutase or catalase or both. The anaerobic bacteria that possess catalase are able to resist the effects of H202.
4. Microbodies are similar in function to lysosomes but are smaller, and they isolate metabolic reactions that involve hydrogen peroxide (H202).
5. Lysosomes are formed when the Golgi complex packages up an especially large vesicle of digestive enzyme proteins.
6. A phagosome is a vesicle that forms around a particle (bacterial or other) within the phagocyte that engulfed it. It then separates from the cell membrane and fuses with and receives the contents of cytoplasmic granules (lysosomes). This coupling
forms a phagolysosome in which digestion of the engulfed particle occurs.
Mature B lymphocytes
B cells are characterized by their surface immunoglobulins. These immunoglobulin markers are made by the cells themselves, and are inserted into the surface membrane where they act as specific antigen receptors.
There are two broad sub-types of lymphocyte. These are known as B cells and T cells. All of them are derived from the bone marrow but T cells undergo a process of maturation in the thymus gland. Mature lymphocytes all have a similar appearance. They are small cells with a deeply basophilic nucleus and scanty cytoplasm. B and T cells circulate in the blood and through body tissues.
B cells complete maturation in the bone marrow and migrate to lymphoid organs. They have a short life span, ranging from days to weeks. These lymphocytes are committed to differentiate into antibody-producing plasma cells involved in antibody-mediated immunity. When an imma¬ture B cell is exposed to a specific antigen (they recognize antigen by membrane-bound immunoglobulin), the cell is activated. It then travels to the spleen or the lymph nodes, differen¬tiates, and rapidly produces plasma cells and memory cells.
T cells complete maturation in the thymus and become thymocytes. They have a long life span, ranging from months to years. They are important in cell-mediated immunity, Type IV hyper¬sensitivity reactions (contact dermatitis), and in the modulation of antibody-mediated immunity. Major classes include Helper T cells (subclassses: Type-1 and Type-2), Cytotoxic T cells (CD8+ lymphocytes), Memory T cells and Suppressor T cells.
1. T cells lack IgG receptors, but have CD3-associated T cell receptors (TCR), which recognize a unique antigen only in conjunction with Major Histocompatibility Complex (MHC) proteins.
2. CD8+ lymphocytes release perforins and induce apoptosis (programmed cell death).
3. IL-2 potentiates the growth of Natural killer (NK) cells and IgG antibodies enhance their cell effectiveness via antibody-dependent cellular toxity (ADCC).
Healing by first intention
Healing is the desired outcome of inflammation. A successful inflammatory response resolves injury or infection by rapid elimination of bacteria or foreign bodies, by repairing damaged tissue with connec¬tive tissue, and by saving the tissue's ability to function. Healing differs from simple repair in that heal¬ing involves regeneration of parenchymal tissue while repair by connective tissue does not. The best healing occurs when the inflammatory response has been quick and effective, resulting in minimal tis-sue damage.
The process of healing begins very soon after inflammation starts. It is not uncommon for inflamma¬tion to occur at the same time as healing, with neutrophils and macrophages engaged in their struggles right next to fibroblasts that are laying down collagen.
Healing by first intention (primary adhesion or primary union): describes healing that occurs in sur-gical wounds that have been closed with sterile suture. They are clean wounds and are (or, at least, had better be) aseptic, so the inflammation does not involve infection.
Healing by second intention (secondary adhesion, secondary union): describes the process of healing a wound without the benefit of surgical closure. In this case, the wound is allowed to "granulate in;" that is, the wound closes by contraction and filling with connective tissue.
Healing by third intention: the slow filling of a wound cavity or ulcer by granulations, with subse-quent cicatrization (the process of scar formation).
1.The major differences between first and secontion intention are that wounds healing by second intention are more open and are more prone to infection, and that much more gran¬ulation tissue is necessary to close the wound. Furthermore, while the timing of the appear¬ance of the various cell types is the same in both cases, healing by second intention will take longer simply because there is a larger wound to fill.
2. The tensile strength of a healing wound depends upon the formation of collagen fibers.
3. Glucocorticoids have been shown to have the greatest effect on granulation tissue.
4. Whether a wound heals by primary intention or secondary intention is determined by the nature of the wound, rather than by the healing process itself.
Painful urination
Sepsis is a severe illness caused by overwhelming infection of the bloodstream by toxin-producing bacteria. Sepsis is caused by bacterial infection that can originate anywhere in the body. Common sites include the following:
• The kidneys (upper urinary tract infection)
• The liver or the gall bladder
• The bowel (usually seen with peritonitis)
• The skin (cellulitis)
• The lungs (bacterial pneumonia)
Meningitis may also be accompanied by sepsis. In children, sepsis may accompany infection of the bone (osteomyelitis). In hospitalized patients, common sites of infection include intravenous lines, surgical wounds, surgical drains, and sites of skin breakdown known as decubitus ulcers or bedsores. In some cases, sepsis leads to a life-threatening condition called septic shock. The main culprits of sepsis seem to be Staphylococcus aureus, Escherichia coli, and Klebsiella. In addition, the LPS (endotoxin) released from the walls of dead gram-negative bacteria when they are lysed can cause septic shock as well as complement-activated anaphylactic shock.
1. Bacteremia refers to the presence of viable bacteria in the circulating blood. This can occur even in healthy individuals. For example, following some dental procedures, such as an oral prophylaxis and extractions, bleeding of the gums results in a transient systemic bacteremia. Clinical signs and symptoms are usually not present.
2. Viremia is defined as a viral infection of the bloodstream. It is a major feature of disseminated infections. The infecting virus is very susceptible to circulating antibodies.
Reticuloendothelial system
The reticuloendothelial system is a diffuse system composed of monocytes and macrophages located in reticular connective tissue (e.g., spleen). These cells are responsible for engulfing (phagocytosis) and removing cellular debris, old cells, pathogens, and foreign substances from the bloodstream. It is a functional, rather than an anatomical system of the body involved primarily in defense against infection and in disposal of the products of the breakdown of cells. Note: This system constitutes all phagocytic cells of the body except granulocytes including the cells present in the bone marrow, spleen, and liver.
Examples include:
• Microglia: macrophages of the CNS.
• Kupffer cells: phagocytic cells that line the blood vessels of the liver.
• Alveolar macrophages (dust cells): macrophages fixed in the alveolar lining of the lungs (also called reticulum cells of the lungs).
• Histiocytes: fixed macrophages in connective tissue.
Inherited disorders of the reticuloendothelial system (classified as Lipid Storage Diseases):
• Gaucher's disease: most common, caused by a deficiency of 0-glucocerebrosidase.
• Niemann-Pick disease: caused by a deficiency of sphingomyelinase (die within a few years).
• Tay-Sachs disease: caused by a deficiency of hexosaminidase A (rapidly fatal).
• Fabry's disease: caused by a deficiency in a-galactosidase.
1. The above disorders are most common in Ashkenazi Jewish ancestry.
Notes 2. They are caused by incomplete lysosomal breakdown of sphingolipids and mucopolysaccharides within phagocytes, leading to their accumulation. 3. They are all autosomal recessive except Fabry's disease which is X-linked recessive.
Dermatophycosis
These organisms, called dermatophytes, are the pathogenic members of the keratinophilic (keratin digesting) soil fungi. Microsporum and Trichophyton are human and animal pathogens. Epidermophyton is a human pathogen.
Infection occurs by contact with arthrospores (asexual spores formed in the hyphae of the parasitic stage) or conidia (sexual or asexual spores formed in the "free living" environmental stage). Infection usually begins in a growing hair or the stratum corneum of the skin. Dermatophytes do not generally invade resting hairs, since the essential nutrients they need for growth are absent or limited. Hyphae spread in the hairs and keratinized skin, eventually developing infectious arthrospores.
In humans, dermatophytoses are referred to as "tinea" infections, and are named with reference to the area of the body involved. Infections can spread to other areas; tinea corporis in children, for example, is often the result of a tinea capitis infection that has spread to the face.
Tinea infections:
• Tinea capitis, most often seen in children, is a dermatophyte infection of the hair and scalp.
• Tinea corporis, or ringworm, occurs on the trunk, extremities and face.
• Tinea barbae is an infection of the hairs and skin in the beard and mustache area, and is usu¬ally seen in men.
• Tinea faciei is seen on the nonbearded parts of the face.
• Tinea cruris is an infection of the groin. Commonly called jock itch.
• Tinea pedis (Athlete's foot) is an infection of the foot.
• Tinea manuum is a dermatophyte infection of one or, occasionally, both hands.
• Tinea unguium is a dermatophyte infection of the nail.
The most effective anti-mycotic (anti-fungal) agent is griseofulvin. Although griseofulvin is prescribed to treat infections of the skin, it cannot be applied as a cream and must be taken in pill form.
They are prokaryotic and lack a cell wall
*** This is false; they are eukaryotic and have a complex cell wall. In addition, they are all gram-positive and grow in Sabouraud's medium and contain both DNA and RNA. Two types of fungi:
1. Yeasts: grow as single cells that reproduce by asexually budding.
2. Molds: long filaments (hyphae) which form a mat-like structure that is referred to as mycelium.
Dimorphism is a characteristic of some fungi, meaning that they form different structures at different temperatures. They exist as molds in the saprophytic, free-living state at ambient temperatures and as yeasts in host tissues at body temperature. These fungi include the major pathogens : Blastomyces, Histoplasma, Coccidioides, and Candida.
Most fungi reproduce asexually by forming conidia (asexual spores) from the sides or ends of specialized structures called conidiophores. Different conidia help in the identification of fungi. Examples of asexual spores (conidia) include: arthrospores, chlamydospores, blastospores, and sporangiospores.
Some fungi reproduce sexually by mating and forming sexual spores. Examples of sexual spores include: zygospores, ascospores, and basidiospores.
1. All fungi except for those belonging to the class zygomycetes, are septated.
2. The cell walls of most fungi contain chitin and 13-1:3-linked glucan.
3. Sterols (ergosterol) are in the cell membrane. Most antifungal agents target this component of fungal cell membranes.
4. Fungal infections generally initiate a type IV delayed hypersensitivity reaction.
5. The formation of granulomas in response to a fungal infection is common (as seen in coccidioidomycosis, histoplasmosis, blastomycosis, etc.).
Lungs
Coccidioidomycosis is an infectious disease caused by inhaling spores of a fungus called Coccidioides immitis. The disease starts out as a respiratory illness and may progress to a persistent infection. Disseminated coccidioidomycosis is the most severe form of the disease and is often fatal. Note: Coccidioidomycosis is also referred to as "valley fever" or "San Joaquin fever."
Antifungal medications used to treat disease include: Amphotericin B, fluconazole, ketoconazole and itraconazole.
Blastomycosis (also called Gilchrist's disease or North American blastomycosis) is a disease caused by a fungus, Blastomyces dermatitidis, which is found in parts of the south-central, south-eastern and mid-western United States. The infection is spread by inhalation of airborne conidia (spores) after disturbance of contaminated soil.
Blastomycosis is not known to be transmitted from person to person. For persons with mild or moderately severe disease, itraconazole may be used for treatment.
Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. H. capsulatum is found throughout the world and is endemic in Ohio and Mississippi river valleys. Infection is usually asymptomatic, but it can cause a granulomatous, tuberculosis-like infection (primary form of disease). It is a frequent cause of pulmonary nodules. The infection may spread throughout the body, and this disseminated form, though uncommon, is quite seri¬ous. Antifungal medications used to treat disease include: Amphotericin B, fluconazole and
itraconazole.
1. In infected tissues, yeast cells of Histoplasma capsulatum are found within Notes macrophages.
2. Histoplasmosis resembles TB, both clinically and pathologically.
3. Histoplasma capsulatum produces chlamydospores.
4. Histoplasmosis and blastomycosis are rarely acquired from another individual.
Mucormycosis
Mucormycosis is a rare but often fatal disease caused by certain fungi (i.e., Mucor sp., Rhizopus sp., and Absidia sp). It is sometimes called zygomycosis or phycomycosis. They are not dimorphic, and are morphologically characterized by the lack of septa in their hyphae.
Mucormycosis is an opportunistic infection that typically develops in patients with weakened immune systems, diabetes, kidney failure, organ transplants, or chemotherapy for cancer. It may also develop in patients receiving an iron chelating drug called desferrioxamine (Desferal) as treatment for acute iron poisoning.
Syndromes associated with mucormycosis include:
• Rhinocerebral infection (infection of sinuses and brain)
- May start as a sinus infection
- May progress to involve inflammation of cranial nerves
- May cause blood clots that block vessels to the brain (thrombosis)
Other opportunistic fungi which normally fail to induce disease in most normal persons but may do so in people with severely suppressed immune systems:
Cryptococcus: Cryptococcus neoformans causes Cryptococcosis. C. neoformans is an oval, budding yeast and is not dimorphic. Cryptococcosis is more common than other fungal infections. This infection is severe only in people with underlying immune system disorders, such as AIDS. Cryptococcosis may spread, especially to the meninges, where the resulting disease is cryptococcal meningitis.
Aspergillus: Aspergillus species, especially Aspergillus fumigatus, causes an aspergilloma ('fungus ball') in the lungs and Aspergillosis. Apergillus species exist only as molds and are not dimorphic. They cause pulmonary infections in people who have AIDS or have undergone organ transplantation.
Candida: Candida albicans, the most important species of Candida, causes thrush, vaginitis, and other diseases. C. albicans is an oval yeast with a single bud. Overgrowth of C. albicans in those with impaired host defenses produces the candidiasis.
Entamoeba histolytica
Amebiasis is an intestinal illness caused by a microscopic parasite called Entamoeba histolytica. Entamoeba histolytica exists in two forms during its life cycle: the active parasite (trophozoite) and a dormant parasite (cyst). The main attribute of Entamoeba histolytica that is responsible for its worldwide distribution may be due to the extreme stability of its cyst in the environment. Contaminated water is the most common mode of the spread of this infection. Acute intestinal amebiasis presents a dysentery (i.e., bloody, mucus-containing diarrhea). Note: E. histolytica can also produce liver (hepatic) abscesses. It is treated with metronidazole.
Giardiasis is a diarrheal illness caused by a flagellated protozoan Giardia lamblia. It also exists in two forms (trophozoite and cyst). Giardia infection has become recognized as one of the most common causes of waterborne disease (found in both drinking and recreational water) in humans in the United States. It is more common in male homosexuals and in people who have traveled to developing countries. It is treated with metronidazole.
Trichomoniasis is a sexually transmitted disease of the vagina (in women) or urethra (in men) caused by a flagellated protozoan Trichomonas vaginalis. T. vaginalis only exists as a trophozoite. Trichomoniasis is one of the most common infections worldwide. Symptoms are more common in women. It is also treated with metronidazole.
- 1. Entamoeba and Trichomonas species are found in the oral cavity. They appear
Notes to be nonpathogenic when located here.
2. Balantidium coli is a ciliated protozoan that can infect the colon causing diarrhea with accompanying abdominal colic, nausea, and vomiting with bloody stools.
3. Balantidium coli is known for being the largest protozoan parasite of humans.
Kidneys, eyes, and brain
Malignant hypertension is a rare but very serious form of high blood pressure that, if left untreated, usually leads to death in 3 to 6 months. The kidneys are especially sensi¬tive to increases in blood pressure and permanent kidney damage is a common compli¬cation of untreated malignant hypertension. Like high blood pressure in general, the exact cause of malignant hypertension is not completely understood.
Nephrosclerosis is a kidney disorder in which the smallest arteries in the kidneys, called the arterioles, are damaged. There are 3 types of nephrosclerosis:
1. Arterial: atrophy and scarring of the kidney due to arteriosclerotic thickenings of the walls of large branches of the renal artery.
2. Arteriolar: renal changes associated with hypertension in which the arterioles thicken and the areas they supply undergo ischemic atrophy and interstitial fibrosis.
3. Malignant: rapid deterioration of renal function caused by inflammation of renal arterioles. This type accompanies malignant hypertension.
Pyelonephritis is an ascending urinary tract infection (usually E. Coll) that has reached the pelvis of the kidney. There are two forms of pyelonephritis:
1. Acute, which is an active infection of the renal pelvis. The pelvis may become inflamed and filled with pus.
2. In chronic cases, extensive scar tissue is formed in the kidney, and renal failure becomes a possibility.
Remember: Chronic hypertension leads to reactive changes in the smaller arteries and arterioles throughout the body. These changes are collectively referred to as arteriosclerosis. The vascular changes are particularly evident in the kidney, where they result in a loss of renal parenchyma, referred to as benign nephrosclerosis.
Calcium stones
*** Calcium stones account for 80-90% of kidney stones. They are composed of calci-um oxalate, calcium phosphate, or both.
Nephrolithiasis is another name for kidney stones. Kidney stones are also called renal calculi. Stones in other parts of the urinary system are called urinary calculi. Both are rock-like pieces that are about the size of a grain of sand. They form most often in the kidneys and get stuck in the ureter. This blocks the flow of urine and causes renal colic (characterized by severe pain in the back, lower abdomen, and groin on the side of the blockage). Complications may include obstruction of the ureter, acute or chronic pyelonephritis, and hydronephrosis.
The formation of a stone within the urinary tract represents a potential complication of many different diseases. In general, renal stones are composed of calcium salts, uric acid, cystine or struvite depending upon the major etiologic entity. Each type of stone has its own group of causes so that management of each entity is specific. However, all four types of renal stones share a common pathogenesis that is based essentially upon excessive supersaturation of the urine with a poorly soluble material. Renal stones grow upon the surfaces of the papillae, become detached and accompany the urine as it travels the collecting system. Since many of these stones are too large to negotiate the narrow conduits of the collecting system, they obstruct the flow of urine and often cause severe pain.
Renal calculi are more common in men than in women and rarely occur in children. The exact cause iS unknown. Predisposing factors include: dehydration, infection, changes in urine pH, obstruction of urine flow, immobilization causing bone reabsorption, metabol¬ic factors, such as hyperparathyroidism (leads to hypercalcemia), renal acidosis, ele¬vated uric acid, and defective oxalate metabolism.
Chronic urinary tract obstruction
Hydronephrosis develops when the pelvis and calyces (urine collecting structures) of the kid¬neys become distended because urine is unable to drain from the kidney down the ureters into the bladder. Hydronephrosis is not a specific disease, but a sign of an underlying problem. Causes include:

• Blockage of the urinary system (present at birth - congenital)
• A kidney or ureteral stone (nephrolithiasis)
• A blood clot
• Scarring of the ureter, usually from injury, radiation therapy or previous surgery

• A tumor in or around the ureter
• Prostate gland enlargement (benign prosta¬tic hyperplasia). This condition is not malig¬nant or inflammatory but is usually progres¬sive and may lead to obstrution of the urethra
• Pregnancy

1. Other disorders that are associated with urinary outflow obstruction:
• Urolithiasis: urinary calculus, formed in any part of the urinary tract. Calcium stones account for 80 to 90% of urinary stones. They are composed of calcium oxalate or calcium phosphate or both. They are associated with gout, hypercal¬cemia, renal infection, and hyperparathyroidism.
• Pyelonephritis: a bacterial infection (usually E. Coli) of the kidney and the ducts that carry urine away from the kidney (ureters). Pyelonephritis most often occurs as a result of urinary tract infection, particularly in the presence of occasional or per¬sistent backflow of urine from the bladder into the ureters or kidney pelvis (vesi¬coureteric reflux). Abscesses often develop. In chronic cases, extensive scar tissue is formed in the kidney, and renal failure becomes a possibility.
2. Kidney infections are usually caused by microorganisms ascending from the lower urinary tract.
Hyperalbuminemia
Nephrotic syndrome (NS) is a condition characterized by marked proteinuria, hypoal-buminemia, hyperlipidemia, and edema. These symptoms result from increased per-meability of the glomerular capillaries. Although NS is not a disease itself, it results from a specific glomerular defect and indicates renal damage. Diseases that can cause nephrotic syndrome include amyloidosis, cancer, diabetes, HIV, glomerulopathies, leukemia, lymphomas, multiple myeloma and SLE. Note: About 75% of the cases of NS result from primary (idiopathic) glomerulonephritis.
The dominant clinical feature of NS is mild to severe dependent edema of the ankles or sacrum, or periorbital edema, especially in children. Edema may lead to ascites, pleu¬ral effusion, and swollen external genitalia. Early symptoms include loss of appetite, a general sick feeling, puffy eyelids, abdominal pain, wasting of muscles, tissue swelling from excess salt and water retention, and frothy urine (high protein content).
Major complications are malnutrion, infection, coagulation disorders, thromboembol-ic vascular occlusion, and accelerated atherosclerosis.
NS can occur at any age. In children it is most common between ages 18 months and 4 years, and more boys than girls are affected. In older people, the sexes are more equally affected.

1. WBC's are more characteristic of pyelonephritis than nephrotic syndrome.
2. With a nephritic syndrome RBC casts (clumps) will be present in the urine.
3. Infarction might lead to the presence of a few RBC's in the urine.
4. Hyperlipidemia associated with nephrotic syndrome is secondary to increased hepatic fat synthesis and decreased fat catabolism.
Streptococcal infection
Kidney disorders in which inflammation affects mainly the glomeruli are called glomerulopathies. When the kidney is injured, it cannot get rid of wastes and extra fluid in the body. If the illness continues, the kidneys may stop working completely, resulting in kidney failure. Although causes vary, glomerulopathies are similar because glomeruli respond to several types of injury in a similar way.
There are four major types of glomerulopathies:
1. Acute nephritic syndrome (also called acute glomerulonephritis or poststreptococcal glomulonephritis) is an inflammation of the glomeruli that results in the sudden appearance of blood in the urine, with clumps of red blood cells (casts) and variable amounts of protein in the urine. It is most common in boys aged 3 to 7 but can occur at any age. It starts suddenly and usually resolves quickly.
2. Rapidly progressive nephritic syndrome (also called rapidly progressive glomerulonephritis or (RPGN)) may be idiopathic or associated with a proliferative glomerular disease, such as acute GN. It is an uncommon disorder in which most of the glomeruli are partly destroyed, resulting in kidney failure. It starts suddenly and worsens rapidly.
3. Nephrotic syndrome is a collection of symptoms caused by many diseases that affect the kidneys. It leads to the loss of large amounts of protein in the urine, along with hypoalbuminemia, generalized edema, hyperlipidemia, and hypercholes¬terolemia.
4. Chronic nephritic syndrome (also called chronic glomerulonephritis) is a slowly progressive disease characterized by inflammation of the glomeruli, which results in sclerosis, scarring, and eventual renal failure. Conditions that can lead to chronic GN include: SLE, Goodpasture's syndrome and Acute GN.
Cirrhosis
Portal hypertension is abnormally high blood pressure in the portal vein, the large vein that brings blood from the intestine to the liver. This condition is often classified by the site of portal venous obstruction:
• Prehepatic: caused by portal and splenic vein obstruction, most often by thrombosis.
• Intrahepatic: caused by intrahepatic vascular obstruction, most often by cirrhosis or metastatic tumor, and more rarely by schistosomiasis (parasitic infection).
• Posthepatic: caused by venous congestion in the distal hepatic venous circulation, most often as a result of constrictive pericarditis, tricuspid insufficiency, congestive heart failure, or hepatic vein occlusion (Budd Chiari syndrome).
Two factors can increase blood pressure in the portal vessels:
1. The volume of blood flowing through the vessels.
2. Increased resistance to the blood flow through the liver: this is by far the most common cause of portal hypertension which is caused by cirrhosis of the liver (common in alcoholics).
The classic complications of portal hypertension are esophageal varices, splenomegaly, and ascites. Splenomegaly is considered by some as the single most important sign of portal hypertension. In many patients the first sign of portal hypertension is bleeding from esophageal varices (which are dilated tortuous veins in the submucosa of the lower esophagus) with associated coughing up of blood (hemoptysis).
Important: One of the most common causes of death in patients with cirrhosis associated with portal hypertension is upper GI hemorrhage from bleeding esophageal varices. This causes massive vomiting of blood (hematemesis), requiring emergency treatment to control hemorrhage and prevent hypovolemic shock.
1. Barrett's esophagus is a columnar metaplasia of the esophageal epithelium that Notes occurs with chronic reflux.
,s 2. Iron deficiency anemia can be associated with esophageal webs. This is called
Plummer-Vinson syndrome and it is quite rare.
