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.
Biochemical examination
This is a method by which the metabolic disturbances of disease are investigated by assay of various normal and abnormal compounds in the blood, urine, etc.
Megaloblastic anaemia
Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-
Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum and jejunum
Causes of deficiency .-
- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)
Features:
(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).
Blood picture :
- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.
Bone marrow:
- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
-Giant stab forms (giant metamyelocytes).
Leukaemias
Uncontrolled proliferation of leukocyte precursors (may be with associated red cell and platelet series proliferation).
Factors which may playa causal role are.
- Viral
- Radiation.
- Genetic.
Classification
1. Acule leukaemia:
a. Lymphocytic (lymphoblastic).
b. Myelocytic and promyelocytic (myeloblastic).
c. Monocytic.
d. Myelomonocytic.
e. Undifferentiated (Stem cell).
2. Chronic leukaemia:
a. Lymphocytic
b. Myelocytic
3. Miscellaneous:
a. Erythroleukaemia (De Guglielmo's disease).
b. Eosinophilic leukaemia.
c. Megakaryocytic leukaemia.
Aplasticanaemia and pancytopenia.
Aplastic anaemia is a reduction in all the formed elements of blood due to marrow hypoplasia.
Causes
- Primary or Idiopathic.
- Secondary to :
1 Drugs :
Antimetabolites and antimitotic agents.
Antiepileptics.
Phenylbutazone.
Chloramphenicol.
2 Industrial chemicals.
Benzene.
DDT and other insecticides.
TNT (used in explosives).
3 Ionising radiation
- Familial aplasia
Pancytopenia (or reduction in the formed elements of blood) can be caused by other conditions also like:
-Subleukaemic acute leukaemia.
-Megaloblastic anaemia
-S.L.E.
-hypersplenism.
-Marrow infiltration by lymphomas metastatic deposits, tuberculosis, myeloma etc
Features:
- Anaemia.
- Leucopenia upper respiratory infections.
- Thrombocytopenis :- petechiae and bruising.
Blood picture:
- Normocytic normochromic anaemia with minimal anisopoikilocytosis in aplastic anaemia. Other causes of pancytopenia may show varying degrees of anisopoikilocytosis
- Neutropenia with hypergranulation and high alkaline phosphatase.
- Low platelet counts
Bone marrow:
- Hypoplastic (may have patches of norm cellular or hyper cellular marrow) which may -> dry tap. .
- Increase in fat cells , fibroblasts , reticulum cells, lymphocytes and plasma cells
- Decrease in precursors of all three-Series.
- Underlying cause if any, of pancytopenia may be seen
Lymphocytosis:
Causes
-Infections in children and the neutropenic infections in adults.
-Lymphocytic leukaemia.
-Infectious mononucleosis.
-Toxdplasmosis.
-Myast'henia gravis.
Multiple sclerosis
a. A demyelinating disease that primarily affects myelin (i.e. white matter). This affects the conduction of electrical impulses along the axons of nerves. Areas of demyelination are known as plaques.
b. The most common demyelinating disease.
c. Onset of disease usually occurs between ages 20 and 50; slightly more common in women.
d. Disease can affect any neuron in the central nervous system, including the brainstem and spinal cord. The optic nerve (vision) is commonly affected.