Systemic Pathology Exam 1

What is the most common cause of iron deficiency in the western world?

chronic blood loss

Describe the progression of coronary artery lesion

from normal to fixed coronary obstruction (typical angina) can lead to either: 1. plaque disruption 2. Severe fixed coronary obstruction plaque disruption will lead to either 1. mural thrombus variable obstruction 2. occlusive thrombus

~ 95% of __________ are carcinomas

primary lung tumors

What is reperfusion important?

process of restoring myocardial blood flow as rapidly as possible reperfusion within 20 mins of the onset of ischemia may prevent necrosis early reperfusion can salvage myocardium and limit infarct size however reperfusion not only salvages reversibly injured cells but also alters the morphology of lethally injured cells. It also causes hemorrhages and endothelial swelling which may further occlude capillaries

What is C-reactive protein? why is it a risk factor for atherosclerosis?

• Acute-phase reactant synthesized primarily by the liver. Expression increased by IL-6 • Immune response - opsonizing bacteria and activating complement. • Secreted from cells within the atherosclerotic intima. • Activates local endothelial cells inducing a prothrombotic state. • Increase the adhesiveness of endothelium for leukocytes. • Predicts the risk of MI, stroke, PAD, and sudden cardiac death.

t/f Most aortic aneurysm are abdominal aortic aneurysm and the majority of abdominal aneurysm occur below the renal artery

true

t/f progressive ischemia leads to collateral vessels which protect against ischemia

true

t/f silicosis DOUBLES the risk for cancer

true Also linked to -pulmonary hypertension -cors pulmonale -increased susceptibility to TB

SCD or sudden cardiac death is not strongly associated with acute myocardial infactions

true MOROPHOLOGY SCD marked coronary atheroscler. -80-90% nonatherosclerotic origin -10-20% acute plaque diruption -50% acute MI-diagnositc changes 25%

t/f Rheumatic heart diseases is the only clinically significant thing that causes mitral valve stenosis (MVS)

true The following 3 things cause aortic valve stenosis: -Rheumatic heart disease -Senile calcific aortic stenosis -Calcification of congenitally deformed valve

t/f Atheromatous plaque of coronary artery are commonly eccentric on cross-section but patchy and assymetrical in shape

true patchiness and asymmetry are a result of local hemodynamics

t/f Heme iron is much more absorbable than inorganic iron. name some things which influence inorganic iron absorption

true Ascorbic acid, citric acid, amino acids and sugars enhance absorption of inorganic iron; tannins (tea), calcium carbonates, oxalates, and phosphates inhibit inorganic iron absorption.

Pott disease

tuberculosis of the spine -Paraspinous "cold" abscesses track along tissue planes and cause abdominal or pelvic mass

Describe cardinoid heart disease Gross findings

• 50% of pts. with carcinoid syndrome. • Tricuspid insufficiency +/- pulmonary valve insufficiency. • Right sided stenosis. • Elaboration of bioactive products by carcinoid tumors. •Products are degraded in the liver and lung - Tends to spare left heart because products broken down in the lung. - Left-sided valvular disease - Right to left shunting; lung tumor; Serotonergic drugs. Gross findings: • Firm, plaque-like endocardial fibrous thickenings. • Inside surfaces of the right cardiac chambers. • Tricuspid and pulmonary valves. • Occasionally involve IVC & PA. Microscopic findings • Plaque-like thickenings. • Smooth muscle cells and sparse collagen fibers. • Acid mucopolysaccharide-rich matrix.

What occurs in Buerger disease? (Thromboangiitis obliterans)

• Acute & chronic inflammation of arm and leg vessels • Can spread from arteries to veins to nerves -only one thats not only just involving the arteries • Big association w/cigarettes • Ulcers/gangrene of extremities

What is Lymphangitis?

• Acute inflammation elicited by the spread of bacterial infections into lymphatics; • Group A β-hemolytic streptococci most common agent, although any microbe can be causal. • Affected lymphatics are dilated and filled with an exudate of neutrophils and monocytes; the infiltrates can extend through the vessel wall, and in severe cases, can produce cellulitis or focal abscesses. • Red, painful subcutaneous streaks (the inflamed lymphatics), and painful enlargement of the draining lymph nodes (lymphadenitis). • If bacteria are not successfully contained within the lymph nodes, subsequent escape into the venous circulation can result in bacteremia or sepsis. Key sign: red streaks across arm and body

What occurs in Churg-Strauss sydnrome?

