midterm patho

• abnormal changes in the size and shape and organization of mature cells
• ☞not considered a true adaptive change but is related to hyperplasia
• ☞is often called atypical hyperplasia
• ☞classified as mild, moderate or severe or low or high grade

• ~reversible replacement of one mature  cell by another
• ~replacement of normal columnar ciliated epithelial cells of the bronchial lining by stratified squamous epithelial cells
• ~thought to develop from reprogramming of stem cells existing in most epithelia or of undifferentiated mesenchymal cells present in connective tissue

• ~activated by dry mouth, hyperosmolarity, and plasma volume 
• ~receptors cause  thirst

• secreted when plasma osmolality increases or circulating blood volume decreases and blood pressure drops
• increased plasma osmolality occurs with a water deficit or sodium excess in relation to water.
• increased osmolality  stimulates hypothalamic osmoreceptors causing thirst and signals the posterior pituitary to release ADH
• ADH increases the permeability  of renal tubular cells to water increasing water reabsorption and promoting the restoration of plasma volume and blood pressure
• urine concentration  increases the reabsorbed water decreases plasma osmolality, returning it toward normal 
• ADH is regulated by a feedback mechanisms. The restoration of plasma osomalility, blood volume and blood pressure then inhibits ADH secretion

• stimulate the release of ADH
• located in the right and left atria and large veins and in the aorta, pulmonary arteries and carotid sinus
• when pressure drops baroreceptors signal the hypothalamus to release ADH
• ADh also stimulate arterial vasoconstriction

• an elevated serum phosphate level of more than 4.5 mg/dl develops with exogenous or endogenous addition of phosphorus to the ecf or with significant loss of glomerular filtration
• hypoparathyroidism can cause elevated phosphate levels by increasing renal tubular reabsorption of phosphate
• high levels of serum phosphate also lower serum calcium levels and increase amounts of phosphate and calcium deposited in bone and soft tissue
• may cause symptoms of hypocalcemia and tetany
• symptoms are related primarily to low serum calcium levels and are comparable to hypocalcemia
• to correct administered aluminum hydroxide may be administered because it binds phosphate in the GI tract and is eliminated

• is a major intracellular cation
• 40-60 stored in muscle and bone and 30 in the cell
• regular metabolism is balanced by the small intestines and kidney
• low serum levels caues renal conservation of mag
• mag is a cofactor in intracellular enzymatic reactions, protein synthesis, nucleic acid stability, and neuromuscular excitability
• Calcium and magnesium often interact in reactions at the cellcular level
• reduces vulnerability to oxygen derived free radicals and systemic inflammation, improves human endothelial function  and inhibits platelet function , including aggregation and adhesion

• occurs when serum concentration is less than 1.5 meq and increases in neuromuscular excitability and tetany are present
• is associated with insulin resistance, diabetes mellitus
• magnesium inhibits potassium channels, loss of mag results in movement of potassium out of the cell with renal excretion resulting in hypokalemia
• sign and symptoms og hypomag are similar to hypocalcemia

• magnesium concentration is greater than 2.5 meq
• is rare and unusual caused by renal failure
• excess magnesium depress skeletal muscle contraction and nerve function
• signs and symptoms include nausea  vomiting, muscle weakness,hypotension,bradycardia and respiratory depression

directional movement of cells along a chemical gradient formed by chemotactic factor

• attracts neutrophils and ECF-A attracts eosinophils to site of inflammation
• neutrophils are the predominant leukocytes at work during the early phase of acute inflammation and eosinophils have several functions in the inflammatory process

activated mast cells begin new synthesis of other mediators of inflammation including those derived from  plasma membrane lipids cytokines and factors that stimulate cell growth and angiogenesis

• are acidic sulfur-containing  lipids that produce effects similar  to those of histamine, namely smooth muscle contraction, increased vascular permeability, and perhaps neutrophil and eosinophils chemotaxis
• appear to be important in later stages of the inflammatory response because they stimulate slower and more prolonged responses than histamines

• product of arachidonic acid and cause increased vascular permeability and neutrophil chemotaxis
• induces pain
• is blocked synthesis  by aspirin and other anti-inflammatory  drugs

