NEET MDS Lessons
General Pathology
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
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).
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.
Infectious Mononucleosis
It is an Epstein Barr virus infection in children and young adults.
Features
-Constitutional symptoms.
-Sore throat.
-Lymphnode enlargement.
-Skin rashes
-Jaundice.
-Rarely pneumonia, meningitis and encephalitis.
Blood Picture
- Total count of I0,000. 20,000 /cu.mm.
- Lymphocytosis (50-90%) with atypical forms. They are larger with more cytoplasm which may be vacuolated or basophilic. Nucleus may be indented. with nucleoli (Downy type I to III).
- Platelets may be reduced.
- Paul Bunell test (for heterophil antibody against sheep RBC) is positive
Respiratory Viral Diseases
Respiratory viral infections cause acute local and systemic illnesses. The common cold, influenza, pharyngitis, laryngitis (including croup), and tracheobronchitis are common.
An acute, usually afebrile, viral infection of the respiratory tract, with inflammation in any or all airways, including the nose, paranasal sinuses, throat, larynx, and sometimes the trachea and bronchi.
Etiology and Epidemiology
Picornaviruses, especially rhinoviruses and certain echoviruses and coxsackieviruses, cause the common cold. About 30 to 50% of all colds are caused by one of the > 100 serotypes of rhinoviruses.
Symptoms and Signs
Clinical symptoms and signs are nonspecific.
After an incubation period of 24 to 72 h, onset is abrupt, with a burning sensation in the nose or throat, followed by sneezing, rhinorrhea, and malaise.
Characteristically, fever is not present, particularly with a rhinovirus or coronavirus. Pharyngitis usually develops early; laryngitis and tracheobronchitis vary by person and causative agent. Nasal secretions are watery and profuse during the first days, but become more mucoid and purulent.
Cough is usually mild but often lasts into the 2nd wk.
PARASITIC DISEASES
AMEBIASIS (Entamebiasis)
Infection of the colon with Entamoeba histolytica, which is commonly asymptomatic but may produce clinical manifestations ranging from mild diarrhea to severe dysentery.
Etiology and Pathogenesis
Amebiasis is a protozoan infection of the lower GI tract. E. histolytica exists in two forms: the trophozoite and the cyst.
Two species of Entamoeba are morphologically indistinguishable: E. histolytica is pathogenic and E. dispar harmlessly colonizes the colon. Amebas adhere to and kill colonic epithelial cells and cause dysentery with blood and mucus in the stool. Amebas also secrete proteases that degrade the extracellular matrix and permit invasion into the bowel wall and beyond. Amebas can spread via the portal circulation and cause necrotic liver abscesses.
Symptoms and Signs
Most infected persons are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. There may be tenderness over the liver and ascending colon, and the stools may contain mucus and blood.
Amebic dysentery, common in the tropics but uncommon in temperate climates, is characterized by episodes of frequent (semi)liquid stools that often contain blood, mucus, and live trophozoites.
Chronic infection commonly mimics inflammatory bowel disease and presents as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss.
Metastatic disease originates in the colon and can involve any organ, but a liver abscess, usually single and in the right lobe, is the most common
Wilson’s disease
Caused by a decrease in ceruloplasmin, a serum protein that binds copper, resulting in metastatic copper deposits.
Common organs affected include:
(1) Liver, leading to cirrhosis.
(2) Basal ganglia.
(3) Cornea, where Kayser-Fleischer rings (greenish rings around the cornea) are observed.