Co-Director, Hackensack Meridian School of Medicine at Seton Hall University
Howell Jolly body erectile dysfunction type of doctor order viagra 75mg with mastercard, hypersegmentation of neutrophils erectile dysfunction pills wiki buy viagra 75 mg online, basophilic stippling are also seen (Refer to impotence definition inability viagra 75 mg low price. The typical example of this type of anemia is megaloblastic anemia that occurs due to defi ciency of vitamin B12 or folic acid weak erectile dysfunction treatment buy 50 mg viagra mastercard. Etiological Classification Blood Loss Anemia Anemia due to blood loss mainly occurs due to acute hem orrhage or chronic hemorrhage. Acute hemorrhage: Anemia due to acute hemorrhage depends on the extent of blood loss and the time that has lapsed since bleeding. Respiratory diseases: Respiratory diseases that produce epistaxis, hemoptysis as occurs in pulmonary tuberculo sis or bronchogenic carcinoma produce anemia. Genitourinary diseases: Diseases that cause hematu ria and hemoglobinuria produce anemia. Diseases of genital tract: In females, loss of blood from genital tract like menstrual disorders (menorrha gia, metrorrhagia) and uterine pathologies produce anemia. Aplastic Anemia Aplastic anemia is the anemia due to impaired red cell production. Hemolytic Anemia Hemolytic anemia results from increase in the rate of red cell destruction. Defects causing premature red cell destruction may be divided into two broad categories: intracorpuscular, and extracorpuscular (Table 15. However, when the compensatory mechanisms set in to expand the blood volume, hemodilution decreases hemoglobin content. Therefore, estimation of hemoglobin after few hours of acute blood loss does not assess the actual degree of anemia. Chronic hemorrhage: Chronic hemorrhage occurs mainly in gastrointestinal, genitourinary and respiratory tract diseases. Gastrointestinal blood loss: Peptic ulcer, hemor rhoids, hiatus hernia, carcinoma of the stomach and colon, esophageal varices, chronic aspirin ingestion, ulcerative colitis, hookworm infestation, etc. Increased physiological demand for iron as occurs in pregnancy, lactation, growing children. Pathological blood loss like bleeding peptic ulcer, piles, worm infestations, epistaxis, hemoptysis etc. Hemoglobinopathies: Sickle cell anemia, abnormal hemoglobins like, Hb-C, Hb-E, Hb-D, etc. Enzyme defects: Deficiency of pyruvate kinase and glucose-6 phosphate dehydrogenase. Immune mechanisms: Warm and cold antibodies, hemolytic diseases of newborn, incompatible blood transfusion, drug induced anemia. Hereditary Hereditary Spherocytosis this is a hemolytic anemia in which the fundamental abnormality is the increased defect of red cell mem brane (due to decreased quantity of spectrin) that results in spherocytic shape of the cell. Spherocytes have a decreased surface area to volume ratio and the cells are more rigid (less deformable). The usual features are anemia, jaundice, enlarged spleen, and may present with gall stone. Sickle-cell Anemia this is a hereditary disorder in which red cells contain an abnormal hemoglobin called Hb S. Hb S is the hemoglobin in which glutamic acid is replaced by valine at the 6th position of beta chain. In the deoxygenated state, confor mational changes induced by Hb S makes the cell more rigid and deformed to take the shape of a sickle. Diagnosis is usually made by sickle test (demonstrat ing sickling of red cells when the blood is mixed with freshly prepared solution of a reducing agent like sodium metabisulphite). Note microcytic hypochromic red cells in peripheral blood smear and micronormoblasts in bone marrow with decreased iron store. Note the presence of many spherical red cells (indicated by arrows, in the schematic picture B). Thalassemia Thalassemia is a genetically determined heterogenous group of commonest monogenic disorder in which the rate of synthesis of one or more types of hemoglobin polypeptide chain is decreased. Thus, there are two major classes of thalassemia: thalassemia and thalassemia, in which and globin genes are involved respectively. There are many homozygous and heterozygous, and major and minor forms of the disease. In thalassemia major, anemia develops in first few months of life and becomes progressively severe. The