Bilirubin
Jaundice is a condition produced when excess amounts of bilirubin circulating in the blood stream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the excep-tion of physiologic jaundice in the newborn (normal newborn jaundice in the first week of life), all other cases of jaundice indicate overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.
These defects in bile excretion produce elevated levels of conjugated or unconjugated bilirubin and other components of bile in the blood. It is very common and is the lead¬ing manifestation of liver disease. It can occur at any age and in either sex.
Common causes of jaundice:
• Increased destruction of red blood cells with rapid release of bilirubin into the blood (unconjugated).
• Obstruction of the bile ducts or damage to liver cells which results in the inability of bilirubin to be excreted into the GI tract (conjugated).
1. Bilirubin is the waste product that results from the breakdown of hemoglo-/Notes bin molecules from worn out red blood cells. Ordinarily, it is excreted from the body as the chief component of bile.
2. Conjugated bilirubin is formed by the conjugation of bilirubin with glucuron¬ic acid.
3. Free bilirubin (unconjugated), unlike that bound to albumin or conjugated with glucuronic acid, is toxic.
4. High levels of bilirubin in the bloodstream can cause permanent damage to certain areas of the brain in newborn infants; this is known as kernicterus. This can result in a characteristic form of crippling called athetoid cerebral palsy.
Cirrhosis
Hepatocellular carcinoma is cancer that arises from hepatocytes, the major cell type of the liver. About 80% of people with hepatocellular carcinomas have cirrhosis. Chronic infection with the hepatitis B virus and hepatitis C virus also increases the risk of developing hepatocellular carcinoma. Aflatoxins, which are produced by a mold that is a contaminant of nuts (most commonly peanuts), grains, and beans, have also been implicated as a major risk factor for causing hepatocellular carcinoma.
Remember: Previously, viral hepatitis that was not caused by the type A or type B virus was called "non-A, non-B hepatitis." Recently three more viruses that cause some of these non-A, non-B infections have been identified. These viruses include:
• Hepatitis C: is a serum hepatitis that is caused by a virus antigenically different from Hepatitis viruses A and B. Most cases of post-transfusion hepatitides are of this type. It is usually much milder than A or B but is otherwise clinically indistinguish-able from them. There is a higher incidence of chronic disease (chronic hepatitis), cirrhosis and hepatocellular carcinoma.
Important: Hepatitis C is now the most common reason for liver transplantation in the United States.
• Hepatitis D: requires coinfection with Hepatitis B. Drug addicts are at relatively high risk.
• Hepatitis E: is transmitted enterically, much like Hepatitis A. It is a common spo-radic cause of viral Hepatitis in India. It has close to a 20% mortality in pregnant women.
Hepatitis A
Hepatitis A (HAV) is a highly contagious infectious disease involving the liver. It is usu¬ally transmitted by the fecal-oral route. However, it may also be transmitted parenteral¬ly, as can Hepatitis B and D. Hepatitis A usually results from ingestion of contaminated food, milk, or water. Many outbreaks of this type are traced to ingestion of seafood from polluted water. It most often occurs in young adults. The initial symptoms (fever, malaise, abdominal pain, anorexia, jaundice) of Hepatitis A appear after an incubation period of 3-6 weeks. Complete resolution occurs in an overwhelming majority of cases.
Important: There is no association of HAV with either cirrhosis or hepatocellular car-cinoma, as there is for Hepatitis B and C.
Hepatitis B is transmitted by parenteral and sexual contact. Risk factors include multi¬ple sexual partners, intravenous drug abuse, and receipt of blood products. The signs and symptoms are similar to hepatitis A (fever, abdominal pain, nausea, etc.) but there is a longer incubation period (6-8 weeks). The symptoms are slower in developing but are of a longer duration. Most patients recover fully; however, some develop chronic liver disease.
1. An increased serum level of transaminases often indicates hepatocellular damage.
2. The presence of surface antigen (A or B) in a patient's serum indicates that the patient is potentially infectious for Hepatitis (carrier state).
3. Hepatitis viruses are very heat-resistant (more so than the AIDS virus).
4. Proper autoclaving will kill these viruses.
It is twice as common in women as in men
*** This false; it is twice as common in men as in women.
Cirrhosis is characterized anatomically by widespread nodules in the liver combined with fibrosis. The fibrosis and nodule formation causes distortion of the normal liver architecture which interferes with blood flow through the liver. Important: Cirrhosis is associated with an increased incidence of hepatocellular carcinoma.
Among people ages 45-65, cirrhosis is the third most common cause of death, after heart disease and cancer. Cirrhosis often has many complications, including accumulation of fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and confusion or a change in the level of consciousness (hepatic encephalopathy).
Causes of cirrhosis:
• Alcohol abuse: most common cause • Chronic congestive heart failure
• Chronic viral hepatitis B, C and D • Parasitic infections (e.g., schistosomiasis)
• Inherited metabolic diseases • Nonalcoholic steatohepatitis (liver infla-
(e. g., hemochromatosis, Wilson diease) mation that can be caused by fatty liver)
• Chronic bile duct diseases • Long term exposure to toxins or drugs
(e. g. primary biliary cirrhosis)
Signs of hepatic failure:
• Men with cirrhosis of the liver often develop gynecomastia from increased production of estrogens.
• Flapping tremor (Asterixis): this tremor commonly results from liver failure.
• Hypoalbuminemia: low albumin level.
• Spider telangiectasias or spider angiomas: small lesions on the skin containing a centrally dilated, enlarged, blood vessel from which several smaller vessels radiate.
Panacinar (panlobular)
Emphysema is a form of chronic obstructive pulmonary disease (COPD) that involves damage to the air sacs (alveoli). The air sacs are unable to completely deflate (hyperinflation) and are there¬fore unable to fill with fresh air to ensure adequate oxygen supply to the body. A person with emphysema will have labored breathing and an increased susceptibility to infection. This person has two basic problems: the lungs are "fixed" in inspiration and the respiratory surfaces of the lungs have deteriorated so much that they are no longer adequate to accomplish normal gas exchange.
Important: Obstruction results from tissue changes rather than mucus production, which occurs in asthma and chronic bronchitis. The distinguishing characteristic of emphysema is air flow lim¬itation caused by lack of elastic recoil in the lungs. Emphysema also causes an increase in lung compliance. Compliance is the volume change per unit of pressure change across an elastic struc¬ture.
Three types of Emphysema:
1. Panacinar (panlobular): destroys alveoli and alveolar ducts; lower lobes of lungs mostly affected; associated with aging and alphas-antitrypsin deficiency.
2. Paraseptal (distal acinar): commonly causes spontaneous pneumothorax in young adults.
3. Centriacinar (centrilobular): associated with chronic bronchitis and smoking; destroys respiratory bronchioles; upper lobes of lungs mostly affected.
1. Cigarette smoking is by far the most common cause of emphysema.
Notes 2. A naturally occurring substance in the lungs called alphas-antitrypsin may protect
against emphysema. People with alphas- antitrypsin deficiency are at an increased risk for this disease.
3. Symptoms of emphysema include shortness of breath, cough and a limited exercise tolerance.
4. Emphysema and chronic bronchitis frequently co-exist together to comprise chronic obstructive pulmonary disease (COPD).
Type I hypersensitivity reaction of the airways
Asthma is a chronic reactive airway disorder that causes episodic airway obstruction. Such obstruction results from bronchospasms, increased mucus secretion, and mucosal edema. Although this common condition can strike at any age, half of all cases first occur in children under age ten; in this age group asthma affects twice as many boys than girls.
Two types of asthma:
1. Extrinsic (immune) asthma: is mediated by type I hypersensitivity response involving IgE bound to mast cells. Disease begins in childhood, usually in patients with a family history of allergy.
2. Intrinsic (nonimmune) asthma: includes asthma associated with varients such as excercise, cold air, tobacco smoke, respiratory infections, etc. It usually begins in adult life and is not associated with a history of allergy.
Important: There is marked episodic dyspnea and wheezing expiration caused by narrow¬ing of the airways.
Chronic bronchitis is a very common, debilitating respiratory disease, characterized by increased production of mucous by the glands of the trachea and bronchi. This condition has a strong asso-ciation with smoking. Cor pulmonale (enlargement of the right ventricle of the heart), airway narrowing, and obstruction along with squamous metaplasia of the bronchial tree are common results of chronic bronchitis.
Remember: The characteristic pathologic change in chronic bronchitis is hyperplasia of bronchial submucosal glands and bronchial smooth muscle hypertrophy, which can be quantified by the Reid index, a ratio of glandular layer thickness to bronchial wall thickness.
Important: Patients with chronic bronchitis may be predisposed to lung cancer (bronchogenic carcinoma).
Note: A chronic lung abscess, TB, lobar pneumonia, bronchogenic carcinomas, and pulmonary embolism all present with a productive cough (a cough containing sputum). This sputum contains mucus, cellular debris, bacteria, and may contain blood or pus.
Pulmonary edema
Pulmonary edema is the accumulation of fluid in the extravascular spaces of the lungs. It is usually caused by heart failure (left-sided) that results in increased pressure in the pulmonary veins. The failing heart transmits its increased pressure to the lung veins. As pressure in the lung veins rises, fluid is pushed into the air spaces (alveoli). This fluid then becomes a barrier to normal oxygen exchange, resulting in shortness of breath. Physiologically, pulmonary edema is caused by:
• Increased hydrostatic pressure, as a result of left ventricular failure or mitral stenosis
• Increased alveolar capillary permeability, as in inflammatory alveolar reactions, resulting from inhalation of irritant gases, pneumonia, shock, sepis, pancreatitis, ure-mia, or drug overdose
The early symptoms of pulmonary edema include dyspnea, orthopnea, and coughing. Clinical features include tachycardia, tachypnea, dependent crackles, and neck vein
distension. The treatment is designed to reduce extravascular fluid, to improve gas exchange and heart function (i.e., oxygen, diuretics, vasopressors, positive inotropic agents and antiarrhythmics).
Bronchiectasis is an irreversible, abnormal dilatation of the bronchi or bronchioles caused by destruction of their supporting structures by a chronic necrotizing infection. It
is common in children with cystic fibrosis. Most common symptom is a chronic, productive cough with a foul-smelling, purulent sputum. Recurrent pulmonary infection may lead to lung abscess. Note: Bronchiectasis most often invloves the lower lobes of both lungs.
Atelectasis is a shrunken and airless state of the lung, or portion of it. This is due to failure of expansion or resorption of air from the alveoli. Common in premature infants due to a lack of surfactant. Known as atelectasis neonatorum.
Cystic fibrosis
Cystic fibrosis is a generalized dysfunction of the exocrine glands that affects multiple organ systems. It is an inherited disease that affects sodium channels in the body and causes respiratory and digestive problems. It is the most common fatal genetic disease in white children. Cystic fibrosis affects the mucus and sweat glands of the body and is caused by a defective gene. Thick mucus is formed in the breathing passages of the lungs and this predisposes the person to lung infections. CF affects males and females and now carries a life expectancy of 28 years. Complications of cystic fibrosis include chronic pulmonary disease, pancreatic insufficiency, and meconium ileus (a form of intestinal obstruction in newborns). Important: Patients with cystic fibrosis often have impaired exocrine pancreas function, resulting in a deficiency of fat-soluble vitamins.
1. The cause is mutations in the cystic fibrosis transmembrane conductance regular (CFTR) gene, which has been localized to the midsection of the long arm of chromosome 7. This gene codes for a membrane protein that facilitates the movement of chloride and other ions across membranes.
2. The sweat test is an important diagnostic procedure. Secretion by sweat glands of chloride and sodium is normal, but their reabsorption by sweat ducts is impaired.
Von Hippel-Lindau disease is characterized by hemangiomas of the retina and the cerebe¬llum. Also associated with cysts of the liver, kidney, adrenal glands, and pancreas.
Marfan's syndrome is an uncommon hereditary connective tissue disorder that results in abnormalities of the eyes, bones, heart, and blood vessels. Patients are tall and thin with abnormally long legs and arms and spider-like fingers.
Familial Hypercholesterolemia is a genetic defect characterized by anomalies of receptors for low density lipoprotein (LDL receptors). Can result in atherosclerosis and its complicat¬ions.
Anthracosis
Pneumoconioses are environmental diseases caused by prolonged inhalation of inorgan¬ic dust particles. These diseases lead to fibrosis of the lungs. The main symptoms are a chronic dry cough and shortness of breath. Specific types of pneumoconioses include:
1. Anthracosis: is caused by the inhalation of carbon dust. Characterized by carbon-carrying macrophages, it results in irregular black patches visible on gross inspec¬tion.
2. Coal workers' pneumoconiosis: is caused by the inhalation of coal dust, which contains both carbon and silica. Two forms:
• Simple: is marked by coal macules around the bronchioles. In most cases, it pro¬duces no disability.
• Progressive massive fibrosis: is marked by fibrotic nodules filled with necrotic black fluid. It can result in bronchiectasis, pulmonary hypertension or death from respiratory failure or right-sided heart failure.
3. Silicosis (stone mason's disease): is caused by the inhalation of free silica dust. It is characterized by silicotic nodules that enlarge and eventually obstruct the airways and blood vessels. It is the most common and most serious pneumoconiosis and is associated with increased susceptibility to TB (referred to as silicotuberculosis).
4. Asbestosis: is caused by the the inhalation of asbestos fibers. It leads to diffuse interstitial fibrosis, mainly in the lower lobes. It is characterized by ferruginous bod¬ies (yellow-brown, rod-shaped bodies that stain with Prussian blue). Asbestosis results in marked predisposition to bronchogenic carcinoma and to malignant mesothelioma of the pleura or peritoneum.
5. Beryliosis: is caused by the inhalation of berylium particles. It is a systemic gran-ulomatous disorder characterized by non-caseating granulomas and primary pul¬monary involvement. It mimics sarcoidosis.
Lobar pneumonia
Pneumonia is an inflammatory process of infectious origin affecting the pulmonary parenchyma. It is characterized by chills and fever, productive cough, blood-tinged or rusty sputum, hypoxia with a shortness of breath, and sometimes cyanosis.
There are 3 morphologic types of pneumonia:
Bacterial pneumonias:
1. Lobar pneumonia: is most often caused by Streptococcus pneumoniae. It is character¬ized by a predominantly intra-alveolar exudate, with inflammation and consolidation of a lobe or entire lung. It affects middle-aged persons.
2. Bronchopneumonia: is caused by a wide variety of organisms (i. e., Staphylococcus aureus, Haemophilus influenzae, Klebsiella, Streptococcus pyogenes). It is characterized by a patchy distribution involving one or more lobes, with an inflammatory infiltrate extending from the bronchioles into the adjacent alveoli. It affects infants and the elderly.
3. Interstitial pneumonia: is caused by various infectious agents, most commonly Mycoplasma pneumoniae or viruses (i.e., RSV adenoviruses). It is characterized by dif-fuse, patchy inflammation localized to interstitial areas of alveolar walls. It affects young children.
1. Bacterial pneumonias tend to be the most serious. In adults, bacteria are the Notes most common cause, and of these Streptococcus pneumoniae (pneumococcus) is the most common It is the most common fatal infection acquired in the hospital.
2. The virulence of the pneumococcus is associated with its capsular polysac-charide.
3. Respiratory viruses (i.e.,influenza viruses, adenoviruses, rhinovirus, and RSV) are the most common causes of pneumonia in young children, peaking between the ages of 2 and 3.
4. Clinical findings in pneumonia: crackles on auscultation, hypoxia and infil¬trate on chest x-ray.
Staphylococci
A lung abscess is a localized area of liquefactive necrosis of the lung. The abscess is characterized by destruction of lung tissue forming a cavity. The cavity is filled with pus (necrotic debris / liquid) or pus and gas (air). The content of the abscess is extremely foul smelling.
A variety of microorganisms may cause a lung abscess, but more than 60% of cases are associated with anaerobic organisms found normally in the oral cavity. These bacteria predominate in the upper respiratory tract and are heavily concentrated in areas of oral-gingival disease. There are many mechanisms for the development of a lung abscess but the most frequent is aspiration of infective (contaminated with microorganisms) mate¬rial, often in the setting of altered consciousness. Other causes include: bronchial obstruction (often by cancer) bronchiectasis, or perhaps be a complication of bacterial pneumonia.
Important: Alcoholism is the single most common condition predisposing to lung abscess. Persons suffering from drug overdosage, along with epileptics, and patients with neuro-logic dysfunction impairing the gag reflex are also at risk.
1. Almost all patients with a lung abscess present with a cough and fever. Notes 2• One of the most characteristic clinical manifestations is the production of large amounts of a foul-smelling, purulent sputum.
3. Dyspnea, chest pain, and cyanosis may be present. Chest x-ray reveals fluid-filled cavity.
4. Frequent causes include staphylococci, pseudomonas, klebsiella, and pro¬teus, often in combination with anaerobic organisms.
Nodular melanoma
Malignant melanoma involves the cells (melanocytes) that produce pigment (melanin), which is responsible for skin and hair color. Melanoma can spread very rapidly and is the most dead¬ly form of skin cancer. It is the leading cause of death from skin disease.. Melanoma may appear on normal skin, or it may begin at a mole (nevus) or other area that has changed in appearance. Some moles present at birth may develop into melanomas. The development of melanoma is related to sun exposure, particularly to sunburns during childhood, and is most common among people with fair skin, blue or green eyes, and red or blonde hair.
Growth phases:
Radial (initial phase)
• There is growth in all directions but is predominantly lateral within the epidermis and pap¬illary zone of the dermis
• Lymphocyte response is prominent
• Melanomas in the radial growth phase do not metastasize
Vertical (later phase)
• Growth extends into the reticular dermia or beyond
• Prognosis varies with the depth of the lesion
• Lymphatics or hematogenous metastasis may occur
Clinical variants of malignant melanoma:
• Superficial spreading melanoma is the most common type of melanoma. It is usually irregularly bordered with varied pigmentation. Most frequent locations are the trunk and extremities. Radial growth phase predominates.
• Nodular melanoma begins with the vertical growth phase. Poorest prognosis.
• Lentigo maligna melanoma occurs on sun-exposed skin. The radial growth phase pre-dominates. Most often develops from pre-existing lentigo maligna (Hutchinson freckle).
• Acral-lentiginous melanoma is the least common form of melanoma. It most often appears on the hands and feet of dark-skinned persons.
Headaches, palpitations, and diaphoresis
Pheochromocytoma is a rare catecholamine-secreting tumor derived from chromaffin cells of the adrenal medulla. Catecholamines typically secreted, either intermittently or continuously, include norepinephrine and epinephrine and rarely dopamine. Because of excessive catecholamine secretion, pheochromocytomas may precipitate life-threat¬ening hypertension or cardiac arrhythmias. If the diagnosis of a pheochromocytoma is overlooked, the consequences could be disastrous, even fatal; however, if a pheochro-mocytoma is found, it is potentially curable.
These tumors are uncommon, often benign, and may occur in men or women at any age, but are most common between ages 30 and 60. If the tumor is derived from extra-adrenal chromaffin cells, it is called a paraganglioma (metastasis is more common in this tumor). Pheochromocytoma may be a part of or associated with MEN (multiple endocrine neoplasia), neurofibromatosis (von Recklinghausen's disease), or von Hipple¬Lindau disease (multiple hemangiomas).
Increased urinary excretion of catecholamines and their metabolites (metanephrine, normetanephrine, and vanillylmandelic acid) is characteristic. It can also cause hyper-glycemia.
1. A neuroblastoma is a highly malignant catecholamine-producing tumor of
Notes early childhood that usually originates in the adrenal medulla. It is the most common malignant tumor of childhood and infancy. Complications include invasion of abdominal organs by direct spread and metastasis to liver, lung or bone. The first symptoms in many children include a large abdomen, a sensa¬tion of fullness, and abdominal pain. This is followed by an abdominal mass. This tumor causes hypertension. Occasionally this tumor converts into a more differentiated form termed ganglioneuroma.
Adenocarcinoma
Bronchogenic carcinoma is a malignant neoplasm of the lung arising from the epithelium of the bronchus or bronchiole.
Bronchogenic carcinomas begin as a small focus of atypical epithelial cells within the bronchial mucosa. As the lesion progresses, the atypia becomes malignant and the neoplasm grows in size. The neoplasm may grow into the bronchial lumen, along the mucosa or into the bronchial wall and adjacent lung parenchyma. Eventually the neoplasm spreads to regional lymph nodes and distant organs such as the liver, brain and bone. Most bronchogenic carci¬nomas form a mass in or near the hilus. Some neoplasms, especially the adenocarcinomas, form a mass in the periphery of the lung.
Major histologic types of bronchogenic carcinoma:
• Epidermoid (squamous cell) carcinoma: most arise in or near the hilus; appears as a hilar mass and often undergoes ventral cavitation. Important: This neoplasm is most common in men and is closely related to smoking.
• Adenocarcinoma: tend to be smaller than other bronchogenic carcinomas and located in the periphery of the lung. A distinctive type of adenocarcinoma is bronchioloalveolar car¬cinoma. Important: This neoplasm is the most common type in women and non-smokers.
• Small cell (oat cell) carcinoma: most arise in or near the hilus; it is the most aggressive form and highly malignant. Most commonly affects men (80%), and 90% of them are cig¬arette smokers. Important: This neoplasm is strongly related to smoking. It is a very aggressive neoplasm, generally having metastasized at the time of diagnosis.
Note: The oat cell that is observed in these carcinomas is a short, bluntly spindle-shaped, anaplastic cell containing a relatively large, hyperchromatic nucleus with little or no cyto¬plasm.
• Large cell (anaplastic) carcinoma: composed of large, undifferentiated malignant cells; variable location (peripheral or central).
Note: With all of the above the major findings are cough, weight loss, chest pain and dyspnea.
Are two to three times more common in males
These malignant neoplasms arise from lymphoid cells or other cells native to lymphoid tissue. They originate most frequently within lymph nodes or other lymphoid areas. These tumors do not spread in a contiguous manner. The cause of malignant lym¬phomas is unknown, although some researchers suggest a viral source. They occur in all age-groups.
Malignant lymphomas present as circumscribed solid tumors composed of cells that appear primitive or resemble lymphocytes, plasma cells, or histiocytes. Usually the first indication of malignant lymphoma is swelling of the lymph glands, enlarged tonsils and adenoids, and painless, rubbery nodes in the cervical supraclavicular areas. As the lym¬phoma progresses, the patient develops symptoms specific to the area involved and sys¬temic complaints of fatigue, malaise, weight loss, fever, and night sweats.
Important: Burkitt lymphoma is an aggressive B-cell lymphoma. The African form frequently involves the maxilla or mandible; the American form usually involves abdominal organs. There is a close linkage to Epstein-Barr Virus infection (especially in the African variety).
1. Malignant lymphoma is pathophysiologically similar to Hodgkin's disease, but Reed-Sternberg cells are not present, and the specific mechanism of lymph node destruction is different.
2. Histologic characteristics of malignant lymphoma include a "starry-sky" appearance of non-neoplastic macrophages.
3. There appears to be a relationship between diffuse lymphocytic lymphoma and chronic lymphocytic leukemia (CLL).
4. Biopsy differentiates malignant lymphoma from Hodgkin's disease.
Squamous cell carcinoma
Squamous cell cancer involves cancerous changes to the cells (keratinocytes) of the middle portion of the epidermal skin layer. It is usually painless initially, but may become painful with the development of ulcers that do not heal. This cancer may begin in normal skin; in the skin of a burn, injury or scar; or at a site of chronic inflammation (which may occur with many skin disorders). It most often originates from sun-damaged skin areas, such as actinic keratosis. It usually begins after age 50.
Squamous cell cancer is a malignant tumor. It is more aggressive than basal cell cancer, but still may be relatively slow-growing. It occurs most frequently in sun-exposed areas such as the face and back of the hands; in contrast to basal cell carcinoma, squamous cell carcinoma tends to involve the lower part of the face. It is more likely than basal cell cancer to spread (metastasize) to other locations, including internal organs.
1. SCC is also associated with chemical carcinogens, such as arsenic, and radi¬ation or x-ray exposure.
2. It is most often locally invasive; however, SCC can infiltrate underlying tis¬sue or metastasize in lymphatic channels. Treatment consists of complete exci¬sion or radiation therapy.
