Questions for final examin - Pathophysiology

Q29) Abnormalities of hemostasis and coagulation - thrombocytosis and thrombocytopenia!

Clotting : adherent of platelets to exposed collagen of injured blood vessels. Contraction and releasing of ADP and platelet factor 3. Abnormal in nr/function of platelets can interfere with blood coagulation. Thrombocytosis : Thrombocythemia, incr platelet count above 400.000/mm3 - primary : myeloproliferative disorders such as polycythemia vera or chronic granulocytic leukemia (abnormal proliferation of megakaryocytes + other cell lines in BM) - secondary : consequence of underlying cause. Stress, exercise (storage pool release from spleen), hemorrhage or hemolytic anemia (incr BM demands)! Abnormal platelet function -> bleeding and thrombosis. Prolonged bleeding time. - spleen is primary site of platelet storage, and briefly after splenectomy -> thromboctosis! - Doesn´t cause any problems until they are 1 million/mm3 -> bleeding and thrombosis The bleeding is typically mucosal, esp in GIT. Thrombosis at venous side! Mechanism of bleeding : - incr platelet level -> spontaneous platelet aggregate -> block tiny capillaries -> damage capillary wall -> bleeding into tissue Thrombocytopenia (platelet count below 100.000/mm3) - by either decr prod or incr degradation, with/coexisting conditions such as leukemia, liver disease : Causes : 1) decreased production by inhibitors of BM : aplastic anemia, myelofibrosis (fibrosis of BM), acute leukemia and other metastatic carcinomas that replace normal BM 2) decr production by deficiency of Vit.B12, folic acid and chemotherapeutical agents 3) excessive destruction by : - any cause leading to splenomegaly such as hepatic cirrhosis, lymphomas, myeloproliferative diseases (Due to increased space for storage of platelets -> decreaed circulating platelets) - drug induced Ab production (e.g Gold) or autoantibodies (found in lupus erythematosus, CLL, certain lymphomas and idiopathic thrombocytopenic purpura) Symptoms : ecchymosis, prolonged bleeding with minor trauma, petechiae, mucosal, deep tissue and intracranial bleeding in severe loss! Thrombocytopathy : altered platelet function -> prolonged bleeding Caused by : ex Aspirin -> inhibit platelet aggregation, or by macroglobulinemia + multiple myeloma (plasma proteins interfering with normal platelet function) Reduced platelet number : this is called ,,thrombocytopenia" and is generally considered when the platelete count is below 100.000/microL. The spontaneous bleeding associated with these states involves usually small vessels, and common sites are skin and mucous membrane. We can divide these disorders into 4 major categories : - decreased production of platelets : this can occur in diseases that affect the BM generally, such as aplastic anemia or leukemia; In diseases that affect the megakaryocytes selectively; or in deficiency states such as vitamin B12 and folic acid deficiencies. Latter is due to impaired DNA synthesis! - decreased platelet survival : can have an immunologic or non-immunologic etiology. In that states that are associated with immune conditions there are either circulating antiplatelet antibodies or immune complexes. The latter is LESS common!. A common target is the platelet membrane glycoprotein complexes . Non immunologic destruction results by mechanical injury, analogous to RBC destruction, such as prosthetic heart valves and diffuse narrowing of the microvessels (malignant hypertension) - Sequestration : this occurs when there is marked splenomegaly, referred to hypersplenism! - dilutional : transfusions can produce dilutional thrombocytopenia Defective platelet functions : the qualitative defects of platelets can be both congenital and acquire. The acquired disorders can be exemplified by ingestion of aspirin and other NSAIDs. These drugs are potent reversible inhibitors of COX, which is required fro synthesis of thromboxane A2 and prostaglandins! These mediators are important in platelet aggregation and release reactions. Another acquired disorder of platelet function is uremia. The pathogenesis is not fully understood, but there is seen several abnormalities of platelet function. The congenital disorders can be grouped into the following groups on the bsais of the functional abnormality : - defects of adhesion : to the subendothelial matrix, and is best illustrated by the Bernard-Soulier syndrome - defects of platelet aggregation : ex glanzmann´s thromboasthenia, results in failure to aggregate in response to ADP, collagen, epinephrine, or thrombin due to the deficiency or dysfunction of glycoprotein Iib-IIIa, that participates in the formation of ,,bridges" between platelets by binding fibrinogen and vWF - disorder of platelet secretion : in this group there is failure in the secretion of thromboxanes and release of granule-bound ADP. These disorders are so called storage pool disorders!!!!

Q25) White blood cell disorders - acute and chronic myelocytic (granulocytic) leukaemias

Google-a + klára bua þetta til

Q17) Pathophysiology of obesity

Obesity - defined as heterogenous metabolic disorder with multiple etiologies characterized by ; excessive body fat and overweight. The principal pathomechanisms are that calorie intake exceeds the energy expenditure. Overweight, on other hand can be due to different increase in different contents. !!! Overweight is defined as body weight that is higher than ideal, and can be caused by increased ; 1) muscle mass 2) water content, or 3) body fat, hence obesity! There are several simple methods for estimating the degree of obesity. In addition to this simple estimating methods there are more sophisticated techniques, such as measurement of body density, water content etc. ; Body mass index (BMI) : calculates by using the weight and hight of person. Normal BMI is between 20-25 Broca-Index : this is the height in cm (minus) 100 = ideal weight Wasit-to-hip ratio (WHR) : the normal values are for men 0.7-0.95 and for women 0.7-0.85 Skinfold thickness!! Classification of obesity, according to : BMI : 20-25 = very low; 25-30 = low; 30-35 = moderate; 35-40 = high; >40 = very high! Etiopathognesis : primary vs secondary obesity Size and amount of adipocytes : hypertrophic = increased size, hyperplastic hypertrophic = increased size and number of adipocytes Fat distribution in body : - Android type = apple shape, typically in men and mainly abdominal fat. Increased abdominal fat is associated with (increased risk of MI, DM, hypertension and hyperlipidemia)! - Gynoid type = pear shape, primarily in women and mainly gluteal fat! Etiopathogenesis of obesity can be explained by (exogenous and endogenous etiologies). The exogenous etiologies are primarily excess calories. The endogenous etiologies are ; - disorders of food intake : hyperphagia vs hypophagia = Describes food intake according to energy expenditure. Bulimia = increased consumption of food followed by self-induced vomiting! Disorders of Endocrine system* : there is an increased basal and post-stimulation serum insulin concentration in obese persons. The serum level is directly proportional with the degree of obesity. There is also development of insulin resistance in peripheral tissues. This result in an decreased hypoglycemic response since glucose uptake in the peripheral tissues are slower. Another endocrine abnormality is that the level of testosterone in men will decrease, while in women it will increase!!**** Physiologic factors* : it is believed that obese people is directed more by external cues (such as sight, smell and taste) than internal cues (hunger and satiety) Number and size of adipocytes : there occurs adipocyte hyperplasia in excess of food intake. We differ between hypertrophic and hyperplastic hypertrophic obesity! - as the fat cell size increases to upper limit, the number of fat cells will start to increase. The hyperplastic hypertrophic type of obesity is seen in early-onset obesity! Decreased thermogenesis and/or heat loss : there is believed that obese people have a deect in energy expenditure, which would result in positive energy balance! Decreased activity of sympathetic nervous system (SNS) The control of food intake is explained by several theories : - glucostatic theory : the food intake is regulated by glucose concentration. Decreased levels of glucose, increased food intake. Insulin also affects food intake! (Exogenous insulin = incr food intake, while endogenous insulin -> decr food intake) - Lipostatic theory : the intake is regulated by a biologic ,,set point" that maintain body weight. The set point is regulated in the ,,ventromedial hypothalamus". It is believed that obese have higher SET POINT* - Aminostatic theory : intake is regulated by concentration of amino acids! - Thermostatic theory : obese people are believed to have few brown fat cells compared to average individual. Thus, there is less release of energy through heat prod. - Energostatic theory : this theory takes in account the amount of ATP using pumps. It is believed that obeses people have 22% fewer ATPases (enzymes) compared to normal individuals - Lipoprotein lipase theory : lipoprotein lipase (LPL) is responsible for increased fat storage by hydrolyzing TGA into glycerol and FFA, which enter the fat cells. There is believed that obese people have increased amount of LPL

Q13) pathophysiology of thermoregulation

See question 12 for this one!!

Q16) Pathophysiology of Pain

Pain is defined as a complex unpleasant phenomenon composed of sensory experiences that include time, space, intensity, emotion, cognition and motivation. It is uniquely experienced by each individual, it cannot be adequately defined, identified or measured by an observer! Pain threshold is the point at which a stimulus is perceived as pain. This point does not vary significantly. This point does not vary significantly among people or in the same person over time. Perceptual dominance is when intense pain at onel ocation causes an increased pain threshold in another location. Pain tolerance, on the other hand, is duration of time or the intensity of pain that an individual will endure before initiation of overt pain responses. This term is influenced by cultural prescriptions, expectations, role behaviours, and physical and mental health. In general, pain tolerance is decreased with repeated exposures to pain, and it is increased by alcohol consume, medication etc., and varies greatly among people, and in the same persons over time. This seems to decrease in elderly, and women appear to be more sensitive to pain than men! Classification* - Pain can be divided into (somatogenic and psychogenic pain). Somatic pain is with a usually known cause, while psychogenic pain there is no known physical cause! These main pain categories are further divided into acute and chronic pain. Acute pain is defined as a protective mechanism that alerts the individual to a condition or experience that is immediately harmful to the body. The onset of acute pain is usually sudden, it is relieved when the chemical mediators are removed, and stimulation of the autonomic nervous system may be observed during this type of pain (mydriasis, tachycardia, vasoconstriction etc). Chronic pain, on the other hand is more prolonged (lasts more than 6 months). The cause of chronic pain is often unknown, often accompanied with hopelessness, helplessness -> depression! The parts of nervous system that are involved in the pain perception can be divided into the following main parts : - afferent pathways : these pathways are further made up of nociceptros (pain receptors), afferent nerves and spinal cord network - nociceptors are the ends of small, unmyelinated and lightly myelinated afferent neurons. These nerve endings are stimulated by chemical, mechanical and thermal stimuli. The stimulation does not necessarily produce pain, hence the stimulation have to produce signals that have high enough frequency and amplitude to cause pain. The receptors are found in muscles, tendons, subcutaneous tissue and epidermis - the afferent nerves are made up of small Adelta fibers and C fibers, which transmit the signal produced by the nociceptors to the dorsal horn of the spinal cord. Here will, 1st afferent neuron synapses with 2nd afferent neuron, which makes up the spinal cord network. The C fibers are responsible for transmitting diffuse burning or aching stimulations, while the A fibers carry well-localized, sharp pain sensations! - the spinal cord network starts with the 2nd afferent neuron. The A fibers terminate in the substantia gelatinosa, while some larger A fibers and the C fibers terminate into the laminae of dorsal horns. Within the substantia gelatinosa and laminae the 1st neuron synapse with 2nd neuron occur here. These 2nd afferent neurons then transmit the impulses through the ventral and lateral horn with a crossing in the same or adjacent spinal segment. After this crossing the impulses is carried with the spinothalamic tract to the brain. The spinothalamic tract can be divided into the neospinothalamic tract to the brain. The spinothalamic tract can be divided into (neospinothalamic tract and paleospinothalamic tract). The neospinothalamic tract carry information to the midbrain, post-central gyrus, and the cortex, while the neospinothalamic tract carries the impulse to the reticular formation, pons, limbic system and mid-brain CNS : the parts that are involved in the interpretation of the pain signals are the limbic system, reticular formation, thalamus, hypothalamus and cortex! Efferent pathways : some efferent pathways are responsible for modulation of the pain sensation, while other pathways are responsible for different reactions to the pain stimulus! Note : - when tissues are damaged they release a lot of mediators, such as bradykinin, histamine, and prostaglandins which stimulate adjacent nociceptors. The signal is then transported to the spinal cord. The most used theory is the ,,gate-control theory". In this theory, the pain signals is transmitted to the spinal cord with the A and C fibers, and terminate in the substantia gelatinosa (SG). The cells found in this structure function as a gate and control the transmission of impulses to the CNS. If the large fibers are stimulated the cells in SG cause the gate to close, which will result in that there is decreased stimulation of trigger cells, decreased transmission of impulses and diminished pain perception. When the small fibers transmit pain stimuli the gate is opened, which will cause stimulation of trigger cells and increase the transmission of the impulse Pathophysiology of visceral pain : angina pectoris, MI, acute pancreatitis, cephalic pain, prostatic pain, nephrolitiactic pain - Adequate stimuli : abnormal distension and contraction of hollow organs muscle walls -> rapid stretching -> abrupt anoxemia of visceral muscles -> formation and accumulation of pain producing substances (inflammation) -> direct action of chemical stimuli (oesophagus, stomach) -> compression of ligaments and vessels (tumors) -> inflammatory processes -> necrosis (MI) !!! The pain will be dull, deep, not well defined. Difficult to locate because it tends to radiate. Induce strong autonomic reflex phenomena (sweating, increased HR etc)

Q40) Pathophysiology of cholecystitis and cholelithiasis, complications, consequences

Part 1 What is cholecystitis - inflammation of the gallbladder A) What is the origin/cause of this condition? - mostly due to obstruction of cystic duct with gallstones cholelithiasis), mostly at the neck of the bladder or in the cystic duct. This leads to inspissation (thickening) of bile, bile stasis, and secondary infection by gut organisms, predominantly E.coli and Bacteroides. The gallbladder´s wall becomes inflamed. Extreme cases may result in ,,necrosis and rupture". Inflammation often spreads to its outer covering, thus irritating surrounding structures such as the diaphragm and bowel B) how does it develop & why does it develop? - Risk factors for cholelithiasis and cholecystitis are similar and include the following ; (Incr age, female sex, pregnancy, certain medications, obesity, rapid weight loss)! C) What is the mechanism in onset/developing this condition and how does this influence the body overall? - blockage of the cystic duct with gallstones causes accumulation of bile in the gallbladder and increased pressure within the gallbladder. Concentrated bile, pressure, and sometimes bacterial infection irritate and damage the gallbladder wall, causing inflammation and swelling of the gallbladder. Inflammation and swelling of the gallbladder can reduce normal BF to areas of gallbladder, leading to cell death due to insufficient O2 D) what are the symptoms/signs and why we get them? - there is usually pain in right upper quadrant or epigastric region. The gallbladder may be tender and distended. Symptomatically it differs from biliary colic by presence of an inflammatory component (fever, incr WBC count). More severe symptoms such as high fever, shock and jaundice indicate the development of complications such as abscess formation, perforation or ascending cholangitis. Chronic cholecystitis manifests with non-specific symptoms such as (nausea, vague abd pain, belching and diarrhea) E) how is the PROGNOSIS? - not everyone who has gallstones will go on to develop cholecystitis F) what are the complications due to cholecystitis? - abscess formation, perforation or ascending cholangitis. Another complication, gallstone ileus, occurs if the gallbladder perforates and forms a fistula with the nearby small bowel, leading to symptoms of intestinal obstruction! Part 2 What is cholelithiasis - is a ,,crystalline concretion" formed within gallbladder by accretion of bile components A) what is the origin/cause of this condition? - Gallstone risk increases for females (esp before menopause) around 40 years. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, which is able to reduce oxidative stress to the gallbladder. Researchers believe that gallstones may be caused by combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and low calorie diet! It seems like low-fiber and high-cholesterol diets are contributers to gallstone formation. Other nutritional fators that may increase risk of gallstones include ; rapid weight loss, constipation, eating fewer meals per day; and low intake of the nutrients folate, magnesium, calcium and vitamin C. On the other hand, wine and whole-grained bread may decrease the risk. Pigment gallstones* are most commonly seen in developing world. Risk factors for pigment stones include ,,hemolytic anemias" (such as sickle-cell disease and hereditary spherocytosis), cirrhosis and biliary tract infections. People with prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to Gallstone FORMATION! B) how does it develop & why it develops? - calculi are formed in the gallbladder but may distally pass into other parts of the biliary tract such as the ,,cystic duct, common bile duct, pancreatic duct or ampulla of Vater" C) What is the mechanism in onset/developing this condition? / how does this influence the body? - cholesterol gallstones* develop when bile contains too much cholesterol and not enough bile salts, may also develop due to gallbladder contracts, incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. This can be caused by high resistance to the flow of bile out of the gallbladder. - another cause is presence of proteins in liver and bile that either promote or inhibit cholesterol crystallization into gallstones (ex increased levels of estrogen, as a result of pregnancy or hormonal contraception, may increase cholesterol levels in bile and decrease gallbladder movement, resulting in gallstone formation)!! D) What are the symptoms/sings and why we get them? - may be asymptomatic, even for years, and do not require treatment. A characteristic symptom is intense pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting, that steadily increases for approximately 30 min to several hours. - Patient may also experience referred pain between the shoulder blades or below the right shoulder. These symptoms may resemble those of a ,,kidney stone attack". Often, attacks occur after a particularly fatty meal and almost always happen at night, and after drink. E) what are the complications due to cholelithiasis - may lead to acute cholecystitis, presence of gallstones in other parts of biliary tract can cause obstruction of the bile ducts, which can lead to serious conditions such as ascending cholangitis or pancreatitis! - rarely, in cases of severe inflammation, gallstones may erode through the gallbladder into adherent bowel potentially causing an obstruction termed gallstone ileus Div.: Composition of bile stones ; - 75% cholesterol stones (F x , M x) - 25% pigment stones (unconjugated bilirubin) Cholesterol in bile is present in micelle from cholesterol + bile salts + phosphatidylcholin (lecithin) - maintenance of micelle form is due to balance in cholesterol/bile salts + lecithin ratio. Increased concentration of cholesterol in the bile leads to super saturation of the micelle solution - micelle vesicles. - these micelle vesicles are precursor for crystallization ofthe cholesterol stones Stone composition : - black stones = calcium bilirubate + calcium carbonate + calcium phosphate - brown stones = calcium bilirubinate + stearate + palmitate + cholesterol

Q7 ) Disturbances of immune mechanisms

What does immunity mean and normal function Immune system together with stress leads to synthesis of cytokines activating HPA system which is a model for neuroendocrine control of responses of organisms to stressors. Here the immune cells also possess receptors for hormones of HPA system. Stress hormomnes such as catecholamines, cortisol, endorphins, glucagon, growth hormones can influence immune functions. It is noted that humoral mediators released by inflammatory cells (cytokines) may participate in communication between the site of inflammation and the CNS. Here you get an central action of interleukin 1 (IL-1) on the HPA system. This IL-1 stimulates ACTH release which again is associated with increased CRH concentration in hypophyseal portal venous blood. With this as an ex you may say that there is a link between neuroendocrine and immune system. You here get to share the use of the signal molecules and their receptors What is disturbance of immune mechanism? - is when the immune system reacts inappropriately (e.x immunocompromised patients is 4x more sick/year What does hypersensitivity mean? - it is a state of altered reactivity in which the body reacts with an exaggerated immune response to what is perceived as a foreign substance. Refers to an undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a (pre-sensitized (immune) state of the host)! 1. Allergy : exaggerated activity against environmental antigens. It may be beneficial immune response or harmful 2) Autoimmunity : misdirected activity against host´s own cells Endocrine : hyperthyroidism, autoimmune thyroiditis, primary myxedema (hypothyroidism), DM1, addison´s, infertility Skin : pemphigus vulgaris, vitiligo, dermatitis herpetiformis Neuromusuclar : multiple slcerosis, RF, cardiomyopathy GIT : celiac, ulcerative colitis, crohn´s, atrophic gastritis, primary biliary cirrhosis Conenctive tissue : rheumatic arthritis, collagenosis, scleroderma, polyarteritis nodosa Eye : Sjögren´s syndrome, uveitis Kidney : Goodpasture´s syndrome, immune-complex GN Hematopoietic : autoimmune haemolytic anemia, pernicious anemia Respiratory : Goodpasture´s syndrome! 3) Isoimmunity : activity directed against beneficial foreign tissues (e.g transfusion, transplamnt, fetus (intrauterine))! What does autoimmunity mean? - failure in recognizing its own constituent parts as self, thus leading to an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease! What does immunodeficiency syndromes mean? - is a state in which the immune system´s ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveilance. Most cases of immunodeficiency are acquired (,,secondary") but some people are born with defects in the immune system, or primary immunodeficiency. Transplant patients take medications to suppress their immune system as an anti-rejection measure, as do some patients suffering from an over-active immune system! What does it mean with allergic disorders? - is a hypersensitive disorder. Symptoms include red eyes, itchiness and runny nose, exzema, hives, or an asthma attack. Allergies can play a major role in conditions such as asthma. Allergic reactions occur when a person´s immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called and ,,allergen". These reactions are acquired, predictable, and rapid. Allergy is one of 4 forms of hypersensitivty and is formally called type1(or immediate) hypersensitivity. Allergic reactions are distinctive because of excessive activation of certain WBCs called mast cells and basophils by a type of antibody called immunoglobulin E (IgE). This reaction results in an inflammatory resposne which can range from uncomfortable to dangerous! What does it mean with atopic disease? - is a predisposition toward developing certain allergic hypersensitivity reactions. Atopy may have a hereditary component, although contact with the ,,allergen" must occur before the hypersensitivty reaction can develop. Many physicians and scientists use the term ,,atopy" for any IgE-mediated reaction (even those that are appropriate and proportional to the antigen)! Mechanisms involved in development of different types of hypersensitivity : Type I (allergy, immediately) A) IgE mediated allergic reactions : production of antigen-specific IgE after exposure to antigen (=allergens) most commonly allergic reactions are mediated by IgE B) anaphylaxis : rapid and severe. Cutaneous local inflammation. Systemic you may develop itching, vomiting, abdominal cramps, diarrhea, breathing difficulties, laryngeal edema, vascular collaps, shock, death. C) atopy : express proneness to allergy. Atopic persons produces more than normal IgE and have more Fc receptors in their mast cells. Genetic predisposition to develop allergy (e.g deficiency in IgE suppressor cells) Type II : tissue specific reactions, also known as Ab-dependent/cytotoxic. Here you have tissue specific antigens (TSA) expressed only on plasma membranes of certain types of cells. A) Ab binds to TSA-> fixed complement -> initiation of complement cascade (CCD) -> lysis of cell (autoimmune hemolytic anemia, transfusion reaction to donor blood cells) B) Ab binds to TSA -> macrophages recognize and binds -> phagocytosis -> lysis of cells C) Ab binds to TSA -> Fc receptors on cytotoxic cells recognize antigen on target cell -> binding -> release toxic substances -> lysis of target cell D) Ab binds to TSA -> Ab occupy receptors on target cells -> blockage of normal ligands for these receptors -> changes in cellular functions (e.g Grave´s disease) Type III : Immune-complex mediated reactions (immune complex disease), ex. Antigen-antibody complexes are created in blood -> deposition of the complexes in vessel wall and extracellular tissues -> Ne and Le try to ingest these complexes -> releasing lysosomal enzymes -> tissue gets damaged. Not organ specific reaction (ex. Serum sickness, Raynaud´s phenomenon, Arthus phenomenon) Type IV : (Delayed-type hypersensitivity, cell-mediated immune memory response, antibody-independent) Cell mediated reactions, that do NOT involve antibodies. Mediated by specifically sensitised T-ly (cytotoxic T-ly, lymphokine producing T-ly) (e.g graft rejection, tuberculin reaction Tu rejection, reaction to contact with metals or ivy). Diseases with this reaction type is ,,rheumatoid arthritis" (antigen is type II collagen in joints), Hashimoto´s disease (antigen is protein present in thyroid cells), DM1 (antigen is protein of the beta cells)! Mediator summary : Type I : IgE Type II : IgM, and igG, MAC and complement Type III : IgG, neutrophils and complement Type IV : T-cells

