NEET MDS Lessons
General Pathology
Growth and spread of tumours
Growth in excess of normal is a feature of all tumours but extension to tissue away from the site of origin is a feature of malignant tumours.
Modes of spread of malignant tumours
- local, invasion. This is a feature of all malignant tumors and takes place along tissue spaces and facial planes
o Lymphatic spread. Most often seen in carcinomas. This can be in the form of
o Lymphatic permeation: Where the cells extend along the lymphatics as a solid core
o Lymphatic embolisation: Where a group of tumour cells break off and get carried to the draining mode
-Vascular spread : This is a common and early mode of spread for sarcomas but certain carcinomas like renal cell carcinoma and chorio carcinoma have a predilection to early vascular spread.
Vascular spread is most often due .to invasion of venous channels and can be by permeation or embolisation.
Lungs, liver, bones and brain are the common sites for vascular metastasis but
different tumours have different organ preference for metastasis, e.g. : Bronchogenic carcinoma often spreads to liver and adrenals.
-Body cavities and natural passages
o Gastrointestinal carcinomas spread to ovaries (Krukenberg’s tomour)
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.
Verruca vulgaris
1. Commonly known as warts.
2. Caused by the human papillomavirus (HPV).
3. Warts can be seen on skin or as an oral lesion (vermilion border, oral mucosa, or tongue).
4. Transmitted by contact or autoinoculation.
5. A benign lesion.
Acanthosis nigricans is a pigmented skin lesion commonly present in the axilla which is a phenotypic marker for an insulin-receptor abnormality as well as a marker for adenocarcinoma, most commonly of gastric origin.
EMBOLISM
An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin
99% due to dislodged thrombus
Types:
1. Thrombo-embolism
2. Fat embolism
3. Air embolism
4. Nitrogen embolism
Emboli result in partial or complete vascular occlusion.
The consequences of thromboembolism include ischemic necrosis (infarction) of downstream tissue
PULMONARY THROMBOEMBOLISM
- 95% originate from deep veins of L.L
Special variants: - Saddle embolus: at bifurcation of Pulmonary artery
Paradoxical embolus: Passage of an embolus from venous to systemic circulation through IAD, IVD
CLINICAL CONSEQUENCE OF PULMONARY THROMBOEMBOLISM :
Most pulmonary emboli (60% to 80%) are clinically silent because they are small
a. Organization: 60 – 80 %
b. Sudden death, Right ventricle failure, CV collapse when more than 60 % of pulmonary vessels are obstructed.
c. Pulmonary hemorrhage: obstruction of medium sized arteries.
d. Pulmonary Hypertension and right ventricular failure due to multiple emboli over a long time.
Systemic thromboembolism
Emboli traveling within the arterial circulation
80% due to intracardiac mural thrombi
2/3 Lt. ventricular failure
The major targets are:
1. Lower limbs 75%
2. Brain 10%
3. Intestines
4. Kidneys
5. Spleen
Fat embolism
Causes
1. Skeletal injury (fractures of long bones )
2. Adipose tissue Injury
Mechanical obstruction is exacerbated by free fatty acid release from the fat globules, causing local toxic injury to endothelium. - In skeletal injury, fat embolism occurs in 90% of cases, but only 10% or less have clinical findings
Fat embolism syndrome is characterized by
A. Pulmonary Insufficiency
B. Neurologic symptoms
C. Anemia
D. Thrombocytopenia
E. Death in 10% of the case
Symptoms appears 1-3 days after injury
Tachypnea, Dyspnea, Tachycardia and Neurological symptoms
Air Embolism
causes: 1. Obstetric procedures
2. Chest wall injury
3. Decompression sickness: in Scuba and deep-sea divers ((nitrogen ))
More then 100ml of air is required to produce clinical effect.
Clinical consequence
1. Painful joints: due to rapid formation of gas bubbles within Sk. Muscles and supporting tissues.
2. Focal ischemia in brain and heart
3. Lung edema, Hemorrhage, atelectasis, emphysema, which all lead to Respiratory distress. (chokes)
4. caisson disease: gas emboli in the bones leads to multiple foci of ischemic necrosis, usually the heads of the femurs, tibias, and humeri
Amniotic fluid embolism
- Mortality Rate = 20%-40%
- Very rare complication of labor
- due to infusion of amniotic fluid into maternal circulation via tears in placental membranes and rupture of uterine veins.
- sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures, DIC and coma
- Findings: Squamous cells, languo hair, fat, mucin …..etc within the pulmonary microcirculation
Eczematous Dermatitis
Eczematous dermatitis includes a large category of skin lesions characterized by severe pruritus and distinctive gross and microscopic features.
- type I hypersensitivity is involved with atopic dermatitis in patients who have an allergic history.
- type IV hypersensitivity is involved in contact dermatitis (poison ivy).
- acute eczematous dermatitis is characterized by a weeping, pruritic rash, while a chronic eczematous dermatitis presents with dry, scaly, plaque-like thickening of the skin, a process called lichenification.
Parathyroid hormone
Parathyroid hormone (PTH) is a polypeptide (84 amino acid residues) secreted by the chief cells of the parathyroid glands (four glands: two in each of the superior and inferior lobes of the thyroid; total weight 120 mg).
The main action of PTH is to increase serum calcium and decrease serum phosphate.
Its actions are mediated by the bones and kidneys -
In bone, PTH stimulates osteoclastic bone resorption and inhibits osteoblastic bone deposition. The net effect is the release of calcium from bone.
In the kidney, PTH has the following effects:
- Increases calcium reabsorption.
- Decreases phosphate reabsorption.
- Increases 1-hydroxylation of 25-hydroxyvitamin D (i.e. activates vitamin D).
PTH also increases gastrointestinal calcium absorption.