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.

Acute leukaemia
Lympheblastic is commoner in children and myeloblastic in adults .

Features:
- Anaemia.
- Fever and infections especially oral and respiratory.
- Haemorrhagic tendencies.
- Bone pains and tenderness (sternal).
- Lymphnode enlargement especially in lymphocytic.
- Gum hypertrophy especially in monocytic.

Blood picture:

- Anaemia and thrombocytopenia.
- Leucocyte count usually 20,-50,000/cu.mm. It may be less in subleukaemic leukaemia (even leucopenic levels may be seen).
- Blast cells form 30-90% of cells. Smudge cells and basket cells are seen .The type of balst cell may be recognised  by the associated more mature forms or by special cytochemical stains
- Blasts may be few in peripheral blood in the aleukamic stage

 Bone Marrow

- May be a dry tap , necessitating a trephine biopsy 
- Hypercellular with 70-90% blasts
- Reduction in megakaryocytes and erythroid cells
 

Hematological examination

This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.

Paroxysmal nocturnal haemoglobinuria (PNH).

Feature:

• Acquired RBC rnembrane defect rendering it susceptible  to complement lysis.
• Features of intravascular haemolysis.
• Blood picture of haemolysis anemais with pancytopenia.
• Ham’s acid serum test (lysis at 37COin acid pH) + ve

Malnutrition

 A. Marasmus - calorie malnutrition 
 A child with marasmus suffers growth retardation and loss of muscle. The loss of muscle mass results from catabolism and depletion of the somatic protein compartment.
 With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell-mediated immunity. 
 B. Kwashiorkor - protein malnutrition - importance of protein quality as well as quantity
Marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized, or dependent, edema.

The weight of children with severe kwashiorkor is typically 60% to 80% of normal. 
However, the true loss of weight is masked by the increased fluid retention (edema).

Children with kwashiorkor have characteristic skin lesions, with alternating zones of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a "flaky paint" appearance.

Hair changes include overall loss of color or alternating bands of pale and darker hair, straightening, line texture, and loss of firm attachment to the scalp.

An enlarged, fatty liver (resulting from reduced synthesis of carrier proteins) and a tendency to develop early apathy, listlessness, and loss of appetite. 

 The bone marrow in both kwashiorkor and marasmus may be hypoplastic, mainly because of decreased numbers of red cell precursors. How much of this derangement is due to a deficiency of protein and folates or to reduced synthesis of transferrin and ceruloplasmin is uncertain. Thus, anemia is usually present, most often hypochromic microcytic anemia, but a concurrent deficiency of folates may lead to a mixed microcytic-macrocytic anemia.
 
 
 C. Most cases of severe malnutrition are a combination of A and B usually characterized by:
 
• Failure of growth
• Behavioral changes
• Edema (kwashiorkor)
• Dermatosis
• Changes in hair
• Loss of appetite
• Liver enlargement
• Anemia
• Osteoporosis 
 

EMBOLISM

Definition: transportation of an abnormal mass of an abnormal mass of undissolved material from one part of circulation to another. The mass transported is called embolus.

Types
I .Thrombi and clots.
2. Gas or air.
3. Fat
4.Amniotic fluid.
5.Tumour

Thromboembolism 
This is the commonest type of embolus and may be formed of the primary thrombus  or more often of propagated clot region which is loosely attached.

Emboli from venous thrombi can result In impaction in the pulmonary  arteries and result in sudden death.
Embolism from cardiac or arterial thrombi results in systemic embolism causing infraction and gangrene.

Gaseous
This occurs when gas is introduced into the circulation:
•    Accidental opening of large veins during surgery.
•    Mismanaged transfusion. .
As air is  readily absorbed into blood only  sudden introduction or large quantities of air produces effects
Caisson’s Disease  bubbling of nitrogen from the blood during sudden decompression as seen during deep sea diving.

Fat Embolism
Causes
•    Fractures especially of long bones and multiple
•    Crush injuries.

Sites of impaction:

o    Lungs.
o    Systemic: causing -
    →    petechial skin haemorrhages.
    →    Embolism to brain leading to coma and death.
    →     Conjunctival and retinal haemorrhages
    
Tumor Embolism.

Invasion of vascular channe1.s is a feature of malignant neoplasms and this leads to:
•    Metastatic deposits,
•    DlC