primary form, also called polycythemia vera, is a clonal neoplastic disorder of hematopoietic stem cells. The secondary forms are conditions of increased red cell production that usually occurs due to appropriate or inappropriate increase in secretion of erythropoietin. In primary form, the cause of the disease is the abnormality of hemopoietic stem cells characterized by uncon trolled proliferation of cells of erythroid, granulocytic and megakaryocytic series, resulting in increase of all forms of formed elements of blood. In secondary forms, the cause of the disease is excess erythropoietin secretion that results in increase in red cell production (mostly without increase in granulocytes and platelets). Thus, secondary erythrocytosis is more appropri ate than secondary polycythemia for the secondary forms. Though anemia is usually microcytic and hypochromic, all forms and combinations are not uncommon. Demonstration of Hb-H inclusions (in the absence of sufficient alpha chains, excess of beta or gamma chains aggregate to form HbH) Types of Polycythemia Polycythemia is broadly divided into three forms (Table 15. The secondary Chapter 15: Pathophysiology of Anemia and Polycythemia 115 forms are secondary to other conditions or diseases.
Catecho lamines are stored in granules and secreted by calcium mediated exocytosis of granules in which they are stored erectile dysfunction medication insurance coverage purchase viagra online. Many enzymatic reactions are involved in the process of steroid hormone synthesis: 1 impotence quiz buy viagra 100 mg cheap. On stimulation erectile dysfunction my age is 24 effective 25 mg viagra, the hormones become free form intra cellular proteins and are transported outside the cell usually by diffusion erectile dysfunction tea purchase viagra overnight. Prohormone is then transported into the Golgi appa ratus, where it is converted into hormone. For example, neoplastic tissues of lungs like small cell pulmonary carcinoma produce several hormones. Hormones are also secreted from gastrointestinal tumors and the condition is called carcinoid syndrome. Regulation of Hormone Secretion Normally, concentration of a hormone in circulation is maintained within a narrow range. Increase or decrease in hormone concentration for a longer period results in major dysfunctions. Alteration in hormone concentra tion is mainly checked by regulation of hormone secre tion. Of these control processes, feedback control is the most common and developed mechanism for regulation of hormone secretion. However, many factors arriving from variety of stimuli play simultaneously to achieve an integrated response of hormone secretion. Pathways of Synthesis Peptide Hormone Synthesis Synthesis and secretion of peptide hormones occur in two pathways: the regulated and constitutive pathways. Regulated Pathway In regulated pathway, external stimuli trigger release of hormone which is already synthesized and stored in secretory granules, and also promote synthesis of some addi tional hormones. Feedback Control When the change in concentration of a hormone in plasma alters its rate of secretion, the mechanism is called feed back control. Negative Feedback When increased concentration of a hormone and its metabolites provide feedback inhibitory signal to the gland that secretes the hormone, the mechanism is called nega tive feedback mechanism. Depending on the circuit or the pathway involved in the feedback control, the mechanism may be simple feedback or complex feedback. Simple Feedback Control this is the first order of feedback control in which the hor mone secreted from a gland controls its secretion through Constitutive Pathway In constitutive pathway, secretion of hormones occurs more directly from endoplasmic reticulum or vesicles formed from the Golgi apparatus, in which additional hor mones are formed simultaneously. Thus, regulated pathway is capable of secretion of large amount of hormones, whereas constitutive pathway promotes secretory reserve. Endocrine gland senses biological activity of the hormone and accordingly modulates its secretion. This system operates mainly for control of hypothalamo-pituitary-target endocrine gland axis. The endocrine cells that secrete the hormone also sense the biological activity produced by the hormone: 