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Amyloid may be stained with Congo red and exhibits ‘apple-green birefringence’ under plane-polarised light order female cialis 10 mg without a prescription women's health issues in the military. Wound healing is the process by which tissue restoration of structure and function occurs buy female cialis once a day menstruation ovulation cycle, with restitution of tissue integrity and tensile strength buy female cialis 10 mg free shipping women's health clinic jensen beach fl. Wound healing can be classified into healing by: Primary intention Secondary intention (granulation) Delayed primary (tertiary) intention Wounds can heal by resolution (no scar) or by organisation and repair (invariably results in scar tissue) generic female cialis 10 mg mastercard pregnancy non stress test. The stages of wound healing include: Haemostasis/coagulation Acute inflammation Formation of granulation tissue (endothelial cells, fibroblasts, macrophages) Angiogenesis Epithelialisation, fibroplasia, wound contraction (fibroblasts → myofibroblasts) Maturation and remodelling What factors affect wound healing? Factors affecting wound healing: Local factors – Poor blood supply, haematoma, infection, foreign bodies, surgical technique (excessive wound tension, type of suture material etc. General/systemic factors – Diabetes mellitus, steroids, immunodeficiency, heart failure, renal failure, liver failure, hypoxia, malnutrition, chemotherapy, malignancy (Figure 2. In a keloid scar (Greek kele = claw + eidos = like), the scar extends beyond the wound margins. Keloid scars are more common in patients of Black and Hispanic descent and characteristically occur in the earlobe, chin, neck, shoulder, chest and deltoid regions (Figure 2. An abscess is a localised collection of pus surrounded by granulation tissue/fibrous tissue. An abnormal communication between two epithelial surfaces (or endothelial surfaces e. They can be classified by anatomical site, or output (colostomy, ileostomy, urostomy, tracheostomy, gastrostomy etc. Distal obstruction Malignancy Foreign body Associated undrained infection Radiation injury to tissues Underlying inflammatory condition (e. Crohn’s disease) Mucocutaneous continuity High output Malnutrition How are fistulae managed? Sepsis control Nutritional support Anatomical assessment, Adequate fluid and electrolyte replacement Plan, Protect skin to prevent excoriation Sixty per cent should close spontaneously within 1 month with conservative measures when the sepsis is controlled and distal obstruction has been relieved (Figure 2. Inflammatory bowel disease What are the macroscopic and microscopic differences between Crohn’s disease and ulcerative colitis? It consists of a microscopic aggregation of activated macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear leukocytes, principally lymphocytes and plasma cells. Rupture Thrombosis Embolism Local compressive effects Infection (mycotic) Fistula (e. They can be classified into: Non-neoplastic polyps (hyperplastic [also known as metaplastic], hamartomatous, inflammatory pseudopolyps, lymphoid hyperplasia) Figure 2. In terms of frequency: tubular (65%–80% of cases) > tubulo-villous (10%–25%) > villous (5%–10%). In terms of malignant potential: villous (40% risk of harbouring cancer) > tubulo- villous (22% risk of cancer) > tubular (5% risk of cancer). Malignant transformation Ulceration Bleeding Infection Intussusception Protein and potassium loss Diverticula What is a diverticulum? A diverticula = An abnormal outpouching of a hollow viscus into the surrounding tissues. They can be classified by: Aetiology Congenital (Meckel’s diverticulum) versus acquired Pulsion versus traction. Traction diverticula are much less common and are mostly a consequence of fibrotic healing in lymph nodes secondary to chronic granulomatous disease exerting traction on the neighbouring bowel wall. Zenker’s diverticulum, small intestine, large intestine) Mesenteric (small intestine) versus anti-mesenteric location (Meckel’s diverticulum) Architecture True (Meckel’s diverticulum) versus false (sigmoid colon, pharyngeal pouch) What complications might they undergo? Complications: Perforation Inflammation +/− infection Bleeding Fistulae Strictures Malignancy (e. A thrombus is defined as ‘solid material formed from the constituents of blood in flowing blood’ (when formed in stationary blood = clot). An embolus is defined as ‘an abnormal mass of undissolved material that is carried in the bloodstream from one place to another’. Thrombus Fat Air Atheromatous material Amniotic fluid Tumour cells Foreign material (e. It is reversible upon removing the injurious agent (hence the importance of risk factor modification and primary prevention strategies). The ‘response to injury’ hypothesis seems most plausible in terms of explaining the underlying pathogenesis. It explains how the