3. SCC resembles cervical cancer in histologic appearance and biologic behavior.
4. Malignant epithelial cells have an increased number of laminin receptors. Laminin (a glycoprotein) is a major component of basement membranes and has numerous biological activities including promotion of cell adhesion, migra¬tion, growth, and differentiation.
5. Squamous cell carcinoma accounts for 90% of all diagnosed malignant can¬cers of the oral cavity.
It is a fast-growing, relatively benign skin tumor
*** This is false; basal cell carcinoma is a slow-growing, destructive skin tumor.
Basal cell carcinoma is by far the most common malignant tumor of the skin (it accounts for about 75% of all skin cancers) and actually is the most common form of cancer in the United States. It is derived from basal cells of the epidermis. It tends to involve sun-exposed areas, most frequently the head and neck. In contrast to squamous cell carcinoma, it tends to involve the upper part of the face. The tumor is invasive, ulcerative, often indurated, and locally destructive but does not metastasize.
Classically, it is described as a smooth, pearly-shaped lump often with small veins (telangectasia) snaking around the surface. Depending on where and how long it has been there, BCC can look very different. Left untreated, BCC can eat away at the skin, making it look as if a rat had chewed at it. This type of BCC is called a "rodent ulcer". The prognosis for BCC is good. The neoplasm can usually be cured by surgical resec-
Basal cells are normal skin cells. They may develop cancerous changes, causing a lump or bump that is painless. A new skin growth that ulcerates, bleeds easily, or does not heal well may indicate development of basal cell skin cancer.
Important: Histologically, basal cell carcinoma is characterized by clusters of darkly staining basaloid cells with a typical palisade arrangement of the nuclei of the cells at the periphery of the tumor cell clusters.
1. The incidence of skin cancer has increased greatly in recent years, due in part Notes to greater exposure to UV radiation from the sun.
2. Malignant melanoma is considered to be the most severe tumor of the skin.
Benign tumor of mesenchymal tissue
A leiomyoma (also called a fibroid) is a benign tumor of the smooth muscle of the uterus and thus is an example of a benign tumor of mesenchymal origin. It may occur anywhere in the body, but is most frequently seen in the uterus. It is the most common tumor of women (20% of women over 30 years, during the reproductive years). Other areas where they seem to occur less frequently than the uterus include the stomach, esophagus, and small intestine. The prognosis is good. Note: Profuse, painful menses and infertility are major complications. A leiomyosarcoma is the malignant counterpart.
The cause of fibroid tumors of the uterus is unknown. However, it is suggested that fibroids may enlarge with estrogen therapy (such as oral contraceptives) or with pregnancy. Their growth seems to depend on regular estrogen stimulation, showing up only rarely before the age of 20 and shrinking after menopause. As long as a woman with fibroids is menstruating, the fibroids will probably continue to grow, although growth is usually quite slow. Fibroids can be microscopic, but they can also grow to fill the uterine cavity, and may weigh several pounds. Uterine fibroids are the most common pelvic tumor and they may be present in 15 to 20% of reproductive-age women, and 30 to 40% in women over 30.
1. All neoplasms of muscles are rare, but when encountered they are usually Notes
malignant
2. A rhabdomyosarcoma is a malignant neoplasm derived from the skeletal (striated) muscle. It affects the throat, bladder, prostate, or vagina in infants and it affects large muscle groups of the arm and leg in the elderly. The prognosis is poor.
3. The benign variety, rhabdomyoma, can arise in any skeletal muscle of the body. This benign tumor produces a mass (swelling) in the affected muscle.
Late menarche
Breast cancer is the most common cancer affecting women and is the number two killer (after lung cancer) of women ages 35 to 54. This tumor is almost always an adenocarcino-ma. It is rare before 25 and is increasingly more common with age until menopause, at which time the incidence slows down. The strongest association with an increased risk for breast cancer is a family history, specifically breast cancer in first-degree relatives (mother, sister, daughter). Breast cancer occurs more commonly in the left breast than the right breast and more commonly in the outer upper quadrant. Widespread metastasis can occur by way of the lymphatic system and the bloodstream, through the right side of the heart and lungs, and eventually to the other breast, the chest wall, liver, bone, and brain.
Predisposing factors:
• Positive family history • Obesity
• History of breast cancer in one breast • First pregnancy after 30 years of age
• Early menarche and late menopause • Diet high in animal fat
• Proliferative fibrocystic disease with atypical epithelial hyperplasia
A painless mass in the breast is usually the initial sign or symptom; however, retraction of the skin or nipple and peau d'orange (a swollen pitted skin surface) along with enlargement of the axillary lymph nodes may also be present. Important: Lymph node involvement is the most valuable prognostic predictor.
Fibrocystic disease of the breast is the most common cause of a clinically palpable breast mass in women 28 to 44 years old. Signs and symptoms include lumpiness throughout both breasts. Pain is common, especially prior to the menstruation period. It is not malignant, but may lead to an increased chance of developing carcinoma.
Note: A choriocarcinoma is a rapidly metastasizing malignant tumor of placental tissue that typically causes profuse vaginal and intra-abdominal bleeding. Hyperestrogenism is a major risk factor for the development of endometrial carcinoma.
A persistent cough -- smoker's cough
Bronchogenic carcinoma is the leading cause of death from cancer in both men and women. It is increasing in incidence, especially in women, in parallel with cigarette smoking. Lung cancer usually develops in the wall or epithelium of the bronchial tree. Bronchogenic carcinoma is subclassified into squamous cell carcinoma, adenocarcino¬ma (including bronchioloalveolar carcinoma), small cell carcinoma, and large cell car¬cinoma. Other clinical manifestations may include hemoptysis, hoarseness, wheezing, dyspnea, chest pain, and weight loss.
This type of carcinoma is directly proportional in incidence to the number of cigarettes smoked daily and to the number of years of smoking. Various histologic changes, includ¬ing squamous metaplasia of the respiratory epithelium, often with atypical changes rang¬ing from dysplasia to carcinoma in situ, precede bronchogenic carcinoma in cigarette smokers.
Other diseases due to smoking:
• Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis
• Carcinoma of the larynx and oral cavity
• Increased incidence of carcinoma of the esophagus, pancreas, kidney, and bladder
• Peptic ulcer disease
• Low birth-weight infants
1. Benzpyrene is the carcinogen in cigarette smoke Notes 2. 50% of cases are inoperable at the time of diagnosis
3. The 5-year survival rate is less than 10%
4. While lung cancer can spread to any organ in the body, certain organs, par-ticularly the adrenal glands, liver, brain, and bone, are the most common sites for lung metastasis.
Hodgkin lymphoma
Hodgkin lymphoma (Hodgkin disease) is a malignant neoplasm with features (e.g., fever, inflammatory cell infiltrates) resembling an inflammatory disorder. The first sign of this can¬cer is often an enlarged lymph node which appears without a known cause. The disease can spread to adjacent lymph nodes and later may spread outside the lymph nodes to the lungs, liver, bones, or bone marrow. The cause is not known.
Hodgkin lymphoma characteristically affects young adults (predominantly young men); an exception is nodular sclerosis, which frequently affects young women.
Important: This neoplasm is characterized in all forms by the presence of Reed-Sternberg cells, which are the actual neoplastic cells. Symptoms include anorexia, weight loss, general¬ized pruritus, low-grade fever, night sweats, anemia, and leukocytosis. Prognosis is most favorable with early diagnosis and limited involvement. Lymphocyte predominance is also linked with a favorable prognosis. Note: Reed-Sternberg cells are binucleated, or multinucle¬ated, giant cells with eosinophilic inclusion-like nucleoli.
Classification of Hodgkin lymphoma:
• Lymphocytic-predominance: prognosis is relatively good; no association with EBV infection
• Lymphocytic-rich: association with EBV infection; more common in men
• Mixed cellularity: association with EBV infection; found most often in older persons
• Lymphocytic depletion: least common; association with EBV infection and is also more common in persons with HIV; poorest prognosis
• Nodular sclerosis: most common; more frequently in young women; presence of lacu-nar cells (a Reed-Sternberg cell variant); prognosis is relatively good
1. Many researchers believe that Hodgkin's disease starts as an inflammatory or Notes infectious process and then becomes a neoplasm; others believe it to be an immune disorder. However, the etiology of the disease remains an enigma.
2. Non-Hodgkin lymphoma is a malignant lymphoma characterized by the absence of Reed-Sternberg cells.
Multiple myeloma
Multiple myeloma is a malignant plasma cell tumor usually affecting older persons that typically invloves bone and is associated with prominent serum and urinary protein abnormalities.
Multiple myeloma is characterized by the excessive growth and malfunction of plasma cells in the bone marrow. The growth of these extra plasma cells interferes with the production of red blood cells, white blood cells, and platelets. This causes anemia, susceptibility to infection, an increased tendency toward bleeding.
As the cancer cells grow and expand in the bone marrow, they produce osteolytic lesions throughout the skeleton (flat bones, vertebrae, skull, pelvis, ribs). The bone lesions appear lucent on radiographic examination, with characteristic sharp borders, and are referred to as "punched-out" lesions. Renal failure (kidney failure) is a frequent complication caused by excess calcium in the blood that results from bone destruction. Multiple myeloma accounts for about 1% of all cancers -- mostly in men over the age of 40.
The earliest indication of multiple myeloma is severe, constant back and rib pain that increases with exercise and may be worse at night. The pain arises from pressure created by malignant plasma cells on the nerves in the periosteum of the bone.
Important: The urine often contains significant quantities of free immunoglobulin light chains, either kappa or lambda, which are referred to as Bence Jones protein. The absence of Bence Jones protein does not rule out multiple myeloma; however, its pres¬ence almost invariably confirms the disease.
Other clinical features include: anemia, pathologic bone fractures, increased susceptibil¬ity to infection (most common cause of death), hypercalcemia, renal failure, and amy¬loidosis.
Anaplasia
Differentiation is a measure of a tumor's resemblance to normal tissue. Anaplasia is the absence of differentiation.
Histologic features of malignancy:
• Anaplasia • Hyperchromatism • Pleomorphism • Abnormal mitosis
The host response to a malignancy is best reflected by lymphocytic infiltration at the edge of the tumor. The most characteristic feature of a malignancy "as opposed to an inflammatory lesion" is that malignancy will grow after removal of the causative agent. The most important characteristic of malignant neoplasms, which distinguishes them from benign neoplasms, is their ability to invade and to metastasize.
Dysplasia is a type of nonmalignant cellular growth, but may precede malignant changes in the tissue. It is associated with chronic irritation of a tissue by a chemical agent, such as cigarette smoke, or by chronic inflammatory irritation, such as chronic cervitis. The tissue appears somewhat structureless and disorganized and may consist of atypical cells without invasion. Epithelium exhibits acanthosis (an abnormal thicken¬ing of the prickle cell layer).
Metaplasia is the substitution of one tissue normally found at a site of another. It is com¬mon in the lower esophagus with gastroesophageal reflux disease (GERD). The epithe¬lium undergoes metaplasia in response to the ongoing inflammation from reflux of gas¬tric contents. The most common type of epithelial metaplasia involves replacement of columnar cells by stratified squamous epithelium.
Neoplasms, and malignant neoplasms in particular, can form a fibrous stroma that gives the tumor a characteristic firm or hard feel on palpation. This histologic feature is called desmoplasia. This connective tissue can fix the tumor to surrounding structures.
Ewing's sarcoma
*** The tumor itself is composed of small round blue cells and is classified as a peripheral neuro-ectodermal tumor (PNET). This means the tumor may have started in fetal or embryonic, tissue that has developed into nerve tissue.
Ewing's sarcoma is a cancer that occurs primarily in the bone or soft tissue. Ewing's sarcoma can occur in any bone, but is most often found in the extremities and can involve muscle and the soft tissues around the tumor site. Ewing's sarcoma cells can also metastasize to other areas of the body including the bone marrow, lungs, kidneys, heart, adrenal glands, and other soft tissues. Ewing's sarcoma is the second most common malignant bone tumor in children and adoles¬cents (osteogenic sarcomas are the most common). It most often occurs in children between the ages of ten and 20. The number of males affected is slightly higher than the number of females. The majority of Ewing's sarcomas result from a chromosome rearrangement between chromo¬somes #11 and #22.
Important: Patients almost always present with severe bone pain. The most important aspect of the presentation is to remember that it may be insidious and non-specific.
1. Children may also break a bone at the site of the tumor after a seemingly minor trau¬Notes ma (pathologic fracture).
2. Ewing's sarcoma follows an extremely malignant course with early metastases.
3. Histologically, it is often difficult to distinguish this tumor from a neuroblastoma or a reticulum cell sarcoma.
4. Morphologically, it has a resemblance to malignant lymphoma.
5. Primary malignant bone tumors (also called sarcomas of the bone) are rare, con¬stituting less than 1% of all malignant tumors. Most bone tumors are secondary, caused by seeding from a primary site. Bone tumors may originate in osseous or nonosseous tis¬sue. Osseous bone tumors arise from bony structure itself and nonosseous tumors arise from hematopoietic, vascular, or neural tissues.
6. Metastatic bone tumors are cancers that have spread to bone from their original site elsewhere in the body. Cancers most likely to spread to bone include those of the breast, lung, prostate, kidney, and thyroid.
Keratoacanthoma
Keratoacanthoma (KA) is a common skin tumor. In the past it was regarded as benign, but some of these tumors have been seen to transform into squamous cell carcinoma. Keratoacanthoma is now regarded and treated by many as a malignant growth. It originates in the pilosebaceous glands and pathologically resembles squamous cell carcinoma (SCC). It is characterized by very rapid enlargement, followed by a stable period, and then a slow, natural regression.
Both sunlight and chemical carcinogens have been implicated as major factors in the growth of the tumor. Trauma, human papilloma virus, genetic factors, and immunocom¬promised status also have been implicated as etiologic factors. KAs occur much more frequently in men than in women, usually in their 70s.
I. Dermatofibromas are benign neoplasms that appear as small, red-to-brown Notes, bumps (nodules) that result from an accumulation of fibroblasts.
2. Acrochordon or a skin tag is an extremely common lesion, most often found on the neck, in the armpit, or in the groin.
3. Actinic keratosis is a premalignant epidermal lesion caused by excessive chronic exposure to sunlight. These are common, especially on light-skinned elderly people.
4. Seborrheic keratosis (Seborrheic warts) is an extremely common benign neoplasm of older people. The warts are flesh-colored, brown, or black growths that can appear anywhere on the skin.
5. Acanthosis nigricans is a cutaneous disorder marked by hyperkeratosis and pigmentation of the axilla, neck, flexures, and anogenital region. More than half of the patients with acanthosis nigricans have cancer (GI carcinomas, particularly of the stomach).
Pernicious anemia
Anemia is a condition in which the blood cannot adequately oxygenate the tissues. It shows up as a decreased RBC count, decreased hematocrit or decreased hemoglobin concentration. Anemia may be caused by two major mechanisms:
1. Decreased red cell production resulting from:
• Hematopoietic cell damage from infection, drugs, radiation, and other similar agents.
• Deficiency of factors necessary for heme synthesis (iron) or DNA synthesis (vitamin B12 or folate).
2. Increased red cell loss due to:
• External blood loss
• Red cell destruction (hemolytic anemia)
Pernicious anemia is the most common form of vitamin B12 deficiency megaloblastic ane¬mia. It is considered to be an autoimmune disorder. It is caused by a lack of intrinsic factor, a substance needed to absorb vitamin B12 from the gastrointestinal tract. Vitamin B12, in turn, is necessary for the formation of red blood cells. Because vitamin B12 is needed by nerve cells and blood cells to function properly, pernicious anemia causes a wide variety of symptoms, including fatigue, shortness of breath, peripheral neuropathy, difficulty walking and talking.
1.The erythrocytes that are produced are macrocytic and appear hyperchromic. Notes 2. Stomatitis and atrophic glossitis are common, along with atrophy of the gastric mucosa.
3. An abnormal Schilling test. Is a test used to determine whether the body absorbs vitamin B12 normally.
4.Aplastic anemia is the result of an inadequate production of erythrocytes due to the inhibition or destruction of the red bone marrow. It can be caused by radiation, various toxins, and certain medications. Important: In drug-induced aplastic anemias, the erythrocytes (RBC's) appear to be normochromic (normal conc. of Hemoglobin) and normocytic (normal in size).
Calf
Phlebitis is inflammation of the veins. It is most common in the legs, and almost always takes place in varicose veins. Common causes of vein inflammation include local irritation (for example, because of an IV line), infection in or near a vein, and blood clots. Thrombophlebitis is vein inflammation related to a blood clot. As the venous system is divided in deep veins and superficial veins one can have a clot in each of the systems. Only very rarely does clotting occur in both of the systems at the same time.
Superficial vein thrombosis (abbreviated as SVT) is also called superficial throm-bophlebitis / phlebitis. The skin around the vein is red and painful. Swelling can be present as well. The main cause for the condition are varicose veins. Blood stagnates in these venous pools and will clot easily especially during inactivity.
Deep vein thrombosis (abbreviated as DVT) is usually localized in the deep veins of the calf but it can extend into the deep veins of the thigh and even beyond. The more extensive the clot the more dangerous is the condition. Among the clinical signs are calf pain and swelling of the ankle and possibly calf. It is potentially a dangerous condition as a piece of the clot can "fly" through the venous circulation and lodge in the lungs occluding the pulmonary circulation. This is called pulmonary emboli or PE. It can be fatal if it is massive
1. Congestion (hyperemia) is a localized increase in the volume of blood in /Notes, capillaries and small vessels. There are two types of congestion (hyperemia):
• Active congestion (active hyperemia) results from localized arteriolar dilation (e.g., inflammation, blushing).
• Passive congestion (passive hyperemia) results from obstructive venous return or increased back pressure from congestive heart failure. Two forms:
1. Acute: occurs in shock or right sided heart failure.
2. Chronic : of the lung (most often caused by left-sided heart failure) : of the liver (most often caused by right-sided heart failure)
Kidney disease
There are two broad categories of hypertension - primary (or essential) and secondary hypertension. Approximately 90-95% of patients diagnosed with hypertension have pri¬mary hypertension. Unlike secondary hypertension, there is no known cause of pri¬mary hypertension. Therefore, the diagnosis of primary hypertension is made after excluding known causes that comprise what is called secondary hypertension.
If left untreated, primary hypertension can eventually lead to retinal changes, left ventricular hypertrophy, and cardiac failure. Genetic factors include a family history of hypertension, and it is more common and usually more severe in African Americans. Environmental factors include stress, obesity, cigarette smoking, and physical inactivity.
1. Usually, high blood pressure has no symptoms at all. That is why it is often Notes called the "silent killer."
2. Although HP usually has no symptoms, sometimes the following may be evident: tiredness, confusion, visual changes, nausea, vomiting, anxiety, perspiration, pale skin, or an angina-like pain (crushing chest pain)•
3. The three broad classes of drugs used to treat primary hypertension are
diuretics (to reduce blood volume), vasodilators (to decrease systemic
vascular resistance), and cardioinhibitory drugs (to decrease cardiac output). Secondary hypertension is elevated blood pressure that results from an underlying, identifiable, often correctable cause. Only about 5 to 10 percent of hypertension cases are thought to result from secondary causes. These causes include:
• Renal artery stenosis • Sleep apnea
• Chronic renal disease • Hyper- or hypothyroidism
• Primary hyperaldosteronism • Pheochromocytoma
• Stress • Preeclampsia
• Aortic coarctation
Vitamin K
Dicumarol is an anticoagulant that inhibits the formation of prothrombin in the liver. It is used to delay the clotting of blood especially in preventing and treating thromboem¬bolic disease. Note: Dicumarol has largely been replaced by warfarin.
Circumstances that will cause delayed blood clotting:
• A patient taking heparin, which is an anticoagulant It acts as an antithrombin and antiprothrombin by preventing platelet agglutination and consequent blood clot for-mation.
• A patient with leukemia often has thrombocytopenia, which is a reduced number of platelets.
• Patients with cirrhosis of the liver have hypoprothrombinemia (abnormally small amounts of prothrombin in the circulating blood). Note: Prothrombin is formed and stored in the parenchymal cells of the liver. In cirrhosis there is profuse damage to these cells.
• von Willebrand's disease: deficiency of vWF (von Willebrand's Factor); results in impaired platelet adhesion.
• Long-term treatment with aspirin: it is a cyclooxygenase inhibitor; results in impair¬ed production of thromboxanes, which are important platelet aggregants.
• Bernard-Soulier disease: a hereditary platelet adhesion disorder.
1. Warfarin (Coumadin) is also an anticoagulant that interferes with vitamin Notes K It inhibits the formation of prothrombin in the liver. The effect of delayed blood clotting is useful to prevent and treat thromboembolic disease.
2. Remember: In the presence of thromboplastin and calcium ions, prothrom¬bin is converted to thrombin, which in turn converts fibrinogen to fibrin. Fibrin threads then entrap blood cells, platelets, and plasma to form a blood clot.
Fetus has Rh-positive blood and the mother has Rh-negative blood
The fetus' blood is Rh-positive because the father passed along an Rh-positive trait, which is a dominant trait. The mother responds to the incompatible blood by producing antibod¬ies against it. These antibodies cross the placenta into the fetus' circulation, where they attach to and destroy the fetus' red blood cells, leading to anemia. This is called erythrob¬lastosis fetalis. Note: It can also result from blood type incompatibilities. For example, the mother may have type 0 blood and the fetus have type A or B blood.
Remember: Patients with hemolytic anemias (i.e., egthroblastosis fetalis, sickle cell ane-mia and the thalassemias) often have problems that result from an increase in bilirubin levels. This bilirubin is the breakdown product of hemoglobin which is released from dying erythrocytes.
Examples include:
• Elevated levels of urobilinogen, which is a compound formed in the intestine by the reduction of bilirubin.
• Elevated levels of unconjugated bilirubin, which is water-insoluble bilirubin. Normally, this unconjugated bilirubin would combine with serum albumin to become water-soluble (conjugated bilirubin) in the liver. This would then be secreted with other components of bile into the small intestine. Toxic accumulation of unconjugated biliru¬bin in the brain and spinal cord is called kernicterus.
1. 13-Thalassemia major is also known as Mediterranean anemia or Cooley Notes anemia. It is characterized by marked anemia and splenomegaly, as well as gen¬eralized hemosiderosis.
2. f3-Thalassemia minor-- clinical manifestations include: increase in hemoglo-bin A2.
3. a-Thalassemias are the most common forms of thalassemia in Southeast Asia.
Liver dysfunction
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disorder that is considered a true medical emergency. The disorder is caused by a deficiency of the enzyme von Willebrand factor (vWF) metalloprotease (also called ADAMTS 13). The enzyme promotes degradation of very-high-molecular-weight multimers of vWF, and the enzyme deficiency reults in multimer accumulation in the plasma and consequent platelet microaggregate formation. Treatment is by plasma exchange, and the disorder can be fatal if diagnosis and therapy are delayed.
Idiopathic thrombocytopenic purpura (ITP) is a bleeding condition in which the blood doesn't clot as it should. This is due to a low number of platelets. There are 2 types of ITP. One type affects children, and the other type affects adults. In children, the usual age for get¬ting ITP is between 2 and four years. Most adults with ITP are young women, but it can occur in anyone. ITP does not run in families.
ITP is different in children than in adults. Most children with ITP have a very low platelet count that causes sudden bleeding. The usual symptoms are bruises and the tiny purpura spots (petechiae) on the skin. Nosebleeds and bleeding gums are also common.
In most adults, ITP lasts much longer than it does in children. At the time of diagnosis, most adults have noticed increased bleeding and easy bruising for several weeks, or even months.
In women, increased menstrual blood flow is a major sign.
1. Purpura spots are purplish discolorations in the skin produced by small bleed¬ng vessels near the surface of the skin. Purpura may also occur in the mucous mem¬branes (such as the lining of the mouth) and in the internal organs. Purpura by itself is only a sign of other underlying causes of bleeding.
2.Thrombocytopenia is a condition in which there is a reduced number of platelets. This causes bleeding states in which blood loss occurs through capillaries and other small vessels. It is the most common cause of bleeding disorders.