• mast cell derived lipid
• produced by removal of a fatty acid  from the plasma  membrane phospholipid phosphatidylcholine by phospholipase

assembly,remodeling of the collagen matrix, epithelialization of the wound bed and contraction of the woulnd

• the amino acid methionine that is found in protein is converted to cysteine, the role of which in collagen synthesis is twofold;
• 1 functions as an important  cofactor in the enzymatic reactions required for collagen synthesis
• 2 contains sulfur , which contributes to formation of the strong covalent  bonds in cross-linked collagen fibrils

• raised scar  that extends beyond the original boundaries of the wound 
• invades surrounding tissue and recur after surgical removal

• raised scar that remains within original boundaries of the wound
• regress over time whereas keloids do not
• both keloid and hypertropic are caused by imbalance between collagen synthesis and collagen degradation in which synthesis is increased relative to degradation

• suppressed by antiinflammatory  steroids hypoxia and nutritional deficiencies
• antiinflammatory steroids inhibit phagocyte production of the biochemical mediators required for epithelialization, hypoxemia deprives cells of the energy required for the process, and dietary zinc is necessary for the MMP activity that is crucial to cellular migration

• a member of the retrovirus family  which carries genetic information  in the form of two copies of RNA
• retroviruses use a viral enzyme  reverse transcriptase to convert RNA into double stranded DNA
• using a second viral enzyme  an integrase the new dna is inserted  into the infected cell genetic material  where it may reman dormant 
• if the cell is activated translation of the viral information  may be initiated  resulting in the formation  of new virions, lysis and death  of the infected cell and shedding of  infectious HIV particles

• communicability-ability to spread
• immunogenicity-ability of pathogens to induce an immune response
• infectivity-ability of pathogen to invade and multiply in the host
• mechanism of action-how microorganism damages tissue
• pathogenicity-ability of an agent to produce disease success
• portal of entry-route which organism infects host
• toxigenicity-ability to produce soluble toxins or endotoxins factors that affect degree of virulence
• virulence- capacity of a pathogen to cause severe disease

• endemic-high but constant rates of infection in a particular population
• epidemic-number of new infections in a population greatly exceeds the number 
• pandemic-spreads over a large area such as a continent

• secretion during stress is beneficial
• pooling of amino acids from catabolized proteins may ensure amino acid availability for protein synthesis in certain cells 
• decreased immune cell activity by cortisol may be beneficial in some situations because it prevents immune mediated tissue damage by prolonged cell exposure to high levels of cytokines
• cortisol induced effects are adaptive or destructive may depend on the intensity type and duration of the stressor, and the subsequent concentration and length of cortisol exposure that target  cells of the indidviual

regulated by chemical factor-blood glucose or calcium level and endocrine factors and neural control-stress induced release of catecholamines

• provides precise monitoring and control of cellular environment 
• most common is negative feedback
• negative feedback occurs because the changing chemicals neural or endocrine response to a stimulus negates the initiating  change that triggered the release of the hormone
• negative feedback systems are important in maintaining hormone concentrations within physiologic ranges.

• secretion from the anterior
• pituitary is stimulated by thyrotropin-releasing hormone from the hypothalamus 
• secretion of tsh stimulates the synthesis and secretion of thyroid hormone 
• increasing levels of t4 and t3 then generate negative feedback  on the pituitary and hypothlamus  to inhibit TRH and TSH synthesis

• once released into the circulatory system  they are distributed throughout the body
• peptide or protein hormones are water soluble and circulate  in free forms 
• water soluble hormones generally have short half lives because they are catobolized by circulating enzymes 
• only free hormones can signal a target cell
• because an equilibrium exist  between the concentration  of free hormones  and hormones bound  to plasma proteins , a significant change  in the concentration  f binding proteins  can affect the concentration of free hormones  in the plasma

• target cell receptors have 2 main functions 
• 1. to recognize and bind with high affinity to their particular hormone
• 2. to initiate a signal to appropriate intracellular effectors 

