Patho Exam Review

Cellular function Mitochondria - oxidative phosphorylation - ATP production; contain their own DNA Importance of ATP and oxidative phosphorylation: - 95% of ATP production; 20x more compares to anaerobic metabolism - Cell di erentiation, growth and reproducti...

Cellular function Mitochondria - oxidative phosphorylation - ATP production; contain their own DNA Importance of ATP and oxidative phosphorylation: - 95% of ATP production; 20x more compares to anaerobic metabolism - Cell di erentiation, growth and reproduction, thermogenesis, muscular contraction Homeostasis : pH, temperature, electrolytes, uids regulation Inability to produce ATP via oxidative phosphorylation can negatively impact homeostasis Nucleus-storing and protecting genetic information; protein synthesis, etc Genes - functional segment of DNA Gene expression - transforms coded into in a gene to a nal gene product Protein synthesis - Transcription : DNA —> RNA code —->mRNA produced -messenger RNA: single -stranded nucleic acid; carries a copy of the genetic code for a single gene out of the nucleus and into the cytoplasm - Translation: mRNA attached to ribosome on rough ER - Transfer RNA bring amino acids to ribosomes to build the protein - Once built, mRNA detached and protein is released - Transportation : nished protein secreted into a transport molecule; travels o the GA - GA releases protein into secretory vesicle and is carried to the surface of the cell to be released Lysosomes and peroxisomes - clean up - Peroxisome: detoxi es molecules, uses enzymes: calabash and oxidases; inside has free radicals- hydrogen peroxide - Lysosome : breakdown excess or worn out cell parts, auto digests cells after death, has enzymes, low pH Transport mechanisms - Passive : no energy, di usion with gradient - Simple di usion: across membrane without protein channel - Facilitated : uses protein channel ff ff fi fi ff fl fi - Active: energy required, moves against the gradient Cells need to have low concentration of Na and high of K Outside of the cell should be high Na and low K. Endo and exocytosis - substances are too large for membrane or channel; they are enclosed in vesicle - endo/ expels the contents of - exo Cell adaptation - Normal cell —-> stress—-> adapted - Not adapted—-> cell injury—> mild temporary—-> reversible injury—-> normal cell - Not adapted—> irreversible injury —-> cell death Atrophy- cell shrink but stay alive Hypertrophy- cells get bigger Hyperplasia- increase the number of cells, ex endometriosis Metaplasia- change in the morphology of cells, one type of tissue converts into another Dysplasia - pathological change, not adaptive alteration Neoplasia - abnormal cellular replication, tissue growth and lifespan Cell injury - physiological stress or pathological stimuli; if the injury is too severe a ected cells die Causes of cell injury: Hypoxia, ischemia Chemical agents - drugs and alcohol Physical agents Injections Psychosocial stressors, psychosocial trauma Genetic defects Nutritional defects Aging Free radicals - Chemically unstable and readily react with other molecules, turning them into free radicals - Results in chemical damage ff  - Created by ionizing radiation, redox reactions, metabolism or exogenous substances - If not neutralized they cause cell injury : lipid peroxidation-membrane damage, protein modi cation- increased degeneration or loss of activity, DNA damage- mutations Cell death Necrosis Cell swells up and burst,disorderly, no energy required, cellular contents leak out, in ammation present, not physiological; Apoptosis Cells shrivel up and bleb, orderly, requires energy, cellular contents packaged into apoptotic bodies for digestion, no in ammation, usually physiological - cell turn over Neoplasm Benign Cells similar to normal tissue, grows slow, pushes on but not invades surrounding tissue, does not metastases Malignant Cells lack the di erentiation of normal, slow or fast grow, invades surrounding tissues, metastatic Hallmarks of cancer Self-su ciency in growth signals Insensitivity to growth inhibition Altered cellular metabolism Evasion of apoptosis Immortality Sustained angiogenesis Ability to invade and metastasize Ability to evade the human immune response How cancer spreads Invasion Moves thru the walls of nearby vessels or lymph nodes fl fi ffi ff fl  Grow in the new tissue until a tiny tumor forms Create blood supply which allows it to grow Fluid regulation Extracellular - interstitial and intravascular Intracellular - inside the cell Intracellular ions : K+, phosphate, organic ions Extracellular ions: Na+, Cl-, HCO3 Inside the cell: low Na, high K Outside the cell : high Na, low K Ion imbalances Hypernatremia : thirst, confusion, neuromuscular excitability, seizures, coma Hyponatremia: headache, confusion, stupor, seizures, coma Hyperkalemia : progressive muscle weakness- placid paralysis, arrhythmia