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.

METAPLASIA

A reversible replacement of one type of adult tissue by another type of tissue. It is usually an adaptive substitution to a. cell type more suited to an environment, often at the cost of specialised function.

(1) Epithelial metaplasia:

• Squamous metaplasia. This is the commoner type of metaplasia and is seen in:
  • Tracheobronchial lining in chronic smokers and in bronchiectasis.
  • In Vitamin A deficiency.
• Columnar metaplasia:
  • Intestinalisation of gastric mucosa in chronic gastritis.

(2) Connective tissue metaplasia:

• Osseous-Metaplasia in :
  • Scars.
  • Myositis ossificans
• Myeloid metaplasia in liver and spleen.

Neutropenia: Neutropenia is an abnormally low number of neutrophils  
Causes

-Typhoid, paratyphoid. .
-Viral and ricketseal infections.
-Malaria, Kala azar.
-Hypersplenism.
-Aplastic and megaloblastic anaemia.
-Marrow infiltration by malignancies, lymphomas etc.
-SLE.

Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus 

- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.

Posterior Pituitary Syndromes 

The posterior pituitary, or neurohypophysis, is composed of modified glial cells (termed pituicytes) and axonal processes extending from nerve cell bodies in the hypothalamus. The hypothalamic neurons produce two peptides: antidiuretic hormone (ADH) and oxytocin that are stored in axon terminals in the neurohypophysis.

The clinically important posterior pituitary syndromes involve ADH production and include  
1. Diabetes insipidus and 
2. Inappropriate secretion of high levels of ADH.  

- ADH is released into the general circulation in response to increased plasma oncotic pressure & left atrial distention. 
- It acts on the renal collecting tubules to increase the resorption of free water. 
- ADH deficiency causes  diabetes insipidus, a condition characterized by polyuria. If the cause is related to ADH Diabetes insipidus from - - ADH deficiency is designated as central, to differentiate it from nephrogenic diabetes insipidus due to renal tubular unresponsiveness to circulating ADH. 
- The clinical manifestations of both diseases are similar and include the excretion of large volumes of dilute urine with low specific gravity. Serum sodium and osmolality are increased as a result of excessive renal loss of free water, resulting in thirst and polydipsia. 

- ADH excess causes resorption of excessive amounts of free water, with resultant hyponatremia. 
- The most common causes of the syndrome include the secretion of ectopic ADH by malignant neoplasms (particularly small-cell carcinomas of the lung), and local injury to the hypothalamus and/or neurohypophysis. 

- The clinical manifestations are dominated by hyponatremia, cerebral edema, and resultant neurologic dysfunction.

Chronic hepatitis

Chronic hepatitis occurs in 5%-10% of HBV infections and in well over 50% of HCV; it does not occur in HAV. Most chronic disease is due to chronic persistent hepatitis. The chronic form  is more likely to occur in the very old or very young, in males, in immunocompromised hosts, in Down's syndrome, and in dialysis patients.

a. Chronic persistent hepatitis is a benign, self-limited disease with a prolonged recovery. Patients are asymptomatic except for elevated transaminases. 

b. Chronic active hepatitis features chronic inflammation with hepatocyte destruction, resulting in cirrhosis and liver failure. 
(1) Etiology. HBV, HCV, HDV, drug toxicity, Wilson's disease, alcohol, a,-antitrypsin deficiency, and autoimmune  hepatitis are common etiologies.
(2) Clinical features may include fatigue, fever, malaise, anorexia, and elevated liver function tests. 
(3) Diagnosis is made by liver biopsy.

8. Carrier state for HBV and HCV may be either asymptomatic or with liver disease; in the latter case, the patient has elevate transaminases.
a. Incidence is most common in immunodeficient, drug addicted, Down's syndrome, and dialysis patients. 
b. Pathology of asymptomatic carriers shows "ground-glass"" hepatocytes with finely granular eosinophilic cytoplasm.