Q6) Pathophysiology of inflammation

What does inflammation mean? - part of biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells or irritants What are the gross features of acute inflammation - Rubor = redness, arterioles dilate -> allow more blood into local microcirculation, capillaries become congested with blood. This controlled by HISTAMINE - calor = heat - dalor = pain, due to change in local pH, local concentration of certain ions -> stimulate nerve endings, such as ex. Histamine release ++ -> stimulate nerves. Swelling of inflammed tissue -> increased local pressure -> pain - Tumor = swelling, produced by fluid and cells transferred from blood stream to interstitial tissue. This is called exudate, by increased permeability of capillaries, may be purulent, fibrinous, catarrhal, serous. Contains increased protein content - Functio laesa = altered function (loss of function)!!! What are the mediators of inflammation and their functions - Histamine : vasoactive amine, causes vasodilation and increased vascular permeability. Stored in mast cells - plasma factors : components work as mediators by releasing histamine, increased vascular permeability, and some are potent chemotaxic agents. - arachidonic acid metabolites : released from cell membrane in injury. Metabolized into prostaglandins, thromboxanes and leukotrienes. Has an vascular and chemotactic effect in inflammation! What are the cellular aspect of inflammation? - margination & emigration (e.x arterioles dilate -> blood flow into area -> fluid leaks out due to damage permeability -> elements such as RBC, WBC and platelets are left behind -> increased viscosity -> flow to area decreased -> leukocytes marginates, they may move to periphery of stream, lining vessels -> adhere to endothelium -> causing emigration of leukocytes into surrounding tissue This leukocytes migration is directed by signals called chemotaxis. Infectious agent and damaged tissue may provide these signals -> causing rapid accumulation of significant number of leukocytes to the inflammed area What is the fate of inflammation reaction? - Best result is when there has been little or no destruction of underlying tissue (e.g the offending agent are neutralized and removed -> causing the stimuli for exudation of fluid and cells to disappear). After an inflammation is important to reparate by proliferation of adjacent tissue, this process depends on the significant amounts of tissue that has being destroyed (e.g regeneration will lead to identical tissue replacement, while the scar tissue is the result from proliferation of CT)! What are the factors affecting inflammation and healing, and how do they affect? - inflammatory process depens on intact circulation to the area. If not, persistent infection and poor healing may be a cause. Also important is the supply of normal functioning leukocytes. (Not in BM depressed patients), drugs may also affect inflammations. Nutritional state of patient is also an important factor in wound healing together with foreign materials or necrotic tissue in wounds, they will also have there impact and affecting healing. What is the systemic aspect of inflammation? Fever : by release of endogenous pyrogens from neutrophils and macrophages, these will —> affect temperature regulation center in the body and regulate the ,,set point" Hematological changes : increased release of leukocytes from BM = leukocytosis Blood protein changes : in acute inflammation, (e.g acute-phase proteins prove beneficial, however in chronic inflammation they can contribute to amyloidosis. These proteins include C-reactive protein, serum amyloid A, and serum amyloid P, which cause a range of systemic effects including Fever, increased BP, decreased sweating, malaise, loss of appetite and somnolencec! Other aspects : malaise, anorexia, loss of appetite Important to remember is that ,,Vasodilation" and organ dysfunction are serious problems associated with widespread infection that may lead to septic shock and death!

Q5) Intrinsic factors in disease

What does intrinsic factors mean - genetic disorders that may often (f.x lead to spontaneous abortion)! What are the phenotypical expressions in genetic abnormalities in general? - a phenotype results from the expression of an organism´s genese as well as the influence of environmental factors and the interaction between the two The genotype of an organism is the inherited instructions it carries within its genetic code. Not all organisms with the same genotype look or act the same way because appearance and behaviour are modified by environmental and developmental conditions. Likewise, not all organisms that look alike necessarily have the same genotype. What is chromosomal abnormalities - is a missing, extra, or irregular portion of chromosomal DNA. Be from an atypical number of chromosomes or structural abnormality in one or more chromosomes. It usually occur in cell division error following meiosis or mitosis. There are many types of chromosome anomalies. They can be organized into : - numerical disorders (aneuploidy) : an abnormal number of chromosomes and occurs either if its missing a chromosome from a pair (monosomy) or has more than 2 chromosomes of a pair (trisomy, tetrasomy etc) - structural abnormalities : is when the chromosomes structure is altered, this can take several forms such as deletion, duplication, translocations, inversions etc. What is gene abnormalities -> a disease or disorder that is inherited genetically What are the phenotypical expressions in the most common diseases within chromosomal abnormalities A) due to abnormal number : develop during division. Leads to aneuploidy (cells with abnormal number of chromosomes). Often due to nodisjunction : failure of a homologous pair of chromosomes to separate during meiosis -> 1 daughter cell containing 1 extra chromosome, while the other cell contains one less chromosome. Trisomy : one extra chromosome, ex Down´s syndrome = trisomy 21, has three copies of chromosome 21, rather than two. Edward´s syndrome = trisomy 18 and Patau´s syndrome = trisomy 13 Monosomy : one less chromosome, ex Turner syndrome, where the individual is born with only 1 sex chromosome, an X B) due to abnormal structure : ex. Translocation, when chromosome breaks and the piece is lost or attached to another chromosome. Can lead to balanced or unbalanced rearrangements. Unbalance will lead to loss of genetic materials What are the phenotypical expressions in the most common diseases within gene abnormalities? A) autuosomal dominant disorder : at least 1 parent is affected (genotype Aa or AA). Not common (e.x familial hypercholesterolemia, huntington´s disease, Marfan´s syndrome, von Willebrand disease B) autosomal recessive disorder : both parents Aa, but phenotypically normal. Or if one is aa and Aa C). X-linked : males have only 1 x chr -> hemizygous for these traits (e.g Duchenne´s muscular dystrophy, hemophilia) Down syndrome : nearly always have physical and intellectual disabilities, showing decreased muscle tone in the face, developmental delays, and heart and digestive system defects. They have an increased risk of a number of other health problems, including : congenital heart disease, leukemia, thyroid disorders and mental illness, among others! Turner syndrome : has characteristic physical abnormalities, such as short stature, swelling, broad chest, low hairline, low-set ears, and webbed necks. Girls have typically experience gonadal dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility. Also congenital heart disease, hypothyroidism, diabetes, vision and hearing problems, and many autoimmune disease. Pecific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical and memory areas Cystic Fibrosis results when a lack of certain protein is present and the balance of chloride in the body isn´t restricted. Symptoms include difficulty breathing, recurrent lung infections, digestive and reproductive issues. Huntington Disease : causes degeneration of nerve cells in brain and CNS. Symptoms are uncontrolled movement (chorea), difficulty swallowing, behavioral changes, difficulty balancing/Walking, memory, speech and cognitive loss Sickle cell anemia (SCA) : occurs when RBCs are unable to carry adequate O2 throughout the body due to their deformation. This genetic disease is extremely painful, causing abdominal chest, and bone pain, fatigue, shortness of breath, accelerated heart rate, delayed puberty, stunted growth, fever and leg ulcers!

Q8) Body responses to different noxa

What does noxas generally mean? - they are factors/components that will lead to cellular injury. This injury will occur if the cell is unable to maintain homeostasis! What type of cellular injury does the noxas do? - injurious stimuli include chemical agents, hypoxia, infectious agents, physical and mechanical factors, immunological reactions, fenetic factors and nutritional imbalances. The injuries influences of noxas do not only produce local cell injury but also elicit general body response. Physiological reactivity may lead to pathological reactivity! Chemical injury and hypoxia can lead to : disruption of selective permeability of the plasma membrane, reduced cellular metabolism, lack of protein synthesis, damage to lysosomal membranes and leakage of destructive enzymes into cytoplasm, enzymatic destruction of cellular organelles, cellular death and phagocytosis of dead cell by cellular components of acute inflammatory response. Hypoxia : lack of sufficient O2 -> reduced ATP -> failure of Na-K-ATPase pump, intracellular accumulation of Na, K out of the cell -> Na + water enter cell -> cellular swelling. Damage of plasma membrane -> extracellular Ca moves into mitochondria -> mit swelling -> rapid death of cell due to accumulation of Ca compromising ATP production Chemical injury : damage plasma membrane -> increased permeability. Formation of free radicals, cellular swelling, mitochondrial swelling, decreased cellular pH, lysosomal membrane injury Infectious injury : invade and destroy cells, produce toxins, produce damaging hypersensitivity reactions Immunologic and inflammatory injury : direct contact with cellular and chemical components of the immune and inflammatory responses (e.g phagocytes and histamine/antibodies/proteases) Injury genetic factors : alter cell´s nucleus, plasma membrane, shape receptors, transport mechanisms Injurious nutritional imbalances : cells need adequate amount of nutrients to function normally Injurious physical agents : temperature, pressure, radiation, mechanical factors, noise, vibration! What is the general body responses to NOXAS!? - by integration of CNS by coordinates, interprets and control of the interaction between the individual and the environment, also the endocrine system gets integrated due to mobilization of metabolic reserves this is also for maintain internal homeostasis at a normal level. So, therefore will an integrated cooperation of both CNS and endocrine system help to minimize the response on the organism to the stressful stimuli Stress stimuli is also known as non-specific physiologic response. Stress is physiologic changes that follow the application of a stressor such as cold, trauma, surgical injury, anxiety, depression, anger, fear, obesity, old age, medical treatment, as you see, both somatic and psychological stressors. Both physical and emotional stimuli can cause stress! 3 stages of general adaptation syndrome (GAS) due to stress (,,3 stages of stress") 1) Alarm stage : The CNS is aroused (SNS and pituitary gland is triggered) and the body´s defence is mobilized 2) stage of resistance or adaptation : the mobilization of the body result in a ,,fight or flight" response producing adrenal hormones such as cortisol, norepinephrine and epinephrine. You have here a hyperactivity of the axis of hypothalamus-pituitary gland -suprarenal cortex 3) stage of exhaustion : the continuous stress causes progressive breakdown of compensatory mechanisms and homeostasis. This marks the onset of disease of adaptation. (This is when stress continues and adaptation is not successful). Ultimate sign of exhaustion is impairment of immune response, heart and kidney failure, death! How does stress, disease and adaptation have a connection? - an event or situation can be a stressor for one person and not for another. The perception of stressor depends on the context in which it appears, previous experience with the stressor and individual ability to cope with the stressor. Culture, personal and social factors + vulnerability does also have an influence. Coping = individuals psychological response to the stressor, may be effective coping taht has to do in maintaining homeostasis or it may be ineffective coping that may lead to illness! What is stress response - Complex neuroendocrine reflex (interaction among SNS and pituitary and adrenal gland) initiated by nucleus/PVN), efferent to endocrine glands (hypothalamic-pituitary-adrenal system, HPA) - CRH, corticotropin releasing hormone, is released from PVN in stress -> ant. Pituitary -> ACTH (+ prolactine, GH and antidiuretic hormone) -> adrenal cortex -> corticoids (cortisol) - stressors -> SNS -> adrenal medulla -> catecholamines (epi & NE) Leads to : increased cardiac and respiratory activity, vasoconstriction, increased BP, increased rate of coagulation, increased ability of body to perform vigorous muscle activity, increased mental activity, decreased GIT and kidney functions Other stress hormones that may also be released are : Endorphins : stress-induced analgesia, positive well-being, euphoria Glucagon : hormone of energy shortage, secretion is stimulated by catecholamines, gluconeogenesis and glycogenolysis GH : stimulates proteosynthesis and transport of AA into the muscles Cortisol : gluconeogenesis, protein catabolism, lipolysis & immunosuppressant What are stress related diseases? (Name some examples, with 1 in more detail) Cardiovascular : coronary artery disease, hypertension, arrythmias Muscles : tension headaches, contraction backache Pulmonary : asthma. Hay fever (hypersensitive reactions) GIT : ulcer, irritable bowel syndrome, diarrhea Genitourin : impotence, frigidity, diuresis Skin : eczema, acne, neurodermatitis Endocrine : DM CNS : fatigue, lethargy, overeating, depression, insomnia! Stress hormones are not always good in the long run, why? - because you will then get an accumulation due to that the body will not have the use in all of the stress hormones that has being produced. Such repeated and long acting situations promote some pathophysiological states such as ; 1) increased catecholamines -> heart disturbances 2) increated catecholamines together with cortisol -> hypertension 3) increased rate of coagulation -> thrombotic hyperlipidemia -> premature atherosclerosis 4) decreased glucose utilisation -> insulin resistant DM 5) decreased protein synthesis -> muscular atrophy, osteoporosis 6) increased endorphins -> obesity stress ulcers -> disruption of barrier function and poor perfusion Important is to remembe* is that the multiple hormones that are produced in stress response is due to bring ,,back" appropriate metabolic response such as; hyperglycemia and free fatty acid mobilisation. Hyperglycemia is optained by glycogenolysis and gluconeogenesis in the liver. This decrease in glucose uptake in muscles together with decreased insulin release -> will lead to that the glucose will be preserved for the CNS. The free fatty acid mobilization is for the metabolism in the muscles!

Q11) Acid base disorders

What is acid? It is a proton donor - produced continuously from normal metabolism, it is liberated in solution (H+) in organism you may get acid from! A) volatile acid : can be excreted by lungs. Only CO2. CO2+H2O -> H2CO3 (carbonic acid) -> H+ + HCO3- b) fixed acids : need to be released from kidneys. H2SO4 (sulfuric acid) and H3PO4 (phosphatic acid) c) organic acids : lactic acid, ketoacid. Can lead to acid/base disbalance! What is base? An proton acceptor, substance that combines with H+ (OH-) What does buffer mean? Is a solution state where you may add a strong acid or base to a solution without causing a large change in the pH. A buffer solution contains both a weak acid and its conjugate base. In the body are there 4 main buffer systems : 1. Bicarbonate/carbonic acid system (NaHCO3 and H2CO3) (largest >50%) 2. Disodium/monosodium phosphate system (Na2HPO4 and NaH2PO4) 3. Hemoglobin/oxyhemoglobin system in RBC (HBO2- and HHBO2) 4. Protein system (PR- and HPr) what is the normal pH of the ECF? - ECF = 7.4 (human blood around 7.35-7.45) - (normal values are 40 mmol.l-1 in H+) How does the regulation of ECF-pH work in the body? - by intergraded action between buffer system, lungs and kidneys - buffering systems (immidiate response) : act within seconds to change in pH. Chemical buffering of H+ for both the ECF and the ICF buffer systems Respiration : 2nd line, control level of CO2 by changes in alveolar ventiulation. Happens within minutes Renal : several days, regulates the HCO3- level, restore normal pH what is acid-base balance? - it is the balance based on henderson-hasselbalch equation, where you have the components such as bicarbonate and the carbonic acids put together calculating out the pH. In the body you have balance between one part of acids = 1.2 mmol/l with PCO2 5.3kPa, together with the other 20 parts of base = 24 mmol/l. This balance is the homeostasis of H+ concentration. Where small fluctuations in the concentration of this ion may lead to important effects on the activity of different cellular processes! What is primary acid-base imbalamnce? - acidemia : decreased blood pH <7.35 (7.25 life threatening, 6.8 = death) - acidosis : process causing acidemia - Alkalemia: increased blood pH >7.45 (7.55 = life threatening, 7.8 = death)! - Alkalosis : process causing alkalemia! pH = HCO3 concentration is controlled by kidneys, while PaCO2 concentration is controlled by lungs = 20:1 ration - Metabolic imbalance : disturbances in concentration of bicarbonate - respiratory imbalance : disturbances in concentration of CO2 (increased PaCO2 —> respiratory acidosis , decreased PaCO2 -> respiratory alkalosis) What is the compensatory response to alteration in pH 1. ECF and ICF buffering 2. Respiratory alteration of PaCO2 by hypo or hyperventilation 3. Renal alteration of HCO3- or H+ What is metabolic acidosis (MAC) - decreased HCO3 -> decreased pH, decreased HCO3 -> increased Cl (due to maintainance of electro-neutrality in ECF) = hyperchloermic MAC - what is the origin/cause of this condition? Due to normal anion gap : HCO3 loss via GIT (diarrhea, small bowel fistula) or kidneys (renal tubular acidosis) due to high anion gap : increased noncarbonic acids (lactate, ketoacidosis + Retention of fixed acids) + shock. What is the mechanism in onset/developing this condition? / how does this influence the body? Compensation that may happen ; a) immediately : in ECF that buffers increase H+ with the HCO3 buffer system -> decreased HCO3 in plasma, or when H+ enters cells it gets buffered by proteins and phosphates. When H+ enter cell will K+ leave cell due to electro-neutrality b) ,,in between" : by hyperventilation to decrease PaCO2 (chemoreceptors) c) late : via HCO3 retention in kidneys, H+ secretion as NH4+ or H3PO4 (this do not happen if vomiting is the cause) What are the symtomst/signs?/why do we get this symptoms/signs! - Kausmal breathing (deep and fast ventilation), decreased cardiac contractility, lethargy, renal osteodystrophy, hyperkalemia, and vomiting (intense H+ changes activates vomiting centre) What is metabolic alkalosis (MAL)? Incr HCO3 <—> dec Cl what is origin/cause of this condition? - loss of H+ and Cl- or retention of HCO3. Ex in GIT it is due to prolonged vomiting, nasogastric suction, while in urine it is due to diuretics! What is the mechanism in onset/developing this condition?/how does this influence the body? Comensation : A) immediate via intracellular buffering : H+ exits cells to buffer ECF. K+ moves into cells in exchange of H+ B) via lungs : hypoventilation to increased PaCO2 (chemoreceptors detect increased pH) C) via kidneys : excretion of excess HCO3 what are the symptoms/signs? Why do we get them - tetany (increased neural activity = cramps) (proteins use Ca2+ to buffer H+/albumin binds to Ca2+), increased risk of cardiac dysrythmias, increased affinity of Hb to O2 and hypokalemia! What is respiratory acidosis (RAC) incr PaCO2 What is origin/cause of this condition? Respiratory disorders (hypoventilation -> increased CO2) that may be acute such as acute airway obstruction (laryngospasm, foreign body aspiration, CNS depression) here you don´t have time for compensation, here the pH will be seriously reduced, or it may be chronic such as COPD. Another condition leading to this is sleep apnea, this always accompanied with hypoxemia! What is the mechanism in onset/developing this condition?/how does this influence the body? Compensation : intracellular buffering and by kidneys ia HCO3 retention with H+ excretion What are symptoms/sings?/why do we get this symptoms/signs -CNS dysfunction such as confusion, somnolence, stupor, coma, also increased intracranial pressure (headache, redness of bulbs) due to cerebral vasodilation What is respiratory alkalosis (RAL) decr PaCO2 What is the origin/cause of this condition - alveolar hyperventilation due to anxiety and emotional stress (Most common) or hypermetabolic conditions such as in fever, CNS lesions, thyretoxicosis, or hypoxia due to pneumonia, pulmonary edema, high altitude what is mechanism in onset/developing this condition?/how does this influence the body? Compensation : - intracellular buffering where H+ Is released to buffer alkalosis, or by kidneys via increased renal excretion of HCO3 what are symptoms/signs?/why do we get this symptoms/signs - numbness of fingers and toes, tetany, vomiting, mental confusion and syncope What is MIXED acid-base DISORDERS*** - dysbalance that may arise in cardiopulmonary arrest spesis, pulmonary diseases and DM 1. MAC + RAC - in untreated cardiopulmonary arrest (incr CO2, decrO2) - in COPD person (RAC) going into shock (MAC) - in person with chronic RF (MAC) + respiratory insufficiency secondary to fluid overload and pulmonary edema 2. MAL + RAL (most common mixed disorder)* - COPD (compensated RAC with incr HCO3) patient hyperventilated on a respirator (RAL) 3. MAC + RAL - lactic acidosis complicating septic shock!