Atherosclerosis
Arteriosclerosis ("hardening of the arteries ') is a general term for several diseases in which the wall of an artery becomes thicker and less elastic. The most important and most common of these diseases is atherosclerosis, in which fatty material (called atherosclerotic plaques) accumulates under the inner lining of the arterial wall. Eventually, this fatty tissue can erode the wall of the artery, diminish its elasticity (stretchiness) and interfere with blood flow. Plaques can also rupture, causing debris to migrate downstream within an artery. Typical signs and symptoms of moderate atherosclerosis include changes in skin color and temper¬ature, headache, dizziness, and memory defects.
Consequences of atherosclerosis:
• Ischemic heart disease (coronary artery disease) and heart attack (myocardial infarct)
- IHD represents an imbalance between myocardial oxygen demand, and available blood supply. It has a peak incidence in men over 60 and women over 70. Heart muscle damage and scarring from heart attacks greatly increases the risk of heart failure.
• Stroke or aneurysm formation
Important risk factors include:
smoking, chronic hypertension, heredity, nephrosclerosis, diabetes, and hyperlipidemia (specifically, low-density lipoproteins).
1. Atherosclerosis is described as degenerative changes in the walls of the arteries. Notes 2. Atherosclerosis is more common in men of all age groups. The aorta and coro¬nary arteries are most affected by arteriosclerosis.
3. In very advanced cases, atherosclerotic plaques can become calcified and ulcer¬ated.
Glutamic acid, Valine
Sickle cell anemia is the most common hereditary anemia of persons of African lineage. It is caused by an abnormal type of hemoglobin (oxygen carrying molecule) called hemoglobin S. It is inherited as an autosomal recessive trait; that is, it occurs in someone who has inherited hemoglobin S from both parents. The globin portion of the molecule is abnormal due to the amino acid valine being substituted for glutamic acid in the sixth position of the hemoglobin molecule. When the abnormal hemoglobin molecules are exposed to low concentrations of oxygen (hypoxic conditions), they form fibrous precipitates with the erythrocytes, distorting them into the sickle shape (crescent shape) characteristic of the disease. As a result, they function abnormally and cause small blood clots. These clots give rise to recurrent painful episodes called "sickle cell pain crises."
1. Non-healing leg ulcers and recurrent bouts of abdominal chest pain are charac¬teristic of sickle cell anemia.
2. Patients with sickle cell anemia can become functionally asplenic. As a result, they are prone to infections caused by encapsulated organisms (including Streptococcus pneumonia and Hemophilus influenza). Salmonella bone infec¬tions/osteomyelitis can occur.
3. Repeated episodes of splenic infarction followed by fibrotic healing lead to a fibrotic, shrunken spleen (autosplenectomy) in adult patients with sickle cell ane¬mia.
4. Sickle cell anemia may become life-threatening when damaged red blood cells break down (hemolytic crisis), when the spleen enlarges and traps the blood cells (splenic sequestration crisis), or when a certain type of infection causes the bone marrow to stop producing red blood cells (aplastic crisis). Repeated crises can cause damage to the kidneys, lungs, bones, eyes, and central nervous system.
5. Blocked blood vessels and damaged organs can cause acute painful episodes. These painful crises, which occur in almost all patients at some point in their lives, can last hours to days, affecting the bones of the back, the long bones, and the chest.
The affinity between CO and hemoglobin is 200 times weaker than the affinity between hemoglobin and oxygen
*** This is false; the affinity between CO and hemoglobin is 200 times stronger than the affinity between hemoglobin and oxygen.
One of the imperfections of the human body is that, given a choice between carbon monox¬ide and oxygen, the protein hemoglobin in our blood will always latch on to carbon monox¬ide and ignore the life-giving oxygen. Because of this natural chemical affinity, our bodies, in effect, replace oxygen with carbon monoxide in our bloodstream, causing greater or less¬er levels of cell suffocation depending on the intensity and duration of exposure.
When there are even minute amounts of carbon monoxide in the air that is breathed, they preferentially occupy the oxygen-binding sites of the hemoglobin molecules. This hemoglo-bin-carbon monoxide bond is so strong that very little carbon monoxide is removed from the blood. Patients with acute carbon monoxide poisoning exhibit cherry-red discoloration of the skin, mucosa, and tissues. Ultimately, death will occur due to hypoxia. Important: The symptoms of low-level carbon monoxide poisoning are so easily mistaken for those of the common cold, flu or exhaustion that proper diagnosis can be delayed.
Other environmental chemical agents and their manifestation if ingested:
• Carbon tetrachloride: hepatocellular damage
• Mercuric chloride: severe renal tubular necrosis and GI ulceration
• Cyanide poisoning: prevents cellular oxidation, results in odor of bitter almonds
• Methyl alcohol: blindness
• Bismuth: nausea, vomiting and abdominal pain usually occur within hours and precede features of nephrotoxicity and neurotoxicity
• Lead: basophilic stippling of RBC's, anemia, abdominal pain, and wrist and foot drop
Normal bleeding time, platelet count, thrombin time, and PT; prolonged PTT
Hemophilia A and B are inherited as a sex-linked recessive trait by which males are affect¬ed and females are carriers. The majority of people afflicted with hemophilia have type A and it presents under the age of 25. The signs, symptoms and clinical manifestations include excessive bleeding from minor cuts, epitaxis, hematomas, and hemarthroses. Classifications of Hemophilia:
• Hemophilia A: considered the classical type, caused by a deficiency of coagulation fac¬tor VIII (anti-hemophilic factor).
• Hemophilia B (also called Christmas disease): due to a deficiency in factor IX (plas¬mathromboplastin component).
• Hemophilia C (also called Rosenthal 's syndrome): not sex-linked, less severe bleeding. Due to a deficiency of factor XI (plasma thromboplastin antecedent). Important: A true hemophiliac is characterized by having the following:
• Prolonged partial thromboplastin time (PTT)
• Normal prothrombin time (PT)
• Normal thrombin time
• Normal bleeding time
• Normal platelet count
1. In classic hemophilia, the other lab tests remain normal, because the bleeding time is a measure of platelet plug formation, the prothrombin time a measure of the extrinsic pathway of coagulation, and the thrombin time an assay of the conversion of fibrinogen to fibrin.
2. von Willebrand's disease is inherited as an autosomal dominant bleeding dis¬order, it occurs with equal frequency in both sexes. It results from a deficiency in the von Willebrand factor, which is a large glycoprotein that has binding sites for factor VIII and also facilitates the adhesion of platelets to collagen (important in the
formation of a platelet plug).
Osteoporosis
Osteoporosis is characterized by a decrease in bone mass due to loss of bone matrix. This condition is the most common bone disorder in older persons. Characteristics include fractures, kyphosis, and shortened stature. Predisposing factors include physical activity, hypercorticism, hyperthyroidism, and calcium deficiency. Serum calcium and phosphate levels are typically normal. The leading cause of osteoporosis is a drop in estrogen which is associated with the postmenopausal state in women. Note: Physical inactivity further accelerates bone loss and decreases muscle mass and agility that contributes to falls and fractures.
1. Osteogenesis imperfecta (or brittle bone disease) is an autosomal dominant disorder characterized by multiple fractures with minimal trauma. It is caused by mutations in either of the genes that code for type I collagen.The blue scle¬rae, hearing loss, and dental abnormalities are characteristic. The teeth are poor because of malformation of dentin (dentinogenesis imperfecta).
2. Myasthenia gravis is an autoimmune disorder caused by autoantibodies to postsynaptic acetylcholine receptors of the neuromuscular junction. The disease commonly presents as ptosis, diplopia, and difficulty chewing, speaking, or swallowing. For unexplained reasons, myasthenia gravis is associated with thymic hyperplasia or thymoma.
3. Osteoarthritis (degenerative joint disease) is the most common form of arthritis. It is a chronic inflammatory joint disease. It is characterized by ebur¬nation (polished, ivory-like appearance of bone, due to erosion of overlying cartilage), cystic changes in subchondral bone, and new bone formation. Osteophytes (bony spurs) can form at the distal interphalangeal joints (Heberden nodes) or at the proximal interphalangeal joints (Bouchard nodes).
-eatly increased density of the skeleton
eopetrosis (marble bone disease, Albers-Schonberg disease) is a rare disorder racterized primarily by increased bone density as old bone is not resorbed and replaced i new bone. The cause is failure of osteoclastic activity. It occurs in two major clinical ns: 1) an autosomal recessive malignant infantile form, which is the most severe form of disorder and death, usually occurs in the first decade of life, and 2) a less severe )somal dominat variant.
main features of this disease are:
Multiple fractures in spite of increased bone density
Anemia as a result of decreased marrow space
Blindness, deafness, and cranial nerve involvement due to narrowing and impingement If neural foramina
er non-neoplastic diseases of bone:
Achondroplasia is one of the most common causes of dwarfism. It is an autosomal dom¬nant disorder characterized by short limbs with normal-sized head and trunk.
Scurvy is caused by a vitamin C deficiency. It is characterized by bone lesions leading o impaired osteoid matrix formation which is caused by the failure of the proline and ysine hydroxylation required for collagen synthesis.
von Recklinghausen disease of bone (osteitis fibrosa cystica) is caused by primary or econdary hyperparathyroidism. Widespread osteolytic lesions are characteristic. Osteomalacia is caused by a vitamin D deficiency in adults. Defective calcification of Isteoid matrix is characteristic.
Rickets is caused by a vitamin D deficiency in children.
Fibrous dysplasia is characterized by normal bone being replaced by fibrous tissue. 'here are three classifications depending on extensiveness of skeletal involvement: (1) Vlonostotic: one bone, (2) Polyostotic: more than one bone, and (3) Polyostotic with asso¬iated endocrine disturbances (Albright's syndrome). Pathologic fractures are often the resenting complaint.
Paget's disease of the bone
Paget's disease (osteitis deformans) is a metabolic bone disease that involves bone destruc-tion and regrowth that results in deformity. The cause of Paget's disease is not entirely known, but it is thought to be caused in part from a childhood virus. A virus particle, known as a paramyxovirus nucleocapsid, has been identified within the bone cells of individuals with Paget's disease. This virus particle is not found in normal bone. While this relationship has been identified, a clear connection between the virus and the cause of Paget's disease is not known.
Paget's disease most commonly involves the spine, pelvis, calvarium of the skull, femur, and tibia.The disease may localize to one (monostotic) or two (polyostotic) areas within the skele¬ton, or become widespread.The skull may enlarge head size and cause hearing loss, if the cra¬nial nerves are damaged by the bone growth. Abnormal bone architecture caused by increases in both osteoblastic and osteoclastic activity is characteristic.
1. Intraorally the teeth spread.
Notes 2.These patients are predisposed to developing osteosarcomas.
3. Laboratory findings include: anemia, markedly increased serum alkaline phos¬phatase levels (an index of osteoblastic activity and bone formation), as well as an elevated 24-hour urine level for hydroxyproline (an amino acid excreted by the kid¬neys and an index of osteoclastic hyperactivity).
4. Mixed osteoblastic and osteolytic phase of bone formation leads to a character¬istic mosaic pattern.
5. Serum acid phosphatase levels are elevated in patients with prostate cancer.
6. Von Recklinghausen's disease of bone (osteitis fibrosa cystica) is characteriz-ed by decreased serum phosphorus and an increase in serum calcium and alkaline phosphatase.
7. Condensing Osteitis (sclerosing osteitis) is basically an unusual reaction or inflammatory response of the dental pulp of the tooth to a low grade infection.
Paget's disease of the bone
Paget's disease (osteitis deformans) is a metabolic bone disease that involves bone destruc-tion and regrowth that results in deformity. The cause of Paget's disease is not entirely known, but it is thought to be caused in part from a childhood virus. A virus particle, known as a paramyxovirus nucleocapsid, has been identified within the bone cells of individuals with Paget's disease. This virus particle is not found in normal bone. While this relationship has been identified, a clear connection between the virus and the cause of Paget's disease is not known.
Paget's disease most commonly involves the spine, pelvis, calvarium of the skull, femur, and tibia.The disease may localize to one (monostotic) or two (polyostotic) areas within the skele¬ton, or become widespread.The skull may enlarge head size and cause hearing loss, if the cra¬nial nerves are damaged by the bone growth. Abnormal bone architecture caused by increases in both osteoblastic and osteoclastic activity is characteristic.
1. Intraorally the teeth spread.
Notes 2.These patients are predisposed to developing osteosarcomas.
3. Laboratory findings include: anemia, markedly increased serum alkaline phos¬phatase levels (an index of osteoblastic activity and bone formation), as well as an elevated 24-hour urine level for hydroxyproline (an amino acid excreted by the kid¬neys and an index of osteoclastic hyperactivity).
4. Mixed osteoblastic and osteolytic phase of bone formation leads to a character¬istic mosaic pattern.
5. Serum acid phosphatase levels are elevated in patients with prostate cancer.
6. Von Recklinghausen's disease of bone (osteitis fibrosa cystica) is characteriz-ed by decreased serum phosphorus and an increase in serum calcium and alkaline phosphatase.
7. Condensing Osteitis (sclerosing osteitis) is basically an unusual reaction or inflammatory response of the dental pulp of the tooth to a low grade infection.
Cyanosis
Cardiac tamponade is life-threatening, slow or rapid compression of the heart due to the pericardial accumulation of fluid, pus, blood, clots, or gas, as a result of effusion, trauma, or rupture of the heart. Signs and symptoms include Beck's triad, diaphoresis and cool, clammy skin, anxiety, restlessness, syncope as well as a weak, rapid pulse, tachypnea and orthopnea.
Important: Cardiac tamponade is the most serious complication of pericarditis.
Pericarditis is the name given to a variety of diseases, all of which have the major charac-teristics of inflammation of the pericardium and an increase in volume of the pericardial fluid.
Pericarditis may be acute or chronic:
• Acute pericarditis is accompanied by symptoms of sharp, stabbing chest pain, shortness of breath, fever, perspiration, chills, and the symptoms of the underlying illness. The chest pain may radiate to the neck, back, left shoulder and upper arm. The pain may intensify during respiration, coughing, swallowing, or when one is lying supine or turning.
• If acute pericarditis persists for 6 to twelve months following the acute episode, it is con¬sidered chronic.
Constrictive pericarditis is a serious form of pericarditis in which the pericardium becomes so thickened and scarred that it loses some of its elasticity. It compresses the heart, interferes with the ability of the heart to fill up with blood, and reduces the amount of blood pumped out to the body. Constrictive pericarditis may cause heart failure and lead to kidney disease. Syptoms include: chest pain, difficulty in breathing, swelling of the feet and ankles, fatigue, and weakness.
Important: Aortic dissection, also called dissecting aneurysm characteristically results in aortic rupture, most often into the pericardial sac, causing fatal cardiac tamponade.
Left-sided heart failure
Heart failure is almost always a chronic, long-term condition, although it can sometimes develop suddenly. This condition may affect the right side, the left side, or both sides of the heart. Usually the left ventricle fails first, soon followed by the right-sided failure.
The common signs of CHF include:
• Exertional dyspnea
• Paroxysmal nocturnal dyspnea (patient wakes up gasping for air) *** The above two signs are the earliest and most common signs
• Peripheral edema (swollen ankles)
• Cyanosis
• Orthopnea (sitting or standing in order to breathe comfortably)
• High venous pressure
Left-sided heart failure: • Causes • Clinical manifestations
- Ischemic heart disease, especially MI - Dyspnea and orthopnea
- Hypertension - Pleural effusion with hydrothorax
- Aortic and mitral valvular disease - Reduction in renal perfusion
- Myocardial disease, such as cardiomyopathies - Cerebral anoxia and myocarditis
Right-sided heart failure: • Causes
- Left-sided heart failure, most common cause - Pulmonary hypertension - Tricuspid or pulmonary valvular disease
- Cardiomyopathies and diffuse myocarditis • Clinical manifestations
- Renal hypoxia, leading to fluid retention and peripheral edema - Enlarged and congested liver and spleen
- Distention of the neck veins

Important: Patients with CHF should be in upright position during dental treatment to decrease collection of fluid in lungs. When fully reclined in the dental chair, these patients may experience difficulty in breathing.
Stable angina
Angina Pectoris is recurring acute chest pain or discomfort resulting from decreased blood sup¬ply to the heart muscle (myocardial ischemia). Angina occurs when the heart's need for oxygen increases beyond the level of oxygen available from the blood flowing into the heart. Angina is the classic symptom for coronary artery disease (CAD). The symptoms of angina include mild or severe pain, pressure, or discomfort in the chest. The pain is generally described as a feeling of a squeezing, strangling, heaviness, or suffocation sensation in the chest. Types of angina:
• Stable angina is a repeating pattern of chest pain which has not changed in character, fre¬quency, intensity or duration for several weeks. The level of activity or stress that provokes angina is predictable and the pattern changes slowly. Stable angina is the most common form and it appears gradually. Important: It is precipitated by exertion but relieved by rest or vasodilators, such as nitroglycerin.
• Unstable angina is chest pain that is variable, either increasing in frequency or intensity and with irregular timing or duration. Important: It is prolonged or recurrent pain at rest. It is often indicative of imminent myocardial infarction.
• Prinzmetal's or variant angina is caused by a vasospasm, which is a spasm that narrows the coronary artery and lessens the blood flow to the heart. Important: It is intermittent chest pain at rest.
Coronary artery disease (CAD) is a condition in which fatty deposits (plaques) accumulate in the cells lining the wall of a coronary artery and obstruct the blood flow. As an obstruction of a coronary artery worsens, ischemia (inadequate oxygen supply due to decreased blood flow) to the heart muscle can develop, causing heart damage. The major complications of coronary disease are angina and heart attack.
1. The primary effect of coronary artery disease (CAD) is the loss of oxygen and nutri¬Notes ents to myocardial tissues because of diminished coronary blood flow.
2. Atherosclerosis is the usual cause of CAD. It affects the intimal arterial wall of mainly large elastic vessels. The aorta is usually the most severely involved.
3. The right coronary artery supplies blood from the aorta to the right side of the heart.
Myoglobin
Myoglobin is one of several cardiac markers used to make the diagnosis. Cardiac markers are substances in blood whose levels rise in the hours following a heart attack. Increased levels help diagnose a heart attack; persistent normal levels rule it out.
Cardiac markers elevated after a myocardial infarction: Troponin
• Rises: 3-6 hours • Peaks: 20 hours • Duration: 14 days
Subunits: 1) Troponin T 2) Troponin I (>1.0 suggests Acute MI) Creatine Phosphokinase (CPK)
• Rises: 4-6 hours • Peaks: 12-24 hours • Duration: 4-5 days
Subunits (Fractionate to CK-MB only if CPK increased)
- CK-MB Fraction (duration for 2-3 days)
- CK-MB ( > 5% of total CPK suggests Myocardial Injury )
Myoglobin
Adv: First cardiac marker to increase Disad.: Poor Specificity (only helps if negative)
• Rises: 1-2 hours • Peaks: 4-6 hours • Duration: 1-2 days Glutamic oxaloacetic transaminase (AST, SGOT)
• Peaks: 24-36 hours • Duration: 5 days Lactic Dehydrogenase (LDH)
• Peaks: 24-48 hours • Duration: 14 days
Myocardial infarctions (MI's) are most commonly caused by coronary atherosclerosis which causes an interruption in the supply of blood to the heart.The signs and symptoms include a crushing pain in the area of the chest over the heart, sweating, and GI upset. The prognosis of patients is fairly good if they reach the hospital. Most deaths occur outside the hospital due to arrhythmias causing ventricular fibrillation. Angina pectoris pain is similar to MI pain except it is relieved by rest or nitrates. MI's are common in males and postmenopausal women.
Streptococcus viridans
Infectious endocarditis is an inflammation of the heart valves. Endocarditis is distin-guished from infections of heart muscle (myocarditis) or the lining of the heart (pericarditis).
Many bacteria can cause endocarditis in patients with underlying valve problems, but an organism commonly found in the mouth, Streptococcus viridans, is responsible for approx¬imately half of all bacterial endocarditis. Other common organisms include Staphylococcus aureus and enterococcus. Less common organisms include pseudomonas, serratia, and can¬dida. Staphylococcus aureus can infect normal heart valves, and is the most common cause of infectious endocarditis in intravenous drug users.
Characteristics include large, soft, friable, easity detached vegetations consisting of fibrin an intermeshed inflammatory cells and bacteria. Complications may include ulceration, often with perforation, of the valve cusps or rupture of one of the chordae tendineae.
Classification of infectious endocarditis:
• Acute endocarditis: is caused by pathogens such as Staphylococcus aureus (approxi-mately 50% of cases). This type of endocarditis is often secondary to infection occurring elsewhere in the body.
• Subacute (bacterial) endocarditis: is caused by less virulent organisms such as Streptococcus viridans (approximately 50% of cases). This type of endocarditis tends to occur in patients with congenital heart disease or preexisting valvular heart disease, often of rheumatic origin. Note: Fever is a hallmark of acute and subacute endocarditis.
1. The mitral valve is most frequently involved.
2. The mitral valve along with the aortic valve is involved in about 40% of cases.
3. The tricuspid valve is involved in more than 50% of cases of endocarditis of IV drug users.
4. Murmurs result from changes in blood flow across valves when vegetations col¬lect on the valves.
Ludwig's angina
Although not seen often, Ludwig's angina, when it does occur, usually is an extension of infection from the mandibular molar teeth into the floor of the mouth, since their roots lie below the attachment of the mylohyoid muscle. The infection has the following characteris-tics: First, it is a brawny induration that doesn't pit on pressure. No fluctuance is present. Secondly, three facial spaces are involved bilaterally: submandibular, submental, and sub-lingual spaces. Thirdly, the patient has a typical openmouthed appearance. Note: It has a rapid onset. Dysphagia, dyspnea, and fever are present.
Ludwig's angina may involve swelling to the extent that it blocks the airway. This is an emergency situation! The goal of emergency treatment is to maintain an open airway. This may involve intubation (breathing tube placed through the mouth or nose and into the lungs) or tracheostomy (direct opening to the lungs through surgical placement of a tube at the base of the neck). The goal of treatment of the disorder is eradication of the infection.
Antibiotics, usually penicillin or penicillin-like drugs, are given to treat the infection. Usually these are given intravenously (in a vein) until the symptoms diminish, then the antibiotics are continued as oral medications until cultures are negative. Most cases of Ludwig's Angina appear to be a mixed infection. However, Streptococci are almost always present.
1. Actinomycosis (also called lumpy jaw) is a chronic infection with Actinomyces,
usually A. israelii. It is characterized by slow-growing, deep, lumpy abscesses that
extrude a thin, purulent exudate through multiple sinuses. It develops chiefly in the jaw and neck, less frequently in the lungs and alimentary tract. The disease occurs following tissue damage that is contaminated with the endogenous organism. It can be treated with long-term Pen. therapy. Remember: Actinomyces naeslundii is a gram-positive, branching, filamentous bacteria that is a normal inhabitant of the gingival crevice and tonsillar crypts.
2. Actinomycotic lesions have the characteristic "sulfur granules" in them which are actually colonies of infecting organisms.
Botulinum toxin
Botulinum toxin (BTX) is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. The clinical syndrome of botulism can occur following ingestion of contaminat-ed food, from colonization of the infant gastrointestinal tract, or from a wound infection. Botulism toxins are the most potent toxins known to humans. These neurotoxins act by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect. The inability to transmit impulses through motor neurons can cause respiratory failure, result-ing in death.
1. C. Botulinum spores are highly resistant to heat, but the toxins are not.
2. The toxin is produced within the canned food and ingested preformed.
3. Proper canning and heating of food prevents botulism.
4. Nausea, vomiting and abdominal cramps usually precede the neurological symp¬toms: Dry mouth, diplopia, loss of pupillary reflexes, followed by descending paral¬ysis and respiratory failure.
Tetanus, also known as lockjaw, is an acute exotoxin-mediated infection caused by the anaerobic, spore-forming, gram-positive bacillus Clostridium tetani. It occurs through a puncture wound that is contaminated by soil or dust.
1. Tetanus toxin is a neurotoxin that inhibits glycine release.
2. The toxin enters the CNS along peripheral nerves.
3. Stiffness of the jaw, difficulty swallowing, fever, headache.
4. Risus sardonicus: fixed "smile" and elevated eyebrows.
5. Severe spasms of the neck, back, and abdominal muscles.
Diphtheria toxin: inhibits protein synthesis.