biggest risk factors (namely tobacco toxins, hypertension and turbulent blood flow, lipids and glycosylated haemoglobin in diabetes mellitus) exert their influence and why risk factor modification is so effective in modifying the disease process. Complications of atherosclerosis include: Distal ischaemia Vessel occlusion Plaque ulceration, rupture Thrombosis Haemorrhage into a plaque Embolism – Lipid or thrombus Calcification Aneurysm formation Necrosis and apoptosis What is necrosis? There are several different types of necrosis: Coagulative (structured) necrosis – the most common form of necrosis. Seen in organs supplied by end arteries such as the kidney, heart, liver and spleen. Liquefactive (colliquative) necrosis – Occurs in tissues rich in lipid where lysosomal enzymes denature the fat and cause liquefaction of the tissue. Caseous (unstructured) necrosis – Gross appearance is of soft, cheesy friable material. Fibrinoid necrosis – Seen in the walls of arteries that are subjected to high pressures as in malignant hypertension. Gangrenous necrosis – This is irreversible tissue death characterised by putrefaction. Apoptosis Necrosis Energy dependent (active) Energy independent Internally programmed (suicide) Response to external injury Affects single cells Affects groups of cells No accompanying inflammation Accompanied by inflammation Physiological or pathological Always pathological Plasma membrane remains intact Loss of plasma membrane integrity Cell shrinkage, fragmentation and Cell swelling and lysis formation of apoptotic bodies Hypersensitivity reactions What is a hypersensitivity reaction? A hypersensitivity reaction is a condition in which undesirable tissue damage follows the development of humeral or cell mediated immunity. It represents an exaggerated response of the host’s immune system to a particular stimulus. Hypersensitivity reactions can be classified into four classes according to the Gell and Coombs classification. The original description by Gell and Coombs was based on four classes, with a fifth class subsequently being added later. Gell and Coombs Classification of Hypersensitivity Reactions Type I – Mast cell degranulation mediated by pre-formed IgE bound to mast cells. Humoral antibodies participate directly in injuring cells by pre-disposing them to phagocytosis or lysis. Good examples are transfusion reactions, autoimmune haemolytic anaemia and Goodpasture’s syndrome. Type V – (more recent addition to the original classification): Due to the formation of stimulatory autoantibodies in autoimmune conditions such as Graves’ disease and myasthenia gravis. An ulcer is a break in an epithelial surface the commonest leg ulcers are: Venous (70% of cases) Arterial Neuropathic Other causes include: Infections, e. A tumour marker is a substance reliably found in the circulation of a patient with neoplasia which is directly related to the presence of the neoplasm, disappears when the neoplasm is treated and reappears when the neoplasm recurs.

Myelination of preganglionic fibers Myelinated (white ramus communicans) Myelinated Length of preganglionic fibers Relatively short Relatively long Preganglionic neuron terminal Acetylcholine (nicotinic receptor) Acetylcholine (nicotinic receptor) (and receptor) /neurotransmitter Ganglia of relay effector neuron Paravertebral and plexus along the abdominal aorta Ciliary cheap female cialis american express womens health 3 day cleanse, pterygopalati submandibular buy 20 mg female cialis fast delivery menstrual ovulation cycle calculator, otic order female cialis 20mg with visa pregnancy apps, cardio- and internal iliac artery pulmonary plexus and in the wall of the viscera Ratio of preganglionic fibers to One is many (therefore mass discharge) One is to a few (therefore localized effect neurons of ganglia Myelination of postganglionic fiber Unmyelinated Unmyelinated Length of postganglionic fiber Relatively long Relatively short Postganglionic neuron terminal Noradrenaline (α and β adrenergic receptor) and ace- Acetylcholine (muscarinic receptor) (and receptor) /neurotransmitter tylcholine (muscarinic receptor to sweat gland and some blood vessels to skeletal muscle) Effect Response as in ‘fright-flight-fight’ response Responsible for homeostasis Metabolism Catabolic Anabolic B buy 20mg female cialis amex womens health october 2014. Effects of organ stimulation Eye Dilatation of pupils and contraction of orbitalis and Constriction of pupils and ciliary muscle for smooth muscles of tarsals accommodation Lacrimal gland ------- Secretion Salivary glands Thick, viscous secretion Profuse, watery secretion Heart Increases heart rate, increases contractility Deceases heart rate, decreases Contractility Lung Bronchial smooth muscle relaxation Bronchial smooth muscle relaxation Gastrointestinal tract Decreases motility, contraction of sphincters and Increases motility, relaxation of sphincters and