Aneurysm

An aneurysm is a localized abnormal dilation of a blood vessel or the heart

Types:
1. True aneurysm - it involves all three layers of the arterial wall (intima, media, and adventitia) or the attenuated wall of the heart.
 e.g. Atherosclerotic, syphilitic, and congenital aneurysms, and ventricular aneurysms that follow transmural myocardial infarctions. 

2 False aneurysm 
(also called pseudo-aneurysm) is a breach in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space ("pulsating hematoma"). 
E.g. ventricular ruptures after MI that are contained by a pericardial adhesion
E.g. a leak at the junction of a vascular graft with a natural artery.

Aneurysms are classified by macroscopic shape and size 
Saccular aneurysms 

spherical outpouchings (involving only a portion of the vessel wall, and often contain thrombi. 

Fusiform aneurysms

diffuse, circumferential dilation of a long vascular segment; 

they vary in diameter and length and can involve extensive portions of the aortic arch, abdominal aorta, or even the iliacs.

Aortic Aneurysm 

The two most important causes are: 

1- atherosclerosis : the most common cause 
It causes thinning and weakening of the media. The intimal plaques compress the underlying media and also compromise nutrient and waste diffusion from the vascular lumen into the arterial wall. The media consequently undergoes degeneration and necrosis, thus allowing the dilation of the vessel 

2- cystic medial degeneration of the arterial media. E.g. Marfan syndrome.

3- Other causes include: trauma, congenital defects (e.g., berry aneurysms), infections (mycotic aneurysms), systemic diseases, such as vasculitis.

Mycotic  Aneurysm :  
Infection of a major artery that weakens its wall is called a mycotic aneurysm

possible complications: thrombosis and rupture. 

It can originate from: 
(1) embolization of a septic thrombus, usually as a complication of infective endocarditis 
(2) extension of an adjacent suppurative process; 
(3) circulating organisms directly infecting the arterial wall 

Mycotic AAAs are atherosclerotic lesions infected by lodging of circulating microorganisms in the wall 

- e.g.  bacteremia from a primary Salmonella gastroenteritis. 

Abdominal Aortic  Aneurysm

Atherosclerotic aneurysms occur most frequently in the abdominal aorta ,the common iliac arteries, the arch, and descending parts of the thoracic aorta can also be involved 

Pathogenesis 

AAA occurs more frequently in men and rarely develops before age 50. 

Atherosclerosis is a major cause of AAA 

 hereditary defects in structural components of the aorta (e.g., defective fibrillin production in Marfan disease affects elastic tissue synthesis) 
 
 Morphology :
  Usually positioned below the renal arteries and above the bifurcation of the aorta 
  
  AAA can be saccular or fusiform 
  
  as large as 15 cm in diameter, and as long as 25 cm. 
  
  Microscopically: atherosclerosis with destruction and thinning of the underlying aortic media 
  
  the aneurysm frequently contains a laminated mural thrombus
  
  Syphilitic Aneurysm 
  
  Caused by The spirochetes T. pallidum 
  
  Tertiary stage of syphilis can cause obliterative endarteritis of the involve small vessels in any part of the body, including the vasa vasorum of the aorta 
  
  This results in ischemic medial injury, leading to aneurysmal dilation of the aorta and aortic annulus, and eventually valvular insufficiency. 
  
  valvular insufficiency and massive volume overload lead to hypertrophy of the left ventricle. The greatly enlarged hearts are sometimes called "cor bovinum" (cow's heart).
  
  CLINICAL CONSEQUENCES
  
  1.  Rupture → massive potentially fatal hemorrhage 
  2. Obstruction of downstream vessel → tissue ischemic injury
  3. Embolism → from atheroma or mural thrombus 
  4. Impingement and compression on an adjacent structure 
  5. Presentation as an abdominal mass 

Cholecystitis 
 
It is inflammation of the gall bladder. It may be acute or chronic.
In 80-90% of cases, it is associated with gall stones (Calcular cholecystis). 

Causes and pathogenesis:-
Obstruction of cystic or common bile duct- By stones, strictures, pressure from the outside, tumors etc.
Obstruction , chemical irritation of the gall bladder, Secondary bacterial infection, stone formation, trauma to the wall of gall
bladder 

Secondary bacterial infection

Usually by intestinal commensals E.coli, streptococcus fecalis. They reach the gall bladder by lymphatics. 
S.typhi reaches the gall bladder after systemic infection

Acute cholecystitis

Gall bladder is enlarged edematous and fiery red in color. 
- Wall is edematous, hyperemic, may show abscesses or gangrenous dark brown or green or black foci which may perforate.
Serous covering show fibrinosuppurative inflammation and exudation. Mucosa is edematous, hyperemic and ulcerated.
- If associated with stones, obstruction results in accumulation of pus leading to Empyaema of the gall bladder.