1. When the biological effects are more, the hormone secretion decreases appropriately to maintain normal function of the hormone (Flowchart 52. For exam ple, cells of pancreas secrete insulin that acts on liver and skeletal muscles to regulate blood glucose concen tration. Complex or Hierarchical Feedback Control When the feedback regulation involves second or third order feedback loop or both, the control mechanism is called complex or hierarchical control. This multiorder or complex control system is the usual mechanism for regula tion of many hormone secretions: 1. In this system, the hormone secreted by first (upper) order gland stimulates secretion of second (middle) order gland. Secretion (usually, trophic hormones) of middle order gland stimulates secretion of final (lower) order gland or target gland. Secretion of target gland (target gland hormone) inhibits the secretion of first order or middle order glands (Flowchart 52. Also, secretion of middle order gland (trophic hormone) inhibits secretion of first order gland. As this is an integrated system of control of endocrine functions, disorder at any level of hierarchy influences the function of other levels. The major hormone axes regulated by hierarchial system of feedback control are: Hypothalamopituitarythyroid axis Hypothalamopituitaryadrenal axis Hypothalamopituitarygonadal axis. Loops of Negative Feedback Control Depending on the distance from which the hormone of the target gland inhibits the upper order glands, the inhibition is classified into long loop, short loop and ultrashort loop. In this control system, increase in hormone concentration in plasma stimulates further secretion of that hormone so that the hormone concentration increases steadily to reach a peak plasma level: 1. Other examples are oxytocin secretion during parturi tion, release of oxytocin during breastfeeding and release of melatonin in response to darkness. Alteration in secretion of gonadal hormones at puberty in both boys and girls is the example of developmental hormonal secretion. Example of seasonal variation is change in hormone concentration in different times in a year that mostly occurs due to environmental changes. Neural Control Endocrine glands are usually innervated by both the com ponents of autonomic nervous system: 1. Stimulation of sympathetic or parasympathetic system therefore alters the endocrine secretions. Secre tion of catecholamines from adrenal medulla in response to sympathetic stimulation is an example. However, the receptor types present in the endocrine tissue determine the final secretion from the gland. Besides, innervation of the endocrine tissues may also be cholinergic, serotonergic or dopaminergic depend ing on the neurotransmitter released at the nerve ending.
Obesity eventually leads to hyper insulinemia erectile dysfunction due to zoloft buy discount viagra 75mg, hyperlipidemia and accelerated athero sclerosis that are part of metabolic syndrome (Clinical Box 60 erectile dysfunction medication names trusted viagra 25mg. Adipokines: the chemical signals originating from adi pose tissue are recently proposed to be contributing factors for insulin resistance erectile dysfunction bipolar medication order viagra american express. Fat cells secrete a group of hormones called adipokines that influence insulin resistance erectile dysfunction jacksonville doctor order 100 mg viagra. Decreased second messengers: Knockout of intra cellular second messengers that are usually formed following autophosphorylation of tyrosine kinase has been recently reported to be the major factor in insulin resistance. These patients invariably have microalbuminuria, increased fibrinogen, increased plasminogen activator inhibitor 1, elevated plasma uric acid and increased sympathetic activity. Metabolic syndrome is also called Raven syndrome, and Syndrome X, and is strongly associated with macrovascular disease such as coronary artery and cerebral artery disease. Secondary Diabetes Mellitus Diabetes also occurs due to the diseases of pancreas like pancreatitis, or following pancreatectomy. These forms of diabetes are included under the category of secondary diabetes mellitus. They present with mild hyperglycemia from birth, but they are stable and managed by diet alone. Ketosis Insulin