Q19) Anemias caused by decreased or defective cell productions - hemoglobinopathies, impaired globin system!

What is anemia (see Q18) How does normal globin look like? - globins are a family of a globular proteins, these proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members; myoglobin and hemoglobin, bind both to the heme. Both of these proteins are reversible oxygen binders/transporters R What is hemoglobinopathies - a kind of genetic defect that results in ,,abnormal structure" of one of the globin chains of the hemoglobin molecule. They are inherited single-gene disorders and in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease Thalassemias, in contrast, usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Both, may cause anemia! What is the origin/cause of this condition? - causes leading to decreased or defective RBC production also known as dyserythropoieisis is ; disseminated malignancies (such as in breast cancer and leukemias), chronic diseases (inflammatory, infectious diseases, endocrine disturbances), lack of essential vitamins (B12, folic acid, C-vitamin), lack of iron or due to. BM failure! Sickle cell anemia : mutation in the beta-globin gene, which leads to production of defective hemoglobins. The hemoglobin that are formed after this mutation are known as sickle haemoglobin (HbS) Thalassemia : genetic inherited disorder leading to decreased synthesis of either alpha or beta-globin. Ex. If the deficiency is in the alpha-globin you will have an excess of the beta-globin and vice versa. Usually developed in mediterranean sea, black sea, asia and africa, probably because it provides partial protection against malaria! How does it develop? - Sickle cell anemia : it develops by undergoing aggregation and polymerization when it is deoxygenated. This will lead to that the cytosol is converted to a viscous gel, with further deoxygenation it assembles long needle like fibres causen the shape of the cell to be sickle! What is the mechanism in onset/developing this condition?/how does this influence the body? - Sickle cell anemia : irreversible major organ failure (loss of splenic function, cerebral infarction and intracranial hemorrhage, chronic pulmonary failure, chronic RF, retinopathy, leg ulcers, osteonecrosis) is the direct consequences of sickle cell evoked vasculopathy. The vascular damage begins year before the overal clinical symptoms appear with no pain. Sickle cell is both hemolytic and vasooclusive components. HbS behaves abnormal and also the tendency to polymerise at low oxygen tension leading to sickling phenomenon which seems to be one of the dominant factor in disease pathophysiology! Thalassemia : free (unmatched) globin-chain precipitate in Ery will lead to damage of the Er membrane, further this will lead to hemolysis that will lead to microcyte hypochromic anemia and hemosiderosis. This hemosiderosis will further damage the myocardium, liver, beta cells and lymphatic nodes What are the symptoms/signs? / why do we get this symptoms/signs! - Sickle cell anemia : major signs is severe anemia, vaso-oclusive complications and chronic hyperbilirubinemia - Thalasemia : iron overload, infections, bone deformities, enlarged spleen, slower growth, heart problems What are the consequences? - Sickle cell anemia : worsening of individual´s cickle cell anemia may lead to so called aplastic crises. This is a life-threatening condition. Often, triggered by ,,parvovirus B19" which stops red blood cell production for a couple of days. A blood transfusion can help! - Thalassemia : can cause significant complications, including ; iron overload, bone deformities and cardiovascular illness

Q21 ) Aplastic anemia, iron deficiency anemia

What is anemia - see q.18 What is aplastic anemia? - it is when you have insufficient number of blood cells produced, bone marrow is not doing it´s job!. It is a multifactorial disease, normocytic and normochromatic which is genetically determined, involving primary proliferation defect of the haemopoietic system and an immune reaction directed against it! What is the origin/cause of this condition? - mostly the cause is idiopathic (unknown), but it may also be by virus induced diseases (parvovirus, HBC,HCV,EBV), drug-induced, radiation and chemicals. Div. Interleukins inhibit activity of BM function, but it is unlikely that this is the only cause for the aplasia! What is the mechanism in onset/developing this condition? / how does this influence the body? - it starts with that the BM does not produce anything leading to PANCYTOPENIA (lower amount of RBC+WBCs) leading further to anemia, thrombocytopenia and neutropenia. In long prolonged state this may again lead to acute leukemia! The BM gets ,,hypocellular"* with absent of the progenitor cells that are in the haematopoietic cell line such as erythroblast and all the rest of the cells that go and differentiate to RBC, WBC and so on! - primary disease of haematopoietic tissue -> hypoproliferation -> onset of immune reaction against itself. - If IS is strong -> all abnormal cells are wiped out -> acute severe aplasia! - if IS is weak -> mild chronic pancytopenia! What are the symt/signs/why do we get them (aplastic anemia) - anemia will lead to ; fatigue, shortness of breath (dyspnea), thrombocytopenia will get easy brusing and petichia due to low platelets and coagulation components and due to neutropenia you will get (increased predispose to infection) How is prognosis? - BM transpl, blood transf & immunosuppressive drugs! What is iron deficiency anemia? - anemia caused by insufficient dietary intake and iron absorption, and/or iron loss from bleeding originated from a range of sources such as the intestinal, uterine or urinary tract. The anemia is called ,,hypochromatic microcytic anemia" What is the origin/cause of this condition? - most significant cause in children is parasitic worms (hookworms, whipworms, and roundworms), since they cause intestinal bleeding. This is not always noticeable in faeces, and is damaging to growing children. Malaria, hookworms and vitamin A deficiency contribute to anemia during pregnancy in most underdeveloped countries. - In women >50 years, the most common cause is chronic gastrointestinal bleeding from nonparasitic causes, such as gastric ulcers, duodenal ulcers or gastrointestinal cancer How does it develop?/why do it develop? - parasitosis, blood loss, lack of iron in diet, an inability to absorb iron due to cases where there is a reduction in surface area of the bowel, such as in celiac disease, inflammatory bowel disease or post surgical resection. Here the body can absorb iron, but there is simply insufficient surface area! What are the symptoms/signs / why do we get this symptoms/signs? - Pallor (reduced oxyhemoglobin in skin or mucous membranes), fatigue, light-headedness, and weakness. None of the symptoms are sensitive or specific. Because iron deficiency tends to develop SLOWLY, adapation occurs and the disease often goes unrecognized for some time, even YEARS! Other symptoms and signs of iron-deficiency anemia include : hair loss, sleepiness, palpitation, fainting! How is the prognosis? - sometimes treatable, but certain types of anemia may be lifelong. If the cause is dietary iron deficiency, eating more iron-rich foods, such as beans, lentils or red meat, or taking iron supplements! What are the consequences? - earlier stages of development in children may have greater consequences than in adults. Severe deficient during earlier life cannot recover to normal iron levels even with iron therapy. In contrast, deficiency during later stages of development can be compensated with sufficient iron supplements. Iron-deficiency anemia affects neurological development by decreased learning ability, alter motor functions, and permanently decrease dopamine receptors and serotonin levels. It may lead to decreased myelination of SC, as well as change in myelin composition. GH secretion is related to serum transferrin levels, suggesting a positive correlation between iron-transferrin levels and an increase in height and weight. This is also linked to PICA, as it can be cause!!!!

Q22) Megaloblastic anemias, sickle cell anemias

What is anemia - see q.18 What is megaoblastic anemias - abnormalities in absorption and metabolism of folate or vitamin B12 There are 2 forms of this type of anemia : Vit.B12 and folic acid deficiency. These two anemias are due to impaired DNA synthesis!: This is due to that the mentioned nutrients are coenzmyes in formation of thymidine, the 4th base found in DNA. As the name implies the precursor and red cells are ,,anormally large". The deficiency of these nutrients leads to a defective nuclear maturation. It is also important to remember that the synthesis of RNA and proteins is not majorly affected. Thus, the cytoplasmatic maturation proceeds in advance of nuclear maturation, which is called nuclear/cytoplasmatic asynchrony. There is also seen Pancytopenia, since all myeloid lineages is affected! Most common type of megaloblastic anemia is ,,Pernicious anemia" with highly injurious. This condition is due to defective gastric secretion of IF (intrinsic factor) needed for vitamin B12 absorption. Causes may be congenital deficiency, atrophy of gastric mucosa (by e.g gastritis) and gastrectomy! The consequences will be that it affect both erythrocyte and leukocyte precursor in BM causing megaloblastic anemia and neurological disorders! What is the origin/cause of this condition? - may be due to malnutrition (elderly, alcoholics, teenagers, pregnant women), malabsorption (e.g celiac disease), lack of intrinsic factor (as in pernicious anemia and postgastrectomy), parasitic infections (compete for vitB12), intestinal disease (lead to malabsorption), malignancies or due to chemotherapeutical agents! - Vitamin B12 deficiency alone will not cause the syndrome in presence of sufficient ,,FOLATE", for the mechanism is loss of B12 dependent folate recycling, followed by folate-deficiency loss of nucleic acid syntheis (specifically thymine), leading to defects in DNA synthesis What is the mechanism in onset/developing this condition? / how does this influence the body? - results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis! What are symptoms/signs/Why do we get this symptoms/signs? - malnourished, glossitis, diarrhea and loss of appetite! What are consequences (megaloblastic anemia) a) inhibit DNA synthesis -> cell cycle slowed down -> delay in RBC maturation b) Hb synthesis in cytoplasm is unchanged -> increased size of ER (megaloblasts) -> megalocyte in blood C) formation of granulocytes and megakaryocytes is disturbed D) premature destruction of megaloblasts in BM (inefficient erythropoiesis) and short life of megalocytes (premature hemolysis)!! What is sickle cell anemia? - hereditary blood disorder characterized by RBCs that assume an abnormal, rigid, sickle shape! - Sickling decreases the cells, flexibility and results in a risk of various life-threatening comlications What is the origin/cause of this condition? - occurs because of point mutation in beta-globin chain (chr.11) of hemoglobin, causing hydrophilic amino acid glutamic acid to be replaced with hydrophobic amino acid valine at the sixth position How does it develop?/why do it develop? - the association of two wild-type alpha-globin subunits with 2 mutant beta-globin subunits forms hemoglobin S (HbS). Under low-O2 conditions (ex being at high altitude), the absence of a polar amino acid at position siz of the beta-globin chain promotes the non-covalent polymerisation (aggregation) of hemoglobin, which distorts RBCs into a sickle shape and decreases their elasticity. What is the mechanism in onset/devveloping this condition?/how does this influence the body? -the loss of RBC elasticity is central to the pathophysiology of sickle-cell disease. Normal RBC are quite elastic, which allows them to pass through capillaries. In sickle-cell disease, low O2 tension promotes RBC sickling and repeated episodes of sickling damaging the cell membrane and decrease cells elasticity - These cells fail to return to normal shape when normal O2 tension is restored. As a consequence, these cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia. The actual anemia of the illness is caused by ,,hemolysis", because of their mis-shape. Although the BM attempts to compensate by creating new red cells, it does not match the rate of destruction. Healthy RBCs typically live (90-120 days), but sickle cells only survive 10-20 days! What are symptoms/signs / why do we get them? - no pain with vascular damage occur years before symptoms, such as : leukocytosis and thrombocytosis, impaired growth and development, frequent bacterial infections (especially pneumococcal infect), splenomegaly and swollen and painful hands and feets (from infarction)!!!!

Q20) Anemias caused by decreased or defective cell productions - RBC membrane defects, enzyme deficiency

What is anemia - see q.18 What is normal function of the RBC membrane? - regulates cell surface deformability, flexibility, cell adhesion and immune recognition. Highly dependent on its composition, which defines its properties. - Composed of 3 layers : glycocalyx exteriorly (carbohydrates), lipid bilayer (phospholipids/cholesterol) with transmembrane proteins, membrane skeleton (structural protein network). What is the origin/cause of the RBC membrane defects? - may arise from the hemolytic ,,main branch", then from either heriditary ,,branch" or acquired ,,branch". - hereditary is ex hereditary spherocytosis (minckowski chaufford syndrome) a group of inherited disorders characterized by defects in the RBC cell membrane, causing the cells to be small, sphere-shaped, and fragile instead of donut-shaped and flexible. These abnormal RBC are destroyed by the spleen. (May be detect by test for G6PD = ,,beutler fluorescent spot test") How does it develop?/why do it develop? - hereditary spherocytosis : autosomal dominant or recessive trait (common in Northern European, Japanese families), with div. Molecular defects in genes encoding for spectrin (alpha and beta), ankyrin (most common defect causing dysfunction cytoskeletal instabilities), band 3 protein, protein 4.2, and other erythrocyte membrane proteins that are necessary for maintaining the normal shape of RBC, which is biconcave disk What is the mechanism in onset/developing this condition?/how does this influence the body? - the primary defect in hereditary spherocytosis is —> deficiency of membrane surface area resulting in membrane loss, decreased surface area, and formation of spherocytes with decreased deformability. The spleen normally targets abnormally shaped RBC (which are typically older), it now also destroyes spherocytes. In the spleen, the passage from cords of billroth into sinusoids the erythrocytes need to be flexible in order to pass through. With the deficiency the erythrocytes fail to pass through and get phagocytosed, causing extravascular hemolysis!!! what are the symptoms/signs?/ why do we get them? - process of RBC-rupture results in div.anemia degrees, increased bilirubin in blood (causing Jaundice) and splenomegaly (enlargement of spleen)! How is prognosis? There is no cure, current focuses on interventions that limit the severity of the disease! What are the consequences? - hemolytic crisis, with pronounced jaundice due to accelerated hemolysis, aplastic crisis with fall in hemoglobin level and (reticulocyte count) - decompensation, Folate deficiency caused by increased BM requirement and pigmented gallstones due to increased hemolysis of RBC -> increased bilirubin levels What is the normal function to the enzymes connected with RBC? - they protect the cell against injuries by exogenous and endogenous oxidants. Enzymes for this are produced (ex. In hexose monophosphate shunt of glutathione metabolism. Glucose-6-phosphate dehydrogenase (G6PD) is important. This enzyme is responsible for reducing NADP to NDAPH by the oxidation of glucose-6-phosphate to 6-phosphogluconate, further on this oxidases and reduces other but ends up in finally reduce H2O2 to H2O What type of enzymes do get deficient in connection with anemias? -> G6PD, most clinically hemolytic anemias How does it develop?/why do it develop? - hemolysis in this kind of eficiency occurs after exposure to oxidant stress. This can be after ingested of some type of drugs, exposure to oxidant free radicals generated by leukocytes in the cause of an infection! What is the mechanism in onset/developing this condition? / how does this influence the body? - after oxidant exposure acute intravascular hemolysis may occur, characterized by -> anemia, hemoglobinemia, and hemoglobinuria. The hemolysis is self-limited, since only old RBC are being hemolysed, this occur intermittently, so common sign of chronic hemolytic anemia (splenomegaly/cholelithiasis) are ABSENT! What are the symptoms/signs? / why do we get this symptoms/signs - abnormal RBC breakdown in this condition that can be manifested by prolonged neonatal jaundice (possibly for kernicterus), hemolytic crises in response to Illness (infections), certain drugs, certain foods (broad beans), certain cehmicals and Diabetic ketoacidosis. Very severe crises can cause acute RF! How is the prognosis? - G6PD - deficient individuals do not appear to acquire any illness more frequently than other people, and may have less risk than other people for acquiring ischemic heart disease and cerebrovascular disease!

Q36) Diverticualr and inflammatory disease of the large Intestine

What is the normal condition and function of the large intestine? - It removes water and any remaining absorbable nutrients from the food before sending the indigestible matter to the rectum. It takes 16 hours to finish the food digestion. The colon absorbs vitamins that are created by the colonic bacteria - such as vitamin K (the amount is not enough to maintain adequate blood coagulation therefore do we also need it from diet), vitamin B12, thiamine and riboflavin. It transforms the chyme into feces, and stores fecal matter in rectum until it can be discharged via defecation. The large intestine also secretes K+ and Cl-. Chloride secretion (Increased in cystic fibrosis). Recycling of various nutrients takes place in colon (e.g fermentation of carbs, short chain fatty acids, and urea cycling) What is Diverticular disease of the large Intestine** - It is involvement of the development of small sacs or pockets in the wall of the colon, including diverticulosis (most common lower GIT bleeding), diverticular bleeding and diverticulitis! Diverticulosis - is formation of numerous tiny pockets, or diverticula, in the lining of the bowel. Diverticula, which can range from pea-size to much larger, are formed by increased pressure on weakened spots of the intestinal walls by gas, waste or liquid Diverticulitis - it is inflammation of 1 or more saccules. The saccules are flask-shaped compartment created by herniation of the mucosa through the muscularis! A) what is the origin/cause of this condition - idiopathic (unknown), may be colon motility disorder pattern -> failure of relaxation (constipation) -> build-up of high intraluminal pressure -> herniation. Other factors may be anxiety, stress, low-fiber diet (narrow lumen -> buildup of pressure -> increased stria on the wall), irritable colon syndrome -> diverticulosis!!! B) how does it develop & why it develop? - common site : sigmoid colon, 90% (into mesenteric attachment of colon, since entery of vessels weakens wall) C) what are symptoms/signs & why we get them? - asymptomatic, flatulence, intermittent diarrhea or constipation, discomfort in lower left quadrant. It may limit quality of life because of pain, vomiting, diarrhea, etc, but it rarely fatal on its own! D) what are the consequences? - acute or chronic diverticulitis -> bleeding, perforation and peritonitis, abscess and fistula formation, or intestinal obstruction from stricture Note**** In acute form : you may develop fever, leukocytosis (incr leukocytes), pain and tenderness in lower left quadrant, and the acutely inflamed diverticula may rupture, or if it has small perforation coud this lead to abscess formation. In larger perforations could this lead to that fecal material may enter peritoneum -> causing PERITONITIS! In chronic diverticulits : you have repeated attacks of inflammation -> fibrosis & adhesions -> narrowing lumen -> constipation, intermittent diarrhea + abdominal distension. Pericolic abscess may be formed in the occluded lumen-> fistula. (Most common is ,,vesico-colonic fistula" What is inflammatory disease of the large intestine? - Group of inflammatory conditions of colon and small intestine. Major types are (Crohn´s disease & ulcerative colitis) 1) Ulcerative colitis : non-specific inflammatory disease of colon, has remissions and exacerbations, causing abd pain, diarrhea and rectal bleeding! (Mucosa & submucosa gets inflammatory lesion -> causing ulcerations!) Note : etiology is unknown (idiopathic), but it may have a conenction to genetics, autoimmunity and psychological stress IMPORTANT* - It all starts with lesion of the mucosa + abscess in crypts. In early stage you have edema (swelling) and congestion of mucosa -> bleeding from minor trauma, then in advanced stage the crypt abscess breaks through the wall of crypts and spread to the submucosa -> mucosa is shed into the bowel lumen -> ulcer areas (first shallow and scattered ulcers, then whole layers -> considerable loss of proteins, tissue and blood) - Complications : Toxic dilatation/megacolon* = paralysis of motor function of transverse colon! -> dilatation ->> often lead to perforation + massive hemorrhage. With this condition you may have a increase risk for carcinoma and other systemic complications such as ,,pyoderma gangrenosum, episcleritis, uveitis, arthritis, anyklosing spondylitis". It may also influence the hepatic function + cirrhosis formation!!! 2) Crohn´s Disease (granulomatous colitis) : - Transmural inflammatory lesions, discontinuous with NO rectal bleeding, you may have FISTULA formation* and anal abscesses together with stricutres and finger clubbing!!!

