Block II Histology 			                        

Blood Cells

Anemia         decrease in the concentration of RBC

Polycythemia    increase in RBC adaptation to high altitude often associated with diseases
		 (increase blood viscosity)

Sickle cell    	inherited disease where valine is substituted for a glutamic acid.

HbS		when HbS is deoxygenated it polymerizes can lead to tissue anoxia
		               ‑
Anemia           decrease in the concentration of RBC caused by: decreased production of RBC,
		or increase destruction of RBC's

Hypochromic 	normal number of cells but reduced amount of heme related to dietary deficiency in iron

Reticulocytes    increase in blood during recent ascent to altitude

hypersegmented 	typical of old cells; but may represent pathology in young cells 
neutrophils
               
Pus		dead neutrophils, bacteria, and semi digested material
               
Eosinophilia	increase in the number of eosinophils associated with allergic and parasitic infections.

Cutaneous	dermatologic disease where basophils are the major cell type basophil at the infxn. 
hypersensitivity	

HEMATOPOIESIS
Hematopoietic diseases rarely result from the malfunctions of the hematopoietic organ stroma. They are usually caused by suppression or enhancement of undifferentiated cell production, with a consequent reduction (or overproduction) hematopoietic cells. In some diseases, however, sequential or simultaneous suppressed and enhanced proliferation of more than one type of cell can occur. There are, in such cases reduced number of some cells (eg aplastic amenia‑‑decrease production of hematopoietic cells) coinciding with increased numbers of others (eg. leukemia abnormal increase in WBC. The initial experiments translating normal bone marrow to lethally irradiated mice established the basis for bone morrow transplantation, now routinely used to treat some hematopoietic cell growth disorders.

aplastic amenia   decrease production of hematopoietic cells
               
Shift to the left	appearance of large number of immature neutrophils (band) in blood
			indicates a bacterial infection
                    
Neutrophilia	1)   increase in number of neutrophils does not necessary imply an increase in
 production of      neutrophils. Intense muscular activity or the administration of epinephrine causes neutrophils in the marginating compartment to move into the circulating compartment causing an apparent neutrophilia
     		2)   may result from the medullary storage compartment. This type is  transitory
		and is followed by a recovery period which no neutrophils are released 
3)   bacteria infection cause an increase in production of neutrophils and a shorter stay in the medullary storage compartment. Increase in the number of immature forms such as band, neutrophilic metamyelocytes and even myelocyte in blood. Neutrophilia form infection is longer lasting than the others.

Leukemia	abnormal increase in WBC 
		malignant clones of WBC precursors
		release of large number immature cells into blood
		symptoms due to lack of some type of WBC and increase of others anemia and
		infections

Lymphocytic leukemia 	leukemia in lymphatic tissue

myelogenous leukemia 	leukemia in bone marrow

Bone marrow aspiration	put stuff on slide and stain with monoclonal antibodies more precise dx
               
Thrombocytopenic purpura	decreased in platelets
platelets bound to cytoplasm of megakaryocytes indicating a defect  in the liberation mechanism of platelets			
	        .
RESPIRATORY

Immotile cilia syndrome (Kartagener's syndrome), a disorder that causes infertility in males and chronic respiratory‑tract infections in both sexes, is caused by immobility of cilia and flagella induced by deficiency of dynein, a protein normally present in the cilia. This protein is responsible for the sliding of the microtubules, a process that is necessary for ciliary movement.
From the nasal cavity through the larynx, pioti6ns of the epithelium are stratified squamous. This type of epithelium is evident in regions exposed to direct air flow 6r physical abrasion (e.g. oropharynx, epiglottis, vocal folds); it provides more protection from attrition than does typical respiratory epithelium. If air‑flow currents are altered or new abrasive sites develop, the affected areas can covert from typical ciliated pseudostratified columnar epithelium to stratified squamous epithelium. similarly, in smokers, the proportion of ciliated cells to goblet cells is altered in order to aid in cleaning the increased particulate and gaseous pollutants (e.g. CO, 502). Although the greater numbers of goblet cells in a smoker's epithelium provide fora more rapid clearance of pollutants, the reduction of ciliated cells caused by excessive CO results in a decrease in the movement of the mucous layer and frequently leads to congestion of th6 smaller airways. These reversible changes in tissue organization are referred to as metaplasia,
Allergic reactions and inflammation can cause abnormal engorgement of swell bodies in both fossae and result in a severely restricted air flow.