prevents lipolysis, and therefore, decreases release of free fatty acids into the circulation. Insulin also facili tates utilization of ketone bodies (acetoacetate, acetone, and bhydroxybutyrate) by the tissue. Presence of excess acetyl-CoA also facilitates conversion of aceto acetylCoA to acetoacetate in the liver. Acidosis the hydrogen ions liberated from ketone bodies (aceto acetate and bhydroxybutyrate) are usually buffered: 1. Diabetic acidosis is a medical emergency that requires immediate and appropriate replacement of electrolyte and fluid. Coma Coma in diabetes is of two types: Acidotic coma (due to acidosis) and hyperosmolar coma (due to hyperosmolality of plasma): 1. In acidosis, loss of water and electrolyte causes dehydration that results in coma (Flowchart 60. Increased glucose concentration in plasma to a very high level increases its osmolality to the extent that it causes dehydration of brain cells that results in coma without affecting pH. Polyuria In diabetes, when plasma glucose concentration increases above renal threshold (above 180 mg%), glucose appears in urine. Increased concentration of glucose in the tubular fluid causes osmotic diuresis that result in polyuria. Polydipsia In diabetes, because of polyuria water is lost in excess from the body. Weight Loss In diabetes, food intake is more due to stimulation of feeding center. However, in spite of more food intake, glucose is not utilized by the cells due to deficiency of insulin. Hyperglycemia and Glycosuria Insulin is the only hormone that decreases plasma glu cose concentration. When plasma glucose concentration exceeds renal threshold (180 mg%) glucose appears in urine (glycosuria). Diagnosis Diagnosis of diabetes is done by demonstrating persistent hyperglycemia and glycosuria. Estimation of fasting and postprandial blood glucose is performed to demonstrate hyperglycemia, and estimation of glucose in urine is car ried out to demonstrate glycosuria. HbA1c indi cates the state of persistent hyperglycemia at least more than three months. Generally, insulin preparations are divided into three categories depending on their duration of action: 1. Pork insulin differs from human insulin only by one amino acid and therefore, has low antigenicity. These drugs are usually prescribed for Treatment Diabetes is usually treated by insulin and oral hypogly cemic agents. However, change in life style improves the condition to a greater extent as recently diabetes has been found to be closely associated with chronic stress. Metformin acts mainly by decreasing gluconeogenesis; therefore, it decreases hepatic glucose output. Other group of drugs like thiazolidine-diones (trogl itazone is an example of this group) are also used. Calorie intake: Food intake should be adjusted to ensure appropriate nutritional requirements. Diet should have less carbo hydrate and fat, more fibers and adequate proteins and vitamins. Regular exercise: Morning walk and freehand exercises improve insulin release and decreases insulin resistance. Relaxation of body and mind: Healthy body and mind without stress will not only cure diabetes, but also prevent other diseases. Practice of yoga: Yoga is very helpful in reducing the intensity of diabetes, and reducing the complications.
Scientist contributed Theodor Schwann advanced the concept of cellular organization of living beings erectile dysfunction drugs available over the counter purchase viagra 100 mg with visa, described the structure of neurilemma (covering of the nerve) and showed the necessity of air for embryonal growth impotence mayo order viagra 100mg overnight delivery. His intense study on digestion was important erectile dysfunction at 21 viagra 75mg on-line, in which he discovered pepsin and its action erectile dysfunction 35 generic viagra 100mg with visa, and highlighted the importance of bile in digestion. His discovery of yeast and its role in purification and fermentation T Schwann was an important revelation. Timing of Myelination during Development Myelination of different types of nerve fibers takes place at different times. Chapter 22: Structure and Functions of Neurons 219 Axoplasmic Transport Transfer of substances between cell body and axon terminal is called axoplasmic transport. Various proteins, organelles and other