• Allergic angiitis, and granulomatosis. • Nose, sinuses, lungs, heart, intestine and nerves. • Inflammation also may affect the kidneys, muscles, or joints. • Associated with asthma and eosinophils

What occurs in Wegener Granulomatosis?

• An example of a small to medium-sized vessel disease • Cause unknown, but c-ANCA in 95% of patients Classic Triad: • Necrotizing/granulomatous inflammation of small to medium sized vessels • Necrotizing granulomas of upper/lower respiratory tract including ear, sinuses, oral cavity • Necrotizing glomerulonephritis • Male > Female • 5th decade- 50 • Persistent pneumonitis w/bilat cavitary and nodular infiltrates • Chronic sinusitis, mucosal ulcerations of nasopharynx, renal disease • Variety of other sx. • Strawberry Gingiva** ***Lung involvement - this is what differentiates it from PAN Respiratory involvement (nose->lungs)

What occurs in hemangiomas?

• Capillary • Cavernous • Pyogenic granulomas are capillary hemangiomas that present as rapidly growing red pedunculated lesions on the skin, gingival, or oral mucosa. They bleed easily and are often ulcerated -->recall these are not actually granulomas However these are benign

How do smooth muscle cells and macrophages interact in terms of endothelial injury

smooth muscle cells serves as ligands for recognition by scavenger receptors of macrophages lymphocytes induce polirization to M1 (minimally oxidized LDL) or M2 phenotype (highly oxidized LDL)

what 3 lab tests can be used for anemia?

CBC with differentials Peripheral blood smear Reticulocyte count

What occurs in angular cheilitis (perleche)?

Erythema and fissuring of the oral commissures. Inflammation of one or both of the corners of the mouth. Often with opportunistic infection of fungi and/or bacteria. seen in megoblastic anemias

What is Anemia?

A deficiency of red blood cells (RBCs) and/or hemoglobin. Most common disorders of RBCs. Reduction in the oxygen-transporting capacity of blood. Lab findings: decreased hemoglobin (Hgb) and hematocrit (Hct)

What is Aphthous Stomatitis?

A.k.a. canker sore or Sutton's disease. A type of mouth ulcer found inside the mouth giving intense pain due to the break in the lining of mucous membranes. Chronic and recurring.

what are the dangers of acute blood loss?

External or internal blood loss Immediate threat is hypovolemic shock rather than anemia If the patient survives, hemodilution begins, blood volume replenish in 2-3 days. Normocytic and normochromic anemia due to hemodilution. Compensatory hematopoiesis: erythropoietin, stimulate hematopoiesis.

What are the dangers of anemia caused by folate deficiencies?

Folate Acts as an intermediate in the transfer of one-carbon unites in process such as purine synthesis. A deficiency of folic acid results in a megaloblastic anemia without the neurologic changes seen in vitamin B12 deficiency. Folic acid (or FH4 derivatives): rich in green vegetables and certain fruits, extremely sensitive to heat (5 to 10 minutes of heat destroys up to 95% of the folate) The megaloblastic anemia of folic acid deficiency is identical to vitamin B12 deficiency. Diagnosis of folate deficiency: Decreased folate levels in the serum or red cells. Frequently increased homocysteine levels. Therapy - folic acid.

What are some clinical manifestations of megoblastic anemia?

General clinical presentation of anemia: pallor, fatigue, dyspnea. Mild jaundice due to destruction of erythroid precursors. Atrophic glossitis; Angular chelitis (perleche); Aphthous Stomatitis Vitamin B12 deficiency only: neurologic complications: the spinal cord disease begins with symmetric numbness, tingling, and burning in feet or hands, followed by unsteadiness of gait and loss of position sense, particularly in the toes.

What are some causes of CHRONIC BLOOD LOSS? what kind of anemia are you in danger of due to it?

Gynecological: pregnancy, menstrual loss. GI tract: tumor, hemorrhoids, peptic ulcer, diverticula. Urinary tract: tumor, infection Gradual depletion of iron stores leads to iron deficiency anemia

What 2 mechanisms are anemia classified under

Increase of red blood cell loss (mainly due to peripheral not directly by the bone marrow) Decrease of red blood cell production (this is mainly due to bone marrow loss)

What occurs in hereditary spherocytosis?

Inherited (intrinsic) defects in the red cell membrane --> formation of spherocytes --> sequestration and destruction in the spleen. 75% autosomal dominant. 25% more severe autosomal recessive.

What is the osmotic fragility test?

It is a measure of the resistance of erythrocytes to hemolysis by osmotic stress in a hypotonic saline solution. A normal RBC is able to swell because of its volume to surface ratio. Spherocyte lost its stretch-ability. Once the limit is reached lysis occurs.