inhibition of secretion stimulation of secretion Urinary bladder Relaxation of detrusor and contraction of involuntary Contraction of detrusor and relaxation of invo- sphincter vesicae luntary sphincter vesicae Male sex organs Ejaculation Erection Skin Contraction of erector pili and secretion of sweat ----------- glands Blood vessels Vasoconstriction, dilation in some vessels Chapter 32: Parasympathetic System 303 Fig. The cell bodies are located superior salivary nuclei in the rostral medulla and then in the Edinger-Westphal nucleus. The postganglionic fibers innervate the lacrimal gland ron in ciliary ganglion, which is located inside the orbit and the glands of nasal and palatal mucosa. The postganglionic axons enter eyeball near the optic the chorda tympani nerve to synapse in the subman- nerve and innervate sphincter muscle of the iris (sphinc- dibular ganglion. These postganglionic fibers from submandibular gan­ ciliary muscle that focuses the lens for accommodation glion innervate submandibular and sublingual glands. They stimulate intestinal motility, branch of 5th cranial nerve to innervate parotid gland, secretion, digestion and absorption. Chemosensory information of blood gasses from caro­ tid bodies and baroreceptor information of blood Application Box 32. The energy lost during activities must be restored by adequate rest that stimulates parasympathetic system. It is not only the physical rest, but also the mental rest that promotes Cranial Nerve X vagal activity. Therefore, both mental and physical relaxations as Vagus nerve arises from the nucleus ambiguous and dorsal occurs by regular practice of yoga are advised for improving health motor nucleus of vagus in the medulla. This nerve has an in general, apart from achieving stable cardiac functions and blood extensive autonomic component. People having hypersympathetic personality (always anxious and restless) are usually thin and do not maintain good health, and in that vagal output comprises up to 75% of total parasym- the contrary, individuals with hyperparasympathetic personality (lazy pathetic activity. Preganglionic fibers travel in the vagus nerve to gang­ parasympathetic state (stable sympathovagal balance) is required to lia located in the organ, i. Sympathetic postganglionic fibers intermingle and travel in the Neurotransmitters and Receptors same nerve trunk with the parasympathetic pregangli­ onic fibers to the target tissues. The vagal efferents to the lung control bronchial Muscarinic Receptors smooth muscle (constriction of bronchioles), and Cholinergic muscarinic receptors are present in heart, secretory cell activity. Vagal fibers innervate esophagus, stomach, small intestine and large intestine upto two­third of trans­ vated by acetylcholine and muscarine. Preganglionic fibers originate in the intermediolateral Nicotinic Receptors gray column of the sacral segments S2, S3, and S4 of spinal cord. The preganglionic fibers terminate in ganglia in or near ganglia (both sympathetic and parasympathetic), neuro- the viscera that include descending colon, sigmoid muscular junctions and adrenal medulla. These receptors colon, rectum, internal anal sphincter, urinary bladder are activated by acetylcholine and nicotine. Nicotinic effects are blocked by ganglion blockers ments herald parasympathetic activation. Except on cardio­ such as hexamethonium that prevent action of acetyl­ vascular system, most parasympathetic effects are stimu­ choline in the ganglia and at neuromuscular junction latory, especially for the processes that facilitate energy by curare drugs. In parasympathetic system (craniosacral outflow), preganglionic fibers are very long as ganglions are located close to the organs. Parasympathetic activation is considered to be similar with vagal activation, as 75% of parasympathetic functions are mediated by vagus nerve. Parasympathetic ganglia, Parasympathetic cranial nerves, Parasympathetic neurotransmitters and receptors, Effects of parasympathetic stimulation, Parasympathetic functions, Vagal tone, may come as Short Questions in exams. Effects of stimulation of sympathetic and para­ sympathetic systems are usually opposite. Therefore, sympathetic and parasympathetic divisions are also reciprocal to each other. Consequently, under normal circumstances exces­ sive stimulation or activation of both the systems, which might have deleterious effects, is avoided. Autonomic functions are regulated by various reflexes and supraspi­ nal mechanisms. However, afferent fibers also constitute an important component of from visceral organs reach the spinal cord through autonomic system and sensory input from visceral struc­ afferent fibers and, from there, the second order of tures is part of autonomic organization. Sensory information in the afferent pathways may not afferent limb of autonomic reflexes. The information always reach higher center for finer integration and Chapter 