NEET MDS Lessons
General Pathology
Blood-Lymphatic Pathology
Disorders of primary hemostasis
1. General characteristics of disorders of primary hemostasis (due to problems of blood vessels or platelets):
a. Occur early in life.
b. Unlike secondary hemostasis, bleeding occurs in more superficial areas such as skin and mucous membranes rather than in secondary hemostasis.
c. Signs include petechiae.
d. Can be caused by vascular and platelet abnormalities or alterations in the plasma proteins required for adhesion of platelets to vascular subendothelium.
e. Laboratory findings include prolonged bleeding time, as seen in platelet disorders.
2. Vascular abnormalities
Scurvy
(1) Caused by a vitamin C deficiency leading to decreased synthesis of collagen. Note: vitamin C is necessary for the formation of collagen via hydroxylation of lysine and proline.
(2) Symptoms include:
- Delayed wound healing.
- Petechiae and ecchymosis.
- Gingival bleeding, swelling, and ulcerations.
3. Platelet abnormalities
a. Thrombocytopenia
(1) Characterized by a decreased number of platelets.
(2) The most common type of bleeding disorder.
(3) Can be caused by a number of diseases, such as irradiation, acute leukemia, disseminated intravascular coagulation (DIC), or idiopathic thrombocytopenic purpura (ITP).
b. Thrombocytopenic purpura
(1) Idiopathic: An autoimmune disease characterized by the presence of autoantibodies against platelets, resulting in the removal of platelets by splenic macrophages.
(2) May also be drug-induced.
Disorders of secondary hemostasis
1. General characteristics of disorders of secondary hemostasis (due to problems with clotting factors):
a. Symptoms occur later in life.
b. As compared to disorders of primary hemostasis, bleeding occurs in deeper areas and larger vessels (i.e., joint spaces).
c. Laboratory findings include abnormal:
- Partial thromboplastin time (PTT)—measures the intrinsic and common clotting pathway (i.e., tests all coagulation factors except factor 7).
- Prothrombin time (PT)—measures the extrinsic pathway.
- Does not affect the bleeding time.
Hemophilia
a. Caused by a deficiency of particular clotting factor(s).
b. All types of hemophilia affect the intrinsic pathway of the clotting cascade.
c. Signs and symptoms include:
- Prolonged PTT.
- Continuous bleeding from cuts or trauma, which can lead to excessive blood loss.
- Bleeding into joint cavities (hemarthroses) and muscle.
Two types:
(1) Hemophilia A (classic hemophilia)
- Caused by a deficiency of factor 8 (antihemophilic factor).
- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.
(2) Hemophilia B (Christmas disease)
- Caused by a deficiency of factor 9 (plasma thromboplastin).
- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.
- Lower incidence rate than hemophilia A.
(3). Vitamin K deficiency
- Causes include malnutrition and malabsorption of fats.
- A decrease in clotting factors 2, 7, 9, and 10 and prothrombin is observed.
- Prolonged PT.
Disorders of both primary and secondary hemostasis
1. von Willebrand’s disease
a. Characterized by a defective von Willebrand’s factor (vWF). Defective vWF affects both primary hemostasis by affecting platelet adhesion to
endothelium, and secondary hemostasis, by a defective factor 8.
b. Genetic transmission: autosomal dominant.
It is the most common hereditary bleeding disorder.
2. Liver disease—disease of the liver results in a decreased production of coagulation factors and therefore can lead to problems with hemostasis.
3. Disseminated intravascular coagulation a condition in which clots form throughout the vasculature. This uses up all available clotting factors and platelets, resulting in problems with bleeding.
Cor pulmonale
a failure of the right side of the heart. It is caused by prolonged high blood pressure in the right ventricle of the heart, which in turn is most often caused by pulmonary hypertension - prolonged high blood pressure in the arteries or veins of the lungs. People with heart disease, or lung diseases such as cystic fibrosis, are at greater risk.
Pathophysiology
There are several mechanisms leading to pulmonary hypertension and cor pulmonale:
Pulmonary vasoconstriction
Anatomic changes in vascularisation
Increased blood viscosity
Primary pulmonary hypertension
Causes
Acute:
• Massive pulmonary embolization
• Exacerbation of chronic cor pulmonale
Chronic:
• COPD
• Loss of lung tissue following trauma or surgery
Hepatitis
Hepatitis viruses—this group of viruses causes hepatitis, a disease affecting the liver.
1. General characteristics of hepatitis.
a. The general presentation of hepatitis is the same regardless of the infecting virus; however, the time and severity of symptoms may differ.
b. Symptoms of hepatitis include fever, anorexia, malaise, nausea, jaundice, and brown-colored urine.
c. Complications of a hepatitis infection include cirrhosis, liver failure, and hepatorenal failure.