Fate:-  Healing by fibrosis and adhesions.

Complications:-  
- Pericholecystic abscess.
- Rupture leading to acute peritonitis.
- Ascending suppurative cholangitis and liver abscess 

Chronic cholecystitis
May follow Acute cholecystitis or starts chronic. Gall stones are usually present. 

Pathology

1. If associated with obstruction: Gall bladder is dilated. Wall may be thickened or thinned out. Contents may be clear, turbid or purulent. 
2. If not associated with obstruction: - Gall bladder is contracted, wall is markedly thickened.
3. Serosa is smooth with fibrous adhesions. Draining lymph nodes are enlarged.  
4. Wall is thickened, opaque and gray-white with red tinge.
5. Mucosa is gray- red with ulcerations and pouches.
6. Stones are usually present

Smallpox (variola)
 - vesicles are well synchronized (same stage of development) and cover the skin and mucous membranes.
 - vesicles rupture and leave pock marks with permanent scarring.

Osteonecrosis (Avascular Necrosis) 

Ischemic necrosis with resultant bone infarction occurs mostly due to fracture or after corticosteroid use. Microscopically, dead bon trabevulae (characterized by empty lacunae) are interspersed with areas of fat necrosis.

The cortex is usually not affected because of collateral blood supply; in subchondral infarcts, the overlying articular cartilage also remains viable because the synovial fluid can provide nutritional support. With time, osteoclasts can resorb many of the necrotic bony trabeculae; any dead bone fragments that remain act as scaffolds for new bone formation, a process called creeping substitution.

Symptoms depend on the size and location of injury. Subchondral infarcts often collapse and can lead to severe osteoarthritis. 

FUNGAL INFECTION

Mucormycosis (Zygomycosis; Phycomycosis)

Infection with tissue invasion by broad, nonseptate, irregularly shaped hyphae of diverse fungal species, including Rhizopus, Rhizomucor, Absidia, and Basidiobolus.

Infection is most common in immunosuppressed persons, in patients with poorly controlled diabetes, and in patients receiving the iron-chelating drug desferrioxamine.

Symptoms and Signs

Rhinocerebral mucormycosis is the most common form, but primary cutaneous, pulmonary, or GI lesions sometimes develop, and hematogenous dissemination to other sites can occur. Rhinocerebral infections are usually fulminant and frequently fatal. Necrotic lesions usually appear on the nasal mucosa or sometimes the palate.

Miscellaneous Bone Tumors 

1. Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET) are primary malignant small round-cell tumors of bone and soft tissue. They are viewed as the same tumor because they share an identical chromosome translocation; they differ only in degree of differentiation. PNETs demonstrate neural differentiation whereas Ewing sarcomas are undifferentiated. After osteosarcomas, they are the second most common pediatric bone sarcomas. Most patients are 10 to 15 years old. The common chromosomal abnormality is a translocation that causes fusion of the EWS gene with a member of the ETS family of transcription factors. The resulting hybrid protein functions as an active transcription factor to stimulate cell proliferation. These translocations are of diagnostic importance since almost all patients with Ewing tumor have t(11;22).

Pathological features

• Ewing sarcoma and PNETs arise in the medullary cavity but eventually invade the cortex and periosteum to produce a soft tissue mass.
• The tumor is tan-white, frequently with foci of hemorrhage and necrosis.

Microscopic features

• There are sheets of uniform small, round cells that are slightly larger than lymphocytes with few mitoses and little intervening stroma.
• The cells have scant glycogen-rich cytoplasm.
• The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) indicates neural differentiation, and hence indicates by definition PNET. 

Ewing sarcoma and PNETs typically present as painful enlarging masses in the diaphyses of long tubular bones (especially the femur) and the pelvic flat bones. The tumor may be confused with osteomyelitis because of its association with systemic signs & symptoms of infection. X-rays show a destructive lytic tumor with infiltrative margins and extension into surrounding soft tissues. There is a characteristic periosteal reaction depositing bone in an onionskin fashion. 

2. Giant-Cell Tumor of Bone (GCT) is dominated by multinucleated osteoclast-type giant cells, hence the synonym osteoclastoma. GCT is benign but locally aggressive, usually arising in individuals in their 20s to 40s. Current opinion suggests that the giant cell component is likely a reactive macrophage population and the mononuclear cells are neoplastic. Tumors are large and red-brown with frequent cystic degeneration. They are composed of uniform oval mononuclear cells with frequent mitoses, with scattered osteoclast-type giant cells that may contain 30 or more nuclei.

The majority of GCTs arise in the epiphysis of long bones around the knee (distal femur and proximal tibia).
Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex is frequently destroyed, producing a bulging soft tissue mass with a thin shell of reactive bone. Although GCTs are benign, roughly 50% recur after simple curettage; some malignant examples (5%) metastasize to the lungs