Q32) Gastritis - acute and chronic, stomach cancer (Carcinoma 90-95%)

What is the normal condition and function of the stomach? -> main function is to break down and digest food in order to extract necessary nutrients from what you have eaten! Under normal conditions the main functions are, firstly; acts as place of storage, so that 2 or 3 meals a day can provide all our energy (ATP) needs! Without this, we would have had to eat bits and pieces all day. Secondly, it also aids the digestive process, as it is here that food is turned into a semi-liquid substances so that the nutrients can be absorbed from it. Thirdly the stomach is the destruction of contaminants that the food may contain bacteria and other micro-organisms. Very little is absorbed into the bloodstream straight through the stomach walls aspirin and alcohol being exceptions to this rule! What is acute gastritis? - it is acute mucosal inflammatory process, that is accompanied with hemorrhage (bleeding) into the mucosa, since it´s acute it have also infiltration of neutrophils 1) what is origin/cause of this condition Pathogenesis is not fully understood (idiopathic), but factors may be for example (heavy use of NSAIDs (aspirin), alcohol consumption, smoking, cancer chemotherapeutic drugs, stress, ischemia/shock, trauma and gastric irritation 2) How does it develop?/why do it develop? - all the factor causes may lead to increased acid secretion, decreased production of bicarbonate buffer, decreased BF, disruption of mucous layer and direct damage of the epithelium. 3) what is mechanism in onset/developing this condition/how does this influence the body? - NSAIDs inhibit cyclooxygenase-1 or COX-1, an enzyme responsible for the biosynthesis of eicosanoids in stomach, which increases the possibility of peptic ulcers forming. Also, aspirin, reduces a substance that protects the stomach called ,,Prostaglandin" Note : - in mild form you may see ,,moderate edema (swelling) of lamina propria" & slight vascular congestion. In more severe cases you may see ,,erosion, hemorrhage w/acute inflammatory infiltrate & extrusion of fibrin containing purulent(bacterial) exudate" into the lumen called -> Acute erosive hemorrhagic gastritis*** What is chronic gastritis - it is chronic mucosal inflammatory changes that may lead to ,,mucosal atrophy (decrease in size) & intestinal metaplasia. In this condition you have infiltration by specific inflammatory cells (lymphocytes & plasma cells) 1) what is the origin/cause of this condition - it is associated with chronic infection by H.PYLORI*, autoimmune, toxic substances (alcohol/smoking), post-surgical, motor & mechanical, radiation & granulomatous conditions. 2) How does it develop? And why!!!! - chronic infection by H.pylori develops since it has motility function so it will swim through the viscous mucous, it has elaboration of urease which produces ammonia & CO2 that will function as a buffer against the gastric acid, it has bacterial adhesion & bacterial toxic expression! What is Autoimmune gastritis It is due to presence of autoantibodies, in connection with gastric gland parietal cells. The antibodies are against acid-producing enzyme H+K+ATPase, gastrin receptor and intrinsic factor (This type of condition is also seen together with other autoimmune disorders such as ; Hashimoto thyroiditis, Addison´s disease and diabetes mellitus type 1) What is the mechanism in onset/developing this condition?/ and how does it influence the body? - Chronic inf by H.pylori : it stimulates production of pro-inflammatory cytoines which are gastric acid inhibitors and by direct injury of epithelial cells. It may lead to 1 of 2 pattern of gastritis, one is the Antral-type gastritis with high acid production and increased risk for ,,duodenal ulcer" together with low production of cytokine (it alters the interplay between gastrin and somatostatin secretion, affecting gastrin-secreting cells & somatostatin-secretin D cells), secondly the Pan-gastritis that is followed by multifocal atrophy with lower acid secretion and higher cytokine production with/also higher risk for developing AdenoCa* - Autoimmune : only the glands are being destructed togethe with mucosal atrophy and loss of acid production in less severe cases, while in more severe cases the production of intrinsic factor is lost leading to pernicious anemia! What are symptoms/signs + why we get them (chronic + autoimmune gastritis)! - both of these can be ASYMPTOMATIC, or epigastric pain, nausea & vomiting (may be clear, green or yellow, blood-streaked, or completely bloody, depending on severity of stomach inflammation). Note : if gastritis is accompanied by hemorrhage (bleeding) there may be seen ,,hematemesis & melena", resulting in potentially fatal blood loss - Other signs & symptoms may include : early satiety, loss of appetite & unexplained weight loss How is prognosis ? - epithelial changes can become ,,DYSPLASTIC" & initiate development of carcinoma What is stomach CANCER aka (GASTRIC CANCER)! - arises from inner layer (,,epithelium") of the stomach Cancers arising from stromal elements (ex GIST or from MALT are completely different entities, and not included in the term ,,gastric cancer") 1) what is origin/cause of this condition? - increasing the risk for cancer is due to genetic factors, carcinogenic factors in diet (ex benzopyrene found in smokers and preserved food), autoimmune gastritis & gastric adenomas or polyps. Chronic infections with H.pylori appears to serve as a cofactor in some type of gastric carcinomas 2) How does it develop? - 50-60% of gastric cancers will occur in ,,pyloric region, or adjacent to antrum". Compared with benign ulcer which has smooth margins & is concentrically shaped, gastric cancer tend to be larger, are irregular in shape and have irregular margins 3) what are the symptoms/signs? / why do we get this symptoms/signs? - usually they are asymptomatic until later in their course. When they do occur they include indigestion, anorexia, weight loss, vague epigastric pain, vomiting and abdominal mass 4) how is the prognosis - depending on location and extent of the lesion, surgery in form of radical subtotal gastrectomy usually is the treatment of choice. Irradiation and chemothp is usually for palliative purposes or to control MTS Note : - MTS of gastric Ca is found in supraclavicular sentinel node firstly, then in periumbilical region called ,,sister mary joseph nodule" - visceral Tu´s can also MTS to 1 or both ovaries it is called Krikenberg Tumor** Krukenberg Tu : MTS from stomach to ovaries (can be bilateral)

Q31) Esophageal disorders - achalasia, diffuse esophageal spasms, esophagitis, Tumor

What is the normal condition and function to esophagus? - it is a fibromuscular tube through which food passes, aided by peristaltic contractions, from pharynx -> stomach ACHALASIA - disorder where you have failure in ,,smooth muscle fibres" and ,,lower esophageal sphincter" (LES) causing (aperistalsis, partial or incomplete relaxation ability of LES, and also with incr resting tone of LEG. It can happen at various points along the GIT, in rectum, (eg. Hirschsprung´s disease) How does it develop & why does it develop? - it is usually idiopathic (unknown etiology). Thus, it seems there is an autoimmune context to achalasia, most likely caused by viral triggers. Other studies suggest hereditary, neurodegenerative, genetic and infective contributions! - Chagas disease may result in ,,secondary achalasia"* due to infection with ,,Trypanosoma cruzi" which cause destruction of myenteric plexus in the whole GIT, except stomach! What is the mechanism in onset/developing this condition / how does this influence the body? - LES pressure and relaxation are regulated by excitatory (ex. Acetylcholine, substance P) and inhibitory (ex. Nitrix oxide (NO), vasoactive intestinal peptide (VIP) neurotransmitters. But when you have this condition you will lack nonadrenergic, nocholinergic and inhibitory ganglion cells causing an imbalance in excitatory and inhibitory neurotransmission. The result is a hypertensive nonrelaxed esophageal sphincter. What are the symptoms/signs , why do we get them? Clinical features manifested in young adults, with symptoms like progressive dysphagia (difficulty swallowing), nocturnal regurgitation (insufficiency) and aspiration (food & liquid, incl saliva, are retained in the esophagus and may be inhaled into the lungs). Also have regurgitation, and sometimes chest pain behind the sternum also known as cardiospasm and non-cardiac chest pain can often be mistaken for a heart attack. Some people may also experience coughing when lying in a horizontal position!!! What are the consequences -> may develop into SqCC* What is Esophageal spasms -> uncoordinated contractions of esophagus. It is though to result from motility disorders of esophagus. - these spasms do not proper food effectively to the stomach! What is origin/cause of this condition? ,,not well understood", thought that it is causd by uncontrolled (brain signals) running to nerve endings. Therefore, suppression medication is often first line therapy such as ,,anti-depressants" & ,,ati-epileptic medications" are prescribed Note : it has also been reported that very cold or hot beverages can trigger this esophageal spasms!!! What are the symptoms/sigs & why do we get them? - DYSPHAGIA*, regurgitation and chest pain What is esophagitis (infl of mucosa of Esophagus) - what is origin/cause of this condition? Reflux esophagitis (gastro-esophageal reflux disease GERD) = means reflux/regurgitation of gatric content into lower/distal esophagus, this is caused by decreased efficacy of esophageal antireflux mechanisms especially the LES tone, sliding Hiatal hernia, sloer esophageal clearance of refluxed material, delayed gastric emptying and incr gastric volume or by reduction in reparative capacity of esophageal mucosa!!! What is Barret´s Esophagus => metaplasia of distal squamous mucosa towards Columnar epithelium, due to reponse to long-standing (GERD)! Short overviews (Infectious & chemical esophagitis) ; - they can arise due to ,,ingestion of mucosal irritants (e.g alcohol, corrosive acids or alkalis + heavy smoking), infection following bacteriemia or viremia, fungal infection as well as in immunosuppressed patients? - infectious & chemical esophagitis ; all the different causative agents have different ,,morphological picture", but with same common features such as severe acute inflammation, superficial necrosis & ulceration with formation of granulation tissue - how does it develop? And reason why it does!!! Barrett Oesophagus ; - can be divided into : long segment (>3cm above GE junction) & short segment (<3cm above junction). Note : it is said that there is alteration in differentiation program of ,,stem cells" found here in the mucosa. The lesions are red mucosa that is found in patches or as broad irregulat circumferential band What are symptoms/signs? And why do we get them? - GERD : dysphagia, heartburn + sometimes regurgitation (insufficiency) of hematemesis or melena (dark, tarry-stool). The degree of symptoms is usually not proportional with histological changes due to short duration of the regurgitation Note : regarding Barret´s oesophagus there is long history of ,,heratburn", with massive and more prolonged attacks of reflux - How is prognosis? GERD : main risk factors is bleeding, ulcerations, development of stricutres and progression to Barret esophagus and into Adeno-Ca! Barrett Esophagus : there is increased incidence of ulceration w/bleeding & strctures, it is main risk factor that may develop into esophageal Adenocarcinoma**** Tumors of Esophagus - name some types, but important to go into more details with only most common types!!! Most common benign - Leiomyomas, other benign are ,,fibrovascular polyps & Sq papillomas" -> leiomyomas are made up from combination of (fibrous, vascular or adipose tissue covered with ,,intact mucosa") Most common malignant = SqCC & Adenocarcinoma What is origin/cause of this condition? A) Squamous cell carcinoma - it may be due to ,,Achalasia", due to dietary & environmental factors (f.x alcohol & Tobacco), genetic alterations (such as : mutated p53 (suppressor gene) & amplification of cyclin D1, c-MYC & epith growth factor receptor) & chronic esophagitis, but they may also start as ,,in situ" (precancer) lesions. B) Adenocarcinoma (due to Barret´s esophagus, distal p) How does it develop and why? SqCC - when there is accumulation of mutations & other genetic alteration the development of Tu is higher. In chronic esophagitis the result is ,,incr epith turnover with exposure to carcinogenic environment" that will lead to dysplasia of the epithelium. - Occurence of this neoplasm is 20% in upper (1/3), 50% in middle & 30% in lower esophagus Note : early lesions is a small ,,plaque-like elevation", later into protruded growth, polypoid exophytic lesion, flat growth or excavated/ulcerated growth which appears as a necrotic cancerous ulceration. Adenocarcinoma - epithelial cells of Barrett esophagus have a higher proliferative rate and thereforea higher risk to progress into dysplasia, when dysplasia develops there are found amplifications of (c-ERB-B2 & translocation of the beta-catenin)*** - In this Tu you also have over-expression of p53 together with other genetic alterations what are symptoms/signs + why we get them!!! - DYSPEPSIA* is common due to progressively larger obstruction. Patient changes therefore their diet into more liquid food - note : you may alos develop extreme ,,weight loss" due to the obstruction and to the Tu itself How is the prognosis for Esophageal Tu´s? - it is quite POOR, because most patients present with advanced disease. By the time the first symptoms such as dysphagia starts manifesting themselves, the cancer has already well progressed. - overall 5-year survival rate : around 15%m with most people dying within first year of prognosis! - Note : individualized prognosis depends largely on stage of the tumor. Restricted entirely to esophageal mucosa = 80% 5YSR, submucosa = <50%, muscularis propria = 20% 5YSR, extension to structures adjacent to esophagus = 7% 5YSR - Patients with distant MTS and not candidates for curative surgery have <3% 5YSR*

Q38 ) Hepatitis and cirrhosis

What is the normal function of the liver? - metabolism of carbohydrates (glycogen storage, glycogenolysis, glucogenesis, glucose uptake, lactic acid up-take, metabolizing of ther sugar molecules, pentose-cycle - NADPH, regulation of blood glucose), fat (production of TAG and VLDL, cholesterol synthesis, FFA synthesis and degradation, ketogenesis), proteins (degradation of AA, production of urea, synthesis of plasmatic proteins), steroids (synthesis of bile acids from cholesterol, their conjugation and elimination into the bile, their action is detergent, bile acid have enterohepatal circulation), hormones (effect on hepatic function, or degradation, insulin, glucagon, GH, glucocorticoids, catecholamine, thyroxin, other steroid hormones), vitamins (A,D,B12), purines (uric acid) & of water and minerals(iron) Other functions are ,,hemopoiesis" - restricted to in utero-fetal development, in pathological situations extramedullary hemopoiesis could be activated by hematological malignant tumors affecting bone medulla, detoxification (endogenous and exogenous substances) by biotransformation involving several phases such as inactivation of the former active molecule by chemical reactions, conugation with glycin, taurin, glucuronic acid - conversion into soluble molecules and final elimination by urine or bile excretion, last function is due to Thermoregulation* IMP - What is Hepatitis* - this is inflammation of the liver and characterized by presence of inflammatory cells in the tissue of the organ. The condition can be self-limiting (healing on its own) or can progress to fibrosis (scarring) and cirrhosis A) what is origin/cause of this condition? - viral hepatitis is the most common cause they are (HAV,HBV,HCV,HDV) - which requires hepatitis B to cause disease! And HEV. Other causes are non-viral hepatitis (e.g toxic and drug induced, alcoholic, autoimmune, fatty liver, and metabolic disorders). - less common are bacterial, parasitic, fungal, mycobacterial and protozoal infections. Additionally, certain complications of pregnacy and decreased BF to the liver can induce hepatitis. Cholestasis (obstruction of bile flow) due to hepatocellular dysfunction, biliary tract obstruction, or biliary atresia can result in liver damage and hepatitis! B) what is mechanism in onset/developing this condition?/how does this influence the body? - the specific mechanism varies and depends on the underlying cause for this condition. In viral hepatitis, the presence of virus in the liver cells causes the IS to attack the liver, resulting in inflammation and impaired function. In autoimmune hepatitis, the IS attacks the liver due to autoimmune disease. Some hepatitis, often including hepatitis caused by alcoholism, fat deposits accumulate in the liver, resulting in fatty liver disease! C) what are the symptoms/signs - why do we get them? - in acute the initial features are of nonspecific flu-like symptoms, common to almost all acute viral infections and may include malaise, muscle and joint aches, fever, nausea or vomiting, diarrhea and headache. More specific symptoms are profound loss of appetite, dark urine, yellowing of eyes and skin and abdominal discomfort - physical findings are usually minimal, apart from jaundice, tender enlargement of the liver, enlarged LNs in 5% and enlargement of the spleen! Chronic hepatitis may cause nonspecific symptoms such as ; malaise, tiredness and weakness, often no symptoms at all. Commonly identified on blood tests! The presence of jaundice indicates advanced liver damage. On physical examination there may be enlargement of the liver Acne, abnormal menstruation, lung scarring, inflammation of the thyroid gland and kidneys may be present in women with autoimmune hepatitis! D) how is the prognosis? - the outcome of hepatitis depends heavily on the disease or condition that is causing the symptoms. For some causes, such as subclinical hepatitis A ifnection, the person may not experience any symptoms and will recover without any long term effects. Other can result in irreparable damage to the liver can result in formation of scar tissue called ,,fibrosis" and can result in nodules that block the liver from functioning properly this condition is called cirrhosis and is not reversible. Cirrhosis may indicate a liver transplant is necessary* - another complic of chr hepatitis is liver cancer, specifically hepatocellular carcinoma (>50 women) E) what are the consequences? - a small proportion of people with acute hepatitis progress to acute liver failure, in which the liver is unable to remove harmful substances from the blood (leading to confusion and coma due to hepatic encephalopathy) and produce blood proteins (leading to peripheral edema and bleeding) What is cirrhosis - it is a result of advanced liver disease. Characterized by replacement of liver tissue by fibrosis (scar tissue) and regenerative nodules (lumps occurring due to attempted repair of damaged tissue). Changes leads to liver function loss. A) what is origin/cause of this condition - most commonly caused by alcoholism, HBV,HCV and fatty liver disease. Some cases are unknown (idiopathic) B) waht is the mechanism in onset/developing this condition?/how does this influence the body? - pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma. This scar tissue blocks the portal flow of blood through the organ therefore disturbing normal function. - Recent research shows the stellate cell, that normally stores vitamin A, has an influence in the development of cirrhosis. Damage of the hepatic parenchyma (due to inflammation) leads to activation of the stellate cell, which increases fibrosis (called myofibroblast) and obstructs blood flow in the circulation. In addition, it secreted TGF-beta1, which leads to a fibrotic response and proliferation of CT. Furthermore, it secretes TIMP 1 & 2, naturally occurring inhibitors of matrix metalloproteinases, which prevents them from breaking down fibrotic material in the extracellular matrix. The fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased BF throughout. Portal hypertension is responsible for most severe complications of cirrhosis*** In addition the spleen gets affected and becomes congested, which leads to hypersplenism and increased sequestration of plateletes C) What are the symptoms/signs and why we get them? Cirrhosis has many possible manifestations. These signs and symptoms may be either as a direct result of the failure of liver cells or secondary to the resultant portal hypertension! - in extensive damage to and scarring of liver leads to weight loss, easy bruising and bleeding, peripheral edema (swelling of legs) and accumulation of ascites (fluid in abdomen) The following features area as a direct consequences of liver cells not functioning (as they should properly)!!! - spinder angiomata (spider nevi) = central arteriole surrounded by many smaller vessels occurs due to an increase in estradiol! - palmar erythema = is reddening of palms at the thenar and hypothenar eminences also as a result of increased estrogen - gynecomastia, is caused by increased estradiol - hypogonadism, manifests as impotence, infertility, loss of sexual drive, and testicular atrophy (decr. In size), can result from primary gonadal injury or suppression of hypothalamic/pituitary function. Hypogonadism is associated with cirrhosis due to alcoholism and hemochromatosis! - liver size can be enlarged, normal, or shrunken in patients with cirrhosis! - ascites, accumulation of fluid in peritoneal cavity, gives rise to flank dullness (1500 ml to detect flank) - fetor hepaticus - is a musty breath odor resulting from increased ,,dimethyl sulfide" - jaundice - is yellow discoloration of the skin and mucus membranes due to increased bilirubin (at least 2-3 mg/dL or 30 mmol/L). Urine may also appear black in colour! Note** Liver cirrhosis increases resitance to blood flow and higher pressure in the portal venous system, resulting in portal hypertension. Effects of portal hypertension inlcudes following ; - splenomegaly, esophageal varices (from collateral portal blood flow through vessels in the stomach and esophagus, a process called portacaval anastomosis), Caput medusae (dilated periumbilica collateral veins) - is when blood goes from portal venous system and gets shunted through the periumbilical veins and ultimately to the abdominal wall veins & Cruveilhier-Baumgarten murmur that is a venous hum heard in the epigastric region due to collateral conenctions forming between portal system and the periumbilical veins as a result of portal hypertension! How is the PROGNOSIS? - Ascites (fluid retention in the abdominal cavity) is the most common complication of cirrhosis. It is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices and hepatorenal syndrome (kidney dysfunction), - cirrhosis is irreversible, and treatment usually focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a LIVER TRANSPLANTATION!!!!

Q26) White blood cell disorders - acute and chronic lymphocytic leukaemias

Acute lymphocytic leukemia (ALL) - in children with abnormal proliferation of lymphoblasts in BM and extramedullary organs (LNs and spleen) signs and symptoms : similar to (AML), related to suppression of normal BM elements -> anemia, bleeding, infections, enlarged LNs, hepatosplenomegaly, CNS : headaches, vomiting, seizures, visual disturbance! Findings : increased WBCs count and lymphocytosis, decr platelets, decr RBC count, HYPERcellular BM with infiltrating lymphoblasts! Subclassified according to T or B cell - arupt onset, rapidly progress to DEATH!!!! Chronic lymphocytic leukaemia (CLL) - in elderly, with proliferation of abnormally mature lymphocytes in BM, peripheral blood and extramedullary sites - Normally B cell —> insufficient Ig synthesis + depressed antibody response Symptoms : lymphadenopathy, splenomegaly, later hepatomegaly, hypermetabolic state : massive organ enlargement -> pressure on stomach -> discomfort, irregular bowel infections! (ALL) - a group of neoplasms that are composed of immature precursor B or T cells. 85% of the ALLs are of pre-B cell origin, and are typically manifested in the childhood. These leukemias have extensive BM and variable peripheral blood involvement. The pre-T-cell ALL tend to be present as lymphoma in adolescent male with thymic involvement (,,lymphomas"). The pre-T-cell and pre-B-cell ALLs have both (MORPHOL & CLINICAL similarities)!!! It is important to distinguish ALL from acute myelogenous leukaemias (AML), since these 2 types have identical signs and symptoms. The lymphoblast found in ALL has condensed chromatin, inconspicuous nucleoli and scant agranular cytoplasm. These features are not found on the myeloblast (Auer rods). The definitive diagnosis of ALL is made by the detection of B and T lymphocyte -specific markers with antibodies. In 95% of the lymphoblasts found in ALL are immunostained for terminal deoxynucleotidyltransferase (TdT) positive! The differentiation of pre-B between pre-T ALLs is done with further staining of lineage-specific markers! Although the immunophenotypical and genotypical features of ALL and AML are different, are the clinical features are the same for these 2 leukaemias. In both forms will there be an accumulation of neoplastic blast cells (lymphoblast vs myeloblast) in the BM that will suppress normal hematopoiesis, resulting in anemia, neutropenia and thrombocytopenia. Other clinical features can be summarized in the following points : abrupt stormy onset, symptoms related to depression of normal BM function, bone pain and tenderness due to marrow expansion, generalized lymphadenopathy, splenomegaly and hepatomegaly. Note : all of these are more common in ALL*, and CNS manifestations due to meningeal spread! Prognosis for this neoplasm is GOOD : with aggressive chemotx more than 90% cases have complete remission, but several factors are associated with worsening prognosis: 1) age <2 years, 2) presentation in adolescence of adulthood, 3) peripheral blood blast counts higher than 100.000, and 4) the presence of ph chromosome Chronic lymphocytic leukaemias (CLL) - there are found 2 forms of chronic lymphocytic leukaemias, which are called chronic lymphoytic leukaemias (CLL) and small lymphocytic lymphoma (SLL). These 2 diseases are similar in Morphology, phenotype and genotype! - only features that differs from these 2 are degree of ,,peripheral blood lymphocytosis" CLL is the most common form of ADULT leukaemia in Western worlds, while SLL makes only up 4% of NHLs! Peripheral blood in CLL is made up of an increased number of small, round lymphocytes with scant cytoplasm. These cells are fragile and disrupt easily in blood smears, forming so called smudge cells. There is observed bone marrow involvement in all cases of CLL, and in most cases of SLL. In SLL is there also seen infiltrations of the red and white pulp, and the hepatic portal tract! Clinical feature of CLL/SLL -> usually ASYMPTOMATIC, but when symptoms appear they are nonspecific and include easy fatigability, weight loss and anorexia. In 50-60% cases there are (generalized lymphadenopathy & hepatosplenomegaly) - patients are usually >50years, with median age at 60 - total leukocyte count is variable : in patients with SLL and marrow involvement leukopenia can be found, while in patients with CLL and heavy Tu burdens the leukocyte count can be as high as 200.000/mm3 Note : Both CLL and SLL disrupt normal immune function through unknown mechanisms. It is common with hypogammaglobulinemia, which leads to increased risk of infections. In other patients, about 10-15% will there develop autoantibodies against RBCs or platelets, leading to autoimmune hemolytic anemia or thrombocytopenia!!!