cellular substances required for the development, growth, and maintenance of the neuron are transported mainly along the length of the axon. Axoplasmic transport can be abolished by application of colchicine, dinitrophenol, azide, cyanide, and prolonged anoxia. Colchicine disrupts the movement of microtubules; others block the process of oxidative phosphorylation. Types of Axoplasmic Transport In the axoplasm, transport process can occur in both directions by different transport mechanisms. Accordingly, they are called anterograde, retrograde, and transneuronal transports. Anterograde Transport the transport of materials from the cell body toward the axon terminals is known as anterograde transport. For example, various neurotransmitters synthesized in the cell body are packaged in vesicles and get secreted at the nerve endings through axoplasmic microtubules. Fast axoplasmic transport: Fast axoplasmic transport occurs at the speed of about 400 mm/day, which is accomplished by kinesin, a microtubule associated protein that transports many organelles, vesicles and membrane glycoproteins. Slow axoplasmic transport: Slow axoplasmic transport occurs at the rate of about 0. Various structural proteins like actin, neurofilaments and microtubules get transported by slow transport. It has an important role in supplying the required materials for the regeneration of axons following nerve injury. Retrograde Transport Transport of substances from the axon terminals to the cell body is known as retrograde transport. It occurs at a speed of about 200 mm/day, brought about by dynein, another microtubule associated protein. Transport of viruses: the chickenpox virus, known as varicella zoster that causes herpes simplex reaches cell body from nerve terminals in the skin by retrograde transport. The virus may remain in a dormant state in nerve root for many years before causing herpes zoster afterwards. Transport of toxins: Tetanus toxin at motor neuron ending is transported to the cell body by this retrograde process. Transfer of nerve growth factor: Nerve growth factor is taken up by presynaptic terminal and transferred to soma by retrograde transport. Axons surrounded by concentric layers of Schwann cell plasma Axons surrounded by cytoplasm of Schwann cells. Nerve impulse jumps from one node to the other node, which is Nerve impulse travels uniformly along the axolema. Saltatory conduction seen in Myelinated nerves is fast and con- Conduction seen in unmyelinated nerves is slow and consumes sumes less energy. Important Note Concentration of voltage gated Na+ channels: Na+ channels are highly concentrated in the nodes of Ranvier and the initial segment in myelinated nerve fibers. Neurons are always active as the membrane potentials and neuronal cytosolic activities are continuous phenomena. About 70% of total energy required is used to maintain polarization of the membrane by the action of Na+-K+ pump. During the peak activity, the metabolic rate of nerve doubles compared to skeletal muscle cell metabolism. The excitability, conductivity and recovery process from the activities can happen in a nerve for a considerable period in the absence of oxygen. Energy requirement of the resting nerve to maintain polarization of the membrane is supplied primarily by combustion of sugar and phospholipids. Some of the vesicles may be transported back to the cell body and this may provide a feedback signal to the cell body for further synthesis of transmitters. Transneuronal Transport Trophic substances like nerve growth factors are transported across the synapse to the presynaptic membrane of another neuron. The proteins associated with synaptic transmitters are synthesized in Nissl granules of the cell body and are transported to axon terminal by axoplasmic flow. In this region, non-conducted local potential changes generated by synaptic connections are integrated. Axon: the initial segment is the site where propagated action potentials are generated. The axonal process transmits propagated impulses from the cell body to the axon terminal. Growth of Neurons Various factors affecting neuronal development, growth and survival have been isolated and studied. Neurotrophins Neurotrophins are trophic proteins to the neurons, as they promote nerve growth and survival.
