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
Acute pericarditis
1. Characterized by inflammation of the pericardium.
2. Causes include:
a. Viral infection.
b. Bacterial infection, including Staphylococcus, Pneumococcus.
c. Tuberculosis.
d. MI.
e. Systemic lupus erythematosus.
f. Rheumatic fever.
3. Signs and symptoms include:
a. Pericardial friction rub on cardiac auscultation.
b. Angina.
c. Fever.
4. Consequences include constrictive pericarditis,which results from fusion and scarring of the pericardium. This may lead to the restriction of ventricular expansion, preventing the heart chambers from filling normally.
Parasitic
1. Leishmania produce 3 kinds of disease in man
- visceral leishmaniasis (kala azar) due to Leishmania donovani complex,
- cutaneous leishmaniasis due to Leishmania tropica complex, and
- mucocutaneous leishmaniasis due to Leishmania braziliensis.
- cutaneous (Oriental sore) and mucocutansous leishmaniasis limit themselves to the skinalone (ulcers) in the former disease and skin plus mucous membranes in the latter variant.
- the diagnosis of cutaneous or mucocutaneous leishmaniasis is made by biopsy, culture, skin test, or serologic tests
- the laboratory diagnosis of visceral leishmaniasis is made by performing a bone marrow aspirate and finding the leishmanial forms in macrophages, by culture, by hamster inoculation, or by serology.
- recovery from the cutaneous form incurs immunity.
- treatment: stibogluconate
Bacillus anthrax
- large Gram (+) rods that produce heat resistant spores; Clostridia and Bacillus species are the two bacterial spore formers; they do not form spores in tissue; produces a powerful exotoxin.
- contracted by direct contact with animal skins or products
- four forms of anthrax are recognized → cutaneous (MC), pulmonary, oraloropharyngeal, and gastrointestinal.
- cutaneous anthrax (90 to 95% of cases) occurs through direct contact with infected or contaminated animal products.
- lesions resemble insect bites but eventually swell to form a black scab, or eschar, with a central area of necrosis ("malignant pustule").
Huntington’s disease
a. Causes dementia.
b. Genetic transmission: autosomal dominant.
c. Characterized by the degeneration of striatal neurons, affecting cortical and basal ganglia function.
d. Clinically, the disease affects both movement and cognition and is ultimately fatal.
Malnutrition
A. Marasmus - calorie malnutrition
A child with marasmus suffers growth retardation and loss of muscle. The loss of muscle mass results from catabolism and depletion of the somatic protein compartment.
With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell-mediated immunity.
B. Kwashiorkor - protein malnutrition - importance of protein quality as well as quantity
Marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized, or dependent, edema.
The weight of children with severe kwashiorkor is typically 60% to 80% of normal.
However, the true loss of weight is masked by the increased fluid retention (edema).
Children with kwashiorkor have characteristic skin lesions, with alternating zones of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a "flaky paint" appearance.
Hair changes include overall loss of color or alternating bands of pale and darker hair, straightening, line texture, and loss of firm attachment to the scalp.
An enlarged, fatty liver (resulting from reduced synthesis of carrier proteins) and a tendency to develop early apathy, listlessness, and loss of appetite.
The bone marrow in both kwashiorkor and marasmus may be hypoplastic, mainly because of decreased numbers of red cell precursors. How much of this derangement is due to a deficiency of protein and folates or to reduced synthesis of transferrin and ceruloplasmin is uncertain. Thus, anemia is usually present, most often hypochromic microcytic anemia, but a concurrent deficiency of folates may lead to a mixed microcytic-macrocytic anemia.
C. Most cases of severe malnutrition are a combination of A and B usually characterized by:
• Failure of growth
• Behavioral changes
• Edema (kwashiorkor)
• Dermatosis
• Changes in hair
• Loss of appetite
• Liver enlargement
• Anemia
• Osteoporosis
Thrombosis
Definition-The formation from constituents of the blood, of a mass within the venous or arterial vasculature of a living animal. Natural defense of the body to acute vascular injury.
Pathologic thrombosis includes deep venous thrombosis (DVT), pulmonary embolism (PE), coronary artery thrombosis leading to myocardial infarct and cerebrovascular thrombosis leading to stroke.
Coagulated blood- clots formed
Clot – formation of solid mass of blood components formed outside the vascular tree
Thrombosis with resulting embolic phenomena is important cause of morbidity and mortality.
Haemostatic system allows blood to remain in fluid form under normal conditions and causes the development of temporary thrombus at site of vascular injury.