Q14) Pathophysiology of Carbohydrate metabolism

Diabetes mellitus is defined as a group of metabolic diseases with the common feature hyperglycemia, which results fro mdefects in insulin secretion, insulin action, or both. The classification that is used now is based on the pathogenesis of each of the different variants (ex. Type 1 DM is characterized with absolute deficiency of insulin that is caused by destruction of pancreatic beta-cells) Type 2 DM, is caused by a combination of peripheral insulin resistance and inadequate secretory response of the pnacreatic beta-cells - however, the long-term complications are the same for both of the types. Type 1 diabetes (destruction of beta-cells and absoulte insulin deficiency). Immune mediated or idiopathic (unknown) Type 2 diabetes (insulin resistance with relative insulin deficiency) Genetic defects of cell function : maturity onset diabets of the young (MODY), caused by mutations in different genes (MODY1-6). Mitochondrial DNA mutations Genetic defects in insulin processing or insulin action, genetic syndromes associated with diabetes Exocrine pancreatic defects, endocrinopathies, infections, drugs Gestational diabetes! Pathogenesis of type 1 DM - is based on cell destruction, which is immunologically mediated. This cell destruction is primarily caused by T-cells that react against not known beta-cell antigens. The clinical manifestations of diabetes do not occur until 90% of the beta-cells have been destroyed - T-cells react against beta-cell antigens and cause beta-cell damage. Involved in this destruction are CD4+ T cells (helper cells), which cause tissue injury and activate macrophages, and CD8+ T cells (suppressor cells), which directly kill beta-cells and secrete cytokines that activate macrophages - cytokines produced is also responsible for damage of beta-cells. The cytokines that are involved are IFN-gamma that is produced by T-cells, and TNF and IL-1, produced by macrophages - autoantibodies are also found in the blood of 70-80% of the patients with diabetes. These autoantibodies react with beta-cell antigens, including the above mentioned Glutamic acid decarboxylase (GAD) Pathogenesis of Type 2 DM - - involves ,,environmental factors" ; such as sedentary life style and dietary habits, the environmental factors have been shown to trigger autoimmune reactions that destruction the beta-cells. Also genetic factors play a large role in this kind of diabetes. Type 2 DM is characterized by the decreased ability of peripheral tissues to respond to insulin (insulin resistance), and beta-cell dysfunction manifested as inadequate insulin secretion. Symtoms of type 1 DM* - appear abruptly when (80-90%) of beta cells have been destroyed. The onset of the disease is in childhood/puberty. The usual symptoms are ,,polyuria, polydypsia, polyphagia, fatigue, weight loss and weakness". The disease is determined by glucose tolerance test. In this test the patient is 75g glucose orally after 8 hours of fasting. The blood glucose is then tested every 30 min for 3 hours. In diabetic persons is the initial fasting blood glucose (126 mg/dl (normal <110 mg/dl)), and will then rise to greater than 200 mg/dl after the ingestion of glucose (normal <140 mg/dl). The amount of glucose will be higher than tubular reabsorption and glucose will appear in urine! In untreated DM1 will it be elevated levels of blood glucose and ketones. The hyperglycemia is due to ,,decreased uptake of glucose" by peripheral tissues because of inhibited insulin-dependent GLUT transporters. There will also be increased hepatic gluconeogenesis and production of glucose. The ketosis results from increased mobilization of fatty acids from adipose tissue with resulting production of ketone bodies in the liver. Increased amount of ketone bodies can result in (DIABETIC KETOACIDOSIS)*. Since there are so many fatty acids that are transported to the liver not all will be converted to ketone bodies. The excess fatty acids is converted to TAGs and packed in VLDL particles. The enzyme that is responsible for the degradation of these particles, lipoprotein lipase, has decreased activity when insulin is not present! Type 2 DM develops gradually without obvious symptoms . Polyphagia and polyuria MAY occur. This type has milder metabolic alterations compared to DM1 since there is some insulin secretion that restrain ketogenesis. Diagnosis is based on the presence of hyperglycemia (blood glucose > 126 mg/dl). DM2 is characterized in that the target tissues (liver, adipose tissue and musce) are not able to respond properly to normal circulating levels of insulin. The most common cause of this type is obesity, but obesity alone will not lead to DM2. - The beta cells do also have to be impaired with (decreased insulin secretion). In OBESE patient that are only insulin resistant the level of circulating insulin will only. Increase to compensate for insulin resistance. Insulin resistance (increased with weight gain & decrease with weight loss), which implies that fat accumulation is important for development of insulin resistance!!!

Q18) Anemias caused by increased red blood cell loss - mechanisms involved in occurring this kinds of anemias (bleeding, destruction), main kinds of anemias caused by increased red blood cell loss!

If there is ,,deficiency of RBCs", amount of hemoglobin, or hematocrit in the blood it is called ANEMIA!, this results in a decreased oxygen-carrying capacity of the blood. - more correctly is anemia defined as a ,,reduction below normal limits of total circulating red cell mass". In practice anemia is defined as ,,reduction below normal in the volume of packed red cells; measured by hematocrit, or reduction in total blood haemoglobin concentration". There are different classifications of anemia. One is based on the underlying mechanisms : blood loss, haemolytic (increased rate of destruction) and impaired red cell production. Another way to classify anemias is on the basis of the changes in morphology of the RBCs. The most used ,,morphological parameters" are : - mean cell volume : average volume of RBCs - mean cell haemoglobin : average content of haemoglobin/RBCs - mean cell haemoglobin concentration : average concentration of hemoglobin in a given amount of packed RBCs - red cell distribution width : coefficient of variation of RBC volume Whatever the cause, the clinical picture of patient suffering from anemia is the same ; - pale, weakness, malaise and easy fatigability is common symptoms. Dyspnea on mild exertion, and nails that become brittle, loose their usual convexity and assume a concave spoon shape is also seen (clubbing). The anoxia can cause fatty changes in the liver, myocardium and kidney. If the myocardial hypoxia is severe or it is accompanied by pre-existing coronary disease, angina pectoris is manifested. CNS hypoxia can lead to headache, dimness of vision and faintness! What is anemia? - reduction below the normal level in the number of erythrocytes (M: 4.3-5.3 x 10*12/l, F : 3.8-4.8 x 10*12/l), the quantity of hemoglobin (M : 13.5-16.5 g/dl, F: 12.1-15.1 g/dl), lower in children and pregnant women), and VOLUME of packed RBCs (hematocrit ; around 45)! What is the origin/cause of this condition that leads to RBC loss? - bleeding or by hemolysis How does it develop?/why do it develop? - bleeding due to peptic ulcer (upper GI bleeding, polyps in the colon, malignancy and hemorrhoids or by hemolysis because of the defect of rBC itself or changed environment. Condition in which RBC itself is defective is due to hemoglobinopathies (ex. Sickle cell disease), impaired globin synthesis (ex. Thalassemia), RBC membrane defects (ex. Hereditary spherocytosis) and by enzyme deficiencies! Post-hemorrhagic anemias (anemias due to blood loss) - normocytic since the sudden blood loss is in individuals with normal IRON stores!!! Clinical and morphological reactions to acute blood loss ,,depends on rate of haemorrhage and whether the bleeding is internal or external", The immediate effect is mainly due to loss of intravascular volume, which can ead to cardiovascular collapse, shock and death. After this reaction, and if the patient survives, there is a shift of water from the interstitial fluid compartment to the intravascular compartment. This is a process is called ,,hemodilution" and result in a decrease in hematocrit, which subsequentally will lower the oxygenation of the renal juxtaglomerular cells that trigger increased production of erythropoietin. If the bleeding is externally there can be LOSS of iron, with subsequent hampering of the haematopoiesis of RBCs. The early peripheral blood picture is leukocytosis due to mobilization of granulocytes from marginating pools, and the RBCs look normal in size and shape. After the marrow production of red cells increases there is an increase in reticulocyte (early RBC formation) count! nOTE : anemia found in patients with chronic blood loss appears only when the loss exceeds the regenerative capacity of the marrow or when the iron stores are depleted!! Hemolytic anemia : premature RBC gets destructed. - there are 3 common features for different forms of hemolytic anemias : 1. Shortened red cell life span, so increasing the erythropoiesis will not make the condition better since the production cannot keep up with the destruction. May be due to acquired (extrinsic noxas) or hereditary (intrinsic noxas) causes : 2. Elevated erythropoietin levels, with subsequent elevated erythropoiesi s 3. Accumulation of the products of haemoglobin catabolism! Hemolysis of RBCs can be divided into ,,intravascular and extravascular" : - extravascular hemolysis occurs in the mononuclear phagocyte system, while the intravascular occur within the vascular compartment. The extravascular hemolysis is more common compared with intravascular! What is the mechanism in onset/developing this condition?/how does this influence the body? Posthemorrhagic anemia : develops by a hemorrhage that causes the need of replacement of lost plasma and RBC. To do so the blood volume gets replaced first by water and electrolytes from the tissue and from blood from the blood stores!. Then you get an acceleration in the hematopoiesis causing new RBC to be produced by BM (restoration of erythrocytes take : 4-6 week, hemoglobin : 6-8 weeks)! Hemolytic anemia : there are many ways on causing this types of anemia, but you have 3 autoimmune hemolytic anemias where it may be mediated by IgG Ab (warm Ab disease where you get intravascular destruction of Ery), bu different IgM specific for Er antigens (cold Ab disease, you get hemolysis if the Ab do not dissociate from the Er when it get reheated) or by drug induced anemia (different connection to the Er surface leading to complement cascade and hemolysis). Other mechanism that lead to this may be physical destruction of Er by ex trauma, thermal hemolysis induced by radiation, structural defect of Er leading to increased fragility of Er, or caused by defective hemoglobin structure and function - read about this comp (page 50-55) What are the symptoms/signs?/why do we get this symptoms/signs? - Symptoms common to many types of anemia include the following : easy fatigue and loss of energy, unusually rapid heart beat, particularly with exercise, shortness of breath and headache, particularly with exercise, difficulty concentrating, Dizziness, pale skin, leg cramps, insomnia What are the main kinds of anemias caused by increased RBC loss? - mainly Posthemorrhagic anemia & hemolytic anemia, but you have also Sickle cell anemia, iron-deficiency anemia (due to blood loss from menstruation and the increased blood supply demands during pregnancy)!!!

Q24) White blood cell disorders - leukocytosis, leukopenia, agranulocytosis

Normal values of white blood cells : 4,500-10.000 white blood cells/mcL Leukocytosis : increased leukocytes, physiologic response to protect body from invading microorganisms - Neutrophilia : increased demand for neutrophils in infection -> more immature neutrophils released - as infection subsides : decreased neutrophils, increased monocytes - further : lymphocytosis + eosinophilia! !! Neutrophilia also occurs after stress. - Eosinophilia : occurs with skin disorders (mycosis fungoides and eczema), with allergy states (asthma, hey fever), drug reactions and due to parasitic infections - monocytosis : in recovery phase of infections and in TBC and sarcoidosis (chronic granulomatous diseases) - lymphocytosis : by viral and antigenic stimuli, infectious mononucleosis, infectious hepatitis, toxoplasmosis, measles, mumps, some allergic reactions (serum sickness), drug sensitivity, malignant lymphoma ! In addition these patients will also have : (Hepatosplenomegaly + lymphadenomegaly)** Leukopenia : decreased nr. Leukocytes Neutropenia : decreased Neu, incr risk for infections Causes : hypoplastic or aplastic anemia (from cytotoxic drugs, viral infection), starvation, replacement of BM by malignant cells (leukemia) Lead to : ineffective and defective Neu production Agranulocytosis : extremely decr leukocyte count and absence of neutrophils!! Cause : drug that interfere with cell formation or enhances cell destruction (capable : antihistamines, antibiotics, analgetics) Symptoms : infections, general malaise (discomfort, lassitude, headache, muscle aches), ulcerations of mucus membranes, fever, tachycardia Untreated : sepsis & death!

Q15) Pathogenesis of DM

See Q14 (what is DM) What is pathogenesis of main complication of DM (development explanation) Complications of DM can be divided into ,,acute and chronic complications" - note : acute are primarily metabolic!!!! Acute complications : 1) Hypoglycemia : this is blood glucose < 2,1 mmol/l. The symptoms are caused by both epinephrine release (sweating, shakiness, headache, palpitations) ; and by lack of glucose in the brain (bizarre behavior, dullness and coma). It results from both exogenous and endogenous causes: - exogenous causes ; overdose of insulin, increased exercise, overdose of oral hypoglycemic agents, alcohol - endogenous causes : Insulinoma, extrapancreatic neoplasm, inborn error in metabolism 2) Diabetic ketoacidosis : this is the most serious complication of DM. It occurs due to ,,severe insulin insufficiency", which trigger a complex metabolic reaction involving : - decreased glucose utilization -> hyperglycemia and glycosuria - acceleration of gluconeogenesis -> hyperglycemia - decreased lipogenesis and increased lipolysis -> increased oxidation of free fatty acids -> production of ketone bodies -> hyperketonemia -> metabolic acidosis 3) Hyperosmolar hyperglycemic nonketotic coma : - this occurs when insulin is present to some degree to inhibit fat breakdown, resulting in lack in ketosis. But the effectivity is less than needed for glucose transport, which result in hyperglycemia with glucosuria and polyuria. This is accompanied by body fluids depletion and intracellular dehydration -> neurologic disturbances! Chronic complications : 1) Neuropathies : pathogenesis of this is divided into (vascular, metabolic damages, and non-enzymatic glycozylation of proteins). The vascular damage is due to microvascular damage of ,,vasa nervorum". The metabolic damage is due to insufficienty energy sources to maintian normal resting membrane potential 2) Microvascular disease : this is lesion in capillaries and arterioles. The damage is characterized by thickening of the basement membrane, and increased accumulation of glycoproteins in the wall. - Retinopathy : this is due to retinal ischemia and is due to increased retinal capillary permeability with formation of microaneurysms. There will also be narrowing of small arteries and neovascularization with fibrous tissue formation. This will finally result in BLINDNESS!! - Nephropathy : this is due to glomerular changes. There is thickening of the glomerular basement membrane (GBM)! 3) Macrovascular disease : this is primarily due to atherosclerosis of larger arteries (coronary, brain and peripheral). The disturbances that are seen are accumulation of ,,sorbitol, hyperlipoproteinemia and lod coagulation" - Coronary artery disease - stroke - peripheral vascular disease

Q10) Fluid and electrolyte balance disturbances - disturbances of body fluid volume

See questions 9!

Q28) Abnormalities of hemostasis and coagulation - changes of hemostasis and coagulation caused by vascular defect :

Vascular defects : Symptoms : cutaneous hemorrhages often involving mucous membranes Hemorrhages : Non-allergic purpura : no true allergy present, but vasculitis develop (inflammation of vessels), most common in systemic lupus erythematosus, (collagen-vascular disease where patient develop autoantibodies). The vasculitis destroys the integration of vessels -> purpura Senile purpura : occur with ageing, deteriorating of vascular supportive tissue, cutaneous hemorrhages on dorsum of hands and forearms, aggravated by trauma and non threatening condition long term corticosteroid therapy : similar cutaneous manifestation, resulting from protein catabolism in vascular supportive tissue! Scurvy : related to malnutrition and alcoholism, affect integrity of CT of vascular wall Inherited : Osler-Weber-Rendu disease and Ehlers-Danlos syndrome! Allergic purpura : result from immunologic damage to vessels petechial hemorrhages on dependent portions of the body (buttocks)! - Henoch-Schönlein purpura : affects children Symptoms : purpura and mucosal bleeding, GI symptoms, arthritis Preceded by infectious state -> inflammation of vascular tree, capillary level -> vascular disruption -> loss of RBC -> bleeding! Complication : glomerulonephritis! Bleeding disorders or hemorrhagic diatheses is caused by abnormalities in the vessels, platelets, coagulation or a combination of these! Vessels wall abnormalities : these kinds of disorders are sometimes called ,,non-thrombocytopenic purpuras" and are relatively COMMON. They cause small haemorrhages (petechiae and purpura) in the skin and mucous membranes that are usually not serious. We can divide the etiologic factors into the following! Infections : this is probably due to microbial damage to the microvasculature or disseminated intravascular coagulation (DIC). The most serious is meningococcemia and other forms of septicaemia! Drug reactions : drugs may sometimes induce petechiae or purpura. The vascular injury is mediated by drug-induced antibodies and deposition of immune complexes in the vessel walls, including hypersensitivity Scurvy and Ehlers-Danlos syndrome : these disorders are associated with impaired formation of collagen needed for support of vessel walls Henoch-Schönlein purpura : this is a systemic hypersensitivity disease that is characterized by (purpuric rash, which results from circulating immune complexes within vessels) Hereditary hemorrhagic telangiectasia : this is hereditary disorder characterized by (dilated, tortuous blood vessels within thin walls. These vessels are more susceptibility to bleeding)! Amyloid infiltration of blood vessels : this leads to weakening of blood vessel wall!

Q2. General concept of health and disease!

What are the main kinds of pathogenic noxas? Physical noxas : temperature extremes, changes in atmospheric pressure, radiation, illumination, mechanical factors , noise and prolonged vibration. (Ex. Crush syndrome, blast syndrome, decompression sickness) Chemical injuries : causing increased permeability, free radicals, destruction of endoplasmic reticulum, cellular swelling, mitochondrial swelling (accumulation of Ca2+), decreased cellular pH, lysosomal membrane injury Biological injury : disease producing potential of microorganism depends on ability to invade and destroy cells, produce toxins, produce damaging hypersensitivity reactions (ex. Pathogenecity (virulence) have the ability to survive and proliferate in human body))! Psychological and ergonomic : psychological stress, enormous strain (physical and/or psychological) Immunologic and inflammatory injury : cellular membranes are injured by direct direct contact with cellular and chemical component of immune and inflammatory responses (ex phagocytic cells (lymphocytes&macrophages) and ex histamine, Ab, proteases and complements which are the ones responsible for many membrane alterations occurring during in this types of injuries! Genetic factor injuries : factors that alter the cells nucleus, plasma membrane structure, shape, receptors or transport mechanism Nutritional imbalance injuries : without essential nutrients such as proteins, carcs, lipids, vitamin and minerals the body will not function normally. May therefore cause pathological cellular effect in excess or depletion of some of the components Hypoxia : most common cause of (cellular injury). Reduction of ATP, sodium-potassium pump to fail, sodium and water freely enter causing cell to swell. Plasma membrane damage also moved calcium into the cell causing mitochondria to swell leading to rapid cell death! What are the essential forms of pathological reactions to noxas? - pathological reaction that is the most simple reaction, it is usually short and quantitative/qualitative different from physiological reactions (e.g allergic reactions, decreased BP for a short duration) - pathological process that is a complex of pathological reactions, both adaptive and defensive reactions that are induced by noxas (e.g malignant neoplasms, inflammations, fever, edema) - pathological states which are the results of pathological process or accident that have lasted for years or during the whole life (e.g congenital disease, deafness, leg amputation) - general body response : noxas may produce local cell injury but also general body responses such as influencing NS and endocrine system. The nervous system is the co-ordinator, interprets and controls the interactions between the individual and surrounding environment, while the endocrine is to maintain internal homeostasis despite changes in the external environment. CNS and ES are in anatomical connection through hypothalamus, so therefore if the CNS is altered so is usually the ES as well, it helps therefore to maximize the response of the organism to injurious (e.g stressful) stimulies How is the spreading to noxas through organism? - spread of noxas are done through 6 ways : hematogenous lymphatic, nerves, canalicular ways (lungs, kidneys), and per continuitatem (single tissue) and contiguitatem (other tissues) What is the etiology of noxas Noxas = injurious stimuli including chemical agents, lack of sufficient oxygen (hypoxia), infectious agents, physical and mechanical factors, immunological reactions, genetic factors and nutritional imbalances What is pathogenesis of noxas - for example mechanism causing chemical and hypoxic injury can both lead to disruption of selective permeability (transport mechanisms) of the plasma membrane, reduction or cessation of cellular metabolism, lack of protein synthesis, damage to lysosomal membranes, with leakage of destructive enzymes into cytoplasm, enzymatic destruction of cellular organelles, cellular death and phagocytosis of the dead cell by cellular components of the acute inflammatory response