What are 5 types of anemia?

Jaundice Gall stone Hepatomegaly Splenomegaly Nails - brittle, concave spoon shape (koilonychia)

Which 4 anemia's cause Decrease of red blood cell production?

Megaloblastic anemia (B12 and folate deficiency) Iron deficiency anemia Anemia of chronic disease Aplastic anemia

Describe iron def. anemia

Most common cause of anemia in both developed and developing countries. Iron balance is maintained largely by regulating the absorption of dietary iron in the proximal duodenum, little by regulating iron excretion (1 to 2 mg per day lost by shedding of mucosa and skin epithelium).

Describe Sickle cell disease what are the Two major consequences arising from the sickling of red cells:

Most common hereditary hemolytic anemia in the world. Occurs primarily in individuals of African descent. Caused by a point mutation at the 6th codon of the Beta-globin gene leading to the substitution of a valine residue for glutamate residue. Heterozygous (sickle cell trait) ~ 40% HbS, 60% HbA - Mostly asymptomatic. - 8-10% of Africa American in U.S (~ 2 million individuals). Homozygous (sickle cell disease) -100% HbS. - 0.2% in U.S. Two major consequences arising from the sickling of red cells: Chronic hemolytic anemia Microvascular obstructions result in tissue ischemia, infarction and pain crises

What are some features of RBC's/erythrocytes?

No nucleus. Size: 6-8 micron (normal). Shape: biconcave disc. Hemoglobin content: normochromic (central pallor ~ 1/3 of RBC diameter). Function: transportation of oxygen.

What treatment is there for hereditary spherocytosis? what are some of its clinical features?

No specific treatment Splenectomy Anemia: moderate degree Jaundice Splenomegaly (500-1,000 grams) Pigmented gall stones: 40-50% of patients

What lab tests can be used to test for sickle cell disease? What are some treatments and usual prognosis?

Peripheral blood smears - sickle cells Sickle cell screen test Hemoglobin electrophoresis (alkaline and acid electrophoresis) High pressure liquid chromatography (HPLC) Molecular diagnosis Treatment: Supportive care Red blood cell exchange Drug therapy: Hydroxyurea, increases Hb F in red cells Prognosis: ~ 90% of patients survive to age 20 ~ 50% survive beyond the fifth decade

Describe the structure of hemoglobin?

Two α and two β subunits Non-protein heme and iron

What are the 6 diagnostic features of Vitamin B12 def.

(1) Low serum vitamin B12 levels (2) Elevated levels of homocysteine and methylmalonic acid (3) Serum antibodies to intrinsic factor (4) Megaloblastic anemia (5) Leukopenia with hypersegmented granulocytes (6) A dramatic reticulocytic response (within 2 to 3 days) to parenteraladministration of vitamin B12

What is seen in Pulmonary hypertension Arteriopathy?

-Decreased luminal diameter of vessel with thick walls--> Cause and consequence of hypertension

What is Adult polycystic disease?

-a hereditary disorder where you have multiple expanding cysts of both kidneys destroy parenchyma and cause RF -A systemic disroder with cysts in other organs (1/3 have cysts in livers) -Bilaterally enlarged kidneys filled with fluid -Flank pain/ dragging sensation - Majority develop hypertension (75%) -Need renal transplantation -death due to uremia to hypertensive crisis

What is minimal change disease?

-also known as lipoid nephrosis** -relatively benign disorder -most frequent cause of nephrotic syndrome in children -despite massive proteinuria (abumin selective), renal function remains good with no hematuria or hypertension -no immune complexes present*** - immune dysfunction...circulating cytokines affecting visceral epithelial cells and proteinuria -uniform and diffuse effacement of foot processes of visceral epitehlium, no cellular proliferation -Tubular cells filled with lipid due to lipid reabsopriton through diseases glomeruli...lipoid nephrosis Dramatically responsive to corticosteroid therapy

What occurs in childhood polycystic disease?

-autosomal recessive inheritance -bilaterally enlarged kidney with smooth external appearance -many small cortical and medually cysts....sponge like appearance

Vascular Ectasias

-group of abnormally PROMINENT capillaries -nervus flammeus

List in order foam cells thrombosis fatty streak atheroma

1 decade foam cells 2 fatty streaks 3-4 atheroma form 5 thrombosis

What are the 2 reasons glomerular diseases of the kidney occur

1. Antibodies within the glomerulus reacting with intrinsic antigens or planted extrinsic antigens 2. Deposition of soluble circulating antigens- antibody complexes in the glomerulus (SLE, Hep B, HIV)

What are 4 Glomerular syndromes

1. Asymptomatic hematuria or proteinuria 2. Acute nephritic syndrome 3. Nephrotic syndrome 4. Chronic renal failure (end stage kidney disease)

What are the 4 morphological components of the kidney?

