NEET MDS Lessons
General Pathology
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.
Cryptococcosis
An infection acquired by inhalation of soil contaminated with the encapsulated yeast Cryptococcus neoformans, which may cause a self-limited pulmonary infection or disseminate, especially to the meninges, but sometimes to the skin, bones, viscera, or other sites.
Cryptococcosis is a defining opportunistic infection for AIDS, although patients with Hodgkin's or other lymphomas or sarcoidosis or those receiving long-term corticosteroid therapy are also at increased risk.
AIDS-associated cryptococcal infection may present with severe, progressive pneumonia with acute dyspnea and an x-ray pattern suggestive of Pneumocystis infection.
Primary lesions in the lungs are usually asymptomatic and self-limited
Pneumonia usually causes cough and other nonspecific respiratory symptoms. Rarely, pyelonephritis occurs with renal papillary necrosis development.
Most symptoms of cryptococcal meningitis are attributable to brain swelling and are usually nonspecific, including headache, blurred vision, confusion, depression, agitation, or other behavioral changes. Except for ocular or facial palsies, focal signs are rare until relatively late in the course of infections. Blindness may develop due to brain swelling or direct involvement of the optic tracts. Fever is usually low-grade and frequently absent.
Pyelonephritis
- A bacterial infection that affects the renal tubules, interstitium, and renal pelvis.
- One of the most common renal diseases.
- Usually caused by gram-negative, rod-shaped bacteria that are part of the normal flora of the enteric tract. Most commonly caused by Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter.
- The infecting bacteria are usually from the patient’s own enteric flora an example of an endogenous infection.
- Usually associated with a urinary tract infection (acute pyelonephritis) or involved with another precipitating condition, such as obstruction (chronic pyelonephritis).
Pemphigus
1. Ulcerative lesions on the skin and oral mucosa.
2. An autoimmune disease in which patients have autoantibodies against hemidemosomal attachment of epidermis cells.
3. Histologically characterized by acantholysis, in which epidermal cells appear to detach and separate from each other, as seen by Tzanck smears.
4. Can be life-threatening if untreated.
5. A positive Nikolsky sign is observed.
Because of sloughing of the epidermis, a red blister forms after pressure is applied to affected skin.
6. Treatment: corticosteroids.
CARCINOMA IN SITU
Epithelial malignancy which has not yet invaded even -the local confines viz basement membrane is termed as carcinoma in situ (intra epithelial neoplasia, pre-invasive cancer)
This lesion merges morphologically with severe dysplasia
Common sites for carcinoma-in-situ :
- Cervical squamous epithelium
- Oropharynx
- Bronchial epithelium.
- Breast ducts and lobules.
- Skin, in the form of Bowen's disease.
- Glans penis and vulva in the form of Erythroplasia of Queyrat
Immunoglobulins. (Ig)
These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)
Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).
Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.
Characteristics of Immunoglobulin subclasses
I. Ig G:
(i) Predominant portion (80%) of Ig.
(ii) Molecular weight 150, 000
(iii) Sedimentation coefficient of 7S.
(iv) Crosses placental barrier and to extra cellular fluid.
- (v) Mostly neutralising effect. May be complement fixing.
(vi) Half life of 23 days.
2.IgM :
(i) Pentamer of Ig.
(ii) Molecular weight 900, 000
(iii) 19S.
(iv) More effective complement fixation and cells lysis
(v) Earliest to be produced in infections.
(vi) Does not cross placental barrier.
(vii) Halflife of 5 days.
3. Ig A :
- Secretory antibody. Found in intestinal, respiratory secretions tears, saliva and urine also.
- Secreted usually as a dinner with secretory piece.
- Mol. weight variable (160,000+)
- 7 S to 14 S.
- Half life of 6 days.
4.Ig D :
- Found in traces.
- 7 S.
- Does not cross placenta.
5. Ig E
- Normally not traceable
- 7-8 S (MoL weight 200,000)
- Cytophilic antibody, responsible for some hypersensitivity states,
PRIMARY LYMPHEDEMA
can occur as:
1- A congenital defect, resulting from lymphatic agenesis or hypoplasia.
2- Secondary or obstructive lymphedema
- blockage of a previously normal lymphatic; e.g. Malignant tumors
- Surgical procedures that remove lymph nodes
- Postirradiation
- Fibrosis
- Filariasis
- Postinflammatory thrombosis and scarring