Anemia (Disorder of Hematopoietic System) - Probably the most common effect of nutritional deficiency. Any factor that decreases hematopoiesis can cause an anemia.

A. Iron deficiency - Widely recognized as the most important cause of anemia, It is indicated that ½ of all pregnant women and infants are affected, as are ~13% of all adult women.

1. Dietary factors - Availability of iron from different food sources and mixtures.
2. Malabsorption – One third of patients with inflammatory bowel disease (IBD) have recurrent anemia and 30% or more of patients who have had partial gastrectomy will develop iron deficiency anemia.
3. Blood loss - Menses, gastrointestinal bleeding 
4. Increased demand - Pregnancy, growth in children.
5. Congenital - Atransferrinemia
6. Importance of multiple factors.
7. Pathophysiology - Initially iron is mobilized from reticuloendothelial stores and increased intestinal absorption occurs. Total iron stores are depleted, serum iron levels fall. In severe cases in peripheral blood, the red cells become smaller (microcytic) and their hemoglobin content is reduced (hypochromic).  

B. Megaloblastic anemias- Characterized by the presence of abnormal WBCs and RBCs. In severe cases, megaloblasts (abnormal red cell precursors) may be present. These anemias are a consequence of disordered DNA synthesis.
1. Folate deficiency - Can be caused by:
a. Dietary deficiency
b. Malabsorption (celiac disease)
c. Increased demand (pregnancy & lactation)
d. Drugs - methotrexate, anticonvulsants, oral contraceptives, alcoholism.
e. Liver disease

2. Cobalamin (vitamin B12) deficiency - Almost always a secondary disorder that can  be caused by:

a. Intrinsic factor deficiency (pernicious anemia due to autoimmune destruction of the gastric mucosa)

b. Malabsorption

3. Pyridoxine (vitamin B6) deficiency- most commonly associated with alcoholism.

C. Other factors known to be frequently associated with anemia would include protein-calorie malnutrition, vitamin C deficiency, and pyridoxine deficiency (usually associated with alcoholism).

D. Other anemias not particularly associated with nutritional disease would include hemolytic anemia
(decreased red cell life span) and aplastic anemia (failure of marrow to produce new cells).  

Nevus
1. Commonly known as moles.
2. A benign, pigmented tumor of melanocytes, found deep within connective tissue.
3. Types of skin nevi:
a. Junctional nevus—found in the epidermis.
It is the only type of nevus that may be considered to be premalignant.
b. Compound nevus—found in both the epidermis and underlying dermis.
c. Intraepidermal nevus—found in the dermis.

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. 

Congestive heart failure (CHF)
A. Left-sided CHF

1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.

B. Right-sided CHF

1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.

Achrondroplasia 
is a major cause of dwarfism. The underlying etiology is a point mutation in the fibroblast growth factor receptor, which causes inhibition of chondrocyte proliferation, which is associated with suppression of the normal epiphyseal growth plate expansion. Thus, long bone growth is markedly shortened.
The most conspicuous changes include disproportionate shortening of the proximal extremities, bowing of the legs, and a lordotic posture. 

Microscopically, the cartilage growth plates are disorganized and hypoplastic. 

Rickettsial Diseases

Epidemic Typhus

An acute, severe, febrile, louse-borne disease caused by Rickettsia prowazekii, characterized by prolonged high fever, intractable headache, and a maculopapular rash.

Symptoms, Signs, and Prognosis

After an incubation period of 7 to 14 days, fever, headache, and prostration suddenly occur. Temperature reaches 40° C (104° F) in several days and remains high, with slight morning remission, for about 2 wk. Headache is generalized and intense. Small pink macules appear on the 4th to 6th day, usually in the axillae and on the upper trunk; they rapidly cover the body, generally excluding the face, soles, and palms. Later the rash becomes dark and maculopapular; in severe cases, the rash becomes petechial and hemorrhagic. Splenomegaly occurs in some cases. Hypotension occurs in most seriously ill patients; vascular collapse, renal insufficiency, encephalitic signs, ecchymosis with gangrene, and pneumonia are poor prognostic signs. Fatalities are rare in children < 10 yr, but mortality increases with age and may reach 60% in untreated persons > 50 yr.