Anthrax toxin: is made up of three proteins. One is a protective antigen and two are enzymes that are called edema factor and lethal factor, respectively.
Aspirin
Reye's syndrome is a potentially deadly disease that typically occurs in children aged 4 to 12 years old. It is associated with the use of aspirin to treat chickenpox (varicella) or influenza. It is characterized by encephalopathy, coma, and microvascular fatty liver.
The basic rule: Don't give aspirin to a child, unless specifically recommended by the child's doctor. When a child is taking aspirin, steps must be taken to minimize the risk of acquiring a viral illness (such as influenza and varicella vaccinations).
1. Influenza (flu) is a viral infection that causes a fever, runny nose, cough, headache, malaise, and muscle ache. It is the fever and constitutional symptoms that distinguish influenza from the common cold. Influenza viruses (A, B, and C) are the only members of the orthomyxovirus family. Influenza A is by far the most common and causes the most severe disease.
2. Remember: The influenza viruses have 2 envelope glycoprotein spikes, hemagglutinin and neuraminidase, which exhibit the majority of antigenic changes. This is important in increasing the ability of the virus to attach to human cells during the establishment of an infection.
3. Amantadine (Symmetrel) inhibits the replication of the influenza A virus by interfering with viral attachment and uncoating. It is effective in the prophylax¬is and treatment of the influenza A virus. Other antiviral medications include Rimantidine, Zanamivir and Oseltamivir. The main mode of prevention is the vaccine, which consists of killed influenza A and B viruses.
Secondary tuberculosis
An acute or chronic infection caused by Mycobacterium tuberculosis, tuberculosis (TB) is char¬acterized by pulmonary infiltrates, formation of granulomas with caseation, fibrosis, and cav¬itation. The lungs are primarily involved, but the infection can spread to other organs. Symptoms include minor cough, mild fever, fatigue, weight loss, coughing up blood, night sweats and eventually a cough producing phlegm. Note: Fever and night sweats, the typical hallmarks of TB, may not be present in elderly patients, who instead may exhibit a change in activity or weight.
Types of Tuberculosis:
1. Primary tuberculosis:
• Initial infection, characterized by the primary, or Ghon complex (primary lesion in the lung + calcified hilar lymph node)
• Most often asymptomatic, it usually does not progress to clinically evident disease
2. Secondary tuberculosis:
• Usually results from activation of a prior Ghon complex, which spreads to a new pul¬monary or extrapulmonary site.
• Localized lesions favor upper lobes of the lung, involvement of hilar lymph nodes is common.
• Tubercle formation: caseous granulomas frequently rupture and the contents are expelled and result in cavitary lesions. Important: Cavitation is a characteristic of sec¬ondary, but not primary, tuberculosis.
1. Secondary TB may be complicated by lymphatic hematogenous spread, resulting in Notes miliary TB or disseminated TB. This results in the seeding of several organs with multiple, small, millet, seed-like lesions.
2. Granulomatous inflammation is characteristic of both primary and seccondary TB.
3. The granuloma of TB is referred to as a tubercle.
4. TB is treated with a combination of isoniazid + rifampin + pyrazinamide + etham¬butol. Serious side effects include ototoxicity, nephrotoxicity, and muscle weakness.
Acute appendicitis
Acute Appendicitis:
• Highest incidence is 10-19 year olds. It is unusual under the age of 1 year
• Appendectomies are the most common emergency surgical procedures performed
Physical findings:
• The child will often walk into the office bent over, limping, and holding his or her right side
• The child will look ill and lay quietly
• There is often diffuse abdominal tenderness
• Point tenderness at McBurney's point which lies half-way between a line drawn from the umbilicus to the anterior iliac spine.
• Rebound tenderness -- pressing the abdomen at McBurney's point causes tenderness in a patient with appendicitis. When the abdomen is pressed, held momentarily, and then rapidly released, the patient may experience a momentary increase in pain. This "rebound tender¬ness" suggests inflammation has spread to the peritoneum.
1. If the appendix ruptures, the pain may disappear for a short period and the patient may
Notes feel suddenly better. However, once peritonitis sets in, the pain returns and the patient becomes progressively more ill. At this time the abdomen may become rigid and extremely tender. For uncomplicated appendicitis, surgery (appendectomy) is per¬formed as soon as possible after the diagnosis is made.
2. The appendix has no known physiological function but most likely is a vestigial struc¬ture representing a degenerated portion of the cecum.
3. Crohn's disease is a chronic inflammation of the intestinal wall. The cause is not known and it has no cure. It is characterized by non-necrotizing granulomatous inflam¬mation with ulcers, strictures, and fistulas.
4. The carcinoid tumor is the most common neoplasm of the appendix. In this location it rarely metastasizes.
5. Ulcerative colitis is a chronic disease in which the large intestine becomes inflamed and ulcerated, leading to episodes of bloody diarrhea, abdominal cramps, and fever.
Pelvic inflammatory disease (PID)
Gonorrhea is a sexually transmitted disease (STD). Gonorrhea is caused by Neisseria gon-orrhoeae, a bacterium that can grow and multiply easily in the warm, moist areas of the reproductive tract, including the cervix, uterus, and fallopian tubes in women, and in the ure-thra in women and men. The bacterium can also grow in the mouth, throat, eyes, and anus.
It is second only to chlamydial infections in the number of cases reported to the Centers for Disease Control and Prevention (CDC). The early symptoms of gonorrhea often are mild. Symptoms usually appear within 2 to 10 days after sexual contact with an infected partner. Gonorrhea is usually treated with a single injection of ceftriaxone plus doxycycline. When women have symptoms, the first ones may include:
• Bleeding associated with vaginal intercourse
• Painful or burning sensations when urinating
• Vaginal discharge that is yellow or bloody
*** In women, gonorrhea is a common cause of pelvic inflammatory disease, which is a general term for infection of the uterus, fallopian tubes and other reproductive organs. It is a common and serious complication of some sexually transmitted diseases, especial¬ly chlamydia and gonorrhea.
Men have symptoms more often than women, including:
• Acute purulent urethritis and a burning sensations during urination that may be severe *** In men, gonorrhea can cause epididymitis, a painful condition of the ducts attached to the testicles that may lead to infertility if left untreated.
1. Gonorrhea often occurs together with chlamydia and syphilis.
2. Chlamydial cervicitis is the most common sexually transmitted disease. It is caused by C. trachomatis. It is most often asymptomatic.
3. Young women who contract chlamydial cervicitis may also acquire salpingitis (inflammation of the fallopian tubes).
Condyloma lata
Syphilis is a contagious, systemic venereal or congenital disease caused by the spiro¬chete Treponema pallidum. It begins in the mucous membranes and quickly spreads to nearby lymph nodes and the bloodstream. Transmission occurs primarily through sexu¬al contact during the secondary stage of infection. Transmission from a mother to her fetus is possible (spirochetes can cross the placenta and result in fetal malformation). There are three stages of syphilis:
Primary: firm, painless ulcer known as a chancre which appears 3-6 weeks later at the site of local contact. The lips are the most common site for chancres to appear in primary oral syphilis.
Secondary: highly infectious stage; it occurs 6 weeks after non-treatment of primary syphilis. A maculopapular rash and condyloma lata (gray, flattened, wart-like lesions) appear on the skin and mucosal surfaces.
Tertiary: occurs in 30% of infected persons many years after non-treatment of sec-ondary syphilis. The gumma (focal nodular mass) typifies this stage. Most common¬ly occurs on the palate and tongue. Neurologic symptoms are also evident at this stage.
Note: The prognosis is good if treated early; tertiary syphilis causes irreversible heart failure, dementia and disability. Parenteral Penicillin G is the drug of choice for treating all stages of syphilis.
Condyloma acuminatum is a benign squamous cell papilloma caused by human papil-loma virus (HPV). It is a sexually transmitted disease and is most common in the anogenital region. It often has multiple lesions. Condyloma is treated by surgical exci¬sion.
Viral infection
Encephalitis is a severe inflammation of the brain, usually caused by a mosquito-borne or, in some areas, a tick-borne virus. However, transmission by means other than arthropod bites may occur through ingestion of infected goat's milk and accidental injection or inhalation of the virus.
In encephalitis, intense lymphocytic infiltration of brain tissues and the leptomeninges caus¬es cerebral edema, degeneration of the brain's ganglion cells, and diffuse nerve cell destruc¬tion.
Encephalitis generally results from infection with arboviruses specific to rural areas. However, in urban areas, it is most frequently caused by enteroviruses (coxsackievirus, poliovirus, and echovirus). Other causes include herpes virus, mumps virus, HIV, and aden¬oviruses.
All viral forms of encephalitis have similar clinical features. Usually, the acute illness begins with sudden onset of fever, headache, and vomiting and progresses to include signs and symptoms of meningeal irritation (stiff neck and back) and neuronal damage (drowsiness, coma, paralysis, seizures, ataxia, tremors, nausea, vomiting and organic psychoses).
In meningitis, the brain and spinal cord meninges become inflamed. It is caused by a num-ber of microorganisms, the most common in adults being the Neisseria meningitidis and Streptococcus pneumoniae. Hemophilus influenzae is the most common cause of menin-gitis in children under the age of two. The organisms are thought to enter the body through the nose and throat. Signs and symptoms include high fever, severe headache, and stiffness of the neck.
Note: Waterhouse-Friderichsen syndrome is an overwhelming, rapidly progressing infec-tion caused by Neisseria meningitidis. It produces severe diarrhea, vomiting, seizures, inter-nal bleeding (bilateral adrenal hemorrhage), low blood pressure, shock, and often death.
Childhood diease, with a peak incidence at age 4
Leukemias are malignant neoplasms of either lymphoid or hematopoietic cell origin. They are the leading cause of cancer death in children under 15 years of age, and the seventh most common form of cancer death overall. Leukemias are primary disorders of bone marrow. The etiology of leukemia is unknown. Leukemic cells usually spill into the blood, where they may be seen in large numbers. Infiltration of leukemic cells in the lymph nodes, liver, spleen and other organs is common.
Acute leukemias usually appear with symptoms resulting from suppression of normal marrow function. These symptoms include: anemia, with accompanying fatigue; fever, usually reflecting an infection; and/or bleeding, usually caused by thrombocytopenia. Chronic leukemias, on the other hand, can appear with non-specific symptoms, including fatigue, weight loss, anemia, or an abnormal sensation in the abdomen caused by splenomegaly.
Acute leukemias are usually fatal within weeks if left untreated, while patients with untreated chronic leukemia usually survive much longer. Acute vs. chronic leukemia can be distinguished histologically by the fact that acute leukemias are characterized by the presence of immature, blast cells, while chron¬ic leukemias are usually associated with more mature and well-differentiated cells. Some chronic leukemias may, however, transform into an acute phase, a so called "blast crisis."
Besides the acute or chronic designation, leukemias can be subdivided into those which are lymphoblas¬tic (originating from a precursor of a B- or T- lymphocyte) and those which are myelogenous (originat¬ing from a precursor of granulocytes, monocytes, erythrocytes, or megakaryocytes). Thus, leukemias can be classified into four general types: acute lymphoblastic leukemia (ALL), chronic lymphoid leukemia (CLL), acute myeloblastic leukemia (AML), and chronic myeloid leukemia (CML).
1. ALL is the form of acute leukemia that is the most responsive to therapy and is most com¬mon in children. Associated with exposure to radiation and chemicals.
2.• Acute myeloid leukemia (AML) is the most malignant type. It makes up about 90% of acute leukemias diagnosed in adults. It more commonly affects men than women. Incidence increases with age.
• Chronic lymphocytic leukemia (CLL) is the least malignant type. It is rarely diagnosed in individuals younger than 40 years old. It has a very slow progression.
• Chronic myelogenous leukemia (CML) is associated with the Philadelphia (Ph) chromo¬some. It is more common in middle-aged and elderly individuals
The duration of the course of the untreated illness
Each of the two major types of leukemia, myelogenous and lymphocytic, include both acute and chronic forms.
Acute essentially refers to a disorder of rapid onset. In the acute myeloblastic leukemias, the abnormal cells (myeloblasts) grow rapidly and do not mature. Most of these immature cells tend to die rapidly. In the acute lymphoblastic leukemias, growth of the lymphoblasts are not as rapid as that of the myeloblastic cells. Rather, the cells tend to accumulate. Common to both types of leukemia is their inability to carry out the functions of healthy white blood cells. Untreated, death occurs within weeks or a few months.
Other important features of acute leukemias:
• A predominance of blast cells, which are immature precursors of either lympho-cytes (lymphoblasts), or granulocytes (myeloblasts). They do not normally appear in peripheral blood. When they do, they can be recognized by their large size, and primitive nuclei (ie the nuclei contain nucleoli).
• Abrupt onset (few months) with sudden high fever, weakness, malaise, severe anemia, and generalized lymphadenopathy; bone and joint pain common in chil¬dren.
• Principal organ involved: bone marrow (along with the spleen and liver).
• Bone pain and tenderness are experienced as a result of marrow expansion.
• Petechiae and ecchymosis in skin and mucous membranes, hemorrhage from various sites; bacterial infections common.
• Laboratory findings: leukocytosis 30,000-100,000 per cu.mm. with immature forms (myeloblasts and lymphoblasts) predominating.
• In 75% of the cases of acute lymphocytic leukemia, the lymphocytes are neither B nor T-cells and are called "null cells."
Remember: Acute leukemias occur most often in children. They exhibit a second peak incidence after 60 years of age. Leukemia can modify the inflammatory reaction.
50%
Survival rates of leukemia have risen dramatically in the last 40 years with improvements in diagnosis and treatment. The highest survival rates occur in children with the so-called "com¬mon" ALL type.
Chronic leukemias have a slower onset and progression than acute leukemias. They also have a longer, less devastating clinical course than acute leukemias but are less responsive to therapeutic intervention. Chronic leukemias are characterized by proliferation of lymphoid or hematopoietic cells that are more mature than those of the acute leukemias.
Other important features of chronic leukemias:
• Insidious onset with weakness and weight loss; disease may be detected during examin¬ation for some other condition, e.g., anemia, unexplained hemorrhages, or recurrent intr¬actable infection.
• Organ involvement similar to acute type: massive splenomegaly is characteristic of chronic myelogenous leukemia; lymph node enlargement is the main pathologic finding in the lymphocytic type.
• Petechiae and ecchymoses, recurrent hemorrhages, bacterial infections; CLL maybe complicated by autoimmune hemolytic anemia.
• Laboratory findings: leukocytosis above 100,000 per cu. mm with mature forms (granulocytes and lymphocytes) predominating; Philadelphia (Ph) chromosome, and low levels of leukocyte alkaline phosphatase are common in chronic myeloid leukemia (CML).
• Median survival time for patients with chronic myelogenous leukemia (CML) is four years with death due to hemorrhage or infection; chronic lymphocytic leukemia (CLL) runs a variable course; older patients may survive years even without treatment.
Note: The Ph Chromosome describes a specific translocation between chromosomes 9 and 22. The resulting abnormal gene (BCR-ABL) codes for an enzyme (a tyrosine kinase) that is hypothesized to drive the growth of CML cells.
Chronic myelogenous leukemia (CML)
About 95% of patients with CML have the Philadelphia (Ph) chromosome, an abnormality in which the long arm of chromosome 22 is translocated, usually to chromosome 9. Radiation and carcinogenic chemicals may induce this chromosomal abnormality.
As a result of this translocation, the BCR gene in chromosome 22 is fused with the ABL gene in chromosome 9. The resulting BCR-ABL gene codes for a bcr-abl tyrosine kinase (TK) enzyme that is constitutively active. This TK enzyme interacts with other proteins to speed up cell division while inhibiting DNA repair. The resulting genetic instability may lead to a blast crisis.
Clinically, CML is a disease with slow progression. The following phases can be observed:
1. Chronic phase: this phase is usually asymptomatic. Fatigue and abdominal fullness (as a result of severe splenomegaly) are the most common complaints.
2. Accelerated phase: fifty percent of CML cases progress into this phase. Increasing anemia, new thrombocytopenia and additional cytogenic abnormalities indicate progression of the disease towards a blast crisis.
3. Blast crisis: the other fifty percent abruptly move into a blast crisis. Clinically, this last phase of CML is of rapid progression with low survival rates.
Patients in the chronic and accelerated phases are treated with TK inhibitors (i.e., Gleevac) that specifically inhibit the activity of a subset of tyronase kinases.
Patients in a blast crisis are treated with a high dose of chemotherapy followed by bone marrow transplantation.
Note: The Ph chromosome is also present in a small percentage of acute lymphoblastic leukemia (ALL) and in acute myelogenous leukemia (AML).
No definitive causes have been identified for leukemia. Possible risk factors include:
• Genetic predisposition: Down syndrome has a higher incidence of acute leukemias
• Environmental exposure to: chemicals (benzene, some anti-cancer drugs) : radiation -- usually myelogenous type leukemias
• Viruses: HTLV-1 -- adult T-cell leukemia
:leukemic patients have a high antibody titer to the Epstein-Barr Virus (EBV)
Humoral immunity
Humoral immunity (also called antibody-mediated immunity) is immunity produced by the activation of the B-lymphocyte population. B-cells, like T-cells, have surface recep¬tors which enable them to recognize the appropriate antigen, but do not themselves inter¬act to neutralize or destroy the antigen. On recognition of an antigen, B-cells take up res¬idence in secondary lymphoid tissue (such as lymph nodes and spleen) and with addi¬tional stimuli from T-helper cells, they differentiate into either an activated plasma cell or a memory B-cell. The short lived plasma cells produce antibodies and release them into the circulation at the lymph nodes. The memory B-cells continue to produce small amounts of the antibody long after the infection has been overcome. There are 5 classes of antibodies. Each is called an immunoglobulin and then allocated a code letter (IgG, IgM, IgA, IgE, and IgD). Important: The key to humoral immunity is the ability of antibodies to react specifically with antigens. This type of immunity provides protec¬tion against encapsulated bacteria.
Cellular immunity is immunity mediated by T-Iymphocytes either through release of lymphokines or through exertion of direct cytotoxicity, transmissible by transfer of lym¬phocytes but not serum; it comprises delayed hypersensitivity reactions, systemic response to viral and microbial infections, contact dermatitis, granulomatous reactions, allograft rejection, and graft-versus-host reactions. It is a specific acquired immunity involving T-cells. It acts to resist most intracellular pathogens (bacteria and viruses). The main function of the immune system is to prevent or limit infections by microorganisms such as bacteria, viruses, fungi, and parasites. Protection is provided primarily by the cell-mediated and antibody-mediated (humoral) arms of the immune system. The other two other major components of the immune system are complement and phagocytes. The cell-mediated arm consists primarily of T-lymphocytes whereas the antibody-mediated arm consists of B-lymphocytes.
Jaundice
Atopic allergies result from a localized expression of Type I hypersensitivity reactions. The interaction of antigens (allergens) with cell-bound IgE on the mucosal membranes of the upper respiratory tract and conjunctival tissues initiates a localized type I hypersensitivity reaction. Most allergy sufferers are said to be atopic. An atopic allergy is one where heredity plays an important role (i.e., allergies run in families). Atopic individuals are genetically programmed to produce an abundance of IgE (immunoglobulin E) antibodies. These IgEs strongly react against allergens in the environment (pollen, moulds, household dust, etc.). It is possible to become allergic without being atopic, but atopy increases the risk!
Note: A child with one parent who has suffered from allergies runs a 30% risk of also becoming allergic. If both parents have suffered from allergies, the risk doubles to 60%. However, allergies can "jump" a generation.
• Allegic rhinitis: also known as hay fever, it takes place when the allergen interacts with sensitized cells of the upper respiratory tract. Symptoms include coughing, sneezing, congestion, tearing eyes, and respiratory difficulties.
Note: The primary mediator is histamine, which is released from sensitized mast and basophil cells.
• Allergic asthma: the allergic reaction primarily affects the lower respiratory tract. It is common in children and is characterized by shortness of breath and wheezing.
Note: Specific IgE antibodies or nonspecific inhaled irritants provoke mast cell degranulation; histamine, leukotrienes (SRS-As), and other mediators are released to cause bronchospasm and bronchial mucus secretion.
• Atopic dermatitis: commonly referred to as eczema, is a chronic skin disorder categorized by scaly and itching rashes. Eczema is most common in infants, and at least half of those cases clear by age 36 months. In adults, it is generally a chronic or recurring condition. A hypersensitivity reaction occurs in the skin, causing chronic inflammation.
Impaired elimination of microbial antigen and circulating immune complexes
The complement system plays an essential role in host defense against infectious agents and in the inflammatory process. It consists of about twenty plasma proteins (designated CI, C2, C3, and so forth) that function either as enzymes or as binding proteins. In addition to these plasma proteins, the complement system includes multiple distinct cell surface receptors that exhibit specificity for the physiological fragments of complement proteins that occur on inflammatory cells and cells of the immune system.
Important: Complement activation is a feature of type III hypersensitivity reactions. There are three major pathways of complement activation:
• The classical pathway, which is activated by certain antibody isotypes (antigen bound IgG or IgM) binding to Cl.
• The alternative pathway, which is activated by C3 binding to microbial cell surfaces.
• The lectin pathway, which is activated by plasma lectins which bind to mannose residues on bacterial cells.
The alternative and lectin pathways are activated in an antibody independent fashion and appear to be of major importance in host defense against invading microorganisms.
All three pathways result in the production of C3 convertase. The protein properdin com-plexes with C3b and stabilizes alternate pathway C3 convertase. C3 convertase initiates acti¬vation of the late components of the complement system resulting in the formation of the membrane attack complex (MAC) and ultimate lysis of the target cell.
1. Cytolysis refers to the lysis of bacteria or of cells such as tumor or red blood cells Notes by insertion of the membrane attack complex derived from complement activa¬tion.
2. Characteristics of Cl: • It is a constituent of the classic complement pathway.
• Composed of three proteins (Clq, Clr, and Cls).
• Calcium is required for activation of Cl.
Hapten
Haptens have antigenic determinants, but are too small to elicit the formation of antibodies by themselves. They can do so when covalently bound to a "carrier" protein. Many drugs (e.g., penicillin) are haptens and the catechol in the plant oil that causes poison oak is a hapten. Haptens are not immunogenic because they cannot activate helper T-cells.
Important: Antibody production involves activation of B-lymphocytes by the hapten and helper T-lymphocytes of the carrier
Remember that an antigen is any substance that can specifically bind antibodies or the T-cell antigen receptor. Those antigens that can stimulate an immune response are immunogens; therefore all immunogens are antigens, but not all antigens are immuno-gens. A large variety of biological molecules (i.e. proteins, carbohydrates, lipids and nucleic acids) are able to bind to antibodies, while only peptides are recognized by T-cells. In order to be immunogenic, antigens must be foreign, with a high molecular weight, a certain degree of chemical complexity, and, for T-cell antigens must be able to interact with the host's major histocompatibility complex (MHC).
Note: Epitope is the specific portion of an antigen to which the antibody binds.
I. Plasmids are extrachromosomal genetic structures that can replicate Notes!' independently within a bacterial cell. These molecules of DNA are separate-u,
from the bacterial chromosomes and determine traits not essential for the viability of the organism but in some way change the organism's ability to adapt. R (resistance) factor is an example. Most antibiotic resistance in bacteria is caused by genes that are carried on plasmids. Plasmids may be passed from one bacterium to another, and they are replicated in later generations of any
bacterium carrying them.
The proteins are synthesized mainly by the kidney
***This is false; complement proteins are synthesized mainly by the liver. Some are made in macrophages. Note: Cl is made in GI epithelium.
The immune system is composed of cells and soluble substances. The major cells of the immune system are the white blood cells (macrophages, neutrophils, and lymphocytes). Soluble substances are molecules that are not contained in cells but are dissolved in a liquid, such as plasma. The major soluble substances are antibodies, complement proteins, and cytokines. The soluble substances act as messengers to attract and activate other cells.
The complement system comprises about twenty plasma proteins. These proteins act in a cascade, with one protein activating the next protein.
There are three major pathways of complement activation:
• The classical pathway, which is activated by certain antibody isotypes (antigen bound IgG or IgM) binding to Cl
• The alternative pathway, which is activated by C3 binding to microbial cell sur-faces
• The lectin pathway which is activated by a plasma lectins that bind to mannose residues on bacterial cells
1. The complement system functions to destroy foreign substances, either !Notes' directly or in conjunction with other components of the immune system.