• the sensitivity of the target cell  to a particular hormone  is related to the total number of receptors per cell; the  more receptors the more sensitive the cell
• low concentration of hormone increase the number of receptors  per cell called up-regulation
• high concentration of hormone  decrease the number of receptors  called down regulation
•  the cell can adjust it sensitivity to the concentration of the signaling hormone

• secretes 2 polypeptide hormones 
• 1. ADH
• 2.oxytocin they differ by only 2 amino acids
• they are synthesized  with carrier proteins  in the supraoptic and paraventricular nuclei of the hypothalamus
• once synthesized  these hormones are packaged  in secretory vesicles and are moved down axons of the pituitary stalk to the pars nervosa storage 
• the posterior pituitary can be seen as a storage  and releasing site for hormone synthesized in the hypothalamus
• the release of adh and oxytocin is mediated by cholinergic and adrenergic neurotransmitters the stimulus release is glutamate whereas major inhibitory input through GABA

• major homeostatic function of the posterior pituitary is the control plasma osmolality  regulated by adh
• adh acts as a vasopressin 2 receptors of the renal tubular cells to increase their permeability leads to an increase in water reabsorption into blood and the production of more concentrate urine 
• the secretion of adh is regulated primarily by the osmoreceptors of the hypothalamus, located near or in the supraoptic stimulated, the rate of adh secretion increases, more water reabsorbed from the kidney, and the plasma is diluted to set point osmolality

• thyroid gland produces 90% t4 and 10%t3
• once released into circulation t3 and t4 are transported bound to one of three proteins
• 1 thyroxine-binding globulin
• 2 thyroxine-binding prealbumin
• 3 thyroxine-binding albumin
• t4 is converted to t3
• t3 binds to 3 diff receptors tra1, trb1 trb2
• thyroid hormone affect metabolism by altering protien,fat, and glucose metabolism and as a result heat production and oxygen consumption are increased
• t3 stimulates the synthesis of specific contractile proteins
• hyperthyroidism which is associated with elevated level or thyroid hormone cardiac effects include increased heart rate and cardiac output
• thyroid hormone also affect the respiratory center
• thyroid hormone stimulates bone resorption and hyperthyroidism is associated with osteopenia,hypercalcemia and hypercalciuria
• c-cells are found in the tissue of the thyroid are parafollicular cells
• c-cells secrete various polypeptides including calcitonin which acts to lower serum calcium levels by inhibiting bone reabsorption osteoclast

• produces pth which works with vitamin d by increasing serum calcium concentration
• hyperphosphatemia leads to hypocalcemia because of calcium phospahet precipitation in soft tissue and bone

• pathophysiologic features of siadh are enhanced renal water retention which results from the action of adh on renal collecting ducts where it increases their permeability to water thus increasing water reabsorption by the kidneys
• symptoms of siadh results from hypotonic hyponatremia and are associated with hypervolemia and weigh gain
• thirst impaired taste, anorexia,dyspnea on exertion fatigue and dulled sensorium occur when the serum sodium level decreases
• severe gastrointestinal symptoms occur with drop of sodium level 
• diagnosis of siadh requires documentation of the following manifestation
• 1)serum hypoosmolality<280 and hyponatremia sodium level <135 
• 2) urine hyperosmolarity
• 3)urine sodium excretion that  matches sodium intake
• 4) normal renal adrenal, and thyroid function
• 5) absence of conditions that can altar volume status

• evaul include measurement of tropic hormones from the pituitary and target endocrine glands 
• radiographic assessment of the pituitary
• treatment of hyperpituitarism involves replacing target gland hormones  that are deficent

• pituitary adenoma are usually benign slow growing tumors that arise from cell of the ant pituitary thoses that secrete GH and prolactin
• pathogenesis of pituitary adenoma include hypothalamic and intrapituitary factors, including altered expression of pituitary cell cycle genes 
• local expansion of pituitary adenomas  may neurologic and secretory defects
• neurologically the tumor may impinge on the optic chiasm if it extends upward from the sella turcica
• pituitary adenomas arise from hormone producing cells of the pituitary and associated with increased secretion of GH and prolactin