Hypokalemia - spastic paralysis, fatigue, cramps, arrhythmia Hypercalcemia - cognition chances, confusion, coma, muscle weakness, arrhythmias Hypokalemia - irritability, anxiety, paresthesia, brochospasms, heart failure, muscle cramps Capillaries - can become leaky- increased capillary permeability - caused by : infection, meds, in ammation, burns - Leaking water, ions, proteins, cells to interstitial space Fluid pressure Hydrostatic - pressure exerted by a uid against a barrier or wall Oncotic - is the osmotic pressure generated by large molecules - especially proteins - insulation. It results from di erence within the extracellular uid between the protein contents of plasma and interstitial uid. fl ff fl fl fl  Filtration - movement of uid moving out of the vascular space; major force is hydrostatic pressure pushing uid out of the capillary Reabsorption - movement of uid moving back into the vascular space; major force is capillary oncotic pressure There is always net ltrate and lymph system drains excess out of the interstitial space Edema Common causes: blood clot, renal failure, in ammation, lymph blockage, liver failure, heart failure. Increased capillary permeability caused loss of plasma proteins in interstitial space and increased tissue oncotic pressure, which causes edema. Lymph obstruction causes uid movement into tissues and edema. Increased capillary hydrostatic pressure ( venous obstruction, salt and water retention, heart failure) cause uid movement into tissue —> edema. Decreased synthesis of plasma proteins; increased loss of plasma proteins( nephritic syndrome) , increased plasma Na and H2O retention cause decreased capillary oncotic pressure—> edema. RAAS Decreased renal perfusion or low oxygen is detected by kidneys and they release renin. Angiotensinogen ( liver ) is activated by renin into angiotensin I. Angiotensin I into angiotensin II thanks to angiotensin-converting enzyme ( lungs) Angiotensin II stimulates adrenal cortex to produce aldosterone. Angiotensin II causes arterioles to constric—-> BP goes up Aldosterone causes kidneys to retain sodium and water—> increased extracellular uid—> higher BP Anti-diuretic hormone Secreted by the posterior pituitary gland Production of more concentrated urine to reduce uid loss from urination Syndrome of inappropriate ADH secretion ( SIADH) Too much is secreted Urine is excessively concentrated; too much free water is retained Leads to hyponatremia fl fl fi fl fl fl fl fl fl Inadequate ADH- Diabetes Insipidus Urine is excessively dilute; too much free water is lost Hypernatremia Hematology Acid/ base balance -even small changes in hydrogen ion concentration can alter the rates of metabolic reactions; shift the distribution of other ions, modi cation of hormone actions. Metabolic Acidosis fi  - excessive buildup of acid or excessive loss of bicarbonate- anion gap can help determine the cause - pH low, CO2 ok, HCO3 low Anion gap - Di erence in cation+ and anion- in the plasma. Tells us if metabolic acidosis is build- up of hydrogen or loss of bicarbonate. - Normal anion gap is 12 mmol/L. - Causes: chronic diarrhea, pancreatic issues, renal tube acidosis. Elevated anion gap: - Excessive build-up of acid - Causes: lactic acidosis, ketoacidosis, other renal failures, medications, inherited metabolic disorders Metabolic alkalosis -loss of acid from blood, excess bicarbonate -Excessive vomiting, hyperaldosteronism, diuretics. - pH high, CO2 ok, HCO3 high Respiratory acidosis - excessive build -up of carbon dioxide - Hypoventilation, dissuasion issues, obstructive disease - pH low, CO2 high, HCO3 ok Respirator alkalosis - Excessive loss of CO2 - Hyperventilation, altitude sickness, panic attacks - pH high, CO2 low, HCO3 ok The body is comprised of a large amount of water which is distributed between the intracellular and extracellular (interstitial and intravascular) compartments. ff  Ions and other solutes are maintained in these compartments by energy-dependent mechanisms. The Starling equation predicts if uid will e ltered into the interstitial space of reabsorbed into the vasculature, depending on hydrostatic (push uid out) or oncotic forces ( pull uid in). Forces on the arterial side of the capillary favor ltration while in the venous side favor reabsorption. Components of blood: plasma, RBC, WBC, platelets. Plasma -liquid portion of the blood- 55% - contains albumin, globulins, clotting factors ( brinogen and prothrombin) - Plasma proteins are made in liver - except for Ig- made by plasma cells in lymph tissue - Most abundant is albumin - has role in maintaining the oncotic pressure. Cells and platelets - 45% of blood - 99% of formed elements are RBC, increased oxygen carrying capacity of blood - Kidney detects increased oxygen and shuts down EPO production when adequate Hemoglobin -protein consisting f 4 heme rings each with an iron atom -iron in heme carries oxygen -each heme ring can carry one oxygen molecule - 1 Hgb carries 4 oxygen molecules - Removed by macrophages in the spleen, liver or bone marrow; heme broken into iron and bilirubin, global broken into amino acids, bilirubin is excreted Hemoglobin A- most common, majority of healthy adults Others - HgbF, Hgb S Nutrients needed to make heme components: - Iron - needs vitamin C to keep iron in 2+ state, and copper to brig it from tissues to the bone marrow.  - Heme ring needsB6 and pantothenic acid - Cells: need folate, B12, B2 and protein to carry Hb - Also need niacin and vitamin E. Oxygen carrying - PaO2- partial pressure of oxygen - oxygen is dissolved in arterial blood; measure go how well O2 is able to move from lungs into blood stream and tissues. -Oxygen saturation- % of Hb sites in the blood that are carrying oxygen relative to all Hb -O2 a nity - how much does Hb want to bind oxygen to itself. Oxygen -Hb dissociation curve LEFT shift - higher Hb-O2 a nity - more binding of O2, less letting it go into tissues - Lower CO2 - Higher pH - basic -alkalosis - Lower temperature RIGHT shift - reduced a nity Hb-O2; Hb wants oxygen to leave and go the tissues - higher CO2- - Lower pH- acidic- acidosis -lactic acid - Higher temperature Anemia Normocytic, normochromic: - normal cells, normal color - Low RBC production or high consumption - Causes : bone marrow defects, leukemia preventing production, chronic disease, hemorrhage, hemolysis, malignancy ffi ffi ffi  Microcytic, hypochromic - small cells, low color -not enough heme - Chronic blood loss from malignancy, iron de ciency, hemoglobin defects Macrocytic, normochromic - big cells, normal color Folate or B12 de ciency Signs and symptoms - Fatigue - Tachycardia, - DOE - Diaphoresis - Leg cramps - Insomnia Diagnosis: -CBC: Hb, Htc, MCV, - iron levels Sickle Cell Anemia -autosomal recessive disease -Proteins undergo polymerization- sickling of RBC’s -B/L pain, edema, acute chest syndrome, glomerular disease, infection -Abnormal HbS present —> hypoxemia, low pH, low temp and /or decreased plasma volume —-> persistent hypoxemia —-> either reversal of hypoxemia or sickled cells clog vessels —> increased sickling, slow blood ow —> decreased blood pH, decreased Hb a nity for O2, PO2 drops —> increase in sickling, ffi fi fi fl  Coagulation 1. Constriction of blood vessels 2. Formation of temporary platelet plug 3. Activation of clotting cascade 4. Formation of ring plug Platelets - Regulate blood ow to damaged areas of blood vessels - Form platelet plug to stop further bleeding - Activate clotting cascade - Initiate repair processes including eventual clot breakdown Platelet activation - initiated by damage to the endothelial lining of blood vessel wall - Bing to the defect, change shape and stick together, activate the clotting cascade to bind brinogen and deposit brin - Involves thrombin, vonWillenbrand factor etc. Intrinsic pathway - Activated by the internal damage to the vascular endothelium, such as exposed collagen - Plasma factors: FXI, FIX and FVIII Extrinsic pathway - activated by external trauma, such as tissue factor released by endothelial cells - Tissue factor and plasma factor VII/VIIa Common pathway -Factor X—> Xa—-> prothrombin into thrombin -Thrombin activated brinogen —-> brin fi fi fl fi fi fi  - Factor XIIIa brin into stable brin clot Clotting factors are made mainly in liver, endothelial cells, lungs. Vitamin K - makes coagulation factors functional - II, VII, IX and X are dependent on vit K - Comes from diet and intestinal bacteria Factor 8 - produced by endothelium vWF - circulates in blood carrying factor 8 De ciencies or defects in either lead to -Hemophilia A or vWD. Hemophilia - X-linked recessive disorder, males >females - Bleeding, bruising - Hemophilia A- factor 8 de ciency - Hemophilia B- factor 9 de ciency Fibrinolysis - Plasminogen activated by T-PA and becomes plasmin - Plasmin breaks down the brin clot into brin degradation products fi fi fi fi fi fi fi - T-PA clinical application : as IV med to break down the clots; small doses to break down clots that have formed in venous access devices and larger doses for those having an ischemic stroke to restore blood ow. Lab evaluation -D-dimer in plasma or whole blood indicates that brin has been formed and degraded; - D-dimer is elevated in PE/DVT Counteractions to coagulation -prostaglandins - inhibit platelets aggregation -nitric oxide: inhibits platelet adhesion and aggregation - tissue factor inhibitor - Anti-thrombin III- turn o thrombin Medications -Aspirin -inhibits platelet activation -Plavix - prevents binding to brynogen -Heparin-indirectly blocks thrombin, factor IX,X and XI; testing : PTT and anti-Xa -Warfarin- decreases vitamin K dependent factors, testing :PT/INR PT- measure of seconds it takes for blood to clot PTT- examines clot ampli cation and propagation. INR- normalized