1. Blood vessel -->Rich vascularized -->Main renal artery progressively subdivides into many branches -->Capillary loops merge and exit glomerulus as efferent artioles 2. Glomeruli -->an astonomosing network of capillaries lined by fenestrated epithelium invested by 2 layers of epithelium --> visceral epithelium is part of intrinsic capillary wall; parietal epithelium lines Bowman's capsules where filtrate collects -->susceptible to immune system attacks/diseases/disorder 3. Tubules -The proximal tubular cells have highly developed structure...re-absorption of 2/3 of filtered solutes -The proximal tubles are highly susceptible to ischemic necrosis and chemical injury (hence not given NSAID's) -Medulla is susceptible to ischemic necrosis and chemical injury 4. Interstitium -Normal cortex...compact interstitial space composed of fenestrated peritubular capillaries and cells -Edema or inflammation...abnormal expansion of interstitium

What occurs in ASD? Atrial septal defect

Usually asymptomatic until adulthood Complications include • Pulmonary hypertension • Cardiac failure • Paradoxical embolization but most commonly in location of foramen ovale

What are 5 clinical features of sickle cell disease?

1. Chronic hemolytic anemia: moderate to severe 2. Hyperbilirubinemia, gallstones 3. Vaso-occlusive crisis /pain crises: - Episodes of hypoxic injury and infarction that cause severe pain in the affected region Although infection, dehydration, and acidosis can act as triggers, in most instances no predisposing cause is identified. Most common sites: bones, brain, kidney, liver, spleen, lungs, retina, leg ulcers. Hand foot syndrome in children - dactylitis of hands and/or feet bones Two leading causes of ischemia-related death: o Acute chest syndrome (vaso-occlusive crises of lungs) o stroke 4. Autosplectonomy Increased susceptibility to infection with encapsulated organisms: S. Pneumococci and H. Influenzae. Common causes of death in children: septicemia and meningitis. 5. Aplastic crises -Transient cessation of bone marrow erythropoiesis due to acute infection of erythroid progenitor cells by parvovirus B19. Sudden and rapid worsening of anemia.

what mainly cause ischemia and what are 3 symptoms?

1. Coronary artery atherosclerosis Less commonly: -vasospasm -vasculitis -emboli Symptoms -Angina pectoris -Unstable angina -Acute myocardiac infarction -sudden cardiac death -ischemic cardiomyopathy after 1-2 mins leads to loss of myocyte function after 30-40 mins leads to death

What are the 3 main causes of vitamin B12 deficiencies?

1. Decreased intake Inadequate diet 2. Impaired absorption: a. Intrinsic factor deficiency: Pernicious anemia Gastrectomy b. Malabsorption due to intestinal diseases such as celiac disease, Chron's disease, ulcerative colitis, ileal resection, etc. c. Competitive parasitic uptake: e.g. fish tapeworm. 3. Increased requirements: pregnancy, disseminated cancer, etc.

1. Resorption Atelectasis 2. Compression Atlectasis 3. Contraction Atlectasis

1. Distal to complete obstruction of airway. -prevents passage of air -Air gradually resorbed from parenchyma supplied by obstructed airway. -Alveoli in affected area (entire lung, lobe or patches) collapse. Obstructions include: Mucous plugs Tumors Foreign bodies 2. Lung collapse due to pressure in pleural cavity: -Fluid effusion 2nd to CHF -Pneumothorax (leakage of air) -Blood 3. Fibrosis in lung or pleura hamper expansion -Irreversible******

What are the 2 kinds of restrictive lung diseases? what are some examples?

1. Extrapulmonary -severe obesity -neuromuscular disorders 2. Interstitial - Acute- ARDS -Chronic: -IPF -Pneumoconioses -Sarcoid ON SIP A

what are 3 important complications of a MI myocardial rupture? what are the riskiest days after having one?

1. Hemopericardium 2. cardiac tamponade 3. Rupture of ventricular septum --> acute VSD and L-R shunt Days 4-5 are very risky days -you have a very weak wall of ventricle --> when your heart contract it may blow right through the area of fibrous healing b/c its not very strong at this point =you can die almost instantly you get blood surrounding heart and compressing from outside in

What are 4 primary symptoms of nephrotic syndromes

1. Hyperlipidemia -increased synthesis of liver lipoproteins, abnormal lipid transport, and decreased lipid catabolism 2. Lipiduria -leakage of lipoproteins across glomerular capillary wall 3. Increased risk of infection (loss of immunoglobulins and complement) 4. Increased risk of thrombosis (loss of anticoagulant factors)

what are the 2 defense mechanisms of the conducting region?