Q9) Fluid and electrolyte balance disturbances

What is body fluid (60% water in men, 50% in women) Intracellular fluid (ICF) : 40% K, HPO4 Extracellular fluid (ECF) : 20% Na, Cl, HCO3 - interstitial fluid (ISF) 15% (between cells) - intravascular fluid (IVF) 3-4% (contain more protein then ISF, maintaining volume of IVF, essential for tissue perfusion) - transcellular fluid 1-2% (CSF, GIT secretions) What is electrolytes? Na, K, Ca, Mg, Cl, HCO3, HPO4, SO4 How does the body regulate body fluids and electrolytes? - regulates through the kidneys, cardiovascular, pituitary gland, parathyroid glands, adrenal glands and lungs. The body water balance is primarily regulated by thirs and antidiuretic hormone (ADH), while the sodium balance is primarily regulated by aldosterone (RAA system). Both affects osmolality and volume of ECF! Water balance and osmotic regulation : - mediated by hypothalamus which contain osmoreceptors (sensitive to osmolality of blood) and thirst center. - increased osmolality -> thirst and ADH release Sodium balance and volume regilation : - Na is principal solute holding water within ECF, control total body fluid volume. ECF volume is proportional with Na. - kidney control sodium excretion -> regulate volume (R-A-A system : Na intake and K secretion) ECF potassium regulation : - K+ control volume of cell, aldosterone is the primary control here. There is here an acid/base balance between H+ ions and K+ ions, since they compete for excretion in exchange for Na reabsorption -> leading to hypokalemia, this is often associated with alkalosis, while hyperkalemia is associated with acidosis! What is disorders of fluid volume? - volume imbalances primary affect ECF, involve relatively equal losses or gains of sodium and water What does it mean with deficit of extracellular fluid? (Hypovolemia) - it is when you have isotonic loss of fluids via renal or extrarenal, hemorrhage or loss through GIT due to prolonged vomiting, diarrhea, fistulas, bleeding. You may also loose volume via third spacing due to burns, peritonitis, obstructed GIT (lost to spaces not exchangeable with ECF), other way on loosing is via heavy exercise in hot environments (sweat), abnormal loss of Na+ and H2O in urine due to ex recovery, diuretic, phase of acute renal failure, chronic renal diseases, uncontrolled DM, or addison´s! What happens here as a response and recover is that you get: - decreased venous return -> decreased CO -> lowers BP -> activation of symp -> peripheral vasoconstriction -> decreased renal perfusion -> activation of RAA system + ADH In severe loss of volume you may develop circulatory collaps and shock. Treatment for this type of condition is saline What does it mean with excess of extracellular fluid (hypervolemia) - it is when you have fluid shifting into interstitial fluid compartment -> leading to edema (swelling). This will always be secondary to an increase in total body sodium content -> water retention. Edema is always an alteration of one of the critical starling forces (starling force = increased capillary hydrostatic pressure, decreased plasma oncotic pressure, increased capillary permeability or lymphatic obstruction) together with/retention of water and sodium. Most common conditions is getting this condition is due to congestive heart failure, liver cirrhosis, nephrotic syndrome. This will lead to decreased effective circulatory volume -> activation of SNS + RAA -> sodium + water retention -> edema. In advanced renal failure + edema you will develop imparement of renal excretory function. In Cushing´s syndrome you will get an increased aldosterone activity, also starvation will in end up with edema due to hypoproteinemia! Edema. Via : increased ISF -> decreased EABV (effective atrial blood volume) -> decreased kidney perfusion -> activation of RAA -> Na+ H2O absorption -> increased intravascular volume! What does it mean with deficit of intracellular fluid? - you will be able to loose ICF by either gaining hypertonic fluid due to ex hypertonic saline that will have the function in increased ECF and the total body osmolarity, another way to lower the ICF is by loosing hypotonic fluid, due to ex. Dehydration, diabetes insipidus (,,the kidney is sweating") or by alcohol since alcohol will inhibit the effect of ADH in the kidney tubules causing nephrogenic diabetes insipidus. Here you will have loss of water leading to that the concentration goes up causing the osmotic pressure to work between the compartments. In ex. Haemorrhage, diarrhea and voiting the drop in ICF will not happen right away since it is isotonic fluid that you loose What does it mean with osmolality imbalances? - imbalance between the concentration in the different compartments! Hyponatremia* <130 mmol/L caused by sodium(Na2+) loss = depletional hyponatremia (ex. Diuretics, salt-losing renal disease) or by water excess = dilutional hyponatremia/water intoxication, causing expansion of ECF. (Ex. Continuous intake of hypotonic fluid saline 0.45%) + renal failure) Mechanism : hypotonic solution -> water shifts from ECF to ICF -> cell swelling Clinical features : neurologic dysfunctions; water enters the brain cells -> leading to incr intracranial pressure Symptoms : lethargy, anorexia, nausea. May progress into convulsions and coma! Hypernatremia* >150 mmol/L, causes water to shift from ICF to ECF -> cell dehydration and shrinkage. You may get this condition by insufficient water intake/excess water loss/excess sodium intake (hypertonic solution, 3% saline) also by hypotonic water losses (ex renal failure, diabetes insipidus affects ADH or renal function, osmotic diuresis, glycosuria in uncontrolled DM) Clinical features : cellular dehydration of specially brain cells -> lethargy, agiation, irritability, hyperflexia, spasticity -> coma, seizures, death. Symptoms : thirst, dry mucus membranes, flushed skin, dry and dred tongue. Oliguria and anuria. Fever! Hypokalemia <3.5 mmol/L, may be lost by the GIT due to vomiting (decreased gastric acid -> metabolic alkalosis (HCO3) -> shift of K+ into renal tubular cells, stimulation of excretion of K+), nasogastric suction, diarrhea or by urinary tract. The low amount of kalium is also due to inadequate intake, treatment of diabetic ketoacidosis with insulin and glucose or due to diuretics, which is the most common cause. The K+ may also shifts due to alkalosis Clinical features : cardiac arrest, muscle weakness, cramps, decreased bowel motility -> paralytic ileus + abdominal distension, cardiac dysrythmias Hyperkalemia >5.5 mmol/L, due to inadequate excretion is the most common reason, or by redistribution of K+ in body (internal bleeding -> release of K+ during hemolysis of RBCs), increased intake or by disease such as Addison´s disease. Another cause is due to Acidosis and tissue damage (ex burns or crushing injury) -> K+ out from ICF and into ECF Clinical features : resemble those of hypokalemia + nausea, intestinal colic or diarrhea. Cardiac arrest!!!!

Q12) Pathophysiology of thermoregulation!

What is normal body temperature in different places? - shell T : temperature closer to skin, oral temperature = 36.6 - 37°C - Core T : most important, organs in cranial, thoracic and abdominal cavities, rectal temperature = 37.2°C-37.6°C How does the body regulate temperature? (It´s achieved by activities in 3 sub-systems)! 1) Thermoafferent system : thermoreceptors sends signal from skin, hypothalamus, spinal cord.. - afferent nerve fibres -> rostral brain stem -> thalamic nuclei and hypothalamus -> somatosensory cortex ! Skin in face, neck and chest contain 5x thermoreceptors than rest of body* 2) Integrating system : is present at several levels of CNS (mesencephalon, medulla oblongata) ! Hypothalamus is center for thermoregulation! 3) Effector system : this is where the autonomic nerve system is involved leading to vasodilation and sweating, or vasoconstriction and shivering. The nerve pathways from dorsal hypothalamus is the one that control shivering, the nerve tract emerges and connects to extrapyramidal motor tract -> causing the shivering! What does fever mean? - it is an elevation of body temperature above the normal circadian variations as a result of a change of thermoregulatory center set point. It is a symptom of disease, it is a nonspecific immunologic mechanism which is beneficial for the body to some extent. In certain situation might be dangerous for patients with history of heart diseases, or small children What is the pathogenesis of fever? - pyrogen enters hypothalamus where they activates Phospholipase A2, this influences membrane phospholipids releasing arachodonic acid. Arachidonic acid is further metabolized by cyclooxygenase giving off prostaglandins & leukotriens. This is very shortly the way we get PgE2, and the way to reset the center. In the thermoregulation you will find cold sensitive neurons and warm sensitive neurons, leading to positive/negative regulation! 1) The positive regulation is the preoptic anterior hypothalamus (POAH). This will influence the positive regulation mediators such as PGE2 and CRH (corticotrophin releasing hormone). The PGE function in the PGE function in the way of decreased warm sensitive neuron and increased cold sensitive neurons, the CRH is able to suppress immune response, it has to do with negative feedback control mechanism of fever. 2) the negative regulation is the medial amygdaloid nucleus (MAN) and the ventral septal area (VSA) What are the stages in fever (4 in total)! Stage 1 (prodromal stage) - here bacteria, or viruses is present, immune cells are producing pyrogens, they start their action onto the organism. You will here experience nonspecific ssymptoms of disease such as ; headache, fatigue, dizziness and tiredness! Stage 2 (temperature increase) - you will have dominant production and conservation of heat, no heat loss in this stage, due to sympathetic activity, brown fatty tissue, shivering response and behavioral changes. All mechanism lead to increase of body T. Mechanical changes happening due to increased BT are with carbohydrates (glycogenolysis, incr glucose level), fat metabolism (lipolysis causing free fatty acids oxidation and keton bodies), proteometabolism (protein catabolism causing negative nitrogen balance) and water/electrolyte metabolism/vitamin! Stage 3 (persistent fever) - here the mechanism of heat production are in balance with mechanism of heat loss, and the thermoregulation is maintained at ,,new" level into which the thermostat setpoint was shifted! Stage 4 (fever decreased) - you get cleavage of pyrogens by the treatment applied or spontaneously, by immune response, this will lead to that the set point is shifted BACK to normal temperature value. Now the mechanism of heat loss are dominant causing vasodilatation in skin, sweating, perspiration! What are the different types that causes fever? - concept in fever is that you have endogenous/exogenous pyrogen that are substance that cause fever, released mainly during infection or inflammation - set point of thermoregulatory center - changes body temperature! Exogenous pyrogen are : endotoxin of Gram- bacteria (LPS particle from the envelope of bacteria), Gram+ bacteria also produces, viruses, tumor cells and immune complexes. All these ,,particles" are able to induce immune response and therefore production of endogenous pyrogens! Endogenous pyrogens are : Interleukin-1 (IL-1), interleukin-6 (IL-6), interferon (IFN) and Tu necrosis factor (TNF) such as TNF(alpha) (kachexin) and TNF(beta) (lymphotoxin). - all these endogenous pyrogens are released from immunocompetent cells via action on NF kappaB - which is a important transcription factor regulated via corticosteroids1 What is the benefit of fever - fever rises body temperature so it will kills many microorganisms, fever has adverse effects on the growth and replication of others. It will decrease serum level of iron, zinc, copper, increase lymphocytic transformation. It will cause motility of polymorphonuclears, the immune response gets enhanced. It is the nonspecific discomfort signal of diseases! What are the disorders of body organs and system caused by fever? Body system : increased metabolic state of the body Immune system : enhances the activity Cardiovascular system : increased HR, increased peripheral resistance Gastrointestinal system : decreased gastrin, motility etc., gives you the lack of hunger! Uropoietic system : decreased urination, increased sweat CNS : activating slow waves Respiration : hyperventilation Metabolism !) in long lasting fever ,,crazy" catabolic process may act What is hyperthermia - what is the origin/cause of this condition? May be caused due to generalized anhydrosis (sweat) where you have a lesion in hypothalamus or in the Spinal cord. In central hypothermia you have different causes such as; hypothalamic lesions (infarction, hemorrhage, tumor, trauma, encephalitis), intoxication (anticholinergic and sympato-mimetic drugs, salicylates, amphetamines, cocaine), acute spinal cord transection above T3-4, delirium, catatonia, malignant neuroleptic syndrome (caused by skeletal mm rigidity from treatment with neuroleptic medications (e.x antipsychotics, antidepressants, antiemetics), malignant hyperthermia (rapid and massive skeletal muscle contraction from exposure to anesthesia), dehydration, heat stroke and generalized tetanus! - how does it develop?/why do it develop? Another mechanisms involved in damage of tissue in hyperthermia is : when blood flow is diverted to the skin, decreased perfusion of intestines and other viscera can result in ischemia, endotoxemia, and oxidative stress. Also excessively high tissue temperatures (heat shock >41°C) can produce direct tissue injury. Heat shock, ischemia and systemic inflammatory responses can result in cellular dysfunction, disseminated intravascular coagulation, and multiorgan dysfunction syndrome. This condition may lead to reduced cerebral BF, combined with abnormal local metabolism and coagulopathy, can this lead to dysfunction of the CNS - What are the symptoms/signs?/why do we get this symptoms/signs -Minor intensity of heat illness you will have : Miliaria rubra (heat rash) - results from occlusion of eccrine sweat gland ducts Heat syncope (fainting) - caused by temporary circulatory insufficiency as a result of pooling of blood in the peripheral veins Heat cramps (skeletal muscle cramps) - occur during and after intense exercise and are believed to result from excessive loss of sodium in sweat! Serious heat illness : - Heat exhaustion - a mild to moderate illness characterized by an inability to sustain cardiac output with moderate (>38.5°C) to high (>40°C) body temperatures (hot skin and dehydration) - Heat injury - a moderate to severe illness characterized by organ (ex. Liver, renal) and tissue (ex. Gut, muscle) injury with high body temperatures, usually but not always greater than 40°C - Heat stroke - a severe illness characterized by CNS dysfunction with high body temperatures, usually but not always greater than 40°C What is HYPOTHERMIA? - cold injuries are classified as ,,hypothermia" which is when the whole body geets cooled (below 35°C, with the classic J wave on ECG), or as peripheral cold injuries that are injuries localized to the extremities and exposed skin leading to non-freezing injuries such as chilblain, trench foot, or freezing injuries such as frostbite. Both hypothermia and peripheral cold injuries often occur simultaneously. - What is the mechanism in onset/developing this condition?/how does this influence the body? Cold exposure elicits : - peripheral vasoconstriction to reduce heat transfer between body´s core and shell (skin, subcutaneous fat) - underlying tissues (e.g muscle) constrict to thicken the isolative shell while reducing the body core area - this vasoconstrictor response defends core temperature, but at the expense of declining peripheral tissue temperatures, which contribute to peripheral cold injuries - hypothermia depresses enzymatic activity, interfers with physiologic functions (ex. Clotting, respiration, cardiac conduction and rhythm), impairs expression of cytokines, and can induce cellular injury and death! How does burns influence the body? - is a type of injury to flesh or skin caused by heat, electricity, chemicals, friction or radiation. Burns that affect only the superficial skin are known as ,,superficial or 1st-degree burns". - when damage penetrates into some of the underlying layers, it is a,,partial-thickness or 2nd degree burn" - in a ,,full thickness or 3rd degree burn" the injury extends to all layers of the skin - 4th degree burn additionally involves injury to deeper tissues, such as muscle or bone! How does frostbite influence the body? It is the freezing of tissues - how does it develop?/why do it develop? 1st degree = superficial, 2nd = full skin, 3rd = subcutaneous tissue, 4th = extensive tissue and bone How is the prognosis - the severity of frostbite may take many days to weeks. To determine. The frostbite requires early surgical consultation once the diagnosis is made

Q42) Valvular heart disease - Mitral stenosis (HEART)*

What is normal condition and function of mitral valve - bicuspid function normally, secure one direction blood flow in the heart. During diastole, a normally functioning mitral valve opens as a result of increased pressure from left atrium as it fills with blood (pre-loading). As atrial pressure (increases) above that of left ventricle, the mitral valve opens. Diastole ends with atrial contraction, which ejects the final 20% of blood that is transferred from left atrium to left ventricle (end diastolic volume). - the LV gets filled with blood during early ventricular diastole, with only a small portion of extra blood contributed by contraction of the LA (,,atrial kick") during late ventricular diastole. Mitral valve closes at the end of atrial contraction to prevent a reversal of blood flow What is mitral stenosis - obstruction of diastolic blood flow from left atrium to left ventricle due to inappropriate opening of mitral valve A) what is the origin/cause of this condition? - most common cause is ,,rheumatic fever" with consecutive rheumatic endocarditis. Here the rheumatic process causes primary proliferative inflammation type leading to creation of connections between parts of the valve ending up in stenosis. Sometimes it is clinically silent, or it will appear months or years after. Infective endocarditis, vegetations may favor increased risk of stenosis (narrowing + hypertrophy). Other rare causes include mitral annular calcification, endomyocardial fibroelastosis, malignant carcinoid syndrome, systemic lupus erythematosus, whipple disease, fabry disease and rheumatoid arthritis! B) how does it develop / why does it develop? - when mitral valve area goes below (2cm2), the valve causes and impediment to the BF into LV, you get a pressure gradient across the mitral valve. This gradient may increase by increased HR or CO. As the gradient increases, the amount of time necessary to fill LV with blood will also increase. Eventually, left ventricle requires the atrial kick to fill with blood. As the HR increases, the time that the ventricle is in diastole to be filled up with blood decreasd. When the HR goes above a certain point, the diastolic filling period is insufficient and pressure build up in left atrium, leading to pulmonary congestion. When mitral valve area goes less than (1cm2), there will be an increase in ,,left atrial pressure" due to the ability to push blood through the stenotic valve. Since normal left ventricualr diastolic pressures is about 5 mmHg, a pressure gradient across the mitral valve of 20 mmHg due to severe mitral stenosis will cause a left atrial pressure of about 25 mmHg. This pressure is transmitted to the pulmonary vasculature and causes pulmonary hypertension. The pressure now in pulmonary capillary will lead to imbalance between the hydrostatic pressure and the oncotic pressure, leading to extravasation of fluid from the vascular tree and pooling of fluid in the lungs. This is the function of congestive heart failure causing pulmonary edema C) what are the symptoms/signs and why we get them (EKG) - Dyspnea : it all starts with vascular congestion in lungs, then the J-receptors get stimulated, then stimulation of RAR receptors, increases rigidity of pulmonary tissue, and increased requirements for inspiratory muscles. You will in the end exhaust these muscles leading to irritation of the mechanoreceptors inside muscles, tendons leading to failure in maintaining normal O2 and CO2 levels, chemoreceptors gets activated and you get a complex feeling of dyspnea in cerebral cortex! - Embolization into the arterial system : due to turbulent blood flow in dilated atrium and stagnation of blood leads to formation of thrombus. Atrial fibrillation facilitates this process because then the heart cycle lacks atrial systole. The thrombus may travel to CNS, mesenterical circulation, kidneys and limbs! - Hemptysis : disruption of the anastomosis between the nutritional and functional pulmonary circulation due to thin wall and increase blood pressure in the lungs - Cyanosis : in this condition is of peripheral type meaning ,,cold like" induced. You have vasoconstriction that leads to slowing down the blood flow enhancing extraction of O2 to the tissues (long transitional time). It will disappear after passie hyperaemia (massage), and is not present on tongue and oral mucosa such as in central cyanosis!! Atrial fibrillation : hypertrophy and dilatation of RA, together with increased intraatrial pressure will lead to increased pressure (tension) inside the atrial wall this will cause consumption of increased amount of ATP leading to development of ectopic foci inside the atrium causing this fibrillation. Atrial fibrillation is firstly a disadvantage due to worsening the ventricular filling (unbeneficial tachycardia), secondarly disadvantage is that you lack atria systole causing stagnation of blood with formation of thrombus. - Tiredness, fatigue and decreased physical performance: it is a consequence of decreased CO. The function of LV is thought quite good, so decreased CO is due to low intraventricular end-diastolic volume Auscultation : opening mitral click, diastolic murmur with presystolic accent and changes of 2nd sound (silent??) .. diastolic-presystole rumbling murmur 4th left interspace ECG : left atrial abnormalities (P,,mitral"), right ventricular hypertrophy (S in lead I and V5, R in V1) How is the PROGNOSIS? - the constant pressure overload of the LA will cause the left atrium to increase in size. As the left atrium increases in size, it becomes more prone to develop atrial fibrillation. When atrial fibrillation develops the atrial kick is lost (since it is due to the normal atrial contraction) What are the CONSEQUENCES? - in individuals with severe mitral stenosis, the left ventricular filling is dependent on the ,,atrial kick" due to atrial fibrillation can cause a precipitous decrease in CO and sudden congestive HF What are the changes of hemodynamic condition in this situation? - normal diastolic phase in filling of ventricles is disturbed and the ventricle requires longer time for filling during the whole diastolic phase, this goes slow causing monophasic filling. Mitral stenosis is the cause when you get a reduction of mitral orifice from (6cm2-> 2cm2) Obstruction of mitral orifice leads to accumulation of blood in left atrium and insufficient filling of LV. This accumulation in LA will lead to atrial dilatation and hypertrophy with simultaneous increase of intraatrial pressure! When you have accumulation of blood as well as increased blood pressure in the pulmonary circulation the compensatory mechanisms fail very early leading to -> postcapillary hypertension -> overload for right ventricle to pump the blood toward pulmonary artery -> hypertrophy of RV as a compensatory mechanisms! If the pressure inside the pulmonary capillaries is higher than oncotic pressure, there is possibility for transsudation of fluids into the lungs tissue -> impaired ventilation and oxygenation - dyspnea Paradoxically - RV failrue will progress in pathological process leading to subjective improvement of the symptoms dyspnea. This is due to that the blood supply to the pulmonary circulation is lower due to RV failrue and therefore you will not get vascular congestion in lungs Long lasting hemodynamic changes due to mitral stenosis lead to ,,protective" processes in the pulmonary circulation such as thickness of alveolo-capillary membrane and increased resistance in arteries!! decreased filling of LV leads to -> decr CO with inadequate perfusion of the body tissues -> activation of sympathetic pathway! Note*** - patients with mitral stenosius promts a series of hemodynamic changes that frequently cause deterioration of the patient´s clinical status. A reduction in co, associated with acceleration of HR and shortening of the diastolic time, frequently leads to congestive HF. In addition, when atrial fibrillation sets in, systemic embolization becomes a real danger!