2. The membrane attack complex is the end product of activation of the complement cascade, which contains C5b, C6, C7, C8, and C9. This complex makes holes in the membranes of gram-negative bacteria, killing them and, in red blood cells or other cells, resulting in cytolysis.
Leukotrienes
Leukotrienes are biologically active compounds formed from arachidonic acid and other polyunsaturated fatty acids. Leukotrienes are of importance in host defense reactions and have a pathophysiological role in inflammation and allergic reactions. Once arachidonic acid is generated (by inflammatory cells and injured tissues), it is metabolized through two pathways:
1. Cyclooxygenation: produces prostaglandins and thromboxanes.
2. Lipoxygenation: produces leukotrienes as well as HETEs and diHETEs.
Leukotrienes C4, D4, and ELI are collectively known as slow-reacting substances of
anaphylaxis (SRS-As) and are responsible for the development of much of the clinical symptomatology associated with allergic-type reactions. The leukotrienes are 100 to 1,000 times more potent than a histamine or the prostaglandins in constricting bronchi.
Remember:
Notes 1. In asthma, the allergen reaction occurs in the bronchioles of the lungs. The most important products released from the mast cell are the SRS-As (they are the primary mediators of asthma), which causes spasm of the bronchiolar smooth muscle.
2. Anaphylactic shock (anaphylaxis) is physiological shock resulting from an anaphylactic hypersensitivity reaction (for example, to penicillin or bee bites). In severe cases, death can result within minutes. This anaphylactic reaction involves the degranulation of mast cells and the release of histamine, heparin, platelet-activating factors, SRS-As, and serotonin into the bloodstream.
3. Histamine is responsible for the principal symptoms of anaphylaxis.
IgA
Polymeric IgA is the predominant immunoglobulin in extracellular secretions (i.e., saliva, tears, and breast milk -- especially colostrum). Therefore, secretory IgA is often abbreviated as sIgA. It is composed of two IgA monomers linked by two additional polypeptides: a J (joining) chain and a secretory component. The secretory component protects sIgA from hydrolysis by microbial proteolytic enzymes and keeps it on the mucosal surface by binding to mucus. The primary function of IgA is to collect microorganisms and prevent their colonization. Monomeric IgA exists in serum.
IgA is important in the respiratory, GI, and urinary tracts, where it plays a major role in protecting surface tissues against invasion by pathogenic microorganisms.
IgA provides the primary defense at mucosal surfaces such as the bronchioles, nasal mucosa, vagina, prostate, and intestine. The IgA molecules bind with surface antigens of microorganisms, preventing the adherence and ingress of antigen through the mucosa of the respiratory, GI, and urinary tracts.
Remember: IgA is one of the most prevalent humoral antibodies (second only to IgG) produced by the body.
1. In the primary humoral immune response, the predominant immunoglobulin is Notes
IgM, which appears first in the serum and is followed by IgG.
2. During the secondary humoral immune response (a second exposure to the same antigen, for example when a person receives a third immunization with tetanus toxoid), a more rapid and greater response ensues, which is predominantly composed of IgG, not IgM, as the major class of antibody.
3. As the severity of an infection increases (for example, periodontal disease), there is an increase in plasma cells that produce IgG.
4. No function is yet known for IgD other than as a membrane receptor.
5. IgE is the immunoglobulin responsible for allergic or anaphylactic reactions.
Its activation may produce an anamnestic response
An anamnestic response refers to the development of immunological memory via the pro-duction of memory cells. These cells are produced as part of the adaptive immune response. The components and mechanisms of the immune system are categorized into the innate immune system and the adaptive immune system. Exposure to foreign antigen activates the innate and/or adaptive immune system. This activation generates either an innate or an adap¬tive immune response, conferring the organism with either innate or adaptive immunity.
Innate immunity is conferred by those mechanisms that are always present and ready to rec¬ognize, fight and eradicate microbes by mounting an innate immune response. Characteristics of the innate immune response:
• Elicited by a first-time encounter with an antigen
• Being non-specific, it recognizes microorganisms by their conserved constituents (such as LPS on the membrane of gram-negative bacteria)
• Exposure to pathogenic antigen leads to immediate response
• Produces no anamnestic response
• Humoral components include complement, cytokines (interferon, interleukins, and chemokines), defensins, lysozyme, etc.
• Cellular components inlcude macrophages, neutrophils, eosinophils, and natural killer (NK) cells
• Epithelial barriers include unbroken skin and mucous membranes lining the gastroin-testinal tract, respiratory tract, and genitourinary tract
• Found in nearly all forms of life
The innate immune response is important and necessary because:
1. It "buys" the organism time to tailor a response that is specific to the invading pathogen: an adaptive immune response.
2. It establishes local inflammation that serves to recruit, initially, phagocytes and then activated T and B cells.
It has cellular components but no humoral components
*** This is false; the adaptive immune system response has both cellular and humoral com¬ponents.
The adaptive immune system evolved in vertebrates as a response to pathogens that evolved resistance to the innate immune response. Initiation of the adaptive immune response relies on the activities of the innate immune system.
Characteristics of the adaptive immune response:
• It is activated by the actions of the innate immune system.
• It supplements the protection provided by innate immunity.
• It is NOT activated immediately after exposure to an antigen. Slow response.
• It is a tailor-made response that is highly specific to the invading pathogen: it is able to recognize a specific pathogen.
• It leads to the development of immunological memory (anamnestic response): re-expo¬sure to the same antigen will result in a faster, more intense response.
• It adapts to mount a faster, stronger response with subsequent exposure to a particular pathogen. There are two types of adaptive immunity:
1. Humoral immunity:
• Designed to provide immunity against extracellular pathogens.
• Mediated by antibodies produced by B-cells.
• Antibodies neutralize and eliminate pathogens and toxins from the blood, from mucos¬al surfaces and from the lumen of mucosal organs.
2. Cell-mediated immunity:
• Designed to provide immunity against intracellular pathogens.
• Mediated by T-cells which activate macrophages to kill phagocytosed microbes (T helper cells) kill infected cells, hence eliminating reservoirs of infection (cytotoxic T cells).
It is a glycoprotein secreted by activated plasma cells
*** MHC molecules are membrane glycoproteins that are not secreted by any cell type.
The major histocompatibility complex (MHC) genes are a highly polymorphic group of genes; that is to say that many different variants (alleles) exist simultaneously in a population. In humans, the MHC genes are located on the short arm of chromosome six. They are divided into three sub¬groups: MHC class I, MHC class II and MHC class III. Classes I and II code for membrane gly¬coproteins (see below) while class III codes for proteins of the complement system (C2, C4 and factor B).
The major histocompatibility complex (MHC) molecule is a heterodimeric membrane glyco¬protein encoded by the major histocompatibility complex genes. Their primary function is to present (display) antigenic peptides for recognition by T-lymphocytes. Upon interaction with an MHC/peptide complex, the T-cell can "decide" whether the peptide is self or foreign, and take appropriate action.
There are two structurally distinct types of MHC molecules:
1. MHC class I
• Encoded by MHC class I genes
• Composed of one alpha chain and one beta 2-microglobolin chain
• Expressed by all nucleated cells
• Recognized by CD8+ T-cells
• Binds and presents peptides derived from cytosolic proteins
2. MHC class II
• Encoded by MHC class II genes
• Composed of one alpha and one beta chain
• Expressed only by professional antigen presenting cells (APC), macrophages and B-cells
• Recognized by CD4+ T-cells
• Binds and presents peptides derived from endocytosed proteins
Note: In humans, the MHC molecules are referred to as Human Leukocyte Antigens (HLA). HLA tissue typing is used to match donated tissue/organs/bone marrow with transplant recipients. A mismatch results in acute rejection of the transplanted tissue.
Hypertension
*** This is false; Addison's disease is characterized by hypotension.
Addison's disease (primary adrenocortical deficiency) is a life threatening condition caused by partial or complete failure of adrenocortical function. It is most commonly due to idiopath¬ic adrenal atrophy (autoimmune lymphocytic adrenalitis). It can also be caused by tuberculosis (formerly most common cause), metastatic tumor, and various infections. It is characterized by the insidious onset of weakness, fatigue, depression, hypotension and bronzing of the entire skin. Oral signs consist of diffuse pigmentation of the gingiva, tongue, hard palate, and buccal mucosa. Although cutaneous pigmentation will most likely disappear following therapy, pigmen¬tation of the oral tissues tends to persist.
The adrenocorticotropic hormone test (also known as an ACTH test or a corticotropin test) measures pituitary gland function. The pituitary gland produces the hormone ACTH, which stim¬ulates the outer layer of the adrenal gland (the adrenal cortex). ACTH causes the release of the hormones hydrocortisone (cortisol), aldosterone, and androgen. The most important of these hor¬mones released is cortisol. The ACTH test is used to determine if too much cortisol is being pro¬duced (Cushing's syndrome) or if not enough cortisol is being produced (Addison's disease).
1. Secondary adrenal insufficiency can result from prolonged or improper use of glu¬Notes cocorticoid hormones, which are used to treat rheumatoid arthritis, asthma, and other inflammatory illnesses.
2. Addison's disease is treated by administering cortisol (hydrocortisone).
3. Waterhouse-Friderichsen syndrome is a catastrophic adrenal insufficiency and vascular collapse due to hemorrhagic necrosis of the adrenal cortex. It is characteristi¬cally due to meningococcemia, most often in association with meningococcal menin¬gitis.
4. The adrenal glands are located on top of each kidney. They consist of the outer por¬tion (called the cortex) and the inner portion (called the medulla). The cortex produces three types of hormones: sex hormones, glucocorticoid hormones, and mineralocorti¬coid hormones.
Mechanical trauma to the affected joints ("wear-and-tear")
Osteoarthritis (degenerative joint disease) is the most common form of arthritis. It is a chronic inflammatory joint disease characterized by degeneration of articular cartilage accompanied by new bone formation subchondrally and at the margins of the affected joint. The incidence is greater in women, most often beginning after 50 years of age.
The inflammation is accompanied by pain, swelling, and stiffness. Most commonly it affects joints constantly exposed to wear and tear. The joints most often affected include the intervertebral joints, the phalangeal joints, the knees, and the hips.
Characteristic morphologic changes include:
• Eburnation of bone: polished, ivory-like appearance of bone, resulting from ero-sion of overlying cartilage.
• Osteophyte (bony spur) formation: at the perimeter of the articular surface and at points of ligamental attachment to bone.
- Osteophytes fracturing and floating into synovial fluid along with fragments of separated cartilage are called joint mice.
• Hebernen nodes: osteophytes at the distal interphalangeal joints of the fingers.
• Bouchard nodes: osteophytes at the proximal interphalangeal joints of the fingers.
Types of osteoarthritis:
• Primary osteoarthritis: occurs without known cause. Is mostly related to aging.
• Secondary osteoarthritis: is caused by another disease or condition. Conditions that can lead to secondary osteoarthritis include obesity, repeated trauma or surgery to the joint structures, abnormal joints at birth (congenital abnormalities), gout, dia-betes and other hormone disorders.
Letterer-Siwe disease (acute disseminated Langerhans cell histiocytosis)
Histiocytosis X (Langerhans cell histiocytosis) is a term used to describe a group of differ-ent types of illnesses that share a common origin. Langerhans cells (called histiocytes) are increased in number and invade various tissues of the body. Histiocytes are cells nor¬mally found throughout the body and are most often found in the spleen, lung, liver, and bone marrow. The trigger for the increase of Langerhans cells and their invasion is not known.
Histiocytosis X includes:
• Eosinophilic Granuloma: the most benign or mild form of histiocytosis X, character-ized by a solitary lesion of the bone, which can result in pain and swelling.
- 60-80% of histiocytosis X
- age 5 - 10 yrs
• Hand-Christian-Schuller Disease: usually refers to children with the classic triad of skull lesions, diabetes insipidus, and exophthalmos caused by involvement of the orbit. - age 1 - 3 yrs
• Letterer-Siwe Disease: refers to a generalized disease that has a very aggressive, often fatal ending. Organs that may be involved include bone, lungs, skin, liver, spleen, and bone marrow.
- age 0 - 1 yr
- worst prognosis
The outcome of LCH is extremely variable. The two main factors which influence a child's prognosis appear to be age at the time of diagnosis, and how many organs are involved. Children younger than 2 years at the time of diagnosis have a higher death rate than do older children. Furthermore, the presence of major organ problems (liver, lung, bone marrow) has been shown to be an indicator of poor outcome. The involvement of multiple organ systems is also a poor prognostic sign.
Parathyroid adenoma
Primary hyperparathyroidism is common. Primary HPT can be divided pathologically into adenoma, hyperplasia, and carcinoma. Adenomas clearly are the most prevalent entity repre¬senting 80-85% of cases. Hyperplasia is the second most common diagnosis constituting 15% of cases. Carcinoma represents <1% of total cases.
Laboratory findings include:
• Hypercalcemia • Increased serum alkaline phosphatase
• Decreased serum phosphorus • Increased serum PTH Clinical characteristics include:
• Osteitis fibrosa cystica (also known as von Recklinghausen disease of bone): cystic changes in bone due to osteoclastic resorption. Replacement of resorbed bone may lead to the formation of non-neoplastic tumor-like masses called "brown tumor."
• Nephrocalcinosis: metastatic calcification affecting the kidneys.
• Renal calculi
• Peptic duodenal ulcers
***Dental finding: There is a loss of lamina dura around multiple teeth. Hyperparathyroidism can be classified into three distinct entities:
• Primary hyperparathyroidism is the result of an adenoma, glandular hyperplasia, or car¬cinoma.
• Secondary hyperparathyroidism is a reactive hyperplastic phenomenon in response to decreased concentration of serum calcium.
• Tertiary hyperparathyroidism is a term used to describe the instance where secondary hyperparathyroidism has become "autonomous."
1. In rare instances, hypoparathyroidism is associated with congenital thymic Notes' hypoplasia (DiGeorge's syndrome).
2. Remember: Osteoporosis, central giant cell granulomas, and metastatic calci-fications are all manifestations of hyperparathyroidism.
Hepatitis B virus
Collagen is a tough, glue-like protein that represents 30% of body protein. It shapes the struc¬ture of tendons, bones, and connective tissues. Problems with the immune system can affect these structures. This is known as collagen vascular disease.
Collagen vascular diseases include:
• Polyarteritis nodosa: a serious blood vessel disease of unknown cause characterized by
necrotizing immune complex inflammation of small and medium sized arteries. - There is an association with hepatitis B viral infection
• Dermatomyositis: a muscle disease that causes inflammation and a skin rash. It is a
type of inflammatory myopathy. - The cause is unknown
• Scleroderma: a widespread connective tissue disease that involves changes in the skin,
blood vessels, muscles, and internal organs. - Common in young women
- Widespread connective tissue fibrosis
- Tight and mask-like facial skin, raynaud's phenomenon, pain, stiffness, and swelling of fingers and joints, GERD, increased chance of Barretts esophagus
• Systemic lupus erythematosus (SLE): the prototype connective tissue disease
- SLE (lupus) is an autoimmune disease.
- 80% of SLE patients are women, usually those of childbearing age.
- Fever, malaise, lymphadenopathy, and weight loss
- Characteristic butterfly rash over the cheeks and bridge of the nose (50% of patients),
joint pain and arthritis, raynaud's phenomenon
- Extensive immune complex-mediated inflammatory lesions, the lesions of greatest
clinical importance in SLE are those in the kidney.
• Rheumatoid arthritis (RA): a long-term disease that causes inflammation of the joints and surrounding tissues. It can also affect other organs.
Unknown
Multiple sclerosis is a disorder of the brain and spinal cord (central nervous system) caused by progressive damage to the outer covering of nerve cells (myelin). This results in decreased nerve functioning which can lead to a variety of symptoms. Although the cause and pathogenesis of the disease remain to be elucidated, there is evidence that sug¬gests an autoimmune component to the disease with CD4+ and CD8+ T-cell involve¬ment. The disease involves repeated episodes of inflammation of nervous tissue in any area of the central nervous system (brain and spinal cord). These episodes occur when the body's own immune cells attack the nervous system. The location of the inflamed areas varies from person to person and from episode to episode. The inflammation destroys the covering of the nerve cells in that area (myelin sheath), leaving multiple areas of scar tissue (sclerosis) along the covering of the nerve cells. This results in slow¬ing or blocking the transmission of nerve impulses in that area, leading to the symptoms of MS. Common symptoms of MS include visual disturbances, speech disturbances, paresthesias (tingling, prickling, or numbness), depression, mood swings, etc.
1. Moderate amounts of protein and a small number of lymphocytes in the cerebrospinal fluid are characteristic of MS.
2. Injectable interferon, a relatively new treatment, reduces the frequency of relapses of MS.
3. Multiple sclerosis (MS) affects approximately 1 out of 1,000 people.
4. Women are affected more commonly than men.
5. The disorder most commonly begins between 20 to 40 years old, but can hap¬pen at any age.
Plasma cells
"Amyloidosis" is a generic term used to describe various conditions in which proteinaceous material (amyloid) abnormally deposits and accumulates in tissues and/or organs. These amyloids are primarily composed of insoluble fibrous proteins (scleroprotein).
Amyloidoses are classified according to the physical and chemical nature of the amyloid pro¬tein it is composed of, as well as to the extent of the deposits: systemic (more than one organ or body system is involved) or localized (single organ involvement). Clinically, the systemic and localized designations are further categorized into either primary or secondary, depend¬ing on whether the amyloidosis is related to an immune disease (primary) or a complication of some other chronic inflammatory process (secondary).
• Primary amyloidosis: cause is unknown; it is related to abnormal production of immunoglobulins by malignant plasma cells (i.e. as in multiple myeloma). It is usually systemic in distribution. Typical sites of amyloid buildup are the heart, lungs, skin, tongue, thyroid gland, intestines, liver, kidney, and blood vessels.
• Secondary (reactive) systemic amyloidosis: the amyloidosis is a complication of anoth¬er disease such as TB, rheumatoid arthritis, or familial Mediterranean fever. Amyloid tends to build up in the spleen, liver, kidneys, adrenal glands, and lymph nodes. The heart is rarely involved.
• Hereditary amyloidosis: mostly rare and limited to specific geographic areas, these amyloidoses are the result of genetic mutations. For example, Familial Mediterranean fever, systemic senile amyloidosis and several types of familial amyloidotic neuropathies.
Note: Alzheimer's disease, diabetes mellitus type 2 and Parkinson's disease are some other examples of amyloid associated conditions as they are all characterized by deposits of amy¬loid. For example, diabetes mellitus type 2 is characterized by deposits of amyloid (referred to as amylin) in islet cells.
Unknown
Rheumatoid arthritis is a chronic (long-term) inflammatory disease that primarily affects the joints and surrounding tissues, but can also affect other organ systems. The cause of rheumatoid arthritis (RA) is unknown, but there is a genetic predisposition. RA involves an attack on the body by its own immune cells (some researchers suggest it may be an autoimmune disease).
The disease can occur at any age, but it begins most often between the ages of 25 and 55. The disease is more common in older people. Women are affected 2.5 times more often than men. Approximately 1-2% of the total population is affected. The course and the severity of the illness can vary considerably. Still's disease is a type of RA that occurs in young people.
The onset of the disease is usually gradual, with fatigue, morning stiffness (lasting more than one hour), diffuse muscular aches, loss of appetite, and weakness. Eventually, joint pain appears, with warmth, swelling, tenderness, and stiffness of the joint after inactivi¬ty. Note: Rheumatoid arthritis typically involves small joints of the hands and feet most severely, and there is a destructive pannus that leads to marked joint deformity.
1. Important: The condition is marked by a proliferative inflammation of the Notes3 synovial membranes, leading to deformity, ankylosis, and invalidism.
2. Remember: Osteophyte (bony spur) formation is a cardinal feature of osteoarthritis, not rheumatoid arthritis.
3. Rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, dermatomyositis, and scleroderma are all classified as collagen diseases. They all have in common inflammatory damage to connective tissues and blood vessels with the deposition of flbrinoid material.
Serum Sickness
Immune complex diseases are classified as type III hypersensitivity reactions that occur when excess circulating immune complexes (antibody bound to antigen) deposit in tissues. The glomerular lesions in immune complex diseases result from the deposition of IgG. Note: Normally, immune complexes are effectively cleared by the reticuloendothelial system. These deposited immune complexes activate the complement cascade, resulting in local inflammation. Remember: Histamine does not play a major role in these Type III hypersen¬sitivity reactions.
• Systemic lupus erythematosus (lupus) is an autoimmune disease that results in episodes of inflammation in joints, tendons, and other connective tissues and organs. About 90% of the people who have lupus are young women in their late teens to 30s.
• Serum sickness appears some days after injection of a foreign serum or serum protein, with local and systemic reactions such as urticaria, fever, general lymphadenopathy, edema and arthritis.
• Sjogren's syndrome is the second most common autoimmune rheumatic disorder after rheumatoid arthritis (RA). It is characterized by diminished lacrimal and salivary gland secre¬tion (sicca complex). This syndrome occurs mainly in women (90% of patients) and the mean age is 50.
• Polyarteritis nodosa is a serious blood vessel disease in which small and medium-sized arteries become swollen and damaged when they are attacked by certain immune cells.
• Glomerulonephritis describes inflammation of the kidney's glomeruli, hindering removal of waste products from the blood. It can occur by a type II reaction (Goodpasture's syn-drome), a type III reaction (immune complex glomerulonephritis) or as part of a multisystem vasculitic process (vasculitic glomerulonephritis).
• Rheumatoid arthritis is a chronic, systemic, inflammatory disease. It primarily attacks peripheral joints and surrounding muscles, tendons, ligaments, and blood vessels.
Type II
Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction.
Classification of hypersensitivity reactions:
• Type I (also known as immediate or anaphylactic hypersensitivity) are reactions in which antigens (allergens) combine with specific IgE antibodies that are bound to membrane receptors on tissue mast cells and blood basophils. The antigen-antibody reaction causes the rapid release of potent vasoactive and inflammatory mediators, which may be preformed (e.g., histamine, tryptase, kininogenase) or newly generated from membrane lipids (e.g., the leukotrienes B4, C4 and D4, prostaglandins D2, and PAF). Examples include: Allergic rhinitis, asthma, and anaphylaxis.
• Type II are cytotoxic reactions resulting when antibody reacts with antigenic components of a cell or tissue elements (or with antigen or hapten) that is coupled to a cell or tissue. The antigen-antibody
reaction may activate certain cytotoxic cells (killer T-cells or macrophages) to produce antibody-dependent cell-mediated cytotoxicity. Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement. Examples include: Goodpasture's syndrome, erythroblastosis fetalis, autoimmune hemolytic anemia, and hyperacute transplant rejection.
• Type III are immune complex (IC) reactions (mostly of the IgG class, although IgM may also be involved) resulting from deposition of soluble circulating antigen-antibody ICs in vessels or tissue.
Primary components are soluble immune complexes and complement (C3a, 4a and 5a). The damage is caused by platelets and neutrophils. The lesion contains primarily neutrophils and deposits of immune complexes and complement. Macrophages infiltrating in later stages may be involved in the healing process. Examples include: Serum sickness, systemic lupus erythematosus, and Arthus reaction.
• Type IV hypersensitivity is also known as cell mediated or delayed type hypersensitivity. The classical example of this hypersensitivity is tuberculin (Montoux) reaction. Mechanisms of
damage in delayed hypersensitivity include T-lymphocytes and monocytes and/or macrophages. Circulating antibodies are not involved in nor are they necessary for development of tissue injury. Examples include: Contact dermatitis, tuberculin test, and chronic transplant reaction.
Systemic lupus erythematosus (SLE)
Lupus is a condition characterized by chronic inflammation of body tissues caused by autoimmune disease. Patients with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than foreign infectious agents. Because the anti-bodies and accompanying cells of inflammation can involve tissues anywhere in the body, lupus has the potential to affect a variety of areas of the body. Sometimes lupus can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the condition is called discoid lupus. When internal organs are involved, the condition is called systemic lupus erythematosus (SLE). Both discoid and systemic lupus are more common in women than men (about eight times more common). The disease can affect all ages but most commonly begins between the ages of 20 to 45 years.