ratio of PT across lab ff fi fi fl fi  Immunity Antigen - foreign substance in the body, bacteria, virus etc WBC Granulocytes - neutrophils, eosinophils, basophils - abundant granules in cytoplasm; nonspeci c (innate) resistance to disease Neutrophils - phagocytic; e ective against bacteria, releases cytotoxic chemicals, most common leukocyte Eosinophils- phagocytic, e ective with antigen-antibody complexes, releases antihistamines. Increase in allergies and parasitic infections Basophils- promotes in ammation. Agranulocytes - body defenses Lymphocytes - primarily speci c ( adaptive) immunity. - T- cells directly attack other cells ( cellular immunity) - B-cells release antibodies ( humoral immunity) - Natural killer cells - similar to T cells but nonspeci c. - Initial cells originate in bone marrow, but secondary production occurs in lymphatic tissue; several distinct subtypes; - Memory cells form after exposure to pathogen and rapidly increase responses to subsequent exposure. Monocytes - very e ective phagocytic cells engul ng pathogens or worn out cells; also serve as antigen-presenting cells (APCs) for other components of immune system - Produced in red bone marrow, referred as macrophages after leaving circulation. fi ff fl ff ff fi fi fi  Lines of defense 1. First line — constant, cells involved: epithelial; no memory, peptides: defensins, lactoferin, cathelicidins; protection: physical and chemical. 2. Second line - response to injury, immediate, speci city- broad; cells: Mast cells, granulocytes, NK cells, platelets, endothelial; no memory, peptides: complement clotting factors, kinins; protection: vascular responses, cellular components, activation of plasma protein systems. 3. Third line - delay between primary exposure and maximum response- immediate response the second time; very speci c; cells: lymphocytes, macrophages, dendrite cells, speci c memory; peptides: antibodies, complement; protection: lymphocytes and antibodies. Innate immunity - broad, non-speci c, responds the same way no matter what, comprised of 1st and 2nd lines of defense- barriers and in ammation. In ammation: mast cells, monocytes, neutrophils, dendrite cells, NK cells, histamine, cytokines, clotting factors, complement, kinins. - Mast cells- release histamine : vascular dilation and increased capillary permeability; cytokines- pro-in ammatory. - Monocytes/ macrophages - surround and kill microorganisms, ingest foreign material, boost immune response, remove dead cells. - Granulocytes- 1st response to cellular injury/infection; phagocytosis, part of in ammatory process - Dendritic cells- communicate via cytokines between innate and adaptive immune system; migrate to lymph to present antigens to lymphocytes. fl fl fi fl fi fi fi fl  - Cytokines- can be pro or anti- in ammatory; interleukins - produced by WBC in response to antigen/ in ammation; interferons- protect against viral infections and modulate in ammatory response. Plasma protein system - clotting - prevents spread of infection, traps microorganisms at the in ammation site, form s a clot to stop bleeding. - Kinins- bradykinin- dilates blood vessels, causes smooth muscle contraction, increases vascular permeability, increase white cell recruitment. - Complement - plasma proteins in the body, may destroy pathogens directly, activates or collaborates with every other in ammatory response component - NK cells - cytotoxic lymphocyte, rapid response to virus- infected cells, responds to tumor formation, recognize injured or infected cells, release cytokines that tell infected cell to undergo apoptosis. Acute in ammation ( redness, swelling, warmth, pain) - Vasodialation - redness, heat - Vascular permeability- edema - Cellular in ltration- pus - Thrombosis- clots - Stimulation of nerve endings - pain Healing Three phases - in ammation, proliferation and reconstruction, remodeling and maturation. Primary intention - Clean, edges pulled together, allows for sutures or glue, healing from the top, down; minimal scarring. fl fi fl fl fl fl fl fl Secondary intention - Dont have edges that can be pulled together to promote healing ( eg.ulcers); healing from the bottom, up; likelihood of scarring and infection. Adaptive immunity - recognize self vs not-self; long term, speci c immunity to speci c antigens. Antigens presented by cells to lymphocytes. Central cell is lymphocyte, but each can recognize only one antigen Cell mediated immunity - cytotoxic T, CD4+, NK cells Humoral immunity - CD4+, B cells—> plasma cells—> antibody production and release. MHC receptors- antigen -presenting receptors on cell membranes - MHC Class I - all cells except RBC - MHC Class II- found only on professional antigen presenting cells. MHC I present antigens from inside the cell, CD8 + respond and send cytokines to recruit more cytotoxic T cells; NK T cells kill cells that down-regulate this receptor MHC II - dendritic cells, macrophages, B lymphocytes; present antigen from outside the cell; CD4+ helper T cells respond by telling B - cells to make antibodies; professional APC capture antigen —-> lymph node wave the ag —-> T cells see and ask whats wrong —> T cells tell B cells to clone antibodies. Functions of antibodies: - neutralize, agglutinate, precipitate, - Indirect : complement activation - bacterial destruction by lysis; opsonization - help phagocytes recognize what needs to be eaten fl fi fi  Antibodies IgG - most abundant - long term immunity - vaccines; can cross placenta IgA- founding GI, respiratory and GU tracts IgM- acute exposure - immediate response IgE- specialized to mediate allergic reactions and parasitic infections Passive immunity - type of immunity that occurs when a person receives antibodies from another source, other than producing them thru own immune system - immunoglobulins pass thru placenta or colostrum -only last weeks or months Stages of infections disease Incubation - initial exposure to onset of 1st symptoms; hours to years Prodromal - initial symptoms - fatigue, discomfort Invasion - moves beyond initial area of infection into other tissues Covalescence- recovery/ death/ latency Infectious disease agents: bacteria, viruses, protozoa, fungi, prions, parasites Endotoxic shock - form of septic shock caused by LPS endotoxins - Gran negative bacteria infection producing endotoxins prom LPS on cell wall - Massive production of cytokines - In ammatory tissue injuries - Multi-organ failure fl HIV infecting cell HIV binds to the CD4 receptor on the surface of the target cell- CD4+ T cell Once attached the vial envelope fuses with cell membrane allowing viral RNA and protein to enter the host cell. Inside the cell the HIV uses an enzyme revere transcriptase to convert its RNA to DNA Newly formed viral DNA is transported into nucleus of the host cell; enzyme integrates integrates it into hosts’s genome. Host cell’s machinery is used to produce new viral RNA and proteins based on the integrated viral DNA. Immature HIV bud o the host cell; then virus mature into its infectious form. Process repeats as the virus infects more CD4+ cells and weakens immune system. AIDS diagnosis at CD4+ count increased stretch of cardiac muscle bers—-> increased contraction. This will result in increased stroke volume to a point. Ejection fraction - is measured as a percentage of the total amount of the blood in your heart that is pumped out with heartbeat. Normal ejection fraction is 50% or higher. Cardiac output - Stroke volume x heart rate in liters per minute. Normal range is 5-6 liters per minute at rest. Low cardiac output causes lower bp, high = higher bp Compensatory mechanisms to correct or increase cardiac output ff ff fi  Increased heart rate - hearts beats faster to pump more blood Increased stroke volume - more blood with each beat Increased cardiac muscle mass - due to overworking Increased blood volume - the body increases blood volume Increased cardiac lling pressure Sympathetic nervous system activation - release of catecholamines to constrict blood vessels and increase HR. Ventricular remodeling - the heart increased lenticular volume and heart thickness Neurohormonal systems activation - the body activates neurohormonal systems to maintain tissue perfusion Frank- Sterling mechanism- activated to increase bp and therefore cardiac output. Heart structure: Epicardium - outer smooth layer - part of pericardium Myocardium- heart muscle Endocardium - innermost layer Pericardium - double-walled membranous scar surrounding the heart : parietal- surface layer, visceral- inner layer, epicardium, lies against heart surface. Pericardial cavity - space between the parietal and visceral layers. Contains uid -20ml. Prevents displacement of heart during movement. Protects heart fro infection/in ammation and contains receptors that control HR and BP. Cardiac conduction: SA node - pacemaker of the heart, 60-100 bpm; action potential travels to AV node, where it cases ventricles to contact. Then Bundle of His divides into right and left and they conduct impulses to ventricular apex. Purkinje bers and the end of brunched os the bundle. fl fi fi fl  Cardiac conditions Atherosclerosis - thickening and hardening of the vessels. Chronic in ammatory disease Endothelial dysfunction Plaque development and instability leading to vascular events. LDL cholesterol can penetrate vessel walls and becomes trapped Macrophages with lipids inside accumulate, form a “fatty streak”and release in ammatory cytokines. Cytokines stimulate vessel smooth muscle growth, a plaque forms over the fatty streak Plaque can calcify, obstruct blood ow or rupture and become complicated plaque. Plaque rupture exposes the vessel underneath, clot forms and it can obstruct the vessel. Consequences of atherosclerosis: Stroke, renal artery disease, aneurism, PAD, CAD