ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological

- Foetal involution.
    o    Branchial clefts.
    o    Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
    o    Post-partum uterus.
    o    Post-menopausal ovaries and uterus
    o    Post-lactational breast
    o    Thymus.
(2) Pathological:
- Generalised as in

    o    Ageing.
    o    Severe starvation and cachexia
- Localised :
    o    Disuse atropy of bone and muscle.
    o    Ischaemic atrophy as in arteriosclerotic kidney. .
    o    Pressure atrophy due  to tumours and of kidney in hydronephrosis.
    o    Lack of trophic stimulus to endocrines and gonads.
 

Q Fever

An acute disease caused by Coxiella burnetii (Rickettsia burnetii) and characterized by sudden onset of fever, headache, malaise, and interstitial pneumonitis.

Symptoms and Signs

The incubation period varies from 9 to 28 days and averages 18 to 21 days. Onset is abrupt, with fever, severe headache, chills, severe malaise, myalgia, and, often, chest pains. Fever may rise to 40° C (104° F) and persist for 1 to > 3 wk. Unlike other rickettsial diseases, Q fever is not associated with a cutaneous exanthem. A nonproductive cough and x-ray evidence of pneumonitis often develop during the 2nd wk of illness.

In severe cases, lobar consolidation usually occurs, and the gross appearance of the lungs may resemble that of bacterial pneumonia

About 1/3 of patients with protracted Q fever develop hepatitis, characterized by fever, malaise, hepatomegaly with right upper abdominal pain, and possibly jaundice. Liver biopsy specimens show diffuse granulomatous changes, and C. burnetii may be identified by immunofluorescence.

Keloids
1. Characterized by a progressively enlarging scar.
2. Caused by an abnormal accumulation of collagen at the site of injury.
3. More common in African-Americans.

Nephrolithiasis, urolithiasis

Formation of calculi (calcium stones) in the kidney (nephrolithiasis) or urinary tract (urolithiasis).
Commonly associated with hyperparathyroidism.
Signs and symptoms 

urinary tract obstruction, severe pain, and pyelonephritis.

Note: an enlarged prostate can also cause urinary tract obstruction in males.

Fulminant hepatitis

Fulminant hepatitis leads to submassive and massive hepatic necrosis. 
a. Etiology. HAV, HBV, HCV, delta virus (HDV) superinfection, HEV, chloroform, carbon tetrachloride, isoniazid, halothane, and other drugs (acetaminophen overdose) all may cause fulminant hepatitis.
b. Clinical features include progressive hepatic dysfunction with a mortality of 25%-90%.
c. Pathology

(1) Grossly, one sees progressive shrinkage of the liver as the parenchyma is destroyed. 

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