Sinusitis is an inflammatory process of the sinus that persists for long periods of  time, mainly because of obstruction of drainage orifices. Chronic sinusitis is a  component of Kartagener's syndrome, which is characterized by defective ciliary  action.  This stimulation explains why epinephrine and other sympathomimetic drugs are  frequently employed to relax smooth muscle during asthma attacks. When the  thicknesses of the bronchial and bronchiolar walls are compared, it can be seen that  the bronchiolar muscle layer is proportionately better developed than that of the  bronchii. Increased airway resistance in asthma is believed to be due to mainly to  contraction of bronchiolar smooth muscle.
 
In cases of premature birth, infants frequently exhibit the labored breathing that  signifies respiratory distress. Hyaline membrane disease in such newborns has been  shown to be the result of insufficient surfactant production, and the infant has  difficulty in expanding the alveoli. Fortunately surfactant synthesis can be induced by  administration of glucocorticoids, so that the respiratory distress syndrome usually  represents a short‑term management problem. Recently, surfactant has also been  suggested to have a bactericidal effect, aiding in the removal of potentially dangerous  bacteria that reach the alveoli.

In congestive heart failure, the lungs become congested with blood, and red blood  cells pass into alveoli, where they are phagocytized by alveolar macrophages. In such  cases, these macrophages are called heart failure cells when present in the lung and  sputum; they are identified by a positive histochemical reaction for iron pigment  (hemosiderin).

The destruction of the alveolar wall with the subsequent reduction of the respiratory  portion of the lungs is called emphysema. It usually develops gradually and results in respiratory  insufficiency.  Emphysema, a leading cause of death in the industrialized world, is clearly associated  with  smoking and environmental air pollution.
 
Parasympathetic stimulation, via the vagus nerve, results in bronchial constriction,  while sympathetic stimulation causes bronchial dilatation. Drugs that mimic  sympathetic neurotransmitters, such as isoproterenol, are used to cause bronchial  dilatation during asthma attacks.									

In certain pathologic states, the pleural cavity can become a real cavity, containing  liquid or air in its interior. The walls of the pleural cavity, like all serosal cavities  (peritoneal and pericardial), are quite permeable to water and other substances‑‑thus  the high frequency of fluid accumulation (pleural effusion) in this cavity in pathologic  conditions. This fluid is derived from the blood plasma.  Conversely, under certain conditions, liquids or  gases present in the pleural cavity can   be rapidly absorbed.  Lung tumors, which have historically had their highest incidence in males, are mainly  of epithelial origin. Conclusive evidence has been presented that squamous cell carcinoma, the  principal lung tumor type, is related to the effects of cigarette smoking on the bronchial and  bronchiolar epithelial linking. Chronic smoking induces the transformation of the respiratory epithelium  into a stratified squamous epithelium, an initial step in its eventual differentiation into a tumor.

LYMPH

Helper T cells‑are killed by the retrovirus that causes the immunodeficiency syndrome known as AIDS, crippling the immunity of infected patients and rendering them susceptible to opportunistic infections‑‑microorganisms that usually do not infect  healthy individuals.
The central nervous system also produces peptide hormones for which there are receptors on ‑the surfaces of lymphocytes. This process established a poorly understood communication system of chemical messengers between the brain and the immune system, and gives some biochemical support to the empirical observation that the course of some diseases is influenced by the mood of the individuals involved.

In the congenital disorder DiGeorge!.s Syndrome,. the thymus is either absent or atrophic, and afflicted individuals have low blood levels of lymphocytes (reduced B and‑no T). These individuals have abnormalities in their B cell immunity and no T cell immunity. The requirement for collaboration between T and B cells to provide normal immunologic reactions‑is thus not met in this defect in thymic development, which is responsible for early death from severe infections. Each node receives lymph from, and~is said to be a satellite node of, a limited region of the body. Malignant tumors often metastasize via these nodes.

Sickle cell disease is a molecular disease in‑which a glutamic acid residue in the B chain of normal hemoglobin is replaced by a valine residue. This causes profound changes in the conformation of hemoglobin molecules when they are exposed to hypoxic environments, as in the spleen. Under these conditions, hemoglobin crystalizes and forms long aggregates that deform the red blood cell into a characteristic Sickle shape. These cells, because of their increased rigidity, cannot pass between the endothelial cells lining the splenic sinusoids. The cells are destroyed here, and anemia results. 