Components of haemostatic system:
1. Platelets
2. Vascular endothelium
3. Procoagulant plasma protein clotting factors
4. Natural anticoagulants
5. Fibrinolytic proteins
6. Antifibrinolytic proteins
Normal haemostasis:
1. Primary haemostasis-platelet plug formation
2. Secondary haemostasis-stable plug or thrombus
3. Natural anticoagulants-confines thrombus site and size to maintain blood flow
4. Fibrinolysis-degrades fibrin , limits thrombus size and dissolves thrombus once vessel injury is repaired
Changes in any of these factors may result in pathologic thrombosis.
Pathophysiology of thrombosis:
Virchow’s Triad-Thrombosis results from a) decreased blood flow b) vascular endothelial injury and c) alterations in the components of blood.
Vessel wall:
EC (intima), smooth muscle cells (media) and the connective tissue (adventitia).Vascular endothelium is thromboresistant. EC injury leads to TF expression and thrombosis.
Vessel wall has antiplatelet, anticoagulant and fibrinolytic activities which make it thromboresistant.
Antiplatelet activities:
1. Prostacyclin synthesized by EC in response to thrombin. Inhibits platelet adhesion as well as causes vasodilation
2. NO regulates vascular tone as well as functioning as inhibitor of platelet adhesion. Constitutive expression as well as induced expression by EC in response to cytokines
3. Ectozymes which metabolize ADP and ATP to AMP and adenosine. Adenosine inhibits platelet function, ADP is platelet agonist
Anticoagulant activities:
1. Synthesis of heparin like GAG which inactivate activated clotting factors
2. Protein C and S and thrombomodulin-Thrombin generated binds to thrombomodulin which activates protein C which then binds to Protein S and this inhibits coagulation by its proteolytic effect on Factors Va and VIIIa
3. TFPI is synthesized by EC and regulates TF-VIIa activation of Factor X. Also inhibits vascular cell proliferation
Fibrinolytic activities:
1. Secretion and synthesis of plasminogen activators TPA in response to thrombin and vasoactive stimulants such as vasopressin and histamine
2. Synthesis of urokinase in response to inflammatory cytokines
3. FDP’s generated have antiplatelet and antithrombin activity
4. Secretion of PAI
Prothrombotic properties of vascular endothelium promote coagulation with appropriates stimuli.
EC exposure to stimuli such as trauma, cytokines, atherogenic stimuli, endotoxins and immune complexes result in increased TF expression, reduced Protein C activation and reduced fibrinolysis so converting an antithrombotic surface to a prothrombotic surface.
Inherited conditions which result in abnormalities of EC derived or regulated proteins will cause thrombosis.
Arterial thrombosis:
1. Abnormal vessel wall due to atherosclerotic plaque rupture, arterial outflow obstruction, vessel dissection EC injury promote platelet adhesion and activation
2. Release of contents of platelet granules cause recruitment and activation of additional platelets
3. Thromboxane synthesis induces platelet aggregation
4. Thrombin generation due to presence of PL
Platelets are pathogenetically more important in arterial thrombi thus antiplatelet agents are very important in arterial thrombosis management.
Venous thrombosis:
1. Vessel wall is usually normal except if there is direct vessel trauma, extrinsic venous compression or damage due to drugs like chemotherapy
2. Reduction in venous tone is important in pathophysiology
Venous thrombi can be of two types.
A. Phlebo thrombosis
This is thrombus formation in an uninflammed vein usually due to stasis or changes in coagulability of blood. This occurs mostly in deep calf veins and varicose veins in the legs originating near valve pockets. They may propagate to extend to popliteal ,femoral and iliac-veins. These are a common source of massive emboli ‘Phlegmasia alba dolens’ (painful white leg) is a condition seen in late pregnancy and puerperium. In this condition, in addition to iliofemoral thrombosis , there is arterial spasm
B Thrombophlebitis:
In this condition venous wall is inflamed and initiates thrombosis. This is more firmly attached to the vessel wall and also there is much less tendency for propagation Hence there is little chance or embolism.
Cardiac Thrombosis
Intra cardiac thrombus formation can be at 3 sites
• Valvular: as in endocarditis
• Atrial : as in atrial fibrilation ('ball valve thrombus") over MacCallum’s patch is Rheumatic Fever.
• Ventricular mural thrombus over site of MI
Fate of Thrombus
- Resolution : if small, the thrombus is rapidly covered by endothelial cells. Then it can Resolved by a combination of retraction, phgocytosis , platelet autolysis, and fibrinolysis
- Organisation: there is in growth of vascular granulation tissue. This can result in
a. recanalisation
b. collagenisation and-scarring
- Detachment resulting in thromboembolism