Cholelithiasis (Biliary calculi)
- These are insoluble material found within the biliary tract and are formed of bile constituents (cholesterol, bile pigments and calcium salts). 

Sites: - -Gall bladder, extra hepatic biliary tract.  Rarely, intrahepatic biliary tract. 

Predisposing factors:- 
- Change in the composition of bile. - It is the disturbance of the ratio between cholesterol and lecithin or bile salts which may be due to Hypercholesterolaemia which may be hereditary or the 4 F (Female, Forty, Fatty, Fertile). Drugs as clofibrate and exogenous estrogen. High intake of calories (obesity).
Increased concentration of bilirubin in bile- pigment stones
Hypercalcaemia:- Calcium carbonate stones.

2- Staisis.
3- Infection. 

Pathogenesis   i- Nucleation or initiation of stone formation:- The nidus may be cholesterol “due to supersaturation” Bacteria, parasite
RBCs or mucous.  
ii- Acceleration:- When the stone remains in the gall bladder, other constituents are added to the
nidus to form the stone. 

Complications of gall stones:- 
- Predispose to infection.- Chronic irritation leading to 
a. Ulceration       b. Squamous metaplasia & carcinoma.

Immunohistochemistry

 This is a method is used to detect a specific antigen in the tissue in order to identify the type of disease.

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
 

Seborrheic keratosis
1. A round, brown-colored, flat wart.
2. Most often seen in middle-aged to older adults.
3. A benign lesion.

PERTUSSIS (Whooping Cough)

An acute, highly communicable bacterial disease caused by Bordetella pertussis and characterized by a paroxysmal or spasmodic cough that usually ends in a prolonged, high-pitched, crowing inspiration (the whoop).

Transmission is by aspiration of B. pertussis

Symptoms and Signs

The incubation period averages 7 to 14 days (maximum, 3 wk). B. pertussis invades the mucosa of the nasopharynx, trachea, bronchi, and bronchioles, increasing the secretion of mucus, which is initially thin and later viscid and tenacious. The uncomplicated disease lasts about 6 to 10 wk and consists of three stages: catarrhal, paroxysmal, and convalescent.

Hypoparathyroidism

Hypoparathyroidism is a condition of reduced or absent PTH secretion, resulting in hypocalcaemia and hyperphosphataemia. It is far less common than hyperparathyroidism.

The causes of hypoparathyroidism are:
- Removal or damage of the parathyroid glands during thyroidectomy—most common cause of hypoparathyroidism resulting from inadvertent damage or removal.
- Autoimmune parathyroid disease—usually occurs in patients who have another autoimmune endocrine disease, e.g. Addison’s disease (autoimmune endocrine syndrome type 1).
- Congenital deficiency (DiGeorge syndrome)— rare, congenital disorder caused by arrested development of the third and fourth branchial arches, resulting in an almost complete absence of the thymus and parathyroid gland.

The effects of hypoparathyroidism are:
- ↓ release of Ca²⁺ from bones. 
- ↓ Ca²⁺ reabsorption but ↑ PO ₄³⁻ re absorption by the kidneys
- ↓ 1-hydroxylation of 25-hydroxyvitamin D by kidney.

Most symptoms of hypoparathyroidism are those of hypocalcaemia:
- Tetany—muscular spasm provoked by lowered plasma Ca 2+ 
- Convulsions.
- Paraesthesiae.
- Psychiatric disturbances, e.g. depression, confusional state and even psychosis.
- Rarely—cataracts, parkinsonian-like movement disorders, alopecia, brittle nails.

Management is by treatment with large doses of oral vitamin D; the acute phase requires intravenous calcium and calcitriol (1,25-dihydroxycholecalciferol, i.e.  activated vitamin D).