1. Mucus secreted by glands and goblet cells traps foreign particles 2. Wave‑like beating of cilia on surface of columnar epithelial cells removes particles

Describe vitamin B12 absorption

1. Peptic digestion releases dietary vitamin B12, allowing it to bind a salivary protein haptocorrin (R-binder). 2. Vitamin B12 is released from haptocorrin- B12 complexes by pancreatic proteases in duodenum and binds to intrinsic factor secreted from the parietal cells of the gastric mucosa. 3. The intrinsic factor-B12 complexes are taken up into enterocytes by binding to cubulin, a surface receptor for intrinsic factor, in distal ileum. 4. The absorbed vitamin B12 is transferred to plasma transcobalamin, which delivers vitamin B12 to the liver and other cells of the body

What are the 3 main types of lung cancer?

1. Squamous cell carcinoma 2. Small cell carcinoma 3. Adenocarcinoma

Describe the anatomy of a atheroma

1. Superficial fibrous cap Smooth muscle cells, lymphocytes, collagen, elastin, proteoglycans. Neovascularization. 2. Necrotic lipid core Lipid, foam cells cholesterol crystals 3. Shoulder - Smooth muscle cells MPGS, T cells.

Describe the etiology of squamous cell carcinoma

1. Tobacco smoke 2. Suppressor genes loss or mutation: TP53 CDKN2A RB Genes on chromosome 3p 3. FGFR1 amplification (gene encodes fibroblast growth factor receptor tyrosine kinase).

What 3 things are analyzed for sign and symptoms of kidney disease?

1. Urine analysis -proteinuria due to glomerular or tubular damage -Hematuria; blood in urine - Pyuria- detection of pus in urine is often associated with infections -organized sediments (casts of RBCs/WBCs trapped in the renal tubule) -osmolarity 2. Urine volume -Hyposthenuria- hypotonic urine (inability of tubules to concentrate) -Oliguria- decreased in amount of urine (400 ml/day) -Anuria- lack of urine production (<200 ml/day) 3. Serum analysis -Azotemia -->refers to elevation of Blood, Uria, nitrogen (BUN) and creatinine) --> largely related to decreased GFR -Electrolyte imbalance (High phosphate, low serum calcium, K retention, and Na loss)

What are the 2 main kidney functions?

1. Urine production -Maintains constancy of volume and composition of ECF -Excretion of waste products of metabolism -Precise regulation of body's concentration of salt and water - Matains acidic balance of plasma 2. Endocrine functions -Renin production by juxtomedullary cells...angiotensin system and blood pressure maintaince -Erythropoetin production....hematopoeisis -Calcium metabolism

What 2 things is anemia classified under?

1. increase of RBC loss 2. Decrease of RBC production

what do endothelial cells do after a endothelial injury?

1. induce chemotaxis of monocytes, PMN, and esinophils 2. Induces surface expression of adhesion molecules 3. Induces platelet aggregation 4. Induce inflammatory genes including cytokine release 5. Activate dendritic cells and induces their release of T cells stimulating cytokines

what are some outcomes of anemia

1. jaundice 2. gall stones 3. hepatomegaly 4. spelnomegaly 5. Nails-brittle, concave spoon shape (koiloynychia)

What are 5 clinical findings for Rheumatic Heart Disease

1. migratory polyarthritis 2. pancarditis 3. subcutaneous nodule 4. Erythema marginatum (tea stain looking marks) 5. Syndenham chorea -Sydenham's chorea or chorea minor (historically referred to as Saint Vitus Dance) is a disorder characterized by rapid, uncoordinated jerking movements primarily affecting the face, hands and feet.

What are the 3 fates of heart cells when there is a compromise of myocardial blood supply What are the earliest biochemical consequences of this? how long do you have to restore function before cell death occurs?

1. myocardial Ischemia 2. dysfunction 3. necrosis. Earliest biochemical consequences: Cessation of aerobic metabolism within seconds leads to: • Inadequate production of ATP • Accumulation of metabolites - lactic acid Myocardial function is highly oxygen dependent. • Loss of contractility within 60 seconds. • Cessation of function can precipitate acute heart failure long before myocardial cell death. (in other words heart stops working BEFORE cells start to die) **function CAN be regained if o2 is restored within 30 minutes

What are the 4 locations of immune complexes within the glomerulus?

