Post viral (post hepatitic) cirrhosis (15-20%) 

Cause:- Viral hepatitis (mostly HBV or HCV) 
Acute hepatitis  → chronic hepatitis → cirrhosis.  

Pathology
Liver is shrunken.  Fatty change is absent (except with HCV). Cirrhosis is mixed.

M/E  :-
Hepatocytes-show degeneration, necrosis  as other types of cirrhosis. 
Fibrous septa   -They are thick and immature (more cellular and vascular).
- Irregular margins (piece meal necrosis).
- Heavy lymphocytic infiltrate.

Prognosis:- - More rapid course than alcoholic cirrhosis.Hepatocellular carcinoma is more liable to occur 
 

Psoriasis
1. Characterized by skin lesions that appear as scaly, white plaques.
2. Caused by rapid proliferation of the epidermis.
3. Autoimmune pathogenesis; exact mechanism is unclear.

Cytopathologic techniques

Cytopathology is the study of cells from various body sites to determine the cause or nature of disease.

Applications of cytopathology:

1. Screening for the early detection of asymptomatic cancer

2. Diagnosis of symptomatic cancer

3. Surveillance of patients treated for cancer

Cytopathologic methods

There are different cytopathologic methods including:

1. Fine-needle aspiration cytology (FNAC) -In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure.

Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) can be easily aspirated.

Deep organs, such as the lung, mediastinum, liver, pancreas, kidney, adrenal gland, and retroperitoneum are aspirated with guidance by fluoroscopy, ultrasound or CT scan.

1. Exfoliative cytology

Refers to the examination of cells that are shed spontaneously into body fluids or secretions. Examples include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.

1. Abrasive cytology

Refers to methods by which cells are dislodged by various tools from body surfaces (skin, mucous membranes, and serous membranes). E.g. preparation of cervical smears with a spatula or a small brush to detect cancer of the uterine cervix at early stages.

THROMBOPHLEBITIS AND  PHLEBOTHROMBOSIS 
- The deep leg veins account for more than 90% of cases (DVT) 
- the most important clinical predispositions are: congestive heart failure, neoplasia, pregnancy, obesity, the postoperative state, and prolonged bed rest or immobilization 
- local manifestations: distal edema, cyanosis, superficial vein dilation, heat, tenderness, redness, swelling, and pain 
- migratory thrombophlebitis (Trousseau sign): hypercoagulability occurs as a paraneoplastic syndrome related to tumor elaboration of procoagulant factors 

Nephrosclerosis
 Disease of the renal arteries.

 Clinical manifestations:
 (1) Benign (arterial) nephrosclerosis →  Caused by the formation of atherosclerotic plaques in the renal artery. Results in narrowing of the arterioles.

(2) Malignant nephrosclerosis → Caused by malignant hypertension. Common signs of malignant hypertension include severe hypertension, retinal hemorrhages, and hypertrophy of the left ventricle. Results in inflammatory changes in the vascular walls, which may lead to rupture of the glomerular capillaries.

DIABETES MELLITUS 
a group of metabolic disorders sharing the common underlying characteristic of hyperglycemia.  
Diabetes is an important disease because
1. It is common (affects 7% of the population). 
2. It increases the risk of atherosclerotic coronary artery and cerebrovascular diseases.
3. It is a leading cause of 
   a. Chronic renal failure
   b. Adult-onset blindness
   c. Non traumatic lower extremity amputations (due to gangrene) 
     
Classification 
Diabetes is divided into two broad classes:
1. Type1 diabetes (10%): characterized by an absolute deficiency of insulin secretion caused by pancreatic βcell destruction, usually as a result of an autoimmune attack.

2. Type2 diabetes (80%): caused by a combination of peripheral resistance to insulin action and an inadequate secretion of insulin from the pancreatic β cells in response to elevated blood glucose levels. 

The long-term complications in kidneys, eyes, nerves, and blood vessels are the same in both types.