33: Control of Autonomic Functions and Applied Aspects 307 A B Figs. Local Reflexes A sensory neuron (afferent autonomic fiber) has many ter­ minal branches peripherally. The process results in spreading initial reaction pro­ edition, 2014; Jaypee Brothers Medical Publishers (P) Ltd. Recent evidences suggest if sensory neuron innervates sweat glands, the response that synaptic activity in the ganglia may influence final will be local sweating as a result of sweat gland activa­ efferent output. Persistent activation of such reflexes in nociceptive the activity in ganglia, which in turn alter the visceral afferents following trauma can produce dramatic fea­ activity. Therefore, following spinal injury, or in spinal prepara­ tion in animals, micturition first becomes involuntary and later becomes abnormal. Episodes of hyperten­ sion and piloerection in such patients are other exam­ ples. Supraspinal Regulation Role of Brainstem Brainstem plays important role in autonomic functions. The periaqueductal gray in midbrain coordinates autonomic responses to painful stimuli and induces endogenous analgesia system. The nucleus parabrachialis in pons contribute to respi­ ratory and cardiovascular control. The medullary centers are the key areas for control of edition, 2014; Jaypee Brothers Medical Publishers (P) Ltd. The nucleus tractus solitarius receives sensory infor­ mation from cardiovascular, respiratory and gastro­ and mechanoreceptors in the gut generate afferent intestinal receptors. Vagal efferent fibers arise from action potentials that pass to the spinal cord and then this area in the medulla. Reflexes for regulation of heart rate and blood pres­ and local sensory neurons converge and interact. Role of Hypothalamus and Cortex Spinal Autonomic Reflexes Hypothalamus and cortex provide the highest levels of Many autonomic reflexes are integrated in the spinal autonomic control. These reflexes are coordinated by centers in the lateral hypothalamic areas control homeostatic func­ lumbar and sacral spinal cord. Stimulation of lateral and posterior hypothalamus sexual responses in male cause erection and ejacula­ causes sympathetic activation, and stimulation of poste­ tion and in female produce vaginal lubrication (Fig.

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However buy genuine female cialis line menstrual pills, the antigen- binding specifcity of the antibody molecules with a different IgE: See immunoglobulin E best purchase female cialis menopause 41. The immunoglobulin epsilon (ϵ) chain: 72-kDa best 20mg female cialis women's safety and health issues at work, 550-amino Immunoglobulin D (IgD) (Figure 7 generic female cialis 20mg free shipping breast cancer fundraising ideas. It has the basic four-chain monomeric structure with two δ heavy chains (mol wt 63,000 Da each) and either two κ or two λ light chains (mol wt 22,000 Da each). The half-life of IgD is only 2 to 3 d, and the role of IgD in immunity remains elusive. Surface membrane IgD serves with IgM as an antigen receptor on mature naïve B cell membranes. Immunoglobulin Synthesis, Properties, Structure, and Function 253 F(ab´)2 Fab F ab IgG Peptides Fc pFc´ figure 7. There is no car- it has the basic N-terminal and C-terminal peptides of this boxy terminal portion of the ε chains. The fragments together with small peptides that represent what IgM molecule is pentameric, containing fve monomeric units. Each immunoglobulin mol- ecule yields only one F(ab′)2 fragment which is bivalent Papain (Figure 7. This aids efforts to reveal the molecular structure an IgG molecule deprives it of its ability to fx complement of immunoglobulins. Pepsin digestion molecule on the opposite side of the central disulfde bond is useful in diminishing the immunogenicity of antitoxins. The Fc fragment of papain digestion has no antigen-binding Pepsin digestion refers to a proteolytic enzyme used to capacity, although it does have complement-fxing functions cleave immunoglobulin molecules into F(ab′)2 fragments and attaches immunoglobulin molecules to Fc receptors on together with fragments of small peptides that represent a cell membrane. Each immunoglobulin red blood cell surfaces susceptible to agglutination by incom- molecule yields only one F(ab′)2 fragment, which is bivalent plete antibody. When an IgG molecule deprives it of its ability to fx complement the immunoglobulin is exposed to papain with cysteine pres- and bind to Fc receptors on cell surfaces. Pepsin digestion ent, papain cleaves a histidyl-threonine peptide bond of the is useful in diminishing the immunogenicity of antitoxins. Immunoglobulin fragment is a term reserved for prod- ucts that result from the action of proteolytic enzymes on pFc′ fragment is a fragment of pepsin digestion of IgG immunoglobulin molecules. Pepsin digestion of IgG or of the Fc can be severed by reduction in the presence of denatur- fragment yields low molecular