1. subepithelial deposits 2. Epimembranous deposits 3. Subendothelial deposits 4. Mesangial deposits

What microscopic changes are seen in cases of myocardial infarctions after 12 hours 4-12 changes hrs 12-24 hours 1-3 DAYS

12 hours --> +/- mottling (Mottling is blotchy, red-purplish marbling of the skin) -->2-3 hours immersion highlights infarcts -->triphenyltetrazolium chloridfe immersion 4-12 hours --> this is when the most happens: 1. contraction bands 2. myocytolysis 3. wavy fibers also early coagulative necrosis, edema, and hemorrhage 12 to 24 hours -gross red blue discoloration- stagnated blood -everything mentioned above 1-3 days -mottling with yellow-tan softening -coag. necrosis + brisk neutrophilic infiltrate 7-14 days maximally yellow tan with depressed red-tan-gray infact borders -early collagen deposition -fibrovascular proliferation -phagocytosis of dead cells by mpg 2 weeks to 2 months -gray-white scar which progresses from border to center -increased collagen deposition with decreasing cellularity

Describe the structure of hemoglobin

2 alpha and 2 beta subunits non-protein heme and iron

What % of patients with mesothelioma lack asbestos exposure

20%

What % of cardiac output does the kidney get?

25% of which a majority goes to the cortex

What are 4 types of morphologic precursor (preinvasive) epithelial lesions

4 types of morphologic precursor epithelial lesions: (1) squamous dysplasia and carcinoma in situ (2) atypical adenomatous hyperplasia (3) adenocarcinoma in situ (4) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

Describe the effects of 70 and 90 % occlusion in Chronic Atherosclerosis

70% occlusion --> Symptomatic ischemia precipitated by exercise. 90% occlusion --> Inadequate perfusion at rest.

What are esophagel varicies?

A complication of portal hypertension in cirrhosis • Rupture may cause fatal hematemesis

What are the 2 main symptoms of anemia? what is anemia?

A deficiency of red blood cells (RBCs) and/or hemoglobin. Most common disorders of RBCs. Reduction in the oxygen- transporting capacity of blood. Lab findings: decreased hemoglobin (Hgb) and hematocrit (Hct) 1. Decreased oxygenation -Fatigue -Dyspnea: exertional or at rest** -Myocardial hypoxia - angina pectoris** -Central nervous hypoxia - headache** 2. Hypovolemia -Postural dizziness, lethargy, hypotension, shock and death Other signs: -Pallor (conjunctiva) -Acute blood loss/shock: hypotension, increased HR, oliguria & anuria nails (koilonychia) **= know

Legionnaire's disease

A severe, often fatal bacterial disease characterized by pneumonia, dry cough and sometimes gastrointestinal symptoms. Caused by legionella pneumophilia

What is hepcidin?

A small circulating peptide synthesized and released from the liver in response to increases in intrahepatic iron levels. Iron metabolism is regulated by hepcidin: Hepcidin inhibits ferriportin reduces iron uptake from enterocytes. Suppresses iron release from macrophages, which are an important source of the iron that is used by erythroid precursors to make hemoglobin.

what occurs in aplastic anemias?

A syndrome of bone marrow failure associated with pancytopenia (anemia, neutropenia and thrombocytopenia). Marrow failure stems from suppression of multipotent stem cells. Markedly hypocellular bone marrow. Bone marrow consists of only fat cells, fibrous stroma, and scattered lymphocytes and plasma cells. Peripheral blood: pancytopenia. clinicial features: Usually insidious onset at any age or either sex. Initial manifestations differs based on which cell line is predominantly suppressed, but pancytopenia ultimately appears: Anemia: progressive weakness, pallor, and dyspnea. Thrombocytopenia: petechiae and ecchymosis. Neutropenia: frequent and persistent minor infections or fever. Splenomegaly is usually absent. Laboratory features normocytic and normochromic (slightly macrocytic) anemia; reticulocytes are reduced in number (reticulocytopenia). The diagnosis rests on examination of a bone marrow biopsy.

Someone with amphiboles within their lungs have what condition?

Abestosis Amphiboles (straight, stiff, brittle fibers) are worst type of Asbestos fibers. Asbestos fibers are phagocytosed by macrophages They Activate inflammasome and stimulate release of proinflammatory factors and fibrogenic mediators They go deeper into lungs; through epithelium into interstitium eventually lead to generalized interstitial pulmonary inflammation and interstitial fibrosis. Another type is: Asbestos bodies: golden brown, fusiform or beaded. rods; Asbestos fiber core coated with iron-containing protein

What are some examples of obstruction to flow?

