Valvular disease
A. Generally, there are three types:
1. Stenosis—fibrotic, stiff, and thickened valves, resulting in reduced blood flow through the valve.

2. Regurgitation or valvular insufficiency— valves are unable to close completely, allowing blood to regurgitate.

3. Prolapse—“floppy” valves; may occur with or without regurgitation. The most common valvular defect.

Gout
This is a disorder caused by the tissue accumulation of excessive amounts of uric acid, an end product of purine metabolism. It is marked by recurrent episodes of acute arthritis, sometimes accompanied by the formation of large crystalline aggregates called tophi & chronic joint deformity. All of these are the result of precipitation of monosodium urate crystals from supersaturated body fluids. Not all individuals with hyperuricemia develop gout; this indicates that influences besides hyperuricemia contribute to the pathogenesis. Gout is divided into primary (90%) and secondary forms (10%). 

Primary gout designates cases in whom the basic cause is unknown or when it is due to an inborn metabolic defect that causes hyperuricemia.

In secondary gout the cause of the hyperuricemia is known.

Pathologic features 

The major morphologic manifestations of gout are
1. Acute arthritis
2. Chronic tophaceous arthritis
3. Tophi in various sites, and
4. Gouty nephropathy

Acute arthritis

- The synovium is edematous and congested,
- There is an intense infiltration of the synovium & synovial fluid by neutrophils.
- Long, slender, needle-shaped monosodium urate crystals are frequently found in the cytoplasm of the neutrophils as well as in small clusters in the synovium.

Chronic tophaceous arthritis:

- This evolves from repetitive precipitation of urate crystals during acute attacks. The urates can heavily encrust the articular surfaces and form visible deposits in the synovium.
- The synovium becomes hyperplastic, fibrotic, and thickened by inflammatory cells, forming a pannus that destroys the underlying cartilage, and leading to erosions of subjacent bone.
- In severe cases, fibrous or bony ankylosis occurs, resulting in loss of joint function. 

Tophi

These are the pathognomonic hallmarks of gout.
- Tophi can appear in the articular cartilage, periarticular ligaments, tendons, and soft tissues, including the ear lobes. Superficial tophi can lead to large ulcerations of the overlying skin.
- Microscopically, they are formed by large aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body giant cells, attempting to engulf the masses of crystals.

Gouty nephropathy

- This refers to the renal complications associated with urate deposition including medullary tophi, intratubular precipitations and renal calculi. Secondary complications such as pyelonephritis can occur, especially when there is urinary obstruction.

Pathogenesis

- Although the cause of excessive uric acid biosynthesis in primary gout is unknown in most cases, rare patients have identifiable enzymatic defects or deficiencies that are associated with excess production of uric acid.
- In secondary gout, hyperuricemia can be caused by increased urate production (e.g., rapid cell lysis during chemotherapy for lymphoma or leukemia) or decreased excretion (chronic renal failure), or both. Reduced renal excretion may also be caused by drugs such as thiazide diuretics, because of their effects on uric acid tubular transport.
- Whatever the cause, increased levels of uric acid in the blood and other body fluids (e.g., synovium) lead to the precipitation of monosodium urate crystals. The precipitated crystals are chemotactic to neutrophils & macrophages through activation of complement components C3a and C5a fragments. This leads to a local accumulation of neutrophils and macrophages in the joints and synovial membranes to phagocytize the crystals. The activated neutrophils liberate destructive lysosomal enzymes. Macrophages participate in joint injury by secreting a variety of proinflammatory mediators such as IL-1, IL-6, and TNF. While intensifying the inflammatory response, these cytokines can also directly activate synovial cells and cartilage cells to release proteases (e.g., collagenases) that cause tissue injury.