weight peptides and a pFc′ ing agents such as urea, guanidine, or detergents. Similar cleavage of the heavy chain thymus-dependent and thymus-independent antigens, is more diffcult to achieve. Papain cleaves H chains at (2) augmentation of agglutination by lectins, (3) facilitation the N-terminus of the H–H disulfde bonds, giving two of the escape of cells from contact inhibition and culture, individual portions of the terminus of the molecule, called (4) enhancement of cytotoxicity with or without participation Fab, and the fragment of the C-terminus region, Fc, which of antibodies, and (5) stimulation of B cell proliferation. Thus, the two An antibody fragment is a product of enzymatic treatment Fab fragments will remain joined and are called F(ab′)2. For example, papain treatment which remain noncovalently bonded in dimeric form and leads to the production of two Fab and one Fc fragments, are called pFc′. Further digestion of the pFc′ with papain whereas the use of pepsin yields the F(ab′)2fragment. See the results in smaller dimeric fragments called Fc′Plasmin, individual fragments for further information. It may differ in size or shape ignated Fd, and the heavy chain portion of the Fab′ frag- from one antibody molecule to another. Antibody molecule specifcity is dependent of heavy and light chains on an immunoglobulin molecule on the complementary relationship between epitopes on anti- where antigen binding occurs. It is a 90-kDa enzyme that derives from cleavage of a sin- gle arginyl–valyl bond in the C-terminal region of plas- Binding site: In immunology, the paratope area of an anti- minogen. It consists of two unequal chains, termed heavy body molecule that binds antigen or that part of the T cell (A) and light (B) chains, linked by a single disulfde bond. It is comprised of one light chain and the seg- fbrinolytic activity, plasmin has numerous other functions ment of heavy chain on the N-terminal side of the central Immunoglobulin Synthesis, Properties, Structure, and Function 255 Fab Fd Fab s-s L chain s-s s-s Papain Fc Papain digestion digestion Fc´ figure 7. Fd fragment is the heavy chain portion of a Fab fragment produced by papain digestion of an IgG molecule. Division of the different amino acid num- ber at a given position by the frequency of the amino acid which occurs most commonly at that position gives the index of variability. It is also the extent of variability at each position and is useful in local- called Fc region, or Fc piece. This analytic method revealed that in immunoglobu- region linked by the central disulfde bond and noncovalent lin heavy or light chains most variable residues are clustered forces. This 50-kDa fragment is unable to bind antigen, but it in three hypervariable regions. Immunoglobulin Synthesis, Properties, Structure, and Function 257 is comprised of one light chain linked by disulfde bonds to Fab the N-terminal segment of heavy chain. This 95-kDa immunoglobulin fragment has a valence or antigen-binding capacity of two, which renders figure 7. However, the functions associated fragment consisting of the Fc region and one Fab region of the mol- with the intact IgG molecule’s Fc region, such as comple- ecule bearing a single antigen-binding site. Allelic genes that encode the γ1, γ2, and γ3 nal side of the central disulfde bond at the hinge region of heavy chain constant regions encode the Gm allotypes. IgG subclasses are associated with certain Gm Fab≤ fragment: See F(ab′)2 fragment. For example, IgG1 is associated with G1m(1) and G1m(4), and IgG3 is associated with G3m(5). It is comprised of two noncovalently bonded C 3 domains that An Facb fragment (Figure 7. They are cloned from heavy chain variable Oz isotypic determinant: Oz represents an isotypic marker. Examples of isotypes the class or subclass of heavy chains or the type and subtype include IgG, IgM, and κ light chains. Mice and humans An isotope is an isotypic determinant or epitope of an have fve different Ig heavy chain constant regions, Cμ, Cδ, isotype. Cα, Cγ, and Cε, which defne the fve antibody isotypes IgM, IgD, IgA, IgG, and IgE, respectively. Every normal mem- Isotypic variation refers to differences among antigens ber of a species expresses each isotype. An immunoglobu- found in members of a species such as the epitopes that dif- lin subtype is found in all normal individuals. Among the ferentiate immunoglobulin classes and subclasses and light immunoglobulin classes, IgG and IgA have subclasses that chain types among immunoglobulin chains. They are distinguished according to domain number and size, as well as the number An isoallotypic determinant is an antigenic determinant of both intrachain and interchain disulfde bonds of the con- present as an allelic variant on one immunoglobulin class or stant region. The four isotypes of IgG are designated IgG1, immunoglobulin subclass heavy chain that occurs on every IgG2, IgG3, and IgG4.