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
Viral meningitis
1. Can be caused by many different viruses, including cytomegalovirus, herpes virus, rabies, and HIV.
2. CSF fluid from a spinal tap differs from that seen in a bacterial infection. It shows mononuclear cells, higher levels of protein, and normal levels of glucose.
Varicose Veins
- are abnormally dilated, tortuous veins produced by prolonged increase in intraluminal pressure and loss of vessel wall support.
- The superficial veins of the leg are typically involved
-venous pressures in these sites can be markedly elevated -> venous stasis and pedal edema (simple orthostatic edema)
-Some 10% to 20% of adult males and 25% to 33% of adult females develop lower extremity varicose veins
RISK FACTORS
-> obesity
-> Female gender
-> pregnancy.
-> familial tendency (premature varicosities results from imperfect venous wall development)
Morphology
- wall thinning
- intimal fibrosis in adjacent segments
- spotty medial calcifications (phlebosclerosis)
- Focal intraluminal thrombosis
- venous valve deformities (rolling and shortening)
COMPLICATIONS
- stasis, congestion, edema, pain, and thrombosis
- chronic varicose ulcers
- embolism is very rare.
Iron deficiency anaemia.
Absorption of iron is affected by :
- Iron stores.
- Rate of erythropoiesis
- Acid pH aids absorption.
- Phosphates and phytates in diet impair absorption.
Causes of deficiency:
- Increased demand:
o Growth (in children)
o Menstruation, Pregnancy, lactation.
- Inadequate intake and absorption.
o Dietary deficiency.
o Achlorhydria or gastrectomy.
o Malabsorption states.
- Chronic blood loss
o Peptic ulcer, bleeding piles
o Menorrhagia.
o Hook worm infestation
Features:
- Anaemia.
- Koilonychia.
- Atrophic glossitis and angular stomatitis.
- Dysphagia-Plummer Vinson syndrome.
Blood findings:
- Microcytjc_hypochromic cells, ring cells and pessary cells.
- Anisocytosis and poikilocytosis.
- Low MCV. MCH and MCHC.
- Serum iron is low but iron binding capacity is increased
Bone marrow
Erythroid hyperplasia with imcronormoblasts. Iron stains reveal depleted stores
Differential diagnosis .-
- Sideroblastic anaemia which is also microcytic hypochromic but there is excess iron in the erythroid cells .Some are pyridoxine responsive.
- (ii) Thalassaemia
Immunodeficiency
This may be :-
- Congenital (Primary)
- Acquired (Secondary)
Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.
T Cell Defects :
- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome
These lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.
C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.
Acquired deficiency
A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.
B. Neaplasia of lymphoid system :
- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).
c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.
DEGENERATION
Definition: Reversible cell injury.
(1) Water accumulation in the form of
(i) Cloudy swelling.
(ii) Vacuolar degeneration.
.(ill) Hydropic degeneration.
This change is commonly seen in parenchymal cells e.g. kidneys.
Gross appearance: The organ is swollen, soft and pale.
Microscopic appearance: Cells show varying degrees of swelling. Cytoplasm may be granular, vacuolated, homogenously pale and ballooned out.
(2) Fatty change An excessive, demonstrable accumulation of fat is common in parenchymal cells of liver and heart
In the liver, it can be due to: .
(i) Excess fat entry into the liver as occurs in starvation and in steroid excess due to mobilization from stores.
(ii) Excess triglyceride formation
(iii) Reduced phosphorlyation of fat.
(iv) Decreased release as lipoprotein due to protein deficiency.
Causes
(i) Hypoxia as in severe anaemia and venous stasis
(ii) Protein malnutrition.
(iii) Hepatotoxins like CCl4.
(iv) Alcoholism
(v) Metabolic defects like Diabetes mellitus
(vi) Infections.
Gross appearance: The organ is enlarged, soft and greasy, with a pale yellowish colour. It may involve the organ uniformly or patchily ( thrush breast or tabby cat heart)
Microscopic appearance: The cells contain clear vacuoles (stainable by fat-sudan stains on frozen sections). These may be small and dispersed or large, displacing the nucleus peripherally. Several such cells may fuse to form fat cysts.
(3) Hyaline degeneration
In alcoholic liver damage, the cytoplasmic organelles are damaged and give the cytoplasm a deep eosinophilic staining-Mallory hyaline.
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 coagulatian 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 factars (immune, acquired).
Anticoagulant therapy as in myocardial infarctian.
Haemophilia. Genetic disease transmitted as X linked recessive trait. Comman 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 woundbleeding.
- Easy Bruising with Haemotoma formation
Nose bleed , arthrosis, abdominal pain with fever and leucocytosis
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