Q43) Valvular heart disease - Mitral regurgitation

What is normal condition and function of mitral valve (see Q42) for further information! What is mitral regurgitation - it is the inability of mitral valve to be completely closed during the systole of ventricles. Portion of the ventricular blood is during systole ejected backward into the atrium. Isolated mitral insufficiency is very RARE!, usually is linked with some degree of mitral stenosis A) what is the origin/cause of this condition? - tissue of the valve is damaged or destroyed by different causes (e.g MI, but sometimes are parts of mitral valve connected by fibrous bridges due to proliferative inflammatory process - RF), therefore the valve is not able either to be adequately open and adequately closed. Other causes may be endocarditis, or relative insufficiency due to dilatation of anulus fibrosus. A dysfunction of any of the portions of mitral valve apparatus such as 2 valve leaflets, annulus, papillary muscles and chordae tendinae can cause mitral regurgitation B) how does it develop/ why does it develop? - LA is filling with blood from pulmonary circulation and from the ventricles as well. Left atrium is therefore overloaded by increased volume -> hypertrophy and dilatation of the atrium During the diastolic phase of LV is filling with increased blood volume from atrium - therefore ventricle is volume overload too. Both chambers are volume overloaded*. Therefore both chambers are hypertrophic and dilated due to increased end-diastolic volume in both chambers. C) what are the symptoms/signs + why we get them (EKG) - similar to the ones in mitral stenosis (Q42), but they are milder, because the volume overload is ,,better" then the pressure overload of the heart in the case of mitral stenosis. Other symptoms/signs is Palpitations, which is a sensation of large volume ejected into the arota, it may feel like something is pouring inside the chest!!! Auscultation : holosystolic murmur with propagation into the axillar fossa, weak 1st stroke. Soft, blowing pansystolic murmur at apex. ECG : left ventricular hypertrophy (large S in V1, large R in V4), minor atrial abnormality (broad P) E) what are the changes of hemodynamic condition in this situation? - pressure condition in LA and pulmonary circulation depend on the degree of insufficiency and time interval of the development of MI Chronic process leads to compensatory mechanisms in pulmonary vessels with small increase of pressure in the pulmonary circulation. Acute onset of MI will lead to pulmonary edema (swelling of lungs)!!!!!

Q34) Malabsorption syndrome

What is normal condition and function of stomach related to absorption - see q35 What is malabsorption syndrome - these are group of disease that consists of defects in absorption of fats, vitamins, proteins, carbs, electrolytes, minerals and water (ex. Deficiency of vitamin B12 and iron into the bloodstream has negatively affected) Defective intraluminal digestion : digestion of fat/proteins may be; pancreatic insufficiency, zollinger-Ellison syndrome. Fat solubilization with defect bile secretion : Ileal dysfunction/resection, bile duct obstruction, hepatic dysfunction. Mucosal cell abnormalities : defective terminal digestion such as disaccharide deficiency (lactase intolerane) and bacterial overgrowth, and defective epithelial transport such as Abetalipoproteinemia (inability to synthesize apolipoprotein B), and primary bile acid malabsorption (mutations in the ileal bile acid transporter)! Reduced small intestine surface area : gluten sensitive enteropathy, & crohn´s disease! Infection : acute infectious enteritis, parasitic infection, tropical sprue, Whipple disease (Thropheryma whippelii) Iatrogenic : subtotal or total gastrectomy, short-gut syndrome, distal ileal resection or by-pass! What is the origin/cause of this condition? - malabsorption syndrome occurs when something prevents the bowel from absorbing important nutrients and fluids. May be caused by inflammation, disease or injury. Sometimes, result of the body´s failure to produce enzymes needed to digest some foods. Factors that may cause malabsorption syndrome include; antibiotic use, conditions such as celiac disease, chronic pancreatitis, cystic fibrosis, and dairy protein allergies, congenital (birth) defects or diseases of gallbladder, liver, or pancreas, damage to the intestine (from infection, inflammation, injury or surgery) and radiation therapy (which may injure the mucosal lining of the bowel)! How does it develop and why it develops? Celiac disease : mucosal lesion in small intestine with impaired absorption of wheat ,,gliadins" and related grains causing patient to be sensitive to gluten. You get here a T-cell mediate chronic inflammatory reaction with an autoimmune component. When the small intestinal mucosa is exposed to gluten there is intraepithelial accumulation of CD8+ T cells and large numbers of CD4+ T cells in the lamina propria. - Classical symptoms are ; diarrhea, flatulence, weight loss, and fatigue. Has also extra-intestinal symptoms such as (skin blistering, dermatitis herpetiformis, and neurologic disorders). Long-term risk of malignant disease is present, including NHLs, small intestine adenocarcinoma, and esophageal SqCC Lactase deficiency : deficiency of lactase causing incomplete breakdown of lactose into glucose and galactose. This leads to osmotic diarrhea from the unabsorbed lactose. In the unabsorbed sugar you get bacterial fermentation resulting in ,,increased hydrogen production". It can be inherited or acquired (viral/bacterial infections). Short bowel syndrome : the condition may be a birth defect or result of surgery. The ability of bowel to absorb nutrients is affected any time its surface area is reduced Tropical sprue : may be related to environmental factors such as toxins in foods, infection or parasites. Common in Southeast Asia, Caribbean, and India. Symptoms are anemia, diarrhea, sore tongue and weight loss! Whipple´s disease : rare disease, usually affects middle-aged men. May be caused by a bacterial infection. - Symptoms include : chronic fever, darkening of skin pigment, diarrhea, joint pain and weight loss What are signs and symptoms & why we get them? - symptoms of malabsorption syndrome different depending on nutrients not properly absorbed. Suspection may rise in chronic diarrhea, nutrient deficiencies, or has significant weight loss despite eating a healthy diet. Fats : light-colored, soft/bulky foul-smelling stools (difficult to flush, may float or stick to the side) - proteins : fluid retention (edema), dry hair, or hair loss - sugar : bloating, flatulence, or explosive diarrhea - vitamins : anemia, malnutrition, low blood pressure, weight loss and wasting! what are the consequences? - GIT : diarrhea, flatus, abdominal pain, weight loss and mucositis - hematopoietic system : anemia and bleeding - musculoskeletal system : osteopenia and tetany Endocrine system : amenorrhea, impotence, infertily and hyperparathyroidism Epidermis : purpura, petechia, edema, dermatitis and hyperkeratosis NS : peripheral neuropathy

Q35) Intestinal obstruction (Ileus)

What is normal condition and function of the small intestine? - where much of the digestion and absorption of food takes place. Food from stomach through pylorus (final part of stomach). The small intestine receives ,,bile juice & pancreatic juice" through the hepatopancreatic duct. Enzymes enter small intestine in response to hormone cholecystokinin produced in the small intestine in response to presence of nutrients. The hormone secretin also causes bicarbonate to be released into the small intestine from pancreas in order to neutralize the potentially harmful acid coming from stomach. Proteolytic enzymes, including ,,trypsin & chymotrypsin", are secreted by pancreas and cleave proteins into smaller peptides. Carboxypeptidase, which is a pancreatic brush border enzyme, splits 1 amino acid at a time! - aminopeptidase and dipeptidase free the end amino acid products. Lipids are degraded into fatty acids and glycerol. Pancreatic lipase breaks down triglycerides into FFAs and monoglycerides. Bile salts attack to triglycerides to emulsify them, until the lipase can break them into the smaller components that are able to enter the villi for absorption. Some carbohydrates are degraded into simple sugars, or monosaccharides (e.g glucose). Pancreatic amylase breaks down some carbohydrates (notably starch) into oligosaccharides. Other carbohydrates pass undigested into the large intestine and further handling by intestinal bacteria. Brush border enzymes such as dextrinase and glucoamylase takes over and break down oligosaccharides. Other brush border enzymes are maltase, sucrase and lactase. Cellulose, are not digested at all since they are made out of beta-glucose and not alpha-glucose as the rest! Absorption of majority of nutrients takes place in jejunum, while iron is absorbed in the duodenum, vitamin B12 (extrinsic factor) and bile salts are absorbed in terminal ileum, water and lipids are absorbed by passive diffusion throughout the small intestine, sodium bicarbonate is absorbed by active transport and glucose and amino acid co-transport and fructose is absorbed by facilitated diffusion. Important* - what is Intestinal obstruction (ileus)!! - it is a disruption of the normal propulsive ability of the GIT. It originally referred to any lack of digestive propulsion, including any bowel obstruction! May occur any place of the GIT, but most common in small intestine because of its narrow lumen! What type of obstructions are there? - bowel obstruction is generally a ,,mechanical obstruction" of the GIT. The obstructions may be from Tu and infarct, but may also be from hernias, intestinal adhesions, intussusception and volvulus. - there are also paralysis of the intestine (,,paralytic ileus") that is common side effect of some types of surgery. - it can also result from certain drugs and from variou injuries and illnesses (e.g acute pancreatitis)!! What is the origin/cause of this condition? - cause may be due to intestinal obstruction can be mechanical, or it can be due to myopathies or neuropathy How does it develop? & why it develops? - Intestinal adhesions : after surgical procedures, infections and endometrioses with/localized or general peritonitis Intussusception : it has been associated with ,,rotavirus" infection in children, while in adults the most common cause is due to —> Tumor or intraluminal mass! Volvulus : caused by both intestinal obstruction and infarction! What is the mechanism in onset/developing this condition / how does this influence the body? - Intestinal adhesions : when f.x peritonitis heals there may be formed fibrous adhesions between the bowel segments and abd wall. These adhesions create ,,closed loops" through which other parts of viscera can slide and become trapped (internal herniation) following this may obstruction and strangulation occur. Intussusception : when 1 of the segments are constricted the part of intestine that is trapped becomes propelled further and further into distal intestine in this process the mesentery is also pushed into the intestine Volvulus : here you get a complete ,,twisting" of a loop of the bowel around the mesenteric base of attachment. What are the symptoms/signs - why do we get them? - symptoms of ileus include ; moderate, diffuse abdominal discomfort, constipation, abdominal distension, nausea/vomiting (especially after meals), vomiting of biliatic fluid or bile, lack of bowel movement and/or flatulence and excessive belching!

Q33) Peptic Ulcer Disease

What is normal condition and function of the stomach related to div. Secretion? - see q.32 What is peptic Ulcer Disease - it is chronic, solitary (most often) lesions that occur in any portion of the GIT exposed to aggressive action of acid/peptic juices. It can occur in any age and in the whole git, but it is more predominant in (30-60yrs and in the stomach and duodenum). Duodenal ulcer is male predominant. Acute form of peptic ulcer is the one that is caused by systemic stress or ingestion of NSAIDs - location is mostly in duodenum (first part), stomach (antrum), GE-junction (in the setting of GERD or Barret esophagus), within margins of gastrojejunostomy, in the duodenum, stomach and/or jejunum in Zollinger-Ellison syndrome or within or adjacent to ileal Merckel diverticulum - What is the origin/cause of this condition? Imbalance between gastroduodenal mucosal defence mechanisms and the damaging forces, particularly gastric acid and peptic enzymes. The mucosal defence factors such as ; surface mucus secretion, bicarbonate secretion into mucus, mucosal blood flow, apical surface membrane transport, epithelial regenerative capacity and elaboration of prostaglandins are unfortunately failing (H.pylori may also be a cause)! - What is the mechanism in onset/developing this condition?/how does this influence the body? Infection, predominantly in the antrum of stomach will lead to hypergastrinemia and an increased acid production. Acid injury to the duodenum is thought to promote the development of gastric metaplasia, allowing organism to colonize these area and promote the development of duodenal ulcers H.pylori : induces intense inflammatory and immune response, increased pro-inflammatory cytokine production, which recruits and activates neutrophils. The damage to epithelial cells is contributed by urease, phospholipase and bacterial proteases. The H.pylori will increase gastric acid secretion, while at the same time decrease duodenal bicarbonate secretion. - this will again lead to decreased pH in the lumen, giving the perfect condition to gastric metaplasia! what are the symptoms/signs - why do we get them? - epigastric gnawing, burning or aching pain. In minority will there also be present iron deficiency anemia, hemorrhage or perforation. When perforation happens there will usually be a back pain present, or left upper quadrant or chest. The classical pain is usually relieved by alkalis or food. Other symptoms are nausea, vomiting, bloating, bleching, weigh loss How is the prognosis? - smoking may augment the risk of peptic ulcer by impairing healing. It may be treated by giving H2 receptor antagonist blockers, they will block the place for histamin, gastrin and acetylcholine to stuck on the parietal cell in the stomach leading to decreased gastric secretion and therefore also reducing the pepsin concentration. Other agents for protecting the mucosa are sucralfate and prostaglanding analogs What are consequences - it may lead to malignancy! What is the mechanism involved in peptic ulcer complications? - surgical managements such as using minimally invasive methods. With bleeding ulcers, hemostasis often can be achieved by endoscopic methods, and endoscopic balloon dilation often is effectiv in relieving outflow obstruction. Div. Zollinger-Ellison syndrome : caused by gastrin-secreting tumor (gastrinoma). Here you have gastric acid secretion reaches such levels that ulceration becomes inevitable. Treatment is controlling gastric acid secretion by proton pump inhibitors Multiple endocrine neoplasia type 1 syndrome (MEN1) : is an autosomal dominant disorder causing also hypergastrinemia, it is characterized by hyperparatyroidism and multiple endocrine tumors, including gastrinomas Stress ulcers - Curling ulcer : GI ulceration developed in relation to major physiological stress. High risk are those with larger surface area burns, trauma, sepsis, acute RDS, severe liver failure and major surgical procedures. It is thought to result from ischemia, tissue acidosis, and bile salts entering the sotmach in critically ill persons with decreased GIT motility! Stress ulcer - Cushing ulcer : gastric, duodenal and esophageal ulcers arising with intracranial injury, operations or tumors, they are caused by hypersecretion of gastric acid resulting from stimulation of vagal nuclei by increased intracranial pressure. For preventing and treating this type of ulcers they are use h2-receptor antagonists and proton pump inhibitors!!!

Q39) Pathophysiology of portal hypertension, complications of portal hypertension

What is normal condition in portal circulation? - liver receives the majority of its metabolic requirements from a venous source. The normal liver gets about 70% of its O2 requirement via the portal vein, that also delivers the dietary carbohydrates used to fuel liver activity. The portal system begins in the capillaries and venules of the digestive system. It collects venous blood from the lower esophagus, stomach, duodenum, jejunum, ileum, colon, spleen and to the liver via portal vein. Consequently, portal blood contains the substances absorbed by the digestive tract. Normal portal flow and pressure vary depending upon CO, intra-abdominal pressure, disease process, positioning, feeding schedule, time of day etc. Normal hepatic circulation is a ,,high flow-low resistance" system. Branches of the portal vein deliver (1000-1500 ml/min of blood into the sinusoids of the hepatic lobules. Normal portal venous pressure is 5-10 mmHg. The blood passes through the sinusoids and drains into the IVC that has a pressure range from -5 to +5 mmHg. Portal pressure > 10 mmHg may indicate portal hypertension. What is portal hypertension? - it is long lasting (increse of blood pressure) in portal vein, more than 5-5 mmHg. You have different types of portal hypertension 1) pre-hepatic PHT : causes obliteration of portal vein, lienalis v (infection, trauma, thrombosis, tumor invasion), with the consequences of developing collateral circulation, enlargement of spleen, esophageal varices and ascites, but it is RARE! 2) Hepatic PHT : causes cirrhosis of the liver (alcohol, biliary cirrhosis, hemochromatosis, Wilson´s disease), myeloproliferative diseases (liver & spleen), m. Hodgkin, leukemia (infiltration of periportal fields), sarcoidosis (idiopathic pathogenesis), alcohol induced hepatopathy without cirrhosis, MTS of tumors and cystic diseases of the liver! 3) Post-hepatic PHT : causes block of hepatic veins of IVC (budd-chiary syndrome)*, and extra-hepatic causes such as contrictive pericarditis and severe HF What are the symptoms/signs - why do we get them? - consequences of portal hypertension are caused by blood being forced down alternate channesl by the increased resistance to flow through systemic venous system rather than through the portal system. - signs and symptoms due to that include : ascites, hepatic encephalopathy, increased risk of spontaneous bacterial peritonitis, increased risk of hepatorenal syndrome, splenomegaly with a consequent accumulation of RBC, WBC and platelets, together leading to mild pancytopenia, and portocaval anastomoses such as esophageal varices, gastric varices, anorectal varices (not to be confused with hemorrhoids!!!!) and caput medusae. Esophageal and gastric varices pose an ongoing risk of life-threatening hemorrhage, with hematemesis or melena What are the consequences? - creation of collateral circulation such as ; esophageal submucosal veins (esophageal varices), rectal submucosal veins (haemorrhoids), veins of parietal peritoneum (caput medusa), anastomosis between hepatic capsulla and diaphragm and anastomosis between renal v ein and lienalis vein - increased lymphatic flow in the liver where the lymph contain small admixture of blood - ascites : caused by portal hypertension, circulatory changes tha has to do with vasodilatation and hyperkinetic circulation, hypoalbuminaemia, neuro-humoral changes, decrease of renal perfusion, retention of Na and water and overproduction of hepatic lymph. This condition will lead to consequences such as pressure inside the abd cavity, spontaneous bacterial peritonitis, increased position of diaphragm and decrease of vital capacity of lungs - increase of plasmatic volume leading to volume overload for CVS - hypersplenism leading to enlargement for red pulp in the spleen, enlargement of spleen with peripheral cytopenia and decrease of total leucocytes (leukopenia) and platelet count - esophageal varices bleeding is the most common cause!!!!!**********

Q37) Jaundice states

What is normal function to the liver in connection with bilirubin? - this gland plays major role in metabolism and has number of functions in the body, including glycogen storage, decomposition of RBCs, plasma protein synthesis, hormone production, and detoxification. - In connection with bilirubin which is breakdown product of normal heme catabolism, the liver has the task in conjugating bilirubin with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water, facilitating its excretion into bile As each RBC traverses through the RES, its cell membrane ruptures when its membrane is fragile enough to allow this. Cellular contents, including hemoglobin, are subsequently released into the blood. The hemoglobin is then phagocytosed by macrophages, and splitted into its heme and globin portions. The globin portion, a protein, is degraded into AAs and therefore plays no role in jaundice!. The heme molecule travesl with albumin to be unconjugated. The majority of the bilirubin comes from this breakdown of heme pathway, from expired RBC, but the remaining 20% comes from other heme sources, including ineffective erythropoiesis, and the breakdown of other heme-containg proteins, such as muscle myoglobin and cytochromes What differen types of jaundice do we have? - jaundice is often seen in liver disease such as hepatitis or liver cancer. It may also indicate leptospirosis or obstruction of biliary tract (e.g by gallstones or pancreatic cancer, or less commonly be congenital in origin (e.g biliary atresia) What is the origin/cause of this condition? - classified into 3 categories, depending on which part of the physiological mechanism the pathology affects 1. Pre-hepatic (hemolytic) : pathology is occuring prior to the liver 2. Hepatic (hepatocellular) : pathology is located within the liver 3. Post-hepatic (cholestatic) : pathology is located after the conjugation of bilirubin in the liver Pre-hepatic Jaundice : - it is caused by anything which causes (incr rate of hemolysis), ex malaria can cause jaundice this way. Other causes to this condition are certain genetic diseases, such as sickle-cell anemia, spherocytosis, thalassemia and G6PDH deficiency, also kidney diseases such as hemolytic uremic syndrome, can also lead to coloration. In jaundice secondary to hemolysis, the increased production of bilirubin leads to increased production of urine-urobilinogen. Bilirubin is not usually found in the urine because unconjugated (unsoluble) bilirubin is not water-soluble, so, the combination of increased urine-urobilinogen with no bilirubin in urine suggest hemolytic jaundice! Laboratory findings include : - urine : no bilirubin present, urobilinogen > 2 units in ex hemolytic anemia that causes increased heme metabolism, exception from this is in infants where gut flora has not developed yet - serum : increased unconjugated bilirubin - kernicterus : increased unconjugated bilirubin ; neonates are especially vulnerable to this due to increased permeability of the blood-brain-barrier Hepatocellular (hepatic) jaundice : - caused by acute or chronic hepatitis, hepatotoxicity, cirrhosis, drug-induced hepatitis and alcoholic liver disease. All these conditions causes cell necrosis that reduces the liver´s ability to metabolize and excrete bilirubin leading to a build-up of unconjugated bilirubin in the blood. Neonatal jaundice, is a common as hepatic machinery for the conjugation and excretion of bilirubin does not fully mature until approximately 2 weeks of age! - other causes include : primary biliary cirrhosis leading to an increase in plasma conjugated bilirubin because there is impairment of excretion of conjugated bilirubin into the bile. The blood contains an abnormally raised amount of conjugated bilirubin and bile salts which are excreted in the urine. In hepatic jaundice, there is invariably cholestasis. Laboratory findings depend on the cause of jaundice: - urine : conjugated bilirubin present, urobilirubin >2 units but variable (except in children) !) kernicterus is condition not associated with increased conjugated bilirubin - plasma protein shows characterisitc changes - plasma albumin level is low but plasma globulins are raised due to an increased formation of antibodies! Bilirubin transports across the hepatocyte may be impaired at any point between the uptake of unconjugated bilirubin into the cell and transport of conjugated bilirubin into biliary canaliculi. In addition, swelling of cells and oedema due to inflammation cause mechanical obstruction of intrahepatic biliary tree, causing concentration of both unconjugated and conjugated bilirubin to rise in the blood! In hepatocellular disease, there is usually interference in all major steps of bilirubin metabolism - uptake, conjugation and excretion. However, excretion is the rate-limiting step, and usually impaired to the greatest extent. As a result, conjugated hyperbilirubinaemia predominates! Post-hepatic (obstructive) Jaundice : - caused by an interruption to the drainage of bile in the biliary system. Common causes are gallstones in the common bile duct, and pancreatic cancer in head of pancreas. Also, specific parasites can live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct, biliary atresia, cholangiocarcinoma, pancreatitis and pancreatic pseudocysts In complete obstruction of the bile duct, no urobilinogen is found in the urine. In this case, presence of bilirubin (conjugated) in the urine without urine-urobilinogen suggests obstructive jaundice, either intra-hepatic or post-hepatic The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their colour from bile pigments. However, this may also occur in many intra-hepatic illnesses and are therefore not a reliable clinical feature to distinguish obstruction from hepatic causes of jaundice. - patients also can present with elevated serum cholesterol, and often complain of severe itching or ,,pruritus" because of the deposition of bile salts!!