Abnormal narrowing of chambers, valves or blood vessels. Examples: • Coarctation of aorta • Pulmonary stenosis or atresia • Aortic stenosis or atresia

What occurs in Emphysema?

Abnormal permanent enlargement of air spaces distal to terminal bronchioles Accompanied by destruction of their walls, WITHOUT obvious fibrosis. Emphysema is very common and Usually occurs with chronic bronchitis Cigarette smoking causes both Initially Spaces or holes in parenchyma are due to fusion of adjacent alveoli when septum is destroyed. As disease advances, spaces enlarge →huge bullae "inflate, swell up, blow up"

What occurs in ALI? Acute Lung Injury What is ARDS? Whats DAD?

Abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure ARDS: Acute respiratory distress syndrome -->Manifestation of severe ALI. DAD: Diffuse alveolar damage -->The histologic manifestation of these diseases **Remember the absence of surfactant is NOT the primary problem in ARDS (this distinguishes ARDS from RDS)

Whats the difference between acute and chronic renal failure?

Acute -rapid onset and often reversible -caused by glomular interstitial or vascular injury and acute tubular necrosis Chronic - Gradual onset and irreversible -Prolonged signs and symptoms -The end result of all chronic renal diseases

Whats the difference between acute bacterial endocarditis and subacute bacterial endocarditis?

Acute Bacterial Endocarditis • Rapildy progressive. • Highly destructive. • Highly virulent organisms - Staph Aureus. • Typically infects previously normal heart. Subacute Bacterial Endocarditis • More insidious protracted course. • Less destructive to underlying valves. • Less virulent organisms - Strep Viridans. • Infects deformed valves.

What occurs in acute pyelonephritis? What occurs in chronic pyelonephritis?

Acute P: -sudden onset with pain at costovertebral angle, dever, malaise, and dysuria -Frequency and ugency of urination -Diagnosed via quantitative urine culture Acute P. is a bacterial infection caused either by ascending infections as a result of reflux, obstruction , or other abnormality of the urinary tract, or much less commonly by hematogenous spread of bacteria, it is characterized by abscess formation if the kidneys, sometimes with papillary necrosis Chronic P; -an important cause of ESRD -usually is associated with urinary obstruction or reflux, it results in scarring of the pelvicalyceal system and the interstium of the involved kidneys and gradual progression of chronic kidney disease

what is acute rheumatic carditis? describe its morphology

Acute rheumatic carditis is common during the active phase of RF and may progress to chronic rheumatic heart disease (RHD), and deforming fibrotic valvular disease. morphology: - inflammation and aschoff bodies- any layer of the heart -pancarditis- pericarditis, myocarditis, or endocarditis -aschoff bodies (cytokine activated macrophages) -step M proteins antibodies cross-react with heart antigens

What are the 4 major histologic types of lung carcinomas list in order of most common to least common

Adenocarcinoma (most common) Squamous cell carcinoma SCC Small cell carcinoma SCLC Large cell carcinoma (least common) *Adenocarcinoma is now the most common form of lung cancer in women and, in many studies, men as well

What are some extrinsic influences to plaque?

Adrenergic stimulation can increase BP and vasoconstriction, increasing stress on a plaque. • Waking and rising can cause blood pressure spikes and heightened platelet reactivity. -Circadian periodicity of MI. • Intense emotional stress can contribute to plaque disruption. • Incidence of sudden death increases during disasters Vasoconstriction • Compromises lumen size. • Potentiates plaque disruption by increasing local mechanical forces . Vasoconstriction is stimulated by : • Circulating adrenergic agonists • Platelet contents released • Endothelial cell dysfunction • Impaired secretion of endothelial cell relaxing factors • ? Inflammatory cells mediators

What are congenital diseases of the kidney? Name 3

Affects 10% of people These are hereditary or acquired development defect during gestation Renal agenesis- failure of total formation of the kidney (if bilateral then it is incompatible with life) 1. Renal hypoplasia -failure of complete development of the kidney (smaller, fewer renal lobes or medually pyramid); often unilateral 2. Ectopic kidneys -Development of nephrons in abnormal positions 3. Polycystic kidney disease -A hereditary anomaly affecting both kidneys leading to progressive loss of function

Difference and similarities between aneurysms and dissections?