In certain pathologic conditions (e.g. leukemia), the spleen may reinitiate the production of granulocytes and erythrocytes present during fetal life, undergoing a process known as myeloid metaplasia (the occurrence of myeloid tissues in extramedullary sites; a syndrome characterized by splenomegaly (enlarged spleen), anemia, and the presence of immature granulocytes and nucleated erythrocytes).
                    
PITUITARY & HYPOTHALAMUS

Oxytocin stimulates contraction of the smooth muscle of the uterine wall during copulation and childbirth and contraction of myoepithelial cells that surround the alveoli and ducts of the mammary glands. The secretion of oxytocin is stimulated by a distention of the vagina or of the uterine cervix and by nursing. This occurs via nerve tracts that act on the hypothalamus. The neurohormonal reflex triggered by nursing is called the milk‑ejection reflex. Lesions  the hypothalamus, which destroy the neurosecretory cells, cause diabetes insipidus; a disease characterized by loss of renal capacity to concentrate urine. As a result, an individual suffering from this disease may excrete up to 20 liters or urine per day (polyuria) and will drink enormous quantities of liquids. 

Tumors of the hypophysis are usually benign. About two‑thirds of them have been shown to produce hormones that cause clinical symptoms‑. These tumors‑can produce growth hormone, prolactin, adrenocorticotropin and,‑ less frequently, thyroid‑stimulating hormone. Clinical diagnosis of these tumors can be confirmed by immunocytochemistry after their surgical removal.

Digestive

In certain diseases, such as Hirschsprung's disease or Trypanosoma cruzi infection (Chagas
disease) the digestive tract plexuses are severely injured and most of their neurons are destroyed. This results in disturbances of digestive tract motility with frequent dilatations in some areas. The fact that the digestive‑tract receives abundant innervation from the autonomic nervous system provides an anatomic explanation of the widely observed action of emotional disturbances on the digestive tract a phenomenon of importance in psychosomatic medicine.
 This high rate of collagen renewal in the  periodontal ligament allows processes  affecting protein or collagen synthesis‑‑e.g., protein‑ or vitamin C deficiency  (scurvy)‑‑to cause atrophy of this ligament. As a consequence, teeth become loose  in their sockets; in extreme cases they fall out. This relative plasticity of the  periodontal ligament is important because it allows orthodontic intervention,  which can produce extensive changes in the disposition of teeth in the mouth.
 
Recent evidence suggests that tight junctions around surface and pit cells also  form a part of the barrier to acid. Stress, psychosomatic factors, or substances  (such as aspirin) that cause gastric irritation can disrupt this epithelial layer and  lead to ulceration. The initial ulceration may heal‑, or it may be further  aggravated by the local action of pepsin and hydrochloric acid, leading to  additional gastric and duodenal ulcers.
 
In human disease, the number of parietal cells is correlated with the acid‑producing capacity of the stomach. In cases of atrophic gastritis, both parietal  and chief cells are much less numerous, and the gastric juice has little or no acid  or pepsin activity. Radioautographic studies performed with labeled vitamin B12  suggest that the parietal cells are, in humans, the site of production of intrinsic  factor, a glycoprotein that binds avidly to vitamin Bi 2. In other species,‑  however, this substance may be present in other cells. The presence of intrinsic  factor is normally required ‑for vitamin Bi 2 absorption, which binds strongly to  intrinsic factor in ‑the lumen of the stomach. This complex is absorbed by  pinocytosis into the cells in the ileum. This explains why a lack of intrinsic factor  can lead to vitamin B12 deficiency. This condition results in a disorder of the red  blood cell‑forming mechanism known as pernicious anemia; it is usually caused  by atrophic gastritis. In a certain percentage of cases, pernicious anemia seems to  be an autoimmune disease, since antibodies against parietal cell proteins are often  detected in the blood of patients with the disease.
 
In the fundus of the stomach, 5‑hydroxytryptamine (serotonin) has been shown  to be one of the principal secretory products. Tumors called carcinoids, which  arise from these cells, are responsible for the clinical symptoms caused by  overproduction of serotonin.
 