Q41) Pancreatitis

What is normal function to the pancreas? (Pancreas has 2 main functions) A) to make digestive enzymes which help us to digest food - pancreatic proteases (such as trypsin and chymotrypsin) - which help to digest proteins - pancreatic amylase - which helps to digest carbohydrates (sugars) - pancreatic lipase - which helps to digest fat B) to make hormones which regulate our metabolism - insulin - which helps to regulate sugar levels in the blood - glucagon - which works with insulin to keep blood sugar levels balanced - somatostatin - which helps to control the release of other hormones - gastrin - which aids digestion in the stomach Intro!!! What is pancreatitis? - disease in which the pancreas become inflamed. Pancreatic damage occurs when the digestive enzymes are activated before they are secreted into duodenum and begin attacking the pancreas Acute Pancreatitis = sudden inflammation that occurs over a short period of time. In majority of cases it is caused by gallstones or heavy alcohol use. Other causes are medications, infections, trauma, metabolic disorders and surgery. - the severity may range from mild abdominal discomfort to a severe, life-threatening illness. However, the majority recover completely after receiving the appropriate treatment. In very severe cases, the result is bleeding into the gland, serious tissue damage, infection, and cyst formation. Severe pancreatitis can also create conditions which can harm other vital organs such as heart, lungs and kidneys Chronic Pancreatitis - occurs mostly after an episode of acute pancreatitis and is the result of ongoing inflammation - in about 45% of people, it is caused by prolonged alcohol use. Other causes include gallstones, hereditary disorders of pancreas, cystic fibrosis, high triglycerides and certain medicines. Damage to pancreas from excessive alcohol use may not cause symptoms for many years, but then the person may suddenly develop severe pancreatitis symptoms, including severe pain and loss of pancreatic function, resulting in digestion and blood sugar abnormalities! A) What is the cause? - 80% due to alcohol or gallstones. There is also an inherited form resulting in activation of trypsinogen within the pancreas, leading to autodigestion. Involved genes may include Trypsin1, which codes for trypsinogen, SPINK1, which codes for a trypsin inhibitor, or cystic fibrosis transmembrane conductance regulator. Other common causes include ; trauma, mumps, autoimmune disease, high blood calcium, hypothermia, endoscopic retrograde choangiopancreatography (ERCP) and ,,pancreas divisum" that is an common congenital malformation - DM type 2 has high risk. Less common causes include pancreatic cancer, pancreatic duct stones, vasculitis (inflammation of vessels in pancreas), coxsackievirus infection, and porphyria (particularly acute intermittent porphyria and erythropoietic protoporphyria) B) what are the symptoms/signs and why we get them? - Acute includes ; upper abdominal pain that radiates into the back, swollen and tender abdomen. Nausea and vomiting, fever + increased HR - Chronic includes ; similar to those of acute pancreatitis. Other symptoms may include weight loss caused by poor absorption of food, due to the gland is not secreting enough enzymes to break down the food normally. Alos, DM may develop if the insulin-producing cells of pancreas become damaged! C) What are the consequences? Early complications : shock, infection, Systemic inflammatory response syndrome, low blood calcium, high blood glucose, and dehydration. Blood loss, dehydration and fluid leaking into the abdominal cavity (ascites) can lead to kidney failure. Respiratory complications are often sever!!! - pleural effusion is usually present. Shallow breathing from pain can lead to lung collapse. Pancreatic enzymes may attack the lungs, causing inflammation. Severe inflammation can lead to intra-abdominal hypertension and abdominal compartment syndrome, further impairing renal and respiratory function and potentially requiring management with an open abdomen (laparostomy) to relieve the pressure! Late complications : recurrent pancreatitis and the development of pancreatic pseudocysts (collections of pancreatic secretions that have been walled off by scar tissue). These may cause pain, become infected, rupture and bleed, block the bile duct and cause jaundice, or migrate around the abdomen. Acute necrotizing pancreatitis can lead to a pancreatic abscess, a collection of pus caused by necrosis, liquefaction and infection!!!

Question 1. General Knowledge on pathophysiology

What is pathophysiology? Patho = disease/pain/suffering, physiologia = science of nature. Based on basic/clinical aspects of mechanisms responsible for initiation, development and treatment of pathological processes in humans/animals. (Shortly, you take a closer look at the = function of the diseases!!) It helps us find answers to important questions related to disease processes such as : what is the cause, why do it develop, what is the mechanism responsible for the onset and progression of the disease, what is the mechanism responsible for symptoms/signs? if we do find answers on this question there is more likely to find accurate treatment!!! What is the position in medical education? - it is a biomedical science ,,branch", it is the bridge between sciences and clinical medicine. What is the task in medical education? - to teach about the mechanism of the diseases, help understanding the substances of health and understand the logic of life under pathological conditions (how the diseases influences on out body) What is the relationship to other subjects in medical education? - there is a close relation to f.x histology since the macro and microstructures are essential for understanding pathology, biochemistry due to biochemical changes during pathological conditions, biophysics gives us the basic inproperties of cells, tissue and organs structural and functional characteristics, micro/immunology gives the mechanical info about disease development caused by noxas and immune system disorders, pharmacology due to enabling doctors to treat diseases rationally All in all we need to understand the healthy man for then to be able to recognize pathological functions ! What are the structures of pathophysiology? - based on the content of general and special pathophys What is the constituents of general pathophys? - general pathological processes and pathomechanism involved in pathogenesis that involves more then 1 disease (e.g inflammation, fever, shock, edema, disturbances of control mechanism ++) What is the constituent of special pathophysiology - Pathomechanism involving in ,,functional disturbances" of the organs and system of organism. (E.g hematologic, cardiovascular, respiratory, uropoetic, neurologic, endocrine, metabolic, reproductive and GIT disorders)

Q27) Plasma cell dyscrasias - multiple myeloma, waldenstrom macroglobulinemia

What is plasma cell and it´s function? - they are WBCs that secrete large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Like all blood cells, plasma cells originate in the BM ; however, these cells leave the BM as B cells, before terminal differentiation into plasma cells, normally in LNs What is dyscrasias? - it means ,,bad mixture", used in medical context for unspecified disorder of the blood. It is defined in current medicine as a morbid general state resulting from presence of abnormal material in the blood, usually applied to diseases affecting blood cells or platelets! A) What is Multiple Myeloma? - lymphoproliferative disease associated with plasma cells, malignant neoplastic (new growth) disorder, arise in BM, primary involves bone, older people (60 years). Also known as plasma cell myeloma or kahler´s disease, it is a (Cancer of plasma cells). Here you have a collections of abnormal plasma cells accumulate in the BM, interfering with the production of normal blood cells. - most cases of myeloma also feature the production of a ,,paraprotein" - an abnormal antibody which can cause kidney problems. Bone lesions and hypercalcemia (high blood calcium levels) are also often encountered! What is the mechanism in onset/developing this condition?/how does this influence the body? Multiple myeloma develops in B lymphocytes after they have left the GC of the lymph node. When chromosomes and genes are damaged, may this lead to a translocation of a chromosome where it stimulates an antibody gene to overproduction. A chromosomal translocation between the immunglobulin heavy chain gene and an ocnogene is frequently observed in these patients. This mutation results in dysregulation of the ocogene is proliferation of a plasma cell clone and genomic instability that leads to much of their localized damage, such as ,,Osteoporosis", and creates a microenvironment in which the malignant cells thrive. Angiogenesis (the atraction of new blood vessels) is increased. The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy and other myeloma-associated symptoms! What are the symptoms/signs / why do we get them? - bone pain, hypercalcemia (Ca due to bone destruction), peripheral neuropathy and cord compression, renal failure (by hypercalcemia and Bence Jones proteins damaging renal tubules), anorexia, confusion & coma)! How is prognosis (complications)? - multip myeloma - decr Ig´s + leukopenia -> pneumonia, UTI, bacteremia - incr abn globulin -> incr viscosity -> visual disturbances, headache, somnolence, irritability, confsion - Expanded plasma volume -> may result in congestive heart failure - RBC´s become coated with proteins -> sticky - Globulins interact with plasma coagulation factors + platelets -> bleeding Raunaud´s phenomen : cryoglobulin becomes solid in cold temperature -> white skin + pain + ulcerations of fingertips/toes B) What is Waldstrom macro globulinemia - it is a rare dysproteinemia, (males 50+), appears as malignant lymphoma with B-cells and plasma cells infiltrating the bone marrow. - type of lymphoproliferative disease, which shares clinical characteristics with the indolent NHLs What is mechanism in onset/developing this condtion? / how does this influence the body? - with this condition you synthesize and release a lot of IgM into intravascular space -> incr plasma volume + hyperviscosity. The IgM is nonfunctionalbut can suppress normal production of Ig´s What are symptoms/sign & why do we get them? - increased plasma volume, cision disturbances, dilation of retinal veins, hemorrhages (bleeding), Raynaud´s phenomenon, anemia secondary to BM replacement and lymphadenopathy + hepatosplenomegaly. It RARELY produces Bone damage (unlike multiple myeloma)!!!! Symptoms include ; - blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effect of the IgM paraproteins, which may cause autoimmune phenomenon or cryoglobulinemai - Other symptoms of WM are due to : Hyperviscosity syndrome, that is present in (6-20% of patients). This is attributed to the IgM monoclonal protein increasing the viscosity of the blood by forming aggregates to each other, binding water through their carbohydrate component and by their interaction with blood cells What are the consequences of this disease? —> BACTERIAL INFECTIONS!

Q30) Inherited and acquired plasma coagulation factors disorders - hemophilia, disseminated intravascular coagulation (DIC)

What is plasma coagulation facors? - coagulation (clotting) is the process by which blood changes from liquid to gel. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair! The mechanism of coagulation involves (activation, adhesion & aggregation) of platelets along with deposition and maturation of FIBRIN! - Disorders of coagulation are disease states which can result in bleeding* (hemorrhage or bruising) or obstructive clotting (thrombosis)! Coagulation begins instantly after an injury to the blood vessel has damaged the endothelium lining the vessel. Exposure of blood to the space under the endothelium initiates 2 processes: Changes in platelets, and the exposure of subendothelial tissue factor to plasma factor VII, which ultimately leads to fibrin formation! - platelets immediately form a plug at the side of injury; this is called ,,primary hemostasis". Secondary hemostasis occurs simultaenously: additional coagulation factors or clotting factors beyond factor VII, respond in a complex cascade to form fibrin strands, which strengthen the platelet plug! Problem with coagulation may dispose to ,,hemorrhage, thrombosis and occasionally both" ! A) What is disorders of inherited plasma coagulation factors? - best known coagulation factor disorders are -> HEMOPHILIAS! The three main forms are hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency or ,,christmas diseases") and hemophilia C (factor XI deficiency, mild bleeding tendency)! Note : Hemophilia A & B are X-linked recessive disorders, whereas Hemophilia C is much more rare autosomal recessive disorder most commonly seen in Ashkenazi Jews! Von Willebrand disease (which behaves more like a platelet disorder except in severe cases), is the MOST common ,,hereditary bleeding disorder". It is an inherited autosomal recessive or dominant w/defect in (vWF), which mediates the binding of glycoprotein Ib (GPIb) to collagen. This binding helps to mediate the activation of platelets and formation of primary hemostasis, so this disease prolongs the bleeding time! Mutations in factor XII (F12) have been associated with an asymptomatic prolongation in the clotting time and possibly a tendency towards thrombophlebitis. Other mutations have been linked with a rare form of hereditary angioedema! B) What is disorder of acquired plasma coagulation factors? - decreased production of coagulation factors due to vitamin.K deficiency, since this is required for synthesis of factors (II, VII, IX & X), The vitamin K matures the clotting factors. Cause for this deficiency may be malnutrition, malabsorption, or GIR sterilization by antibiotics! Increased consumption : by (DIC, fibrinolysis)** Liver is the major site for synthesis of factor (II, VII, IX & X). Severe liver impairement such as in acute and chronic liver failure will lead to altering of ,,hemostastic response" (e.g portal hypertension -> splenomegaly -> thrombocytopenia + esophageal varices + coagulation defects -> massive HEMORRHAGE** What is hemophilia? - it is deficiency or functional defect in any of the plasma coagulation factors (except factor XII, prekalikrein, high-molecular weigh kininogen -> doesn´t cause clinical bleeding). You have 3 main types with diverse cause and connection to div. Cofactors! - degree of bleeding is related to the amount of factor activity and severity of injury. Decreased 1% you may develop joint bleeding and deep tissue bleeding, in 5% the bleeding may be related to trauma or surgical procedures (F. VIII & IX) are part of the intrinsic pathway -> PTT prolonged, PT normal)! What are the consequences? - they may be both directly from the disease itself or from its treatment. - haemophilic arthropathy is characterized by chronic proliferative synovitis and cartilage destruction. If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans. The hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more likely to easily rebleed, leading to vicious cycle of hemarthrosis-synovitis-hemarthrosis. In addition, iron deposition in synovium may induce an inflammatory response activating the IS and stimulating angiogenesis, resulting in cartilage and bone destruction! About (DIC) what is it ,,disseminated intravascular coagulation" - it is a pathological process characterized by widespread activation of clotting cascade that results in the formation of ,,blood clots" in small blood vessels throughout the body. This leads to compromise of tissue blood flow and can ultimately lead to multiple organ damage. In addition, as the coagulation process consumes clotting factors and platelets, normal clotting is disrupted and severe bleeding can occur from various sites. IMPORT** - (DIC) does NOT occur by itself but only as a complicating factor from other underlying condition, usually in those with critical illness! The combination of widespread tissue ischemia and simultaneous bleeding carry an increased risk of death in addition to that posed by the underlying disease. - DIC can be overt and severe in some cases, but milder and insidous in other! -> DIAGNOSIS : depends on finding of characteristic laboratory tests & clinical background. -> TREATMENT : mainly geared towards the underlying condition, or by HEPARIN = (antithr anticoagulant) What are the signs/symptoms? + why do we get them? - it all depends on extent & duration of formation of thrombi, organs involved and resultant necrosis and hemorrhage (bleeding state). - organs most frequently involved are : kidney, brain, pituitary gland, lungs, adrenal glands, GIT mucosa, symptoms ; - mucus membrane bleeding, deep tissue bleeding, bleeding around sites of injury, venipuncture, infection & every orifice, hypotension (shock), oliguria & anuria (<100ml), convulsions and coma, nausea & vomiting, diarrhea, abd opain, back pain, dyspnea and cyanosis Process - DIC - in (DIC), processes of coagulation (clotting) & fibrniolysis are dysregulated, and result is widespread clotting with resultant bleeding. Regardless of triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions! Coagulation inhibitors are also consumed in this process, decr inhibitor levels will permit more clotting Acute form of DIC is considered ,,extreme expression" of the intravascular coagulation process with a complete breakdown of normal homeostatic boundaries. DIC is associated with POOR prognosis* & high mortality rate* Note : - One critical mediator of DIC is the release of a transmembrane glycoprotein called tissue factor (TF). This is present on surface of many cell types (incl endothelial cells, macrophages & monocytes) & is normally not in contract with general circulation, but is exposed to the circulation after vascular damage! 2 examples regarding this TF cascade 1) TF is released in response to exposure to cytokines (particularly IL-1), TNF & endotoxin. TF is also abundant in tissues of the lungs, brain and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon exposure to blood and platelets, TF binds with activated factor VIIa forming the extrinsic tense complex. This complex further activates the rest of the factors ednding up in the formation of thrombin and fibrin! 2) ex. Excess circulating thrombin results from the excess activation of the coagulation cascade. The excess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots in the circulation. These excess clots trap platelets to become larger clots, which leads to microvascular and macrovascular thrombosis. This lodging of clots in the microcirculation, in the large vessels, and in the organs is what leads to ischemia, impaired organ perfusion, and end-organ damage that occurs with DIC

Q23) Polycythemia

What is polycythemia? - it is a ,,disease state" in which the proportion of blood volume that is occupied by RBC increases! Blood volume proportions can be measured as hematocrit level. It can be due to an increase in number of RBC called ,,absolute polycythemia" or to a decrease in volume of plasma called ,,relative polycythemia" How does it develop? / why do it develop? - this excess of RBCs will increase the whole blood viscosity + increased blood volume! Relative PC : decreasd plasma volume but normal RBC count, caused by div. Fluid losses (ex. Diuretics, vomiting, burns, fever), decreased fluid intake or by redistribution of fluids from plama to tissues due to crush injury! Absolute PC : increased RBC count - primary : are due to factors intrinsic to red cell precursors. Ex polycythemia vera (PCV) classified as a myeloproliferative disease occurs when excess RBC are produced as a result of an abnormality of the bone marrow (stem cell abnormal)!!!. Often, though also present in other myeloproliferative disorders* Hallmark of polycythemia is an elevated hematocrit, with Hct >55% seen in (83% cases), though also present in other myeloproliferative disorders! Secondary : cardiopulmonal disease leading to decreased O2 saturation -> erythropoiesis. This will lead to increased plasma volume and blood viscosity, following with vasodilatation taht will occur to accomodate the increased RBC volume. This condition is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. This condition resolves when the underlying cause is treated. What are the symptoms and signs / why do we get them? - bloodshot eyes, ,,fullness in head", headache, dizziness, difficulties concentration, visual blurring, post-bathing itching! What are the consequences? - increased blood viscosity -> risk for thrombosis and hemorrhage. May also lead to fibrotized BM and hepatosplenomegaly. Transformation to acute leukemia is RARE! Phlebotomy is the mainstay of treatment* Conditions which may result in a physiologically appropriate polycythemia include : - altitude related - this physiologic polycythemia is a normal adaptation to living at high altitudes. Many athletes train at high altitude to take advantage of this effect ( a legal form of blood doping) - hypoxic disease-associated - (e.g in cyanotic heart disease where blood oxygen levels are reduced significantly. May also occur as a result of hypoxic lung disease (e.g COPD and as a result of chronic obstructive sleep apnea)! - Iatrogenic - secondary polycythemia can be induced directly by phlebotomy (blood letting) to withdraw some blood, concentrate the RBCs, and return them to the body - Genetic - heritable causes associated with abnormalities in hemoglobin oxygen release. This includes patients who have a special form of hemoglobin known as Hb chesapeake, which has a greater inherent affinity for O2 than normal adult hemoglobin. This reduces O2 delivery to the kidneys, causing increased erythropoietin production and a resultant polycythemia! Conditions where the secondary polycythemia occurs irrespective of body needs include : **** - neoplasms ex renal cell carcinoma of liver Tu, von. Hipple-Lindau disease, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing´s syndrome. - people whose testosterone levels are high because of the use of anabolic steroids, including athletes who abuse steroids, or people on testosterone replacement for hypogonadism, as well as people who take erythropoietin may develop SECONDARY POLYCYTHEMIA!!!!

Q3) General concepts of health and disease

What is the definition to disease? - characterized by interactions of pathological processes, defensive and adaptation processes, which results in damage of the organism as a whole. A large amount of the disorders are called psychosomatic diseases. Diseases can be defined as changes in individuals that cause their health parameters to fall outside the range of normal, it therefore means a deviation of the normal state What is the definition to normalcy? - normalcy usually refers to beining in a state of normal. Normality is similarly defined as the condition of being normal. The subtle difference of ,,being in a state of" versus ,,the condition of" (!!! Norm not same as health) What is the connection between disease and illness? - Illness is a term that is commonly used to refer to what is wrong with the patient (what troubles him), while disease is what is wrong with the body. Disease is a process having characterisitcs sett of symptoms and signs while illness is more the feeling of uncomfortability What are the stages of disease? 1st = latent (incubation time w/no sign and symptoms) 2nd = prodromal (mild signs and symptoms) 3rd = manifest 4th = convalenscent Most symptoms do not occur until the organ or system has already gone through several stages of malfunction. In other words, we don´t know we are sick until we experience symptoms; by that time, the body is already significantly compromised (ex. 5 stages: deviation, abnormality, malformation, symptoms, death)! What is the time course of disease? - peracute, acute, subacute and chronic What are the results of disease? - ex recovery, either full restitution or partial, it can become a chronic disease or it can result in death, either the death is physiological (natural death) or pathological (caused by disease/accident) Note : diseases have two course types : benign or malignant course What does exacerbation mean? - it means the occurrence of repeated episodes of acute attacks of the disease in the course of chronic disease What does recidivation mean ? - is when the disease is interrupted by full or partial recovery for a certain time and it flares up again What does remision mean - is when some symptoms and signs disappears or loss their intensity in the course of a chronic disease

Q4) Generla Concepts of health and disease

What is the general etiology of health? - health is defined as the stage of optimal physical, mental and social well being, and not the absence of disease and infirmity. This is the state where the body is able to meet the demands and to adapts to the demands or changes of external environment to maintain resonable constancy of internal environment. - Health is looking at the totality of a person´s existence. Were you have physical, psychological, emotional, social, spiritual and environmental factors playing the overall quality of a person´s life. What is the general etiology of disease? - it has to do with the causes and conditions of diseases onset! (See Q2 about main noxas)** What is the pathogenesis of disease? - in the case of many diseases, multiple factors affect the disease pathogenesis, For example, an individual may have a genetic predisposition to a disease, but the disease may not actually occur unless certain environment factors are also present. Similarly, some kinds of infectious disease are often fought off by an infected individual without any symptoms ever appearing. Such infections might cause disease, for example, only if the bacteria or virus that causes it are present, and at the same time the immunity of the infected person is weakenede by malnutrition or a disorders of the immune system - There are many different types of disease pathogenesis. These include invasion of the body by viruses or bacteria, inflammation as a response to chemicals, physical trauma, the presence of cancerous cells, and many different kinds of genetic disorders. As there are so many possible origins of disease, doctors and researchers who study disease pathogenesis often specialize in one particular field of pathogenesis (See q2 how the noxas act in the body)** How does health and disease have a connection to each other? - there may be a connection since you can measure health in a negative sense by measuring ex disease together with also death, discomfort, disability and dissatisfaction (the 5d*s) - there is also a connection since free from symptoms of the d isease and pain is one of the positive wellness in creating good health. Other involvements in this positive direction is the ability to be active, and being in good spirit!