At its onset, only one organ system may be involved. Additional organs may become involved later. Renal failure commonly occurs and is the usual cause of death. Severe CNS involvement may appear. Acrocyanosis (Raynaud's phenomenon) is often associated with SLE.
1. Many autoimmune diseases are associated with characteristic auto-antibodies. Notes Anti-DNA (also known as anti-nuclear antibodies) and anti-Sm antibodies appear
to be specific for SLE.
2. The characteristic "butterfly" rash over the cheeks and bridge of the nose affects about half of those with SLE. The rash is usually worsened by sunlight.
3. The precise reason for the abnormal autoimmunity that causes lupus is not known.
4. Dozens of medications have been reported to trigger SLE; however, more than 90% of this "drug-induced lupus" occurs as a side effect of one of the following six drugs: hydralazine (used for high blood pressure), quinidine and procainamide (used for abnormal heart rhythm), phenytoin (used for epilepsy), isoniazid [(Nydrazid, Laniazid), used for tuberculosis], penicillamine (used for rheumatoid arthritis). These drugs are known to stimulate the immune system and cause SLE.
Big toe
Gout is an inherited disorder of purine metabolism occurring predominantly in men. It caused by a defect in metabolism that results in an overproduction of uric acid, or a reduced ability of the kidney to eliminate uric acid (almost 25% of all people who have gout develop kidney stones). The exact cause of the metabolic defect is unknown. The condition may also develop in people with diabetes, obesity, sickle cell anemia, and kidney disease, or it may fol¬low drug therapy that interferes with uric acid excretion.
Gout is characterized by the deposition of monosodium urate crystals in joints and other tissues as a result of hyperuricemia. The disorder occurs most frequently in the metatar-sophalangeal joint of the big toe. Acute gouty arthritis is this characteristic location is known as podagra. The instep, ankle, knee, wrist and elbow are common sites, sometimes even the spine. Bouts may vary from days apart to several attacks a year; the first attacks may be in only one joint, lasting for days. Later attacks may affect more joints; there may be joint deformation if unattended. Limitation of joint movement is precipitated by stress or wrong diet. Symptoms include a sharp, needle-like pain on movement of joints; skin is tense, hot, shiny and dusky red or purplish; systemic reactions may include fever, heart rate increase, and chills and malaise.
• Primary gout: most common form, hyperuricemia without evident cause.
- most common in middle-ages men - a marked familial predisposition
• Secondary gout: much less common. Characterized by hyperuricemia with evident cause, such as:
- Leukemia, multiple myeloma, and myeloproliferative syndromes
- Lesch-Nyhan syndrome: hyperuricemia with severe neurologic manifestations - Pseudogout (chondrocalcinosis) - caused by calcium pyrophosphate dihydrate crystal deposition, which elicits an inflammatory reaction in cartilage. Pseudogout clinically resembles gout.
Acute inflammation of the gallbladder
Acute cholecystitis is a sudden inflammation of the gallbladder that causes severe abdominal pain. In 90% of cases, acute cholecystitis is caused by gallstones (cholelithiasis) in the gallblad¬der.
Acute cholecystitis causes bile to become trapped in the gallbladder. The build up of bile caus¬es irritation and pressure in the gallbladder. This can lead to bacterial infection and perforation of the organ.
Chronic cholecystitis is thickening of the gallbladder wall which occurs as a result of exten¬sive fibrosis. It is frequently complicated by gallstones.
Gallstones (cholelithiasis) occur more frequently in women than men and is often associated with obesity and multiple pregnancies. Gallstones become more common with age in both sexes. Note: Native Americans have a higher rate of gallstones.
Stone types:
• Cholesterol stones: are often solitary and too large to enter the cystic duct or the com¬mon bile duct.
• Pigment stones:
- Precipitation of excess insoluble unconjugated bilirubin results in their formation. - Association often includes hemolytic anemia and bacterial infection.
• Mixed stones: most common (75%-80%) - Mixture of cholesterol and calcium salts
1. Cholesterolosis (strawberry gallbladder) is characterized by small, yellow, Notes cholesterol containing flecks that are highlighted against a red background in the lining of the gallbladder.
2. Diverticulosis of the gallbladder: small, finger-like out-pouchings of the gallbladder lining, may develop as a person ages. This may cause inflammation and require gallbladder removal.
3. Gallstones that block the common bile duct result in obstructive jaundice (yellow skin color caused by bile pigments becoming deposited in the skin).
Cretinism
Cretinism is a condition of stunted body growth and impaired mental development. The symptoms, which appear during early infancy, are the gradual development of a characteris¬tic coarse, dry skin, a slightly swollen face and tongue, umbilical hernia, and an open mouth that drools. The baby is usually listless, slow-moving, constipated, and a slow feeder. Cretinism is the result of a congenital deficiency in the secretion of the hormone thyroxine from the thyroid gland.
In cretinism, the base of the skull is foreshortened, the face is wide and short, the mandible underdeveloped, and the maxilla overdeveloped. The eruption of primary and perma¬nent teeth is delayed.The long bones may be thickened and short, the epiphyses appear late and are often irregular and deformed.
Myxedema (hypothyroidism in adults), or underactivity of the thyroid gland, may cause a variety of symptoms and may affect all body functions. The body's normal rate of function¬ing slows, causing mental and physical sluggishness. This condition is considerably more common in women than in men. It is characterized by a puffiness of the face and eyelids and a swelling of the tongue and larynx. The skin becomes dry and rough and the hair becomes sparse. The affected individuals also have poor muscle tone, low strength, and get tired very easily. Mentally they are very sluggish. This condition can be alleviated by administering thyroid hormones. Risk factors include age over 50 years, female gender, obesity, thyroid surgery, and exposure of the neck to x-ray or radiation treatments.
- - 1. The secretion of T3 (triiodothyronine) and T4 (thyroxine) is controlled by the
Notesf> pituitary gland and the hypothalamus, which is part of the brain.
2. Thyroid disorders may result not only from defects in the thyroid gland itself, but also from abnormalities of the pituitary or hypothalamus.
3. The majority of the metabolically-active T3 is formed in the peripheral tissues by conversion of secreted T4.
Red blood cells in the urine
Blood in the urine should never be ignored! Blood in the urine is usually caused by kidney and urinary tract diseases. However, there are a couple of exceptions:
• In women, the blood may appear to be in the urine when it's actually coming from the vagina.
• In men, the urethra carries both urine and semen out of the body and what may be mistaken for urinary bleeding is sometimes a bloody ejaculation usually due to a prostate problem.
• In children, coagulation disorders (such as hemophilia) or other hematologic problems such as sickle cell disease, renal vein thrombosis, or the thrombocytopenias can be underlying reasons for newly discovered blood in the urine. Note: Kidney disease following strep. throat is a classic cause of blood in the urine in children.
1. Hematemesis is the vomiting of bright red blood, indicating rapid upper GI bleeding. It is commonly associated with esophageal varices (common in alcoholics) or peptic ulcers.
2. Hemoptysis is the coughing up of blood from the respiratory tract. Blood-streaked sputum often occurs in minor upper respiratory infections or in bronchitis. Patients suffering from tuberculosis, pneumonia, or bronchogenic carcinoma may also experience hemoptysis. The main symptom of idiopathic pulmonary hemosiderosis (iron in the lungs) is hemoptysis.
3. Glucosuria is the presence of glucose (sugar) in the urine; common in diabetics.
4. Ketonuria is the presence of ketones in the urine; produced by starvation, uncontrolled diabetes, and occasionally alcohol intoxication.
5. Proteinuria is the presence of protein in the urine; usually a sign of kidney disease.
The bridging veins
Subdural hematomas (SDH) occur between the dura and the arachnoid membrane, most often due to venous bleeding from the "bridging" subdural veins which connect the cerebral cortex to the dural sinuses.
Patients with SDH commonly present after acute deceleration injury from a fall or motor vehicle accident, but are rarely associated with skull fracture.
Subdural hematomas are characterized clinically by gradual signs of cerebral compres¬sion occurring hours, days, or weeks after injury.
An epidural hematoma (EDH) is an arterial hemorrhage between the dura and the skull, most often resulting from skull fractures and laceration of the middle meningeal artery. EDH is characterized clinically by a short period of consciousness (lucid interval) fol¬lowed by loss of consciousness and signs of cerebral compression.
Subarachnoid hemorrhage is commonly associated with rupture of a berry aneurysm in the circle of Willis. The rupture is most likely to occur in young to middle age adults.
1. In comparison to SDH, EDH is often associated with skull fractures (85 - 95% Notes `of adult cases) which disrupts the middle meningeal artery.
i 2. A transient ischemic attack is a brief episode of impaired neurologic function
caused by a brief disturbance in cerebral circulation.
3. A brain concussion is the immediate and temporary disturbance of brain function as manifested by dizziness, cold perspiration, visual disturbances, anc loss of consciousness. Most people recover completely within a few hours of days. One complication is postconcussion syndrome.
4. A meningioma is an intracranial tumor arising from arachnoid, usually occur. ring in adults over 30 years of age.
Dystrophic calcification
Pathologic calcification of soft tissues occurs when calcium and other mineral salts are deposited in a tissue or in a passage.
There are three types of pathologic calcifications:
1. Dystrophic calcification is that which occurs in degenerating and previously dam¬aged tissues, such as areas of old trauma, tuberculosis lesions, scarred heart valves, and atherosclerotic lesions. The cause is not hypercalcemia; typically the serum cal¬cium concentration is normal.
2. Metastatic calcification is that in which calcium (and other) salts are deposited in previously undamaged tissue as a result of an excess of salts in the circulating blood. Hyperparathyroidism is an example of metastatic calcification which occurs in kid¬neys and blood vessels.
3. Calcinosis is calcification that occurs in or under the skin. Scleroderma, dermato-myositis, and multiple miliary osteomas are examples of calcinosis.
1. A sialolith is a stone (salivary calculus) within a salivary gland or duct. The
Notes, formation of a sialolith is called sialolithiasis and occurs as a result of precipitation of calcium and phosphate salts around a nidus of mucous or bacterial debris. Sialoliths occur as single or multiple stones and can cause swelling and pain. The pain is experienced during salivary stimulation and is intensified at mealtimes. Most stones are found in the submandibular duct (Wharton's) and gland than in the parotid duct (Stensen's) and gland.
2. Kidney stones are calculi occurring in the kidney. Calculi too large to pass spontaneously range in size from 1 cm to the staghorn stones that occupy the renal pelvis and calyces. Bilateral renal calculi cause additional problems, with infection a common occurrence.
Adenovirus infection
Conjunctivitis is one of the most common and treatable eye infections in children and adults. Often called "pink eye," it is an inflammation of the conjunctiva, the tissue that lines the inside of the eyelid.
Conjunctivitis can be caused by a virus, bacteria, irritating substances (shampoos, dirt, smoke, and especially pool chlorine), allergens or sexually transmitted diseases (STDs). Pink eye caused by bacteria, viruses, and STDs can spread easily from person to person.
-- 1. Trachoma is an eye infection caused by Chlamydia trachomatis. It is the Notes
most common cause of preventable blindness in underdeveloped areas of the
world.
2. Retinopathy of prematurity (retrolental fibroplasia) is due to toxicity of therapeutic oxygen, most often administered because of neonatal respiratory distress syndrome (hyaline membrane disease). It leads to blindness.
3. Diabetic retinopathy is a major cause of blindness.
4. Retinitis pigmentosa is characterized by hereditary night blindness with pro¬gressive loss of central vision. It is caused by early loss of rods and later loss of cones.
5. Macular degeneration of the aged (senile macular degeneration) is a major cause of impaired vision in the elderly. It is often bilateral.
6. Glaucoma - two forms:
- Open-angle: most common form; characterized by gradually increasing ocular pressure, leading to visual impairment and, eventually blindness. - Angle-closure: caused by narrow anterior chamber angle; increase in intraocular pressure on dilation of pupil.
7. Retinoblastoma is a malignant retinal tumor of childhood.
Amylase
Pancreatitis is an inflammation or infection of the pancreas. The pancreas is an elongat¬ed, tapered gland that is located behind the stomach. It secretes digestive enzymes and the hormones insulin and glucagon. Pancreatitis is often caused by the digestion of parts of the organ by pancreatic enzymes that are normally carried to the small intestine with¬in the pancreatic ducts.
In acute pancreatitis, which is caused by obstruction of the normal pathway of secretion of pancreatic juice into the intestine, the zymogens of the proteolytic enzymes are con¬verted into their catalytically active forms prematurely, inside the pancreatic cells. As a result, these powerful enzymes attack the pancreatic tissue itself, causing a painful and serious destruction of the organ, which can be fatal. It is associated with alcoholism and biliary disease. Note: Manifestations or consequences of acute pancreatitis include enzymatic hemorrhagic fat necrosis with calcium soap formation and resultant hypocal¬cemia.
Physical findings of acute pancreatitis:
• The child will often walk into the office bent over, limping, and holding their right side.
• The child will look ill and lay quietly
• There is often diffuse abdominal tenderness.
• Point tenderness at McBurney's point which lies half-way between a line drawn from the umbilicus to the anterior iliac spine.
• Rebound tenderness --- pressing the abdomen at McBurney's point causes tenderness in a patient with appendicitis. When the abdomen is pressed, held momentarily, and then rapidly released, the patient may experience a momen¬tary increase in pain. This "rebound tenderness" suggests inflammation has spread to the peritoneum.
Autosomal dominant disorder
Neurofibromatosis (sometimes known as Elephant Man's disease) ) is a genetic neurologic¬al disorder that affects cell growth in nerve tissue. NF produces tumors of the skin,internal organs, and nerves that may become malignant. It also can affect bones, causing severe pain and debilitation and may result in learning disabilities, behavioral dysfunction, and hearing and vision loss.
Distinguishing features include:
• Multiple neurofibromas in skin and other locations
• Schwannomas of the VIIIth cranial nerve
• Cafe-au-lait spots (light brown-colored birthmarks)
• Lisch nodules (pigmented iris hamartomas)
Skeletal disorders such as scoliosis and bone cysts, and increased incidence of other tumors, especially pheochromocytoma and malignancies such as Wilms tumor, rhab-domyosarcoma, and leukemia, also occur.
Other autosomal dominant disorders:
• Familial hypercholesterolemia: characterized by anomalies of receptors for low-den-sity lipoprotein receptors.
• Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): character¬ized by local telangiectases of the skin and mucous membranes and by recurrent hemor¬rhage from these lesions. Common in Mormon families of Utah.
• Marfan syndrome: characterized by defects in skeletal, visual, and cardiovascular structures. Patients are tall and thin with abnormally long legs and arms, spider-like fin¬gers (arachnodactyly), and hyperextensible joints. Heart problems include: aneurysm of the proximal aorta, mitral valve prolapse and dissecting aneurysm of the aorta.
• Adult polycystic kidney disease: is characterized by numerous bilateral cysts that replace and destroy the renal parenchyma.
An autoimmune disorder
The most common cause of hypothyroidism in adults is Hashimoto's thyroiditis (also called chronic thyroiditis or Hashimoto's disease). It is a common thyroid gland disorder that can occur at any age, but it is most often seen in middle aged women. It is caused by a reaction of the immune system against the thyroid gland.
Clinical characteristics include:
• The onset of the disease is slow, and it may take months or even years for the condi-tion to be detected.
• The symptoms of hypothyroidism are evident (fatigue, slowed speech, cold intoler-ance, dry skin, coarse hair, puffy face, etc.).
• Though the thyroid may initially have been painlessly enlarged, over time the inflam-mation leads to atrophy of the thyroid with hypothyroidism.
1. Hashimoto's thyroiditis is associated with various autoantibodies, most notably antithyroglobulin, antithyroid peroxidase, anti-TSH receptor, and anti-iodine receptor antibodies.
2. Histologic characteristics include massive infiltrates of lymphocytes with germinal center formation.
3. Autoimmune disease refers to a disease resulting from an immune reaction produced by an individual's white blood cells or antibodies acting on the body's own tissues. In the case of Hashimoto's disease, there is the production of anti¬bodies in response to thyroid antigens and the replacement of normal thyroid structures with lymphocytes and lymphoid germinal centers.
4. Primary hyperparathyroidism is most often caused by a parathyroid adenoma.
5. Hypothyroidism (cretinism and myxedema) can be caused by an iodine defi¬ciency.
6. Graves disease is hyperthyroidism caused by diffuse toxic goiter.
Zollinger-Ellison syndrome
Zollinger-Ellison syndrome (ZES) is a rare disorder that causes tumors in the pancreas and duodenum and ulcers in the stomach and duodenum. The pancreas is a gland located behind the stomach. It produces enzymes that break down fat, protein, and carbohydrates from food, and hormones like insulin that break down sugar. The duodenum is the first part of the small intestine.
Peptic ulcers (circumscribed lesions in the mucosal membrane) can develop in the lower esophagus, stomach, pylorus, duodenum, or jejunum. About 80% of all peptic ulcers are duo¬denal ulcers, and occur most commonly in men between the ages of 20 and 50. Gastric ulcers, which affect the stomach mucosa, are most common in middle-aged and elderly men. Esophageal ulcers are caused by the repeated regurgitation of stomach acid (HCL) into the lower part of the esophagus.
Except for peptic ulcers of the stomach, peptic ulcers are always associated with hyper-secretion of gastric acid and pepsin. Ulceration is closely related to gastric Helicobacter pylori infection, which affects essentially all patients with duodenal ulcers and the majority of patients with gastric ulcers.
Peptic ulcers are sometimes associated with:
• The use of aspirin and NSAIDs • Primary hyperparathyroidism
• Smoking • Multiple endocrine neoplasia (MEN) type I
• Zollinger-Ellison syndrome (Wermer syndrome)
The most common symptom of a peptic ulcer is pain. If the erosion is sufficiently severe, blood vessels in the stomach wall are damaged, and bleeding occurs into the stomach itself (this is called a bleeding ulcer). In extreme cases, a peptic ulcer can lead to perforation, which is a hole entirely through the wall of the GI tract. This will cause an acute peritonitis which can lead to death.
Important: The most common complication of peptic ulcers is hemorrhage. It is most like-ly with duodenal ulcers. Malignant change is uncommon.
ADH
Diabetes insipidus (DI) is a rare condition caused by damage to the hypothalamus (specifically the supraoptic nuclei) or pituitary gland (posterior part) in the brain. This is due to the lack of ADH (antidiuretic hormone, vasopressin), which is produced in the nuclei but secreted by the posterior pituitary. ADH promotes water retention through action on the renal collecting ducts.
Diabetes insipidus is characterized by polyuria, with subsequent dehydration and insa¬tiable thirst. Causes may include tumors, trauma, inflammatory processes, lipid storage disorders, and other conditions characterized by damage to the hypothalamus. Note: In diabetes insipidus, the body fluid volumes remain pretty close to normal so long as the person drinks enough water to make up for the increased clearance of water in the urine.
DI should not be confused with diabetes mellitus, which results from insulin deficien¬cy or resistance leading to high blood glucose. Diabetes insipidus and diabetes mellitus are unrelated, although they can have similar signs and symptoms, like excessive thirst and excessive urination.
Diabetes mellitus (DM) is far more common than DI. DM has two forms, referred to as type 1 diabetes (formerly called juvenile diabetes, or insulin-dependent diabetes melli¬tus, or IDDM) and type 2 diabetes (formerly called adult-onset diabetes, or noninsulin-dependent diabetes mellitus, or NIDDM). DI is a different form of illness altogether.
Nephrogenic insipidus is a rare disorder in which the kidneys' ability to respond to ADH is impaired by drugs (like lithium, for example) and by chronic disorders includ¬ing polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders.
Children under age 10
Asthma is a chronic reactive airway disorder that causes episodic airway obstruction. Such obstruction results from bronchospasm, increased mucus secretion, and mucosal edema producing the characteristic wheezing sound. There are two types: allergic asth¬ma (most common form) and idiosyncratic asthma.
In asthma, bronchial linings overreact to various stimuli, causing smooth muscle spasms (bronchospasms) that severely constrict the airways. When the hypersensitive individ¬ual inhales a triggering substance (extrinsic allergen), abnormal antibodies stimulate mast cells in the lung interstitium to release both histamine and the slow-reacting sub¬stance of anaphylaxis (SRS-A). Both of these substances cause swelling of the bronchial smooth muscle thereby narrowing the bronchial lumen. On inhalation, the narrowed bronchial lumen can still expand slightly, allowing air to reach the alveoli. On exhala¬tion, increased intrathoracic pressure closes the bronchial lumen completely. Mucus fills the lung bases, inhibiting alveolar ventilation. Blood, shunted to the alveoli in other lung parts, still can't compensate for diminished ventilation.
1. Important: Nitrous oxide is safe to administer to people with asthma and is Notes
especially indicated for patients whose asthma is triggered by anxiety.
2. If patient is taking steroids, consult physician for the possible need for cor¬ticosteroid augmentation.
3. The inhalation of a short-acting selective beta2-agonist (terbutaline,
albuteral) is the preferred treatment for an acute asthmatic attack.
4. Status asthmaticus is a particularly severe episode of asthma, usually requir¬ing hospitalization, that does not respond adequately to ordinary therapeutic measures. Chronic partial airway obstruction may lead to death from respi¬ratory acidosis.
Graves' disease
Hyperthyroidism (or thyrotoxicosis) is an imbalance of metabolism caused by overproduc-tion of thyroid hormone (thyroxine-T4 and triiodothyronine-T3). Excessive production of the thyroid hormone thyroxin produces the symptoms of hyperthyroidism. The primary role of thyroxin is to stimulate cellular metabolism, growth, and differentiation of all tissues. In excess, therefore, it leads to high basal metabolism, fatigue, weight loss, excitability, ele¬vated temperature, and generalized osteoporosis. Oral manifestations are not too remark¬able, but if the disturbance begins in the early years of life, premature eruption of the teeth and loss of the deciduous dentition are common findings.
Two types of hyperthyroidism:
1. Graves' disease (most common form, occurs most frequently in women ages 40-60) is a thyroid-specific autoimmune disorder in which the body makes antibodies to the thy-roid-stimulating hormone receptor (TSHR), leading to hyperthyroidism, or an abnormally strong release of hormones from the thyroid gland. Normally, the release of thyroid hor-mones is mediated by thyroid-stimulating hormone (TSH), a hormone secreted by the pitu¬itary gland that binds to TSHR to stimulate the thyroid to release thyroid hormones. This normal cycle is self-regulating: the hormones secreted by the thyroid keep more TSH from being produced. The autoantibodies produced in Graves' disease are not subject to neg¬ative feedback, so they continue to be produced and bind to TSHR even when thyroid hormone levels rise too high. These antibodies act as agonists, stimulating more hormones to be released and thus leading to hyperthyroidism. There are a wide range of symptoms from anxiety and restlessness to insomnia and weight loss. In addition, the eyeballs may begin to protrude (exophthalmos) causing irritation and tearing.
2. Plummer's disease (toxic nodular goiter) arises from a long-standing simple goiter and occurs most often in the elderly. Symptoms are those of hyperthyroidism, but the protrud¬ing eyeballs seen in Graves' disease do not occur. Risk factors include being female and over 60 years old. This disorder is never seen in children.
Clostridium perfringens
Gas gangrene results from local infection with the anaerobic, spore-forming, gram-positive rod Clostridium perfringens. These bacteria under anaerobic conditions produce toxins that kill nearby cells. This rare infection generally occurs at the site of trauma or a recent surgical wound. The onset of gas gangrene is sudden and dramatic. Inflammation begins at the site of infection as a pale to brownish-red and extremely painful tissue swelling. Gas may be felt in the tissue as a crackly sensation when the swollen area is pressed with the fingers. The margins of the infected area expand so rapidly that changes are visible over a few minutes. The involved tissue is completely destroyed. Remember: Gangrene is the death of tissue, usually associated with loss of blood supply to the affected area. It is a form of necrosis combined with putrefaction (decomposition or rotting).
Systemic symptoms develop early in the infection. These consist of sweating, fever, and anxiety. If untreated, the individual develops a shock-like syndrome with decreased blood pressure (hypotension), renal failure, coma, and finally death.
Note: It is prevented by proper wound care.