- Repeated bouts of acute arthritis, however, can lead to the permanent damage seen in chronic tophaceous arthritis.

b Pseudogout (chondrocalcinosis) (Calcium pyrophosphate crystal deposition disease). Pseudogout typically first occurs in the age 50 years or older. It involves enzymes that lead to accumulation and eventual crystallization of pyrophosphate with calcium. The pathology in pseudogout involves the recruitment and activation of inflammatory cells, and is reminiscent of gout. The knees, followed by the wrists, elbows,
shoulders, and ankles, are most commonly affected. Approximately 50% of patients experience significant joint damage.

Infectious Arthritis can cause rapid joint destruction and permanent deformities. Microorganisms can lodge in joints during hematogenous dissemination, by direct inoculation or by contiguous spread from osteomyelitis or a soft tissue abscess.

Suppurative Arthritis is a subtype of infectious arthritis in which the bacteria seed the joint during episodes of bacteremia. Haemophilus influenzae predominates in children under age 2 years, S. aureus is the main causative agent in older children and adults, and gonococcus is prevalent during late adolescence and young adulthood. 

There is sudden onset of pain, redness, and swelling of the joint with fever, leukocytosis, and elevated ESR. In 90% of nongonococcal suppurative arthritis, the infection involves only a single joint-usually the knee. Joint aspiration is typically purulent, and allows identification of the causal agent. 

Str. agalactiae

β-hemolytic, with its capsule being the major virulence factor.  Capsule inhibits phagocytosis and complement activation.  The CAMP factor (a hemolysin) is another virulence factor.

Group B strep are normally found in GI tracts and vaginas. 

Major disease is neonatal sepsis/meningitis after passage through infected birth canal.  May lead to meningitis, and CNS damage is high.  Mothers colonized with Group B strep should be treated pre-delivery.

Paroxysmal nocturnal haemoglobinuria (PNH).

Feature:

• Acquired RBC rnembrane defect rendering it susceptible  to complement lysis.
• Features of intravascular haemolysis.
• Blood picture of haemolysis anemais with pancytopenia.
• Ham’s acid serum test (lysis at 37COin acid pH) + ve

Herpes simplex is subdivided into type 1 and 2, the former usually developing lesions around the lips and mouth and the latter producing vesicular lesions in the genital region 
 - contracted by physical contact; incubation 2-10 days.
 - primary HSV I usually is accompanied by systemic signs of fever and Lymphadenopathy, while recurrent herpes is not associate with systemic signs.
 - dentists often become infected by contact with patient saliva and often develop extremely painful infections on the fingers (herpetic whitlow).
 - Herpes viruses remain dormant in sensory ganglia and are reactivated by stress, sunlight, menses, etc. 

 - Herpes gingivostomatitis is MC primary HSV 1 infectionÆpainful, vesicular eruptions that may extend for the tongue to the retropharynx.
 - Herpes keratoconjunctivitis (HSV 1)
 - Kaposi's varicelliform eruption refers to an HSV 1 infection superimposed on a previous dermatitis, usually in an immunodeficient person.
 - laboratory: culture; ELISA test on vesicle fluid; intranuclear inclusions within multinucleated squamous cells in scrapings (Tzanck preps) of vesicular lesions. 

Muscle pathology
1. Myasthenia gravis
a. An autoimmune disease caused by autoantibodies to acetylcholine receptors at the neuromuscular junctions.
b. Characterized by muscle weakness or the inability to maintain long durations of muscle contractions; this worsens during exercise but recovers after rest.
c. Affects various muscle groups, including:
(1) Eyes—diplopia, ptosis.
(2) Neck—dysphagia, problems swallowing or speaking.
(3) Extremities—arms and legs.
d. Treatment: cholinesterase inhibitors(neostigmine), anti-immune therapy.

2. Muscle tumors
a. Rhabdomyoma—benign tumor of skeletal muscle.
b. Leiomyoma
(1) Benign tumor of smooth muscle.
(2) Most common tumor found in women.
(3) Usually affects the uterus, although it can occur anywhere.
c. Rhabdomyosarcoma
(1) Malignant tumor of skeletal muscle.
(2) Most common sarcoma found in children.
(3) Usually affects head and neck region—orbit, nasal cavity, and nasopharynx.