Deficiencies of these disaccharides have been described in human diseases  characterized by digestive in human diseases characterized by digestive  disturbances. Some of these enzymatic deficiencies seem to be of genetic origin.
 
In diseases marked by severe damage to epithelial cells, the transfer of  undigested proteins to the blood increases considerably. The absorption of  metabolites is greatly hindered in disorders marked by atrophy of the intestinal  mucosa caused by infections or nutritional deficiencies, producing the  malabsorption syndrome. 

This high replacement ‑rate explains why the intestine is promptly affected by the administration of antimitotic drugs, as in cancer chemotherapy. The epithelial cells continue to be lost at the tips of villi, but the drugs inhibit cell proliferation. This promotes atrophy of the epithelium, which results in defective absorption of nutrients, excessive fluid loss, and diarrhea. Paneth cells of the    crypts turn over much more slowly, living about 30 days before being replaced.
     
Because the appendix is a blind‑ended invagination, its contents are not renewed rapidly and it frequently becomes a site of inflammation (appendicitis). This inflammation can progress to the point of destruction of this structure with consequent infection of the peritoneal cavity.
     
Approximately 90‑95 % of malignant tumors of the digestive system are derived from intestinal or gastric epithelial cells. Malignant tumors of the large bowel are derived almost exclusively from its glandular epithelium (adenocarcinomas) and are the second most common cause of cancer deaths in the United States.
           
GLANDS ASSOCIATED WITH THE DIGESTIVE TRACT
     
In conditions of extreme malnutrition such as kwashiorkor, pancreatic acinar cells and other active protein‑secreting cells undergo atrophy and lose much of their rough endoplasmic reticulum. The production of digestive enzyme& is hindered.
     
This duality of behavior of the hepatocyte is particularly evident in pathologic specimens, where certain changes occur in either the central or the peripheral cells of the lobule. This zonal arrangement would account for some of the differences in the selective damage of hepatocytes by various noxious agents or various disease conditions.
     
One of the main processes occurring in the smooth endoplasmic reticulum is the conjugation of
hydrophobic toxic bilirubin by glucuronyl transferase to form a watersoluble nontoxic bilirubin glucuronide. This conjugate is excreted by  hepatocytes into the bile. When bilirubin or bilirubin glucuronide is not  excreted, several diseases characterized by jaundice can occur. One of the      frequent causes of jaundice in newborns is the often underdeveloped state      of the smooth endoplasmic reticulum in their hepatocytes (neonatal      hyperbilirubinemia; hyper + Latin, bilis bile, + ruber, red, + Greek, haima).      The current treatment for these cases is exposure to blue light from ordinary      fluorescent tubes; this transforms unconjugated bilirubin to a water‑soluble      photo isomer that can be excreted by the kidneys.
     
Abnormal ‑proportions of these constituents may lead to the formation of  gallstones            (cholelithiasis). Gallstones can block bile flow and cause jaundice, bile pigments  in blood from the rupture of tight junctions around the bile canaliculi.

The observation that the administration of barbiturates to laboratory animals resulted in rapid development of smooth endoplasmic reticulum in hepatocytes led to further studies. These showed that barbiturates can also increase synthesis of glucuronyl transferase and led to the use of  barbiturates in the treatment of glucuronyl transferase deficiencies. This is a typical example of the clinical use and value of data from experimental research in cell  biology.

When a tissue is injured or partially removed, the amount of chalones it produces decreases; consequently, a burst of mitotic activity occurs in this tissue. As regeneration proceeds, the amount of chalones produced is increased and mitotic activity decreases. This process is self‑regulating. The regenerated liver tissue is usually similar to the removed tissue. If there is continuous or repeated damage to this organ, however, liver cell  regeneration and an abundant production of connective tissue occur simultaneously. This excess of connective tissue results in ‑disorganization of the liver structure, a condition known as cirrhosis. Liver function is impaired in this condition, since scar tissue (collagen) not only replaces functional hepatocytes, but also disorganizes the liver, vascular, and bile duct systems.

The majority of malignant tumors of the liver derive from hepatic parenchyma or epithelial cells of the bile duct. Liver carcinomas or epithelial cells of the bile duct. Liver carcinomas are often  preceded by connective tissue proliferation (cirrhosis). Most tumors of the exocrine pancreas   arise from ductal epithelial cells; the mortality rate is high.