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
Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
- genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
- the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
- the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
- the characteristic histologic features of psoriasis include:
- hyperkeratosis
- absence of the granulosa cells (present in lichen planus).
- parakeratosis
- regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
- characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
- 7% develop HLA B27 positive psoriatic arthritis
Infections caused by N. meningiditis
1. Bacteremia without sepsis. Organism spreads to blood but no major reaction.
2. Meningococcemia without meningitis. Fever, headache, petechia, hypotension, disseminated intravascular coagulation. The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.
3. Meningitis with meningococcemia. Sudden onset fever, chills, headache, confusion, nuchal rigidity. This occurs rapidly.
4. Meningoencephalitis. Patients are deeply comatose.
Diagnosis made by examining CSF.
Cartilage-Forming Tumors
1. Osteochondroma (Exostosis) is a relatively common benign cartilage-capped outgrowth attached by a bony stalk to the underlying skeleton. Solitary osteochondromas are usually first diagnosed in late adolescence and early adulthood (male-to-female ratio of 3:1); multiple osteochondromas become apparent during childhood, occurring as multiple hereditary exostosis, an autosomal dominant disorder. Inactivation of both copies of the EXT gene (a tumor suppressor gne) in chondrocytes is implicated in both sporadic and hereditary osteochondromas. Osteochondromas develop only in bones of endochondral origin arising at the metaphysis near the growth plate of long tubular bones, especially about the knee. They tend to stop growing once the normal growth of the skeleton is completed. Occasionally they develop from flat bones (pelvis, scapula, and ribs). Rarely, exostoses involve the short tubular bones of hands and feet.
Pathological features
• Osteochondromas vary from 1-20cm in size.
• The cap is benign hyaline cartilage.
• Newly formed bone forms the inner portion of the head and stalk, with the stalk cortex merging with cortex of the host bone.
Osteochondromas are slow-growing masses that may be painful. Osteochondromas rarely progress to chondrosarcoma or other sarcoma, although patients with the multiple hereditary exostoses are at increased risk of malignant transformation.
2. Chondroma
It is a benign tumor of hyaline cartilage. When it arises within the medullary cavity, it is termed enchondroma; when on the bone surface it is called juxtacortical chondroma. Enchondromas are usually diagnosed in persons between ages 20 and 50 years; they are typically solitary and located in the metaphyseal region of tubular bones, the favored sites being the short tubular bones of the hands and feet. Ollier disease is characterized by multiple chondromas preferentially involving one side of the body. Chondromas probably develop from slowly proliferating rests of growth plate cartilage.
Pathological features
• Enchondromas are gray-blue, translucent nodules usually smaller than 3 cm.
• Microscopically, there is well-circumscribed hyaline matrix and cytologically benign chondrocytes.
Most enchondromas are detected as incidental findings; occasionally they are painful or cause pathologic fractures. Solitary chondromas rarely undergo malignant transformation, but those associated with enchondromatosis are at increased risk.
3. Chondrosarcomas are malignant tumors of cartilage forming tissues. They are divided into conventional chondrosarcomas and chondrosarcoma variants. Each of these categories comprises several distinct types, some defined on microscopic grounds & others on the basis of location within the affected bone, for e.g. they are divided into central (medullary), peripheral (cortical), and juxtacortical (periosteal). The common denominator of chondrosarcoma is the production of a cartilaginous matrix and the lack of direct bone formation by the tumor cells (cf osteosarcoma). Chondrosarcomas occur roughly half as frequently as osteosarcomas; most patients age 40 years or more, with men affected twice as frequently as women
Pathological features
Conventional chondrosarcomas arise within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex. They exhibit malignant hyaline or myxoid stroma. Spotty calcifications are typically present. The tumor grows with broad pushing fronts into marrow spaces and the surrounding soft tissue. Tumor grade is determined by cellularity, cytologic atypia, and mitotic activity. Low-grade tumors resemble normal cartilage. Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures with multinucleate cells and lacunae containing two or more chondrocytes. Dedifferentiated chondrosarcomas refers to the presence of a poorly differentiated sarcomatous component at the periphery of an otherwise typical low-grade chondrosarcoma. Other histologic variants include myxoid, clear-cell and mesenchymal chondrosarcomas. Chondrosarcomas commonly arise in the pelvis, shoulder, and ribs. A slowly growing lowgrade tumor causes reactive thickening of the cortex, whereas a more aggressive high-grade neoplasm destroys the cortex and forms a soft tissue mass. There is also a direct correlation between grade and biologic behavior.
Size is another prognostic feature, with tumors larger than 10 cm being significantly more aggressive than smaller tumors. High-grade Chondrosarcomas metastasize hematogenously, preferentially to the lungs and skeleton.