Pathogenesis
Type 1 diabetes is an autoimmune disease and as in all such diseases, genetic susceptibility and environmental influences play important roles in the pathogenesis. The islet destruction is caused primarily by T lymphocytes reacting against immunologic epitopes on the insulin hormone located within β-cell; this results in a reduction of β-cell mass. The reactive T cells include CD4+ T cells of the TH1 subset, which cause tissue injury by activating macrophages, and CD8+ cytotoxic T lymphocytes; these directly kill β cells and also secrete cytokines that activate further macrophages. The islets show cellular necrosis and lymphocytic infiltration (insulitis). Autoantibodies against a variety of β-cell antigens, including insulin are also detected in the blood and may also contribute to islet damage. 

Type 2 Diabetes Mellitus: the pathogenesis remains unsettled. Environmental influences, such as inactive life style and dietary habits that eventuates in obesity, clearly have a role. Nevertheless, genetic factors are even more important than in type 1 diabetes. Among first-degree relatives with type 2 diabetes the risk of developing the disease is 20% to 40%, as compared with 5% in the general population. 
The two metabolic defects that characterize type 2 diabetes are 1.  A decreased ability of peripheral tissues to respond to insulin (insulin resistance) and 2. β-cell dysfunction manifested as inadequate insulin secretion in the face of hyperglycemia. In most cases, insulin resistance is the primary event and is followed by increasing degrees of β-cell dysfunction.

Morphology of Diabetes and Its Late Complications

The important morphologic changes are related to the many late systemic complications of diabetes and thus are likely to be found in arteries (macrovascular disease), basement membranes of small vessels (microangiopathy), kidneys (diabetic nephropathy), retina (retinopathy), and nerves (neuropathy). These changes are seen in both type 1 and type 2 diabetes. 

The changes are divided into pancreatic & extrapancreatic 
A. Pancreatic changes are inconstant and are more commonly associated with type 1 than with type 2 diabetes.
One or more of the following alterations may be present.
1. Reduction in the number and size of islets
2. Leukocytic infiltration of the islets (insulitis) principally byT lymphocytes.  

3. Amyloid replacement of islets; which is seen in advanced stages

B. Extrapancreatic changes 

1. Diabetic macrovascular disease is reflected as accelerated atherosclerosis affecting the aorta and other large and medium-sized arteries including the coronaries. Myocardial infarction is the most common cause of death in diabetics. Gangrene of the lower limbs due to advanced vascular disease, is about 100 times more common in diabetics than in the general population. 
2. Hyaline arteriolosclerosis
 is the vascular lesion associated with hypertension. It is both more prevalent and more severe in diabetics than in nondiabetics, but it is not specific for diabetes and may be seen in elderly nondiabetics without hypertension.
3. Diabetic microangiopathy
 is one of the most consistent morphologic features of diabetes, which reflected morphologically as diffuse thickening of basement membranes. The thickening is most evident in the capillaries of the retina, renal glomeruli, and peripheral nerves. The thickened capillary basement membranes are associated with leakiness to plasma proteins. The microangiopathy underlies the development of diabetic nephropathy, retinopathy, and some forms of neuropathy.
4. Diabetic Nephropathy: renal failure is second only to myocardial infarction as a cause of death from diabetes.

Three lesions encountered are: 
1. Glomerular lesions
2. Renal vascular lesions, principally arteriolosclerosis; and
3. Pyelonephritis, including necrotizing papillitis.  

Glomerular lesions:  these include 
a. diffuse glomerular capillary basement membrane thickening
b. diffuse glomerular sclerosis : diffuse increase in mesangial matrix; always associated with the above.  
c. nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) refers to a rounded deposits of a laminated matrix situated in the periphery of the glomerulus 

Pyelonephritis: both acute and chronic pyelonephritis are more common & more severe 

Ocular Complications of Diabetes: Visual impairment up to total blindness may occur in long-standing diabetes. The ocular involvement may take the form of 
a. retinopathy 
b. cataract formation
c. glaucoma 

In both forms of long-standing diabetes, cardiovascular events such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents are the most common causes of mortality. Diabetic nephropathy is a leading cause of end-stage renal disease. By 20 years after diagnosis, more than 75% of type 1 diabetics and about 20% of type 2 diabetics with overt renal disease will develop end-stage renal disease, requiring dialysis or renal transplantation. 
Diabetics are plagued by an enhanced susceptibility to infections of the skin, as well as to tuberculosis, 
pneumonia, and pyelonephritis. Such infections cause the deaths of about 5% of diabetics.