EMBOLISM

Definition: transportation of an abnormal mass of an abnormal mass of undissolved material from one part of circulation to another. The mass transported is called embolus.

Types
I .Thrombi and clots.
2. Gas or air.
3. Fat
4.Amniotic fluid.
5.Tumour

Thromboembolism 
This is the commonest type of embolus and may be formed of the primary thrombus  or more often of propagated clot region which is loosely attached.

Emboli from venous thrombi can result In impaction in the pulmonary  arteries and result in sudden death.
Embolism from cardiac or arterial thrombi results in systemic embolism causing infraction and gangrene.

Gaseous
This occurs when gas is introduced into the circulation:
•    Accidental opening of large veins during surgery.
•    Mismanaged transfusion. .
As air is  readily absorbed into blood only  sudden introduction or large quantities of air produces effects
Caisson’s Disease  bubbling of nitrogen from the blood during sudden decompression as seen during deep sea diving.

Fat Embolism
Causes
•    Fractures especially of long bones and multiple
•    Crush injuries.

Sites of impaction:

o    Lungs.
o    Systemic: causing -
    →    petechial skin haemorrhages.
    →    Embolism to brain leading to coma and death.
    →     Conjunctival and retinal haemorrhages
    
Tumor Embolism.

Invasion of vascular channe1.s is a feature of malignant neoplasms and this leads to:
•    Metastatic deposits,
•    DlC
 

 Staphylococcal aureus
 - cutaneous infections
    - furuncles (boils)
    - carbuncles (more complicated furuncle with multiple sinuses)
    - impetigo (often mixed with Streptococcus and has a more bullous appearance than crusted)
    - hidradenitis suppurative (abscess of apocrine glands→e.g., axilla)
    - nail bed (paronychial infection) 
    - postoperative wound or stitch abscess
    - postpartum breast abscesses 
 
toxin related skin rashes
 - infants and young children develop toxic epidermal necrolysis or Ritter's syndrome (scalded baby syndrome)→large, red areas of denuded skin and generalized bulla formation.
 - toxic shock syndrome (TSS) is due to a toxin producing strain of Staphylococcus aureus (bacteriophage induced) usually, but not exclusively in tampon wearing (hyperabsorbent type), menstruating women; 1-4 day prodrome of high fever, myalgias, arthralgias, mental confusion, diarrhea and on erythematous rash that occurs during or soon after menses; rash predominantly on hands and feet with eventual desquamation in 5-12 days. 

Paget Disease (Osteitis Deformans) 

This unique bone disease is characterized by repetitive episodes of exaggerated, regional osteoclastic activity (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and finally by exhaustion of cellular activity (osteosclerotic stage). The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and lacks strength. Paget disease usually does not occur until mid-adulthood but becomes progressively more common thereafter. The pathognomonic histologic feature is a mosaic pattern of lamellar bone (likened to a jigsaw puzzle) due to prominent cement lines that haphazardly fuse units of lamellar bone. (Fig. 12-5) The axial skeleton and proximal femur are involved in the majority of cases. In patients with extensive disease, hypervascularity of the marrow spaces can result in high-output congestive heart failure. Cranial nerves impingement also occurs and can lead to head ache and auditory disturbances. Rarely Paget disease is complicated by bone sarcoma (usually osteogenic). 

Bronchitis

Bronchitis is an obstructive pulmonary disease characterized by inflammation of the bronchi of the lungs

Signs and symptoms

persistent cough that produces sputum

shortness of breath (dyspnea) on exertion

hypercapnia

insufficient oxygenation of the blood hypoxemia leading to cynosis

Severe chronic bronchitis will commonly lead to cor pulmonale and heart failure.

Pathology

an increase in the number of goblet cells with mucus blocking the airway clusters of pigmented alveolar macrophages

the presence of inflammatory cells (e.g. neutrophils) scarring (fibrosis) of the walls of the bronchioles

Diagnosis

• decreased intensity of breath sounds (rhonchi) and extended expiration.
• a sputum culture has pathogenic microorganisms
• a chest x-ray that reveals hyperinflation and increased bronchovascular markings
• a pulmonary function test that shows an increase in the lung's residual volume and a decreased vital capacity

Pathophysiology

• The initiating event in developing bronchitis appears to be chronic irritation due to inhalation of certain chemicals
• earliest clinical feature of bronchitis is increased secretion of mucus by submucousal glands of the trachea and bronchi
• Damage caused by irritation of the airways leads to inflammation and infiltration of the lung tissue by neutrophils
• The neutrophils release substances that promote mucousal hypersecretion
• As bronchitis persists to become chronic bronchitis, a substantial increase in the number of goblet cells in the small airways is seen
• The role of infection in the pathogenesis of chronic bronchitis appears to be secondary.

