Polycystic kidney disease

Characterized by the formation of cysts and partial replacement of renal parenchyma.
Genetic transmission: autosomal dominant.
Clinical manifestations:

 hypertension, hematuria, palpable renal masses, and progression to renal failure. Commonly associated with berry
aneurysms. 

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

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).  

Miscellaneous Bone Tumors 

1. Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET) are primary malignant small round-cell tumors of bone and soft tissue. They are viewed as the same tumor because they share an identical chromosome translocation; they differ only in degree of differentiation. PNETs demonstrate neural differentiation whereas Ewing sarcomas are undifferentiated. After osteosarcomas, they are the second most common pediatric bone sarcomas. Most patients are 10 to 15 years old. The common chromosomal abnormality is a translocation that causes fusion of the EWS gene with a member of the ETS family of transcription factors. The resulting hybrid protein functions as an active transcription factor to stimulate cell proliferation. These translocations are of diagnostic importance since almost all patients with Ewing tumor have t(11;22).

Pathological features

• Ewing sarcoma and PNETs arise in the medullary cavity but eventually invade the cortex and periosteum to produce a soft tissue mass.
• The tumor is tan-white, frequently with foci of hemorrhage and necrosis.

Microscopic features

• There are sheets of uniform small, round cells that are slightly larger than lymphocytes with few mitoses and little intervening stroma.
• The cells have scant glycogen-rich cytoplasm.
• The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) indicates neural differentiation, and hence indicates by definition PNET. 

Ewing sarcoma and PNETs typically present as painful enlarging masses in the diaphyses of long tubular bones (especially the femur) and the pelvic flat bones. The tumor may be confused with osteomyelitis because of its association with systemic signs & symptoms of infection. X-rays show a destructive lytic tumor with infiltrative margins and extension into surrounding soft tissues. There is a characteristic periosteal reaction depositing bone in an onionskin fashion. 

2. Giant-Cell Tumor of Bone (GCT) is dominated by multinucleated osteoclast-type giant cells, hence the synonym osteoclastoma. GCT is benign but locally aggressive, usually arising in individuals in their 20s to 40s. Current opinion suggests that the giant cell component is likely a reactive macrophage population and the mononuclear cells are neoplastic. Tumors are large and red-brown with frequent cystic degeneration. They are composed of uniform oval mononuclear cells with frequent mitoses, with scattered osteoclast-type giant cells that may contain 30 or more nuclei.

The majority of GCTs arise in the epiphysis of long bones around the knee (distal femur and proximal tibia).
Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex is frequently destroyed, producing a bulging soft tissue mass with a thin shell of reactive bone. Although GCTs are benign, roughly 50% recur after simple curettage; some malignant examples (5%) metastasize to the lungs 

Surface Defence Mechanisms

1. Skin:

(i) Mechanical barrier of keratin and desquamation.

(ii) Resident commensal organisms

(iii)Acidity of sweat.

(iv) Unsaturated fatty acids of sebum

2. Oropharyngeal

(i)Resident flora

(ii) Saliva, rich in lysozyme, mucin and Immunoglobulins (lgA).

3. Gastrointestinal tract.-

(i) Gastric HCI

(ii) Commensal organisms in Intestine

(iii) Bile salts

(iv) IgA.

(v) Diarrhoeal expulsion of irritants.

4. Respiratory tract:

(i) Trapping in turbinates

(ii) Mucus trapping

(iii) Expulsion by coughing and sneezing.

(iv) Ciliary propulsion.

(V) Lysozymes and antibodies in secretion.

(vi) Phagocytosis by alveolar macrophages.

5. Urinary tract:

(i) Flushing action.

(ii) Acidity

(iii) Phagocytosis by urothelial cells.

6. Vagina.-

(i) Desquamation.

(ii) Acid barrier.

(iii) Doderlein's bacilli (Lactobacilli)

7. Conjunctiva:

Lysozymes and IgA in tears

HYPERTENSIVE VASCULAR DISEASE 

Malignant hypertension 
A small percentage of HTN patients (5%) present with a rapidly rising blood pressure that, if untreated, leads to death within 1 to 2 years. 

systolic pressures -> 200 mm Hg or diastolic pressures -> 120 mm Hg 
Associated with renal failure and retinal hemorrhages
Most commonly is superimposed on preexisting benign hypertension

Hypertension (HTN) has the following complications

- stroke (CVD) 
- multi-infarct dementia
- atherosclerotic coronary heart disease 
- cardiac hypertrophy and heart failure (hypertensive heart disease) 
- aortic dissection 
- renal failure

Essential HTN Accounts for 90% to 95% of all cases

SecondaryHTN 

Renal - > Acute glomerulonephritis Chronic renal disease 
Endocrine - >  Cushing syndrome, Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (pre-eclampsia)
Cardiovascular  - > Coarctation of aorta 

Neurologic

Psychogenic,  Increased intracranial pressure 

PATHOGENESIS
most cases (95%) are idiopathic (essential hypertension)
Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing 
Gene defects in enzymes involved in aldosterone metabolism 
 Mutations in proteins that affect sodium resorption as in Liddle syndrome
 
 Genetic factors - > familial clustering of hypertension 
 
 Environmental factors such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants

Morphology
HTN is associated with arteriolosclerosis (small arterial disease) 

Two forms of small blood vessel disease are hypertension-related: 
1- hyaline arteriolosclerosis 
2- hyperplastic arteriolosclerosis 

Hyaline arteriolosclerosis
Associated with benign hypertension. 
-marked by homogeneous, pink hyaline thickening of the arteriolar walls, and luminal narrowing. 

Hyperplastic arteriolosclerosis
It is more typical of severe hypertension. 
- "onionskin," concentric, laminated thickening of arteriolar walls and luminal narrowing. 
- The laminations consist of smooth muscle cells and thickened, reduplicated basement membrane. 

DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Several disorders are characterized by inappropriate or exaggerated vasoconstriction of blood vessels: 
1- Raynaud Phenomenon 
2- Myocardial Vessel Vasospasm 

Raynaud Phenomenon
- results from exaggerated vasoconstriction of arteries and arterioles in the extremities (the fingers and toes, but also sometimes the nose, earlobes, or lips). 
-restricted blood flow induces paroxysmal pallor or cyanosis
- involved digits characteristically show "red-white-andblue" color changes from most proximal to most distal 

Myocardial Vessel Vasospasm 

Causes: 1- vasoactive mediators - > prolonged vascular contraction; 
- endogenous (e.g., epinephrine released by pheochromocytomas) or exogenous (cocaine or phenylephrine). 
2- Elevated thyroid hormone -> increase sensitivity of vessels to catecholamines 
3- autoantibodies and T cells in scleroderma vascular instability and vasospasm. 
4- extreme psychological stress (release of catecholamines)

Cardiac raynaud

When vasospasm of cardiac arterial or arteriolar bed is of sufficient duration (20 to 30 min ) myocardial infarction occurs

acute microscopic area of necrosis characterized by mycotic hypercontraction (contraction band necrosis)

subacute and chronic cases - > microscopic foci of granulation tissue or scar