• occurs in adults who are exposed to excessive levels of GH
• increased gh levels on long bone growth is termed gigantism
• most common cause of acromegaly is a primary autonomous gh-secreting pituitary adenoma

• toxic multinodular goiter occurs when there are several hyperfunctioning nodules leading to hyperthyroidism
• if only one nodule becomes hyperfunctioning it is termed solitary toxic adenoma

• rare but dangerous worsening of the thyroxic state in which death can occur in 48 hours 
• symptoms are caused by the increased action of thyroxine and triiodothyronine exceeding metabolic demands

• caused by deficient production of th by the thyroid gland 
• most common disorder of the thyroid 
• primary is most prevelent 
• central is less common includes conditions that couase pituitary or hypothalamic failure with failure to stimulate normal thyroid function 
• subclinical is mild thyroid failure  it is defined as elevation in tsh level with with normal levels of circulating TH
• in primary hypothyroidism the loss of functional thyroid tissue leads to a decrease production of th
• central is caused by pituitary failure  to synthesize adequate amounts of tsh or lack of trh 
• secondary are tumors that compress surrounding cells

• occurs with hypercalcemia and hyperphosphatemia
• in primary hyperparathyroidism hypercalcemia affects proximal renal tubular functions causing hypercalciuria metabolic acidosis and production of alkaline urine 
• hypercalcemia impairs the concentrating ability of the renal tubule by decreasing response to adh it also affects the muscular nervous and GI systems

• abnormally low pth levels caused by damage to the parathyroid gland 
• lack of circulating pth causes a decrease in pth secretion and function 
• lack of pth causes depressed serum calcium level and increased phosphate level

• polyuria and dehydration result from the osmotic diuresis associated with hyperglycemia
• symptoms include kussmaul respiration,postural dizziness, central  nervous system  depression ketonuria,anorexia,nausea abdominal pain thirst and polyuria 
• symptoms include vomiting  abdominal pain dehydration  an acetone odor  on the breath and change in sensorium
• diagnosis: serum glucose level >250:serum bicarbonate level ,18 serum ph ,7.30 presence of anion gap
• and presence of urine serum ketones
• treatment involves admin of insulin to decrease glucose levels and fluids

• is a life threatening emergency  most often precipitated by infection,medication nonadherence to diabetes treatment 
• commonly seen in t ype 2 diabetes 
• differs from dka in the degree of insulin deficiency and degree of fluid deficency 
• is charactrized by lack of ketosis  because the amount of insulin required to inhibit fat break down is less than that needed for effective glucose transport 
• glucose levels are considerable higher than in dka because of volme depletion
• glycouria and polyuria result form extreme serum glucose level elevation which causes sever volume depletion, increased serum osmolarity intracellcuar dehydration and loss of electrolyte including potassium 
• dehydration is more severethan dka

• combination of hypoglycemia followed by rebound hyperglycemia
• rise in blood glucose concentration occurs  because hormones are stimulated by hypoglycemia

early morning rise in blood glucose concentration with no hypoglycemia during the night

• risk factors are advanced age male gender or women after menopause or family hx
• risk include dyslipidemia,hypertension,cig smoking,diabetes,obesity, sedentary lifestyle,atherogenic

• refers to lipids, phospholipids, cholesterol and triglycerides bound to a protein carrier
• low density lipoproteins aka ldl
• increased serum concentration of ldl is a indicator of coronary risk 
• ldl is responsible for delivery of cholesterol to the tissue 
• ldl is controlled by hepatic receptors

• abnormal concentration of serum lipoproteins 
• half of us population has some form

• angina pectoris is chest pain caused by myocardial ischemia pain is caused by buildup of lactic acid or abnormal stretching of the ischemic myocardium that irritate  nerve fibers
• stable angina is caused by gradual luminal narrowing and hardening of the arterial walls ,affected vessels cannot dilate in response to increased myocardial demand

• chest pain attriubutable to transient ischemia of the myocardium that occurs unpredictable at rest 
• pain is caused by vasospasm of one or more major coronary arteries with or without atherosclerosis 
• pain often occurs at night during rapid eye movement sleep and may have cyclic pattern occurrence

