NEET MDS Lessons
General Pathology
Osteomyelitis
This refers to inflammation of the bone and related marrow cavity almost always due to infection. Osteomyelitis can be acute or a chronic. The most common etiologic agents are pyogenic bacteria and Mycobacterium tuberculosis.
Pyogenic Osteomyelitis
The offending organisms reach the bone by one of three routes:
1. Hematogenous dissemination (most common)
2. Extension from a nearby infection (in adjacent joint or soft tissue)
3. Traumatic implantation of bacteria (as after compound fractures or orthopedic procedures). Staphylococcus aureus is the most frequent cause. Mixed bacterial infections, including anaerobes, are responsible for osteomyelitis complicating bone trauma. In as many as 50% of cases, no organisms can be isolated.
Pathologic features
• The offending bacteria proliferate & induce an acute inflammatory reaction.
• Entrapped bone undergoes early necrosis; the dead bone is called sequestrum.
• The inflammation with its bacteria can permeate the Haversian systems to reach the periosteum. In children, the periosteum is loosely attached to the cortex; therefore, sizable subperiosteal abscesses can form and extend for long distances along the bone surface.
• Lifting of the periosteum further impairs the blood supply to the affected region, and both suppurative and ischemic injury can cause segmental bone necrosis.
• Rupture of the periosteum can lead to an abscess in the surrounding soft tissue and eventually the formation of cutaneous draining sinus. Sometimes the sequestrum crumbles and passes through the sinus tract.
• In infants (uncommonly in adults), epiphyseal infection can spread into the adjoining joint to produce suppurative arthritis, sometimes with extensive destruction of the articular cartilage and permanent disability.
• After the first week of infection chronic inflammatory cells become more numerous. Leukocyte cytokine release stimulates osteoclastic bone resorption, fibrous tissue ingrowth, and bone formation in the periphery, this occurs as a shell of living tissue (involucrum) around a segment of dead bone. Viable organisms can persist in the sequestrum for years after the original infection.
Chronicity may develop when there is delay in diagnosis, extensive bone necrosis, and improper management.
Complications of chronic osteomyelitis include
1. A source of acute exacerbations
2. Pathologic fracture
3. Secondary amyloidosis
4. Endocarditis
5. Development of squamous cell carcinoma in the sinus tract (rarely osteosarcoma).
Tuberculous Osteomyelitis
Bone infection complicates up to 3% of those with pulmonary tuberculosis. Young adults or children are usually affected. The organisms usually reach the bone hematogenously. The long bones and vertebrae are favored sites. The lesions are often solitary (multifocal in AIDS patients). The infection often spreads from the initial site of bacterial deposition (the synovium of the vertebrae, hip, knee, ankle, elbow, wrist, etc) into the adjacent epiphysis, where it causes typical granulomatous inflammation with caseous necrosis and extensive
bone destruction. Tuberculosis of the vertebral bodies (Pott disease), is an important form of osteomyelitis.
Infection at this site causes vertebral deformity and collapse, with secondary neurologic deficits. Extension of the infection to the adjacent soft tissues with the development of psoas muscle abscesses is fairly common in Pott disease. Advanced cases are associated with cutaneous sinuses, which cause secondary bacterial infections. Diagnosis is established by synovial fluid direct examination, culture or PCR
Urticaria (hives) refers to the presence of edema within the dermis and itchy elevations of the skin which may relate to either a Type I (MC) or Type III hypersensitivity reaction.
Type III hypersensitivity reaction.
- exaggerated venular permeability MC related to IgE mediated disease and release of histamine from mast cells.
Fanconi’s syndrome
Characterized by the failure of the proximal renal tubules to resorb amino acids, glucose, and phosphates.
May be inherited or acquired.
Clinical manifestations include
glycosuria, hyperphosphaturia, hypophosphatemia, aminoaciduria, and systemic acidosis.
Hyperthyroidism
Hyperthyroidism (Thyrotoxicosis) is a hypermetabolic state caused by elevated circulating levels of free T3 and T4 . This may primary (Graves disease) or rarely, secondary (due to pituitary or hypothalamic diseases).
- The diagnosis is based on clinical features and laboratory data.
Lab Test
- The measurement of serum TSH concentration provides the most useful single screening test for hyperthyroidism, because TSH levels are decreased in primary cases, even when the disease is still be subclinical.
- In secondary cases TSH levels are either normal or raised.
- A low TSH value is usually associated with increased levels of free T4 .
- Occasionally, hyperthyroidism results from increased levels of T3 .
Causes of disease
The causes of disease Diseases can be caused by either environmental factors, genetic factors or a combination of the two.
A. Environmental factors
Environmental causes of disease are many and are classified into:
1. Physical agents
2. Chemicals
3. Nutritional deficiencies & excesses
4. Infections & infestations
5. Immunological factors
6. Psychogenic factors
1. Physical agents
These include trauma, radiation, extremes of temperature, and electric power. These agents
apply excess physical energy, in any form, to the body.
2. Chemicals
With the use of an ever-increasing number of chemical agents such as drugs,
3. Nutritional deficiencies and excesses
Nutritional deficiencies may arise as a result of poor supply, interference with absorption, inefficient transport within the body, or defective utilization. It may take the form of deficiency.
4. Infections and infestations
Viruses, bacteria, fungi, protozoa, and metazoa all cause diseases. They may do so by causing cell destruction directly as in virus infections (for example poliomyelitis) or protozoal infections (for example malaria).
5. Immunological factors
A. Hypersensitivity reaction
This is exaggerated immune response to an antigen. For example, bronchial asthma can occur due to exaggerated immune response to the harmless pollen.
B. Immunodeficiency
This is due to deficiency of a component of the immune system which leads to increased susceptibility to different diseases. An example is AIDS.
C. Autoimmunity
This is an abnormal (exaggerated) immune reaction against the self antigens of the host. Therefore, autoimmunity is a hypersensitivity reaction against the self antigens. 4
6. Psychogenic factors
The mental stresses imposed by conditions of life, particularly in technologically advanced
communities, are probably contributory factors in some groups of diseases.
B. Genetic Factors
These are hereditary factors that are inherited genetically from parents.
Roseola
- alias exanthem subitum; caused by Herpes virus type 6.
- children 6 months to 2 years old; spring and fall; incubation 10-15 days.
- sudden onset of a high fever with absence of physical findings; febrile convulsions are particularly common.
- fever falls by crisis on the 3rd or 4th day → 48 hours after temperature returns to normal macular or maculopapular rash starting on the trunk and spreading centrifugally.
Strep viridans
Mixed species, all causing α-hemolysis. All are protective normal flora which block adherence of other pathogens. Low virulence, but can cause some diseases:
Sub-acute endocarditis can damage heart valves.
Abscesses can form which are necrotizing. This is the primary cause of liver abscesses.
Dental caries are caused by Str. mutans. High virulence due to lactic acid production from glucose fermentation. This is why eating sugar rots teeth. Also have surface enzymes which deposit plaque.