NEET MDS Lessons
General Pathology
Rickets and Osteomalacia
Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion
4. Malabsorption disorders.
Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.
Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.
The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.
The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones
Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.
Microscopic features
• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.
A dermatofibroma is a benign tumor of the dermis, MC located on the lower extremity, where it has a nodular, pigmented appearance.
- composed of benign histiocytes.
HAEMORRHAGIC DISORDERS
Normal homeostasis depends on
-Capillary integrity and tissue support.
- Platelets; number and function
(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation
(b) Vasoactive substances for vasoconstriction
(c) Platelet factor for coagulation.
(d) clot retraction.
- Fibrinolytic system(mainly Plasmin) : which keeps the coagulation system in check.
Coagulation disorders
These may be factors :
Deficiency .of factors
- Genetic.
- Vitamin K deficiency.
- Liver disease.
- Secondary to disseminated intravascular coagulation.or defibrinatian
Overactive fibrinolytic system.
Inhibitors of the factors (immune, acquired).
Anticoagulant therapy as in myocardial infarction.
Haemophilia. Genetic disease transmitted as X linked recessive trait. Common in Europe. Defect in fcatorVII Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).
Features:
- May manifest in infancy or later.
- Severity depends on degree of deficiency.
- Persistant wound bleeding.
- Easy Bruising with Hematoma formation
Nose bleed , arthrosis, abdominal pain with fever and leukocytosis
Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.
Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally
Vitamin K Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.
Deficiency maybe due to:
Obstructive jaundice.
Steatorrhoea.
Gut sterilisation by antibiotics.
Liver disease results in :
Deficient synthesis of factor I II, V, Vll, IX and X Incseased fibrinolysis (as liver is the site of detoxification of activators ).
Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.
Causes
Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .
Hypersensitivity reactions.
Disseminated malignancy.
Snake bite.
Vascular defects : (Non thrombocytopenic purpura).
Acquired :
Simple purpura a seen in women. It is probably endocrinal
Senile parpura in old people due to reduced tissue support to vessels
Allergic or toxic damage to endothelium due to Infections like Typhoid Septicemia
Col!agen diseases.
Scurvy
Uraemia damage to endothelium (platelet defects).
Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.
Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff
It manifests as :
Pulrpurric rashes.
Arthralgia.
Abdominal pain.
Nephritis and haematuria.
Hereditary :
(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.
(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease
.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.
Platelet defects
These may be :
(I) Qualitative thromboasthenia and thrombocytopathy.
(2) Thrombocytopenia :Reduction in number.
(a) Primary or idiopathic thrombocytopenic purpura.
(b) Secondary to :
(i) Drugs especially sedormid
(ii) Leukaemias
(iii) Aplastic-anaemia.
Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.
Manifests as :
Acute self limiting type.
Chronic recurring type.
Features:
(i) Spontaneous bleeding and easy bruisability
(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.
Thrombocytopenia with abnormal forms of platelets.
Marrow shows increased megakaryocytes with immature forms, vacuolation, and lack of platelet budding.
Pathogenesis:
hypersensitivity to infective agent in acute type.
Plasma thrombocytopenic factor ( Antibody in nature) in chronic type
Connective tissue diseases
Marfan’s syndrome
a. Genetic transmission: autosomal dominant.
b. Characterized by a defective microfibril glycoprotein, fibrillin.
c. Clinical findings include tall stature, joints that can be hyperextended, and cardiovascular defects, including mitral valve prolapse and dilation of the ascending aorta.
Ehlers-Danlos syndrome
a. Genetic transmission: autosomal dominant or recessive.
b. This group of diseases is characterized by defects in collagen.
c. Clinical findings include hypermobile joints and highly stretchable skin. The skin also bruises easily. Oral findings include Gorlin’s sign and possible temporomandibular joint (TMJ) subluxation.
The oral mucosa may also appear more fragile and vulnerable to trauma.
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.
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.
Cells Of The Exudate
Granulocytes (Neutrophils, eosinophils, and basophils)
Monocytes (and tissue macrophages)
Lymphocytes
Neutrophils (polymorphs).
Characteristics
(1) Cell of acute inflammation.
(2) Actively motile.
(3) Phagocytic.
(4) Respond to chemotactic agents like.
Complement products.
Bacterial products.
Tissue breakdown
Lysosomal enzymes of other polymorphs
Functions
(1) Phagocytosis and intracellular digestion of bacteria.
(2) Exocytosis of lysosomal enzymes to digest dead tissue as the first step in the process of repair.
Eosinophils
Characteristics
(I) Cell of allergjc and immunologic inflammation.
(2) Motile and phagocytic but less so than a neutrophil.
(3) Response to chemotaxis similar to neutrophil. In addition, it is also responsive to antigens and antigen-antibody complexes.
(4) Steroids cause depletion of eosinophils.
Functions
(1) Contain most of the lysosomal enzymes that polymorphs have
(2) control of Histamine release and degradation in inflammation
Basophils (and mast cells)
Characteristics
(1) Contain coarse metachromatic granules.
(2) Contain, histamine and proteolytic enzymes
Functions
Histamine: release which causes some of the changes of inflammation and allergic
reactions. .
Monocytes .
Blood monocytes form a component of. the mononuclear phagocytic system (MPS), the other being tissue macrophages The tissue macrophages may be :
(a) Fixed phagocytic. cells:
- Kuffer cell of liver.
- Sinusoidal lining cells of spleen and lymph nodes.
- Pleural and peritoneal macrophages
- Alveolar macrophages.
- Microglial cells.
(b) Wandering macrophages or tissue histiocytes.
The tissue histiocytes are derived from blood monocytes.
Characteristics
.(1)Seen in inflammation of some duration, as they -outlive polymorphs.
(2) Actively phagocytic and motile.
(3) Fuse readily to from giant cells in certain situations.
Function
(1) Phagocytosis.
(2) Lysosomal enzyme secretion.
(3) Site of synthesis of some components of complement.
(4) Antigen handling and processing before presenting it to the Immune competent cell.
(5) Secretion of lysosyme and interferon.
Giant cells can be
(A) Physiological
Syncytiotrophoblast, megakatyocytes, striated muscle, osteoclast.
(B) Pathological:
Foreign body: in the presence of particulate foreign matter like talc, suture material etc. and in certain infections_e g fungal.
Langhan's type: a variant of foreign body giant cell seen in tuberculosis.
Touton type in lipid rich situations like Xanthomas, lipid granulomas etc.
(iv) Aschoff cell in rheumatic carditis.
(v) Tumour gjant cells e.g. Reid-Sternberg cell in Hodgkin's Lymphoma, giant cells in any malignancy.
Lymphocytes and Plasma cells
These are the small mononuclear cell comprising the immune system
They are less motile than_macrophages and neutrophils and are seen in chronic inflammation and immune based diseases.