• form of acute coronary syndrome that result in reversible myocardial ischemia 
• occurs when fissuring or superficial erosion of the plaque leads to transient episode of thrombotic vessel occlusion and vasoconstriction at the site of plaque damage
• ecg most commonly reveals st-segment depression and t-wave inversion during pain that resolves as the pain is relieved

• when coronary blood flow is interrupted for an extended period of time ,myocyte necrosis occurs this results in MI
• pathologically there are two major types 1 subendocardial infarction 2 transmural infarction
• plaque progression, disruption and subsequent clot formation  is the same for myocardial infarction as it is unstable angina
• the duration of ischemia determines the size and character of the infarction if the thrombus breaks up before comple  distal tissue necrosis has occurred the infarction will involve only the myocardium
• the infarction usually involves with st-depression and t-wave inversion and is termed non-stemi
• recuurrent clot formation on the dirupted athersclerotic plaque is likelyto occur unless intervention is taken
• if the thrombus lodged permanently in the vessel the infarction will extend through the myocardium to epicardium resulting in cardiac disfunction

• occurs a few weeks after the initial infection in about 50% of pts with acute rheumatic fever
• earliest cardiac manifestation of acute rheumatic fever may be undetected murmur  caused by mitral or aortic semilunar valve dysfunction

• inflammation of one or more joints 
• large joints of the extremities are most commonly affected 
• exudative synovitis causes heart redness and swelling ,severe pain and tenderness  but not permanent diabillit

• failure of the PDA to close result in persistent patency  of the ductus .
• the effect is increased pulmonary blood flow resulting in increased pulmonary venous return to the LA and LV with increased workload on the left side of the heart
• increased workload is caused by increased pulmonary venous return to the la      and increase right ventricular pressure
• infants with pda will have continuous machine type murmur heard in upper sternal border infant will have bounding pulse an active precordium
• chest radiographs will reveal cardiomegaly and increased marking
• most widely used method for pda closure is surgical closure involving ligation and division of the ductus with complete closure
• pda during catheterization catheter is is advanced into ductal opening devices placed into the lumen that prohibit flow 
• closure through VATS

• increased co2 concentration in the arterial blood caused by hypoventilation of the alveoli
• caused by decreased drive to breath or inadequate ability to respond to ventilatory stimulation
• causes include depression of respiratory center by drugs, disease of the medulla,abnormalities  of the spinal conducting pathways, disease of the neuromuscular junction of the respiratory muscles, thoraic cage abnormalities, large airway obstruction ,increased work of breathing
• associated with respiratory acidosis

• reduced oxygenation of arterial blood  caused by respiratory alterations 
• hypoxia is reduced oxygenation of cells in tissue 
• results from 1.oxygen delivery to the alveoli 2. ventilation of the alveoli 3, diffusion of oxygen from the alveoli into the blood 4. perfusion of pulmonary capillaries

• presence of air or gas in the pleural space caused by a rupture in the visceral pleura or the parietal pleura and chest wall
• as air separates it destroys negative pressure of the pleural space 
• disrupts equilibrium that exist between elastic recoil forces of the lung and chest wall

• occurs unexpectedly 
• caused by spontaneous rupture of blebs  on the visceral pleura
• seconady (traumatic)- caused by chest trauma or a surgical procedure  that tears the pleura
• iatrogenic-most common caused by transthoracic needle aspiration
• open-air pressure in the pleural space equals barometric pressure because air that is drawn into pleural space during inspiration is forced back out during expiration
• tension-site of pleural rupture acts as a one way valve permitting  air to enter on inspiration but preventing its escape  by closing during expiration
• physical examination revealed absent or decreased breath sounds and hyperresonance
• treated by insertion of chest tube that is attached to a water seal drainage system

• presence of fluid in the pleural space 
• pleural is relatively  permeable membrane fluid that accumulates in the lung can cross into pleural space  can be transudative and exudative

the fliud or transudate is watery and diffuses out of the capillaries

less watery and contains high concentration of white blood cells and plasma proteins