NEET MDS Lessons
General Pathology
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
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").
HYPERTROPHY
Increase in the size of an organ or tissue due to increase in the size of its Constituent cells.
1. Skeletal muscle due to -exercise.
2. Cardiac muscle of:
- Left ventricle in:
o Hypertension.
o Aortic valvular lesion.
o Severe anaemia.
- Right ventricle in :
o Mitral stenosis
o Cor pulmonale
3. Smooth muscle of:
- GIT proximal to strictures.
- Uterus in pregnancy.
THE THYROID GLAND
The thyroid gland develops embryologically from the developing pharyngeal epithelium that descends from the foramen cecum at the base of the tongue to its normal position in the anterior neck. This pattern of descent explains the occasional presence of ectopic thyroid tissue, most commonly located at the base of the tongue (lingual thyroid) or at other sites abnormally high in the neck.
THROMBOSIS
Pathogenesis (called Virchow's triad):
1. Endothelial* Injury ( Heart, Arteries)
2. Stasis
3. Blood Hypercoagulability
- Endothelial cells are special type of cells that cover the inside surface of blood vessels and heart.
CONTRIBUTION OF ENDOTHELIAL CELLS TO COAGULATION
Intact endothelial cells maintain liquid blood flow by:
1- inhibiting platelet adherence
2- preventing coagulation factor activation
3- lysing blood clots that may form.
Endothelial cells can be stimulated by direct injury or by various cytokines that are produced during inflammation.
Endothelial injury results in:
1- expression of procoagulant proteins (tissue factor and vWF)→ local thrombus formation.
2- exposure of underlying vWF and basement membrane collagen → platelet aggregation and thrombus formation.
RESPONSE OF VASCULAR WALL CELLS TO INJURY( PATHOLOGIC EFFECT OF VASCULAR HEALING)
Injury to the vessel wall results in a healing response, involving:
- Intimal expansion (proliferating SMCs and newly synthesized ECM). This involves signals from ECs, platelets, and macrophages; and mediators derived from coagulation and complement cascades.
- luminal stenosis & blockage of vascular flow
Causes of Endothelial injury
1. Valvulitis
2. MI
3. Atherosclerosis
4. Traumatic or inflammatory conditions
5. Increased Blood Pressure
6. Endotoxins
7. Hypercholesterolemia
8. Radiation
9. Smoking
Stasis
- Stasis is a major factor in venous thrombi
- Normal blood flow is laminar (platelets flow centrally in the vessel lumen, separated from the endothelium by a slower moving clear zone of
plasma)
- Stasis and turbulence cause the followings:
Disuption of normal blood flow
prevent dilution of activated clotting factor
retard inflow of clotting factor inhibitor
promote endothelial cell injury
Causes of Stasis
1. Atherosclerosis
2. Aneurysms
3. Myocardial Infarction ( Non-cotractile fibers)
4. Mitral valve stenosis (atrial dilation)
5. Hyper viscosity syndromes (PCV and Sickle Cell anemia)
Hypercoagulability
A. Genetic (primary):
- mutations in the factor V gene and the prothrombin gene are the most common
B. Acquired (secondary):
- multifactorial and more complicated
- causes include: Immobilization, MI, AF, surgery, fracture, burns, Cancer, Prosthetic cardiac valves
MORPHOLOGY OF THROMBI
Can develop anywhere in the CVS (e.g., in cardiac chambers, valves, arteries, veins, or capillaries).
Arterial or cardiac thrombi→ begin at sites of endothelial injury; and are usually superimposed on an atherosclerotic plaque.
Venous thrombi → occur at sites of stasis. Most commonly the veins of the lower extremities (90%)
Thrombi are focally attached to the underlying vascular surface; arterial and venous thrombi both tend to propagate toward the heart.
→ The propagating portion of a thrombus is poorly attached → fragmentation and embolus formation
LINES OF ZAHN
Thrombi can have grossly (and microscopically) apparent laminations called lines of Zahn; these represent pale platelet and fibrin layers alternating with darker erythrocyte-rich layers.
Such lines are significant in that they represent thrombosis of flowing blood.
Mural thrombi = Thrombi occurring in heart chambers or in the aortic lumen.
Causes: -Abnormal myocardial contraction (e.g. arrhythmias, dilated cardiomyopathy, or MI) -endomyocardial injury (e.g. myocarditis, catheter trauma)
Vegetations ->Thrombi on heart valves
1- Bacterial or fungal blood-borne infections - (infective endocarditis,).
2- Non-bacterial thrombotic endocarditis occur on sterile valves.
Fate of thrombi
1. Propagation → Thrombi accumulate additional platelets and fibrin, eventually causing vessel obstruction
2. Embolization → Thrombi dislodge or fragment and are transported elsewhere in the vasculature
3. Dissolution → Thrombi are removed by fibrinolytic activity (Usually in recent thrombi)
4. Organization and recanalization → Thrombi induce inflammation and fibrosis. - recanalization (re-establishing some degree of flow) - Organization = ingrowth of endothelial cells, smooth cells and fibroblasts into the fibrin rich thrombus.
5. Superimposed infection (Mycotic aneurysm)
Venous thrombi → most common in veins of the legs
a. Superficial: e.g. Saphenous veins. - can cause local congestion, swelling, pain, and tenderness along the course of the involved vein, but they rarely embolize
a. Deep: e.g. Popliteal, Femoral and iliac vein. - more serious because they may embolize - can occur with stasis or hypercoagulable states
THROMBOPHLEBITIS AND PHLEBOTHROMBOSIS
- The deep leg veins account for more than 90% of cases (DVT)
- the most important clinical predispositions are: congestive heart failure, neoplasia, pregnancy, obesity, the postoperative state, and prolonged bed rest or immobilization
- local manifestations: distal edema, cyanosis, superficial vein dilation, heat, tenderness, redness, swelling, and pain
- migratory thrombophlebitis (Trousseau sign): hypercoagulability occurs as a paraneoplastic syndrome related to tumor elaboration of procoagulant factors
Polycystic kidney disease
Characterized by the formation of cysts and partial replacement of renal parenchyma.
Genetic transmission: autosomal dominant.
Clinical manifestations:
hypertension, hematuria, palpable renal masses, and progression to renal failure. Commonly associated with berry
aneurysms.