1. Clostridia are obligate anaerobes, gram-positive bacteria capable of Notes endospore production.
2. Clostridium bacteria produce many different toxins (i.e., alpha, beta, epsilon, iota). The most important is the alpha toxin (lecithinase), which damages cell membranes, including those of erythrocytes, resulting in hemolysis.
3. Remember:
• Clostridium tetani causes tetanus (also known as lockjaw).
• Clostridium botulinum causes botulism.
• Actinomyces israelii causes actinomycosis.
Exudate
*** The edema resulting from inflammation is caused by increased capillary permeability. The edema fluid is called an exudate (commonly called 'pus'). The easiest way to see exu-date is to puncture a blister, the fluid that escapes is exudate. If the fluid is cloudy or discol-ored it is a strong indication of the presence of an infection in the wound. Exudate is charact¬erized by being protein-rich, cell-rich, glucose-poor and having a high specific gravity (exceeding 1.020). Types of inflammatory exudates include: suppurative, purulent, fibrinous, and pseudomembranous.
In addition to water, exudate contains varying amounts of nutrients, oxygen, antibodies and white blood cells (neutrophils). The first role of exudate is to flush away any foreign material from the site of the injury. It also acts as the carrier medium to bring fibrin and other repair materials to the site of the injury. Later in the inflammatory response it acts as the carrier for leukocytes (principally PMN's) and monocytes and supplies them with oxygen and nutrients while they ingest bacteria and other debris in the wound. The presence of exudate also enables the movement of these phagocytic cells within the wound. Later in the healing process the nutrients in the exudate are used by the new tissue to help in the generation of granulation tissue. Finally the exudate acts a lubricant speeding up the migration of epithelial cells across the wound surface to complete the initial repair of the wound.
Transudates result from increased intravascular hydrostatic pressure or from altered osmotic pressure. This fluid is thin and watery and is characterized by few blood cells, low protein content, and a low specific gravity (less than 1.020). It is present in non-inflammatory conditions.
1. Generally most of the common acute inflammatory reactions contain large Notes amounts of neutrophils and are termed suppurative (meaning to produce purulent matter).
2. This suppuration is the result of tissue necrosis, proteolytic enzymes, WBC's, and a buildup of tissue fluid.
Celiac disease
Malabsorption means the failure of the GI tract, usually the small intestine, to absorb one or more substances from the diet. The most common symptoms of malabsorption syn¬dromes are steatorrhea (stool that is a light-colored, soft, bulky and foul-smelling), diar¬rhea, bloating, flatulence, cramping and weight loss.
Malabsorption syndromes:
• Celiac disease: is a condition where the mucosal lining of the small intestine is dam¬aged by ingestion of gluten. One factor thought to play a role in when and how celi¬ac appears is whether a person was breastfed and how long. The longer a person was breastfed, the later the symptoms of celiac disease appear, and the more atyp¬ical the symptoms. Persons with this disease have to avoid wheat, rice and corn. Note: It can be fatal in adults due to the development of lymphoma in the intestine.
• Tropical sprue: the cause of this disease is unknown, but it may be related to an infectious organism. The condition affects residents of or visitors to the tropics. Typical symptoms include steatorrhea, diarrhea, weight loss, and a sore tongue from vitamin B deficiency. Treatment consists of antibiotics, often Tetracycline, for up to 6 months.
• Whipple Disease: is a systemic bacterial (Tropheryma whippelii) illness usual¬ly affecting middle age men and presents diarrhea, anemia, arthritis, fever, weight loss, swollen lymph nodes and skin pigmentation. It is diagnosed by taking a small bowel biopsy through an endoscope, and the treatment is antibiotics (penicillin or tetracycline) for one year or longer.
1. Symptoms of malabsorption syndromes are due to:
• Osmotically active substances remaining in the GI tract (diarrhea, and bloating)
• Nutritional deficiencies (weight loss, glossitis, and megaloblastic anemia)
Autoimmune disease
Sjogren's syndrome is a condition that is most likely of autoimmune origin. It is marked chiefly by chronic inflammation (caused by white blood cell infiltration) of the salivary glands and lacrimal glands. This usually progresses to fibrosis and atrophy of these glands.
The triad of findings found in Sjogren's syndrome includes:
• Keratoconjunctivitis sicca (dry eyes)
• Xerostomia (dry eyes)
• Associated connective tissue disease (most often rheumatoid arthritis)
All three symptoms rarely occur in one patient. A definite diagnosis can be made only when at least two of the symptoms are present. It is less common than rheumatoid arthritis and more prevalent in women than in men.
r---7, 1. The clinical presentation of diminished lacrimal and salivary gland secretion No I is often referred to as sicca complex.
2. Sjogren's syndrome that results from a rheumatic condition is classified as secondary Sjogren's syndrome. Primary Sjogren's syndrome occurs by itself.
3. Sjogren's syndrome is associated with an increased incidence of malignant lymphoma.
4. Occasionally, the lymphocytic infiltration is massive and causes enlargement of the glands (this is called Mikulicz's syndrome).
5. The decrease in salivation may cause rampant caries reminiscent of radia¬tion caries. This is a result of a shift toward a more acidogenic microflora.
6. SS-A (anti Ro) and SS-B (anti La) antibodies, which are directed against two extractable nuclear antigens, have been detected with high frequency in patients with Sjogren's syndrome.
Tetany
Tetany is a clinical neurological syndrome characterized by muscle twitches, cramps, and carpopedal spasm. When severe, laryngospasm and seizures develop. All of these signs and symptoms reflect irritability of the central and peripheral nervous systems. It is usually asso¬ciated with calcium deficiency (hypoparathyroidism), vitamin D deficiency or alkalosis. Note: Acute hypocalcemia in the human being ordinarily causes no other significant effects besides tetany because tetany kills the patient before other effects can develop.
Tetanus:
• Toxin enters the CNS along the peripheral nerves
• Incubation period of 5 to 10 days
• Stiffness of the jaws, difficulty swallowing, fever, headache
• Risus sardonicus: fixed "smile" and elevated eyebrows
• Severe spasms of the neck, back and abdominal muscles
Botulism:
• C. Botulinum spores are highly resistant to heat, but toxins are not
• Proper canning and heating of food prevents botulism
• Nausea, vomiting and abdominal cramps usually precede the neurological symptoms: dry mouth, diplopia, loss of pupillary reflexes, followed by descending paralysis and res-piratory failure
1. Tetany normally will occur when the blood concentration of calcium reaches approximately 6 mg% (normal is about 10 mg%). It is lethal at about 4 mg%.
2. Chvostek's sign: to check for Chvostek's sign, tap the facial nerve above the mandibular angle, adjacent to the earlobe. A facial muscle spasm that causes the patient's upper lip to twitch, confirms tetany.
3. Trousseau's sign: to check for Trousseau's sign, apply a blood pressure cuff to the patient's arm. A carpopedal spasm that causes thumb adduction and phalangeal extension, confirms tetany.
DiGeorge syndrome
DiGeorge syndrome is a rare immunodeficiency disorder characterized by various congenital abnormalities that develop because of defects that occur during early fetal development. These defects occur in areas known as the 3rd and 4th pharyngeal pouches, which later develop into the thymus and parathyroid glands. Developmental abnormalities may also occur in the 4th branchial arch.
Normally the thymus gland is located midline in the upper part of the chest cavity. It lies below the sternum and above the trachea and the heart. In a baby, the thymus is relatively large (as compared to the rest of the baby's body). It then continues to grow until puberty at the end of which it begins to shrink (involute). It is the primary gland of the lymphatic system, which is necessary for the normal functioning of the immune system. The parathyroid glands, located on the sides of the thyroid gland, are responsible for the maintenance of normal levels of calcium in the blood. The thymus and parathyroid glands are missing or underdeveloped in children with DiGeorge syndrome. The symptoms of this disorder vary greatly, depending upon the extent of the missing thymus and parathyroid tissue. The primary problem caused by DiGeorge syndrome is the repeated occurrence of various infections due to a diminished immune system.
— 1. The absence of the thymus results in T-cell deficiency. These children have Noteq normal B lymphocytes and form antibodies, but they have decreased or absent
delayed-type hypersensitivity.
2. These children develop tetany due to hypocalcemia (from the absence of the parathyroids).
3. Up to 75% of myasthenia gravis patients present with an abnormal thymus such as a thymoma (a tumor of the thymus).
Severe Combined Immunodeficiency Disease (SCID)
The most dangerous type of congenital (inherited) immunodeficiency, severe combined immunodeficiency disease (SCID), results from a failure of stem cells to differentiate properly. Individuals with SCID have neither B- nor T-lymphocytes and are incapable of any immunological response. These children generally die before age two. Note: SCID became more widely known in the 1970s when the world learned of David Vetter, a boy with SCID who lived for 12 years in a plastic, germ-free bubble.
The Wiskott-Aldrich syndrome (also called immunodeficiency with eczema and thrombocytopenia) affects only boys and is characterized by defective B-cell and T-cell functions. Its clinical features include thrombocytopenia with severe bleeding, eczema, recurrent infection, and an increased risk of lymphoid cancers.
Ataxia-telangiectasia is an inherited disorder that affects many tissues and systems in the body. Multiple symptoms may include telangiectasis (dilation of capillaries), ataxic (uncoordinated) gait, proneness to infection, defective humoral and cellular immunity and increased risk of malignancies. The most obvious symptoms of the disease are multiple telangiectases that are easily visible in the white of the eye and skin areas such as the ear and nose along with graying of the hair, and irregular pigmentation of the areas exposed to sunlight. In addition, there is decreased coordination of movements (ataxia) in late childhood.
Hyperimmunoglobulin E syndrome (also known as Job syndrome) is an immunodef-iciency disorder characterized by very high levels of IgE antibodies and repeated infections, most commonly by Staphylococcus aureus. Treatment consists of taking antibiotics continually for the infections.
Klinefelter's syndrome
Klinefelter's syndrome is a chromosome abnormality that affects only men and causes hypogonadism. A person's sex is determined by the X and Y chromosomes. Normally, men have an X and a Y and women have two X's. In Klinefelter's syndrome, a male has two X's and a Y.
The condition is common and affects 1 in 500 men. The infant appears normal at birth, but the defect usually becomes apparent in puberty when secondary sexual characteris-tics fail to develop (or develop late). These individuals have small testes, enlarged breasts, a feminine distribution of pubic hair, and frequently mild retardation. These boys tend to be tall, with long legs. This disorder is associated with advanced maternal and paternal age.
Turner's syndrome is a birth defect caused by the absence or defect of an X chromo-some, which inhibits sexual development and usually causes infertility. The incidence is 1 out of 3,000 live births. Girls with Turner's syndrome usually have short stature, webbing of the skin of the neck, absent or retarded development of secondary sexual characteristics at puberty, absence of menstruation, coarctation (narrowing) of the aorta and abnormalities of the eyes and bones. The condition is either diagnosed at birth because of the associated anomalies, or at puberty when there is absent or delayed menses and delayed development of normal secondary sexual characteristics.
Examples of diseases that can be diagnosed by karyotyping:
• Klinefelter's syndrome : XXY
• Trisomy 18: extra chromosome 18
• Down's syndrome: extra chromosome 21
• Turner's syndrome: XO
Peripheral edema
Edema is an abnormal accumulation of fluid in the interstitial spaces or body cavities. Causes of edema:
• Increased capillary permeability (principal factor): occurs in inflammation or with injury to capillary endothelium
• Increased hydrostatic pressure: is exemplified by congestive heart failure
- Right-sided heart failure results in peripheral edema
- Left-sided heart failure results in pulmonary edema
• Decreased oncotic pressure: is from hypalbuminemia, which results from: - Increased loss of protein (seen in nephrotic syndrome) - Decreased production of albumin (seen in cirrhosis of the liver)
• Increased sodium retention
• Blockage of lymphatics: results in lymphedema Types of edema:
• Anasarca: generalized edema
• Hydrothorax: is an accumulation of fluid in the pleural cavity
• Hydrocephaly: is an accumulation of cerebrospinal fluid in the cranial cavity
• Hydropericardium: is an accumulation of fluid in the pericardial cavity
• Hydroperitoneum (ascites): is an accumulation of fluid in the peritoneal cavity
• Transudate: noninflammatory edema fluid that results from altered intravascular hydrostatic or osmotic pressure. It has a low protein content and a specific gravity of less than 1.012
• Exudate: edema fluid resulting from increased vascular permeability caused by inflammation. It has a high protein content and a specific gravity exceeding 1.020 Edema may be generally described in one of two ways:
Notes 1. Pitting edema: when you press a swollen area for 5 seconds and then quickly remove it, an indentation is left that fills slowly. Seen in acute disease.
2. Non-pitting edema: when you press a swollen area for 5 seconds and then quickly remove it, no indentation is left in the skin. Seen in chronic disease.
Smoking
High blood pressure
Increased cholesterol levels
A blood clot within an artery is known as an arterial thrombosis. Arterial thrombosis is responsible for heart attacks, strokes and peripheral vascular disease (thrombosis in leg arteries). Arterial thrombosis usually affects individuals who already have atherosclerosis, or narrowing of the arteries. Atherosclerosis causes the walls of the arteries to 'fur up' with deposits of atheroma, a porridge-like substance.
A thrombus is a solid mass of clotted blood that forms when an alteration in the epithelial lining causes platelet aggregation and consequent fibrin entrapment of red and white blood cells along with additional platelets. Thrombus formation is more rapid in areas where blood flow is slower, because contact between platelets increases and thrombin accumulates. Thrombus formation is enhanced by endothelial injury, an alteration in blood flow, and hypercoaguability of the blood.
Types of thrombi:
• Agonal thrombus forms in the heart during the process of dying after prolonged heart failure.
• Mural thrombus: forms as a result of damage to the ventricular endocardium (usually left ventricle, following myocardial infarct). A major complication of a mural thrombus is a cerebral embolism. It complicates myocardial infarction, atrial fibrillation, and atherosclerosis of the aorta.
• White thrombus: a thrombus composed chiefly of blood platelets.
• Red thrombus: formed rapidly by the coagulation of stagnating blood, composed of red blood cells rather than platelets.
• Fibrin thrombus: formed by repeated deposits of fibrin from the circulating blood. It usually does not completely occlude the vessel.
1. Morphologically, an arterial thrombus shows alternating red and white laminations (lines of Zahn). Venous thrombi are more uniformly red; the lines are distinct.
2. Phlebitis is the inflammation of a vein. Congestion is the accumulation of excessive blood with¬in the blood vessels. Thromolysis is the breaking up of a blood clot.
3. An embolus is a blood clot that moves through the bloodstream until it lodges in a narrowed vessel and blocks circulation. Most emboli are thromboemboli.
4. Deep venous thrombosis (DVT) affects mainly the veins in the lower leg and the thigh It involves the formation of a clot (thrombus) in the larger veins of the area. This thrombus may interfere with circulation of the area, and it may break off and travel through the blood stream (embolize). The embolus thus created can lodge in the brain, lungs (pulmonary embolism), heart, or other area, caus¬ing severe damage to that organ.
Progressive
Shock is complex by its very nature. The pathophysiology of shock many times involves the multiple fail¬ures of organs and even death. Shock at its most basic level is the lack of equilibrium between the cell's need for oxygen and the body's inability to provide that cellular oxygen. The body's response to shock usually occurs in stages. These stages are initial, compensatory, progressive and refractory. The etiolo¬gy of shock can be classified in three categories with one category having three separate subcategories. The three main categories are hypovolemic, cardiogenic and distributive shock. Distributive shock can be further delineated as septic, neurogenic and anaphylactic shock.
The stages of shock:
• Initial stage: here the cardiac output is seen to decrease, causing an impairment of the tissue perfu-sion. This action trips the cell to convert, because of lack of sufficient oxygen, from aerobic to anaero-bic metabolism. The mechanism of anaerobic metabolism causes a sudden increase in waste products called lactic acid that further injures the cells which causes further cell death in a cyclical fashion. After the body enters the initial stage, if the problem is not solved then shock will progress to the compensa¬tory stage.
• Compensatory stage: where the body tries to compensate for the lack of equilibrium. In this stage the body will alter its hemodynamic functions to compensate for poor tissue perfusion. The heart rate will increase, the vessels of the body will begin constricting and the body will begin to retain sodium and water. Additionally as the stage progresses the blood glucose levels will begin to rise and the res-piratory rate will increase (hyperventilation) in an attempt to blow off the effects of lactic acidosis which occurrred in the initial stage when the body switched over from aerobic to anaerobic metabolism. These changes set the stage for the progressive stage.
• Progressive stage: characterized by the beginning of failure of the compensatory stage to bring the body back to equilibrium. The failure of the compensatory stage signals the beginning of the shock cycle being perpetuated. Basically, the cycle begins to self-perpetuate a downward spiral which can end in death. During this stage the cells are functioning on anaerobic metabolism which is causing a buildup of lactic acid. Anaerobic metabolism does not produce enough energy to sustain cellular life and cells begin to die.
• Refractory stage: where the patient will reach a point of no return. This point is where, no heroic measures will save the patient. This is because every organ needs its basic building block, the cell, to survive. If the cells of an organ die then the organ dies. Once one of the organs dies then others will fol¬low suit and multiple organ failure will occur ending in death.
Hypovolemic
The stages of shock reflect a process. The types of shock refer to different initial mechanisms of action that trip those stages. The three main categories are hypovolemic, cardiogenic and distributive shock. Distributive shock can be further delineated as septic, neurogenic and anaphylactic shock.
• Hypovolemic shock is the most common type of shock. It occurs from a lack of sufficient fluid in the intravascular space. The etiology of this is that the hypovolemic shock can occur one of two ways.
The first way is an external loss of body fluid such as blood or plasma. An arterial laceration that is not stopped or does not stop on its own. Another form of hypovolemic shock is when fluid in the body is moved to an area where it is not used such as what is called "third" spacing. An example of extracellular fluid loss is severe sodium deficiency. *** The pathophysiology of hypovolemic shock is that when fluid volume goes down a decrease in the circulating volume of blood is seen. When the circulating volume of blood occurs the preload to the heart is decreased. A decrease in preload causes a decrease in stroke vol¬ume which causes a decrease in the cardiac output. With reduced cardiac output decreased cellular oxygen perfusion will occur. When cells do not receive enough oxygen they die.
• Cardiogenic shock is where the heart is unable to pump forward the amount of blood in one stroke to support life. This can occur for several reasons. The etiology of cardiogenic shock is shown to be one of several problems, that ultimately affect cardiac output. These examples include ischemia of the left ventricle, structural problems, and dysrhythmias. Anything that hinders the flow of blood out of the heart can cause cardiogenic shock. When blood flow out of the heart is decreased, there will be a decrease in oxy¬gen availability to the cells. This decrease in oxygen available to the cell will cause the cells to switch over to anaerobic metabolism, and the whole cycle of shock is started.
• Distributive shock is a condition where the flow of blood is not evenly distributed. It is actually an umbrella for three other forms of shock. They are septic, anaphylactic and neurogenic shock.
- Anaphylactic shock is when the body's antibody-antigen response is triggered by something the per-son is allergic to.
- Neurogenic shock is caused by the suppression or outright loss of sympathetic tone. It is the rarest form of shock. The etiology is anything which causes any disruption of the sympathetic nervous system. Some examples of this are spinal injury, spinal anesthesia, drugs and emotional stress
• Sepsis is the invasion of the body by bacteria which causes an immune response. The resulting fallout is that tissue perfusion is impaired and the cycle of shock is begun once again at the cellular level. The classic example of septic shock is TSS or toxic shock syndrome which is an invasion of the body by a toxin producing gram-positive bacteria.
Methicillin
Methicillin is not frequently used because of the incidence of interstitial nephritis and the availability of equally efficacious alternatives (nafcillin and oxacillin). It is given through IV in severe penicillinase-producing staphylococcal infections.
Remember: Penicillinase is produced by certain bacteria (e.g., some strains of staphy-lococci) that render penicillin inactive. It degrades the beta-lactam ring structure of penicillin. Structural modification of penicillin G for example, methicillin), can render the molecule resistant to penicillinases, but may also narrow the spectrum of action, lim¬iting the primary use of such antibiotics to the treatment of infections caused by Staphylococcus species.
Other penicillinase-resistant penicillins include cloxacillin, dicloxacillin, nafcillin, oxacillin, amoxicillin / clavulonate potassium (Augmentin), ampicillin / sulbactin (Unasyn), piperacillin / tazobactam (Zosyn), and ticarcillin / clavulonate potassium (Timentin).
1. Methicillin-resistant Staph. aureus (MRSA) is a group of resistant Staph.
Notes bacteria that can be life-threatening. These bacteria are resistant to all the peni-cillinase-resistant penicillins and cephalosporins. Such strains are usually resist¬ant as well to aminoglycosides, tetracyclines, erythromycins, and clindamycin. In the past, vancomycin has been used against MRSA. However, microorgan¬isms resistant to vancomycin have been reported and its use has been curtailed.
2. Penicillin will work only on growing cells that contain peptidoglycan in their cell wall. This is why penicillin shows its greatest bactericidal activity against growing gram-positive bacteria (They have a thick peptidoglycan or murein layer in their cell wall.). Remember: Penicillin inhibits the terminal step in peptidoglycan synthesis.
Persons with an allergy to pollen
Published studies have demonstrated an increased risk of developing an allergic reaction to either latex protein (type I) or certain chemicals used in the latex manufactur¬ing process (type IV) in certain groups of people. Current information has not shown a cross-reaction between pollen allergies and water-soluble latex allergens. Individuals who appear to be predisposed to readily developing type I hypersensitivity reactions (i.e., who are atopic), however, can become sensitized to latex allergens more readily than people with few or no allergies.
1. Atopy is the genetic tendency to develop the classic allergic diseases % atopic dermatitis, allergic rhinitis (hay fever), and asthma. Atopy involves the capacity to produce IgE in response to common environmental proteins such as house dustmites, grass pollen, and food allergens.
2. Remember: TH1 & TH2 cells are subsets of T-helper lymphocytes, involved in cell-mediated immune responses.
3. TH1 cells secrete IL-1 and gamma interferon, which enhance cell-mediated responses and inhibit both TH2 subset cell activity and the humoral immune responses. TH1 is inflammatory, produces IL2, IFNgamma, TNFbeta, provides help to B-cells in IgG2a production, activates macrophages and CTL and stimulates delayed-type hypersensitivities (Type IV hypersensitivity).
4. TH2 cells, the other subset of T-helper cells, are also involved in cell-medi¬ated immune responses. TH2 cell activity and secretions are thought to inhibit cell-mediated responses and to enhance the humoral response. TH2 cells pro¬duce IL4 , IL5, IL6, IL10 and IL13, which provide help to B-cells and induce class switch to IgE and IgGl, as well as support eosinophils and mast cells.
Handwashing
Hands have long been recognized as one of the most important vehicles for microbial spread of disease. More than 100 years ago, Semmelweiss and Lister suggested that the hands of medical professionals were sources of cross-infection with pathogenic bacteria and nosocomial infections. For health care workers, handwashing is a primary disease prevention measure. The simple act of handwashing can significantly reduce the number of transient and normal microorganisms that colonize host tissue, thus limiting the poten¬tial for spread of infection between health care providers and patients.
For routine handwashing, a vigorous rubbing together of all surfaces of lathered hands for at least 10 seconds, followed by thorough rinsing under a stream of water is recom¬mended.
The aim of handwashing is to remove microorganisms from the hands, preventing their potential transfer. It is known that organisms survive and multiply on human hands, cre¬ating the opportunity to infect others or the host. Handwashing reduces the number of transient organisms on the skin surface. Although hands cannot be sterilized, most tran¬sient organisms can be removed by 30 seconds of proper scrubbing with soap and water. Proper scrubbing would include vigorous motion with the hands rubbing together and fin¬gers working in between the finger web space and inclusive of the dorsal and ventral sur¬faces of the hands. Microbes that reside in sweat ducts and hair follicles of the skin, how¬ever, cannot be dislodged readily. Surveys show that one in five medical professionals carries potentially pathogenic antibiotic-resistant pathogens on his or her hands. Handwashing by medical professionals occurs at only 30% of the ideal rate. Failure to wash one's hands before and after each patient contact is probably the most important contributor to the spread of infections. These microbes pose a threat to patients with reduced defenses, so scrubbing with an antiseptic prior to contact with these patients is usually recommended.