Treatment

Quit smoking, Oxygen therapy, bronchodilator drugs

Prognosis

Pulmonary hypertension, cor pulmonale, and chronic respiratory failure are possible complications of chronic bronchitis

In severe chronic bronchitis is poor

FUNGAL INFECTION

Aspergillosis

Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.

Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.

Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.

Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.

 Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache

Osteoporosis
 
is characterized by increased porosity of the skeleton resulting from reduced bone mass. The disorder may be localized to a certain bone (s), as in disuse osteoporosis of a limb, or generalized involving the entire skeleton. Generalized osteoporosis may be primary, or secondary

Primary generalized osteoporosis
• Postmenopausal
• Senile
Secondary generalized osteoporosis

A. Endocrine disorders
• Hyperparathyroidism
• Hypo or hyperthyroidism
• Others

B. Neoplasia
• Multiple myeloma
• Carcinomatosis 

C. Gastrointestinal disorders
• Malnutrition & malabsorption
• Vit D & C deficiency
• Hepatic insufficiency 

D. Drugs
• Corticosteroids
• Anticoagulants
• Chemotherapy
• Alcohol 

E. Miscellaneous
• osteogenesis imperfecta
• immobilization
• pulmonary disease 

Senile and postmenopausal osteoporosis are the most common forms. In the fourth decade in both sexes, bone resorption begins to overrun bone deposition. Such losses generally occur in areas containing abundant cancelloues bone such as the vertebrae & femoral neck. The postmenopausal state accelerates the rate of loss; that is why females are more susceptible to osteoporosis and its complications. 

Gross features
• Because of bone loss, the bony trabeculae are thinner and more widely separated than usual. This leads to obvious porosity of otherwise spongy cancellous bones

Microscopic features
• There is thinning of the trabeculae and widening of Haversian canals.
• The mineral content of the thinned bone is normal, and thus there is no alteration in the ratio of minerals to protein matrix

Etiology & Pathogenesis

• Osteoporosis involves an imbalance of bone formation, bone resorption, & regulation of osteoclast activation. It occurs when the balance tilts in favor of resorption.
• Osteoclasts (as macrophages) bear receptors (called RANK receptors) that when stimulated activate the nuclear factor (NFκB) transcriptional pathway. RANK ligand synthesized by bone stromal cells and osteoblasts activates RANK. RANK activation converts macrophages into bone-crunching osteoclasts and is therefore a major stimulus for bone resorption.
• Osteoprotegerin (OPG) is a receptor secreted by osteoblasts and stromal cells, which can bind RANK ligand and by doing so makes the ligand unavailable to activate RANK, thus limiting osteoclast bone-resorbing activity.
• Dysregulation of RANK, RANK ligand, and OPG interactions seems to be a major contributor in the pathogenesis of osteoporosis. Such dysregulation can occur for a variety of reasons, including aging and estrogen deficiency.
• Influence of age: with increasing age, osteoblasts synthetic activity of bone matrix progressively diminished in the face of fully active osteoclasts.
• The hypoestrogenic effects: the decline in estrogen levels associated with menopause correlates with an annual decline of as much as 2% of cortical bone and 9% of cancellous bone. The hypoestrogenic effects are attributable in part to augmented cytokine production (especially interleukin-1 and TNF). These translate into increased RANK-RANK ligand activity and diminished OPG.
• Physical activity: reduced physical activity increases bone loss. This effect is obvious in an immobilized limb, but also occurs diffusely with decreased physical activity in older individuals.
• Genetic factors: these influence vitamin D receptors efficiency, calcium uptake, or PTH synthesis and responses.
• Calcium nutritional insufficiency: the majority of adolescent girls (but not boys) have insufficient dietary intake of calcium. As a result, they do not achieve the maximal peak bone mass, and are therefore likely to develop clinically significant osteoporosis at an earlier age.
• Secondary causes of osteoporosis: these include prolonged glucocorticoid therapy (increases bone resorption and reduce bone synthesis.)
The clinical outcome of osteoporosis depends on which bones are involved. Thoracic and lumbar vertebral fractures are extremely common, and produce loss of height and various deformities, including kyphoscoliosis that can compromise respiratory function. Pulmonary embolism and pneumonia are common complications of fractures of the femoral neck, pelvis, or spine.