Hypertension Consistent elevation of systemic arterial bp Its responsible for increased risk of atherosclerosis. Risks for primary HTN: Fx, age , gender, ethnicity, hight dietary sodium, glucose intolerance, tobacco, obesity, heavy alcohol consumption, low dietary potassium, calcium and magnesium intake. SNS and HTN fl fl fl  In people with HTN, SNS over-activity ca result from increased catecholamines or increased receptor activity RAAS and HTN In people with HTN RAAS can be overreactive leading to salt and water retention and increased blood vessel tone. Complicated HTN: damages the walls of systemic blood vessels Malignant HTN- hypertensive crisis - rapidly progressive, in which diastolic BP is usually > 140mmHg Aneurysm- localized dilation or outpouching of a vessel wall or cardiac chamber. True aneurysm involve all 3 layers of the wall and its weakening of the wall False aneurysm- leaking of the vessel forming a clot outside of the vessel Varicose veins Vein in which bloods pooled causing distortion of the vein, in ammation Usually in saphenous vein Distended, tortuous and palpable veins Cause trauma or gradual venous distention, rendering valves incompetent Higher risk for developing clots Chronic venous insu ciency Inadequate venous return over a long period as a result of varicose veins, valvar incompetence Pain, swelling, skin changes, venous stasis ulcers, infection risk ffi fl DVT Detached thrombus, can lead to PE Clot in large vein, usually saphenous Risk factors: Virchow’s road : Venus stasis, venous endothelial damage, hypercoagulable state ( smoking, oral contraceptives, cancer, pregnancy etc.) CAD Any vascular disease that narrows or occludes coronary arteries Imbalance between coronary supply of blood and myocardial demand for oxygen and nutrients Common cause atherosclerosis Can lead to myocardial ischemia or infarction Non traditional risk factors : C- reactive protein Troponin I Hyperhomocysteinemia Adiponectin and leptin Microorganisms and periodontal disease Air pollution Coronary artery calci cation, carotid wall thickness Acute coronary syndrome Sudden coronary obstruction because of thrombosis formation over a ruptures atherosclerotic plaque. Unstable angina, MI Complications: dysrhythmias, CHF, sudden death fi  Myocardial ischemia Develops if the supply of coronary blood cannot meet the demand of the myocardium for oxygen and nutrients Stable angina - predictable chest pains Prinzmetal angina- unpredictable chest pain Silent ischemia - no symptoms Angina pectoris - transient substernal chest discomfort Unstable angina Angina at rest and usually more than 20min New-onset - new and symptoms with everyday activities Increasing angina - previously diagnosed, but more frequent, longer duration or increased by less activity Signals that plaque has ruptured, infarction may happen soon MI Two major types: subendocardial and transmural STEMI requires immediate intervention non-STEMI suggests that additional myocardium is still at risk for recurrent ischemia and infarction Heart Failure Decreased pumping or lling ability of the heart which results in decreased cardiac output and uid buildup in the lungs Inability to provide enough perfusion to vital tissues fl fi  Causes CAD MI HTN Smoking Obesity Diabetes Cariomyopathy Heart valve disease Other: Congenital heart disease - number one pediatric Arrhythmia Endocarditis Anemia Lung disease Some drugs Neurohormonal mechanisms to compensate HF Catecholamines: increasing HR and PRV Vasopressin : vasoconstriction and renal uid retention RAAS- increases pre and after load Natriuretic peptides- increase in attempt to decrease preload, but compensation is inadequate Cytokines- in ammatory, cause vasoconstriction Most common HF is left-sided, and it’s the most common cause of RHF. fl fl  Signs and symptoms Right HF JVD Peripheral edema Liver and spleen enragement Ascites GI venous congestion- bloating, nausea, constipation, anorexia Fatigue and weakness Left HF Exertion and nocturnal dyspnea Blood tinged sputum Orthopnea Cough Cyanosis Rales/crackles Fatigue S3 gallop Oliguria Systolic vs. diastolic HF Systolic Left ventricle pumping is impaired and blood backed up to the atrium Left atrium has reduced lling capacity to accept blood from the pulmonary veins Blood backs up to the pulmonary veins Increased hydrostatic pressure in the pulmonary vascular bed causes accumulation of uid in the interstitial and alveolar spaces; pulmonary congestion fl fi Diastolic Hearth failure with preserved ejection fraction Decreased compliance in LV and diastolic relaxation Clinical manifestation - dyspnea on exertion and fatigue. Diagnosis HF: h&p, labs, ekg, chest XR, who, bnp. Renal system Primary function is to maintain a stable internal environment for optimal cell and tissue metabolism. Functions: - balancing solute and water transport - Excreting metabolic waste products - Conserving nutrients - Regulating acids and bases - Endocrine functions - Secreting hormones : renin ( BP regulation), EPO ( RBC production), Vit d3 ( calcium metabolism) - Can also perform gluconeogenesis, synthesizing glucose from amino acids  Features of GU - formation of urine is achieved thru processes of glomerular ltration, and tubular reabsorption and secretion within kidney - Bladder stores urine - Ureters move urine from kidney to bladder - Urine removed thru urethra Kidneys are paired organs located in the posterior region of the abdominal cavity behind peritoneum. Renal capsule surrounds the kidney and then kidney is embedded in a mass of fat. Outer layer of kidney - cortex; contains glomeruli, most of proximal tubules and segments of distal tubules. Medulla forms inner part of the kidney and consists of regions called pyramids Apexes of the pyramids project into minor calyces that form major calyces. The major calyces join and form renal pelvis. Nephron - functional unit of kidney - Subunits include : - Renal corpuscle ( glomerulus, bowman capsule, mesangial cells) - Proximal convoluted tubule - Loop of Henle - Distal convoluted tubule - Collecting duct Glomerulus -Tuft of capillaries that loop into Bowman’s capsule; mesangial cells support the capillaries -synthesizes nitric oxide - vasodilator and endothelin-1 - vasoconstriction to regulate blood ow and control glomerular ltration rate (GFR). fl fi fi  - Capillaries are lined with endothelial cells with fenestrae which allow ltration of uid, plasma, solutes and protein and prevent ltration of RBC,WBC and platelets. - A erent arteriole - bring blood in - Juxtaglomerular cells- produce renin - JGA- formed by a erent arteriole and portion on the DCT - regulates renal blood ow and glomerular ltration - Macula densa - portion of DCT- has specialized Na and Cl sensing cells - Podocytes - adhere to basement membrane of glomerbla capillaries, gaps between them allow ltration. - E erent arteriole - exits the glomerulus. Nephron and BP -GFR - ltration of the plasma per unit of time; directly related to renal blood ow -GFR stays constant over wide range of systolic BP 80-180 mmHg Mechanisms that allow that - a erent arteriole resistance increase/ decrease; if BP increased , resistance is increased - to limit the amount of ow to normal despite higher pressure - Tubuloglomerilafeedback - when GFR is decreased ( and Na delivery to macula densa ) , this stimulated a erent arteriole dilation to increase blood ow and GFR; prevents large uctuations in Na and water in the body. Renal vessels, especially a erent, are innervated by SNS bers. When BP decreases, aortic baroreceptors sense it, increase sympathetic output ( epinephrine) which results in vasoconstriction and decrease GFR. Decreased GFR decreases excretion of Na and water resulting in increase in blood volume -> increase BP RAAS - Renin is formed in JGA, released when BP or GFR are low fl ff ff ff fi fi fl ff fi ff ff fl fi fi fl fi fl fl - It triggers formation of angiotensin which leads to aldosterone secretion from the adrenal cortex - Aldosterone - vasoconstriction, increased thirst, and anti-diuretic hormone secretion - all to increase BP and /or blood volume Tubular reabsorption - movement of the uid and water from tubular lumen to peritubular capillary plasma Tubular secretion - from capillary to tubular lumen Excretion - elimination in the nal urine PCT - reabsorption of most ions Loop of Henle : - thin descending - highly permeable to water, - Thick ascending- actively transports ions into interstitium and passes urine into the DCT DCT- reabsorption and secretion of ions, creates dilute uid, secretes H+, contributing to acid-base balance Collecting duct- principal cells reabsorb Na and water, secrete K; intercalated cells secrete H and reabsorb K. Concentration and dilution of urine occurs mainly in the loop, DCT and collecting duct. Final adjustments are made by distal tubule and collecting duct. Concentration - countercurrent mechanism in the loop of Henle; uid ows in the opposite direction along the parallel loops and concentration gradients; the longer the loops, the more concentrated the urine Dilution - anti-diuretic hormone; addition of ADH decreases the permeability of the DCT and collecting ducts to water, allowing more water to move in and dilute the urine. Reabsorption - PCT, collecting duct Secretion - PCT, loop, DCT fi fl fl fl fl  Renal failure - HTN - Edema, - Anemia, - Hypocalcemia - Vit D de ciency - Hypoglycemia - sometimes - Accumulation of toxic metabolites Diuretics - enhance urine ow - Interfere with renal Na reabsorption and decrease extracellular uid volume - Common : osmotic diuretics, loop diuretics, thiazide diuretics, potassium-sparring diuretics Tests for GU system Urine dipstick - Glucose - negative - Leukocyte esterase- negative - Nitrates- negative, positive with some bacteria - Ketones- by products of fat, positive in starvation and diabetic ketoacidosis - Albumin - negative; positive in glomerular failure - Hemoglobin -negative; positive in RBC breakdown - Myoglobin - negative; positive in muscle breakdown Urine sediment / cytology - microscopic analysis - crystals, casts, RBC,WBC, cancer cells fi fl fl  Blood urea nitrogen - BUN - Re ects urine concentrating ability and glomelural ltration - Waste product from liver- BUN - BUN increases when GFR drops - Normal is 10-20mg/dL - Rises in dehydration, acute and chronic renal failure because the passage of uid in renal tubules is slow Plasma Creatinine - when GFR declines, creatinine increases proportionally; doubling creatinine re ects a 50% reduction In GFR - -useful in monitoring over time; it takes 7-10 days to stabilize when GFR declines - Normal is 0.7-1.2 mg/dl Creatinine clearance - estimates GFR - 24h volume of urine and 1 blood draw - GFR=( urine creatinine x urine volume ) / plasma creatinine Renal dysfunctions Renal and urinary function can be a ected by : - Infection - Obstruction by stones, tumors, or in ammatory edema - Dysfunction from kidney disease or systemic disease New renal dysfunction - Vascular - Pre-renal : dehydration, CHF - Renal : nephrotic or nephritic syndromes , acute tubular necrosis, interstitial nephritis - Post-renal - obstructive fl ff fl fi fl fl  Urinary track obstruction - interference with the ow of at any site of urinary tract - Increases rick of infection - Anatomic changes due to obstruction are called obstructive uropathy - Its not a primary disease - Compression, stones, masses- cause increased pressure, dilation of ureter, renal pelvises, calyces and parenchyma prior to obstruction - Increased pressure transmits back to glomerulus, decreasing glomerular blood ow and GFR Hydronephrosis - build-up of urine in kidney due to signi cant obstruction; renal pelvis expands, increasing intra-renal pressure; renal pyramids infarct, nephron’s are destroyed; becomes dysfunctional Calculi - ureters, urethra, bladder; - made of crystals, proteins etc - Renal colic- severe, on and o ank pain, urinary urgency, frequency, blood in urine Lower urinary tract obstruction - disorder of the bladder- urine storage or emptying - Incontinence - Neurogenic bladder - Urethral obstruction - Pregnancy related UTI - in ammation of urinary epithelium usually caused by gut bacteria - Anywhere along the tract - Frequency, dysuria, urgency, low back pain and /or supraubic pain - Can be asymptomatic fl fl ff fl fi fl  - Urine culture 10000 /ml or more - Treated with antibiotics - uncomplicated: mild, - Complicated : include fever, develop when there is abnormality in the urinary tact - Recurrent : 3+ in 12 months, or 2+ in 6mo Cystitis- bladder in ammation Pyelonephritis - in ammation of upper urinary tract UTI risk factors - premies, pre-pubertal children , pregnant and sexually active females, indwelling catheters, DM, neurogenic bladder, obstruction Glomerular disorders Glomerulopathies - directly a ect the glomerulus - Nephrotic vs nephritic - Primary glomerular injury vs secondary - Signi cant cause of CKD Acute glomerulonephritis - in ammation of glomerulus - Primary glomerular injury : immunologic response, ischemia, free radicals drugs, toxins, vascular disorders, infection - Secondary : systemic disease : DM, lupus - Formation of immune complexes in the circulation with deposition in glomerulus =; activation of complement; recruitment and activation of immune cells fl fi ff fl fl - Results in decreased GFR; decreased glomerular perfusion due to in ammation; scarring and thickening of basement membrane, but increased permeability to protein and RBC Acute glomerulonephritis symptoms Nephrotic -increased permeability, loss of plasma proteins decreases oncotic pressure resulting in edema; loss of immunoglobulins - infections - Hypoalbuminemia - Frothy/foamy urine - Anasarca - Urine contains protein >3g/day and microscopic amount of blood or no blood Nephritic -caused by increased permeability of the glomelural ltration membrane; pore size enlarge; RBC and protein pass thru - advanced stages of HTB, uremia, oliguria - usually also extra-renal syndromes - lupus, good pastures, strep - Urine contains massive amount of blood and protein, but not severe 300mg to 500mOsm; fractional exertion of sodium proteinuria Clinical symtoms fl fi fi fl ff fi fl fl - Azotemia - increased levels of serum urea, creatinine etc - Uremia - pro-in ammatory state associated with accumulation of use and toxins - Hypertension, anorexia, nausea’s vomiting, diarrhea or constipation, malnutrition, weight loss, pruritus, edema, anemia, neurologic, cardiovascular disease, skeletal changes. Diabetes insipidus - causes decreased secretion of ADH Loop diuretics can cause electrolyte imbalances -hypokalemia, hypocalcemia because they block their reabsorption fl