P53 protein serves as a transcription factor for many physiological functions that prevent malignancy erectile dysfunction pill purchase viagra 25mg mastercard. Genetic screening of such people to identify the susceptibility of the disease helps in preventing the disease to occur erectile dysfunction among young adults best viagra 100mg. Mutator gene is the faulty caretaker gene that has lost normal surveillance function and therefore helps in gene sis of cancer impotence testicular cancer proven 75 mg viagra. Genetic Basis of Cancer Some cancers such as cancer of colon and female breast what causes erectile dysfunction treatment order 50mg viagra overnight delivery, retinoblastoma, leukemia etc. Ionizing radia tions like exposures to ultraviolet rays produce cancer by causing mutagenesis (damaging the genetic constitution) of the individual. Cancer cells express more telomerase that promotes telomere lengthening and this helps in cancerous proliferation. Tumor Suppressor Gene these are also called anti-oncogenes that prevent genesis of cancer. Cancer Genes There are genes that predispose to cancer and genes that prevent cancers. The proto-oncogenes are normal genes that encode proteins controlling normal cell functions. The factors that promote this conversion are: Chapter 5: Physiology of Genetics and Apoptosis 37 3. Normally, caspases are present in the inactive form in the cell, and stimulated by external and internal stimuli. Internal stimuli: Mitochondria release cytochrome and a protein called smac that causes activation of the caspase 9, which induces apoptosis. External stimuli: External stimuli are various ligands that bind with cell surface to activate apoptosis. Somatic Cell Therapy In humans, somatic (nongametic) cells are used in the gene therapy as changes in these cells cannot be inherited. It is successfully tried in cystic fibrosis of the lung and severe combined immunodeficiency syndrome. In cancer, gene therapy is very useful, in which oncogenic gene is inactivated by introducing a gene like tumor suppressor gene. Molecular Mechanisms of Apoptosis Initiation of Apoptosis Stimuli signaling programmed cell death act either on the cell membrane or intracellularly. It is a form of coordinated and internally planned cell death, which is of greater significance in a variety of physiologic and pathologic conditions. Death of neurons in central nervous system during brain development and synapse formation is an exam ple of apoptosis. During fetal development, degeneration of many this sues like web in the fingers is other example. Scientist contributed For many years, the terms "apoptosis" and "programmed cell death" were not highly cited. What transformed cell death from obscurity to a major field of research were two things: the identification of components of the cell death control and effector mechanisms, and the linkage of abnormalities in cell death to human disease, in particular cancer. The 2002, Nobel Prize in Physiology and Medicine was awarded to Sydney Brenner, Horvitz and John E Sulston for their work identifying genes that control apoptosis. The genes were identified by studies in the nematode C Elegans and these same genes function in humans for apoptosis. Regulation of Apoptosis Once apoptosis is initiated, certain intracellular proteins provide signal for the final programmed cell death, which actually determine the outcome. John E Sulston (Nobel Prize, 2002, for pioneering research on apoptosis) 38 Section 1: General Physiology Flowchart 5. Physiologic involution of cells in hormonedependent tissues such as endometrial shedding in menstrual cycles, regression of lactating breast after cessation of breastfeeding. Changes in Apoptosis Pathophysiologic Changes Changes in apoptosis confuses with the changes in necro sis. In necrosis, cytoplasm is homogenously eosinophilic, and nuclear changes are pyknosis (condensation and clumping of nucleus), karyolysis (disintegration of the nucleus) and karyorrhexis (nucleus fragments into small bits and disperses into cytoplasm). In apoptosis, there is condensation of nuclear chromatin and cell fragments into apoptotic bodies that are phagocytosed by macrophages. Physiologic and Pathologic Processes Apoptosis is a biologic phenomenon, which has both phy siologic and pathologic processes. Chapter 5: Physiology of Genetics and Apoptosis 39 the characteristic changes in apoptosis include the fol lowing: 1. The cytoplasm becomes intensely eosinophilic containing condensed or fragmented nuclear chromatin material. Cell membrane convolutes with formation of mem branebound spherical structures called apoptotic bodies that contain compacted organelles. A glycoprotein molecule called thrombospondin and a phosphoprotein called phosphatidylserine appear on the outer surface of apoptotic bodies, which facilitate recognition by macrophages for phagocytosis. In necrosis, cyto plasm is homogenously eosinophilic, and nuclear changes are pyknosis, karyolysis and karyorrhexis. In apoptosis, there is con densation of nuclear chromatin and cell fragments into apopto tic bodies that are phagocytosed by macrophages. Identification of components of the cell death control and effector mechanisms and the linkage of abnormali ties in cell death to human disease, in particular cancers, has unraveled the research for preventing the cell death. Understanding the concept of apoptosis has promising role in future regenerative medicine.
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