Aneurysms are congenital or acquired dilation of the heart or blood vessels that involve the entire wall thickness. Complications are related to rupture, thrombosis, and embolization Dissections occur when blood enters the wall of a vessel and separates the various layers. Complications arise as a result of rupture or obstruction of vessels branching off the aorta Both result from structural weakness of the vessel wall caused by loss of SMC's or weakening of the ECM, which can be a consequence of ischemia, genetic defects, or defective matrix remodeling

What is Panacinar (Panlobular) Emphysema?

All alveoli in affected area UNIFORMLY enlarged. Changes in alveoli lining respiratory bronchioles and full extent of alveolar ducts. The entire lobule is effected - ducts, sacs, and entire tract Assoc w/ inherited a1-antitrypsin deficiency (liver cirrhosis is also associated with this as well)

What makes up blood vessels? What affects their composition?

All vessels except capillaries share a three-layered architecture • (smooth) Endothelium lined intima • Surrounding smooth muscle media • Supportive adventitia. (fibrous CT) IMA *Dissection is cutting only into the intima Composition of a vessel( smooth muscle cell and matrix content) vary according to hemodynamic demands (e.g., pressure, pulsatility) and functional requirements. *need more muscle in your aorta than in your veins Composition influences the nature and consequence of pathologic injuries.

Why is an alpha 1 antitrypsin deficiency bad?

Alpha-1-antitrypsin (A1AT) is produced in the liver, an one of its functions is to protect the lungs from neutrophil elastase, an enzyme that can disrupt connective tissue. **Alpha-1antitrypsin deficiency (also referred to as Alpha-1) is caused by mutations in the SERPINA1 gene on chromosome 14. This gene codes for an enzyme called alpha-1 antitrypsin. Smoking stimulates proteolytic agents (e.g. elastase) Smoking also destroys its inhibitors Enzyme a1-antitrypsin (in serum, tissue fluids & m'phages) is most important protease inhibitor and it is inhibited by smoking

What occurs in a mitral valve prolapse?

Also called Myxomatous Degeneration of the Mitral Valve One or both mitral valve leaflets are floppy and prolapse into the left atrium during systole. • 3% of adults in the United States. • Commonly an incidental finding, particularly young women. • Mid systolic click is heard*** Mitral valve prolapse can lead to 1 of 4 serious complications 1. Infective endocarditis 2. Mitral insufficiency +/- chordal rupture 3. Stroke or systematic infarct 4. Arrhythmias Gross findings: -leaflets are ballooned- thickened -tendinous cords are elongated and thinned -may involve tricuspid, aortic, or pulmonary valves

where in the lungs are the alveoli found?

Alveoli only in deepest (most distal) part of system In respiratory bronchioles and alveolar ducts

What is the risks of a aortic dissection?

Always starts with the media If it ruptures outwards: (which occurs more often) • catastrophic hemorrhage • Ripping or tearing chest pain as lesion extends if it rupture inwards: -"double barrel aorta" - "chronic dissection"

Describe what occurs during a endothelial injury and what events it leads to

An attempt to heal the endothelial injury simulates a cascade of events involving: • Adhesion and migration of inflammatory cells and lipid. • Accumulation of lipid in foam cells. • Smooth muscle hypertrophy and scarring. • Foam cell apoptosis and release free lipid into the artery wall

Describe a giant cell/temporal arteritis

An example of large vessel vasculitis • Most common vasculitis syndrome • Cause unknown, possibly a T cell mediated immune response to an unknown antigen, In vessel wall • Genetic. Increased in HLA-DR4 • Particularly effects branches of the carotid, particularly temporal, opthalmic arteries • Destructive granulomatous inflammation of the vessel wall • CD4+ T cells • Fragmentation of internal elastic lamina • Usually giant cells Symptoms: • Inflammation leads to intimal thickening...stenosis +/- thrombosis --> leads to lumen getting smaller hence the stenosis and thrombosis • Classic female >50 w/ severe headache and radiating facial pain • 50% ocular symptoms due to involvement of opthalmic artery. Treat early to prevent blindness • About 50% w/ flu-like syndrome w/joint stiffness: polymyalgia rheumatica You see a beading of the vessels around the temple area when it comes to this; beading of temporal artery Amurosis fugax- blindness thats coming and going also jaw claudication/pain when speaking is present as well

What are some Heritable conditions associated with SCD? Sudden cardiac death

Anatomic abnormalities • Congenital anomalies • Hypertrophic cardiomyopathy • Mitral valve prolapse Primary electrical disorders • Heritable arrhythmias • Channelopathies - Mutations in genes of ion channel function.

Describe the 2 types of hemolytic anemia what are the similarities between the two?

Anemias caused by accelerated red cell destruction 1. Extrinsic (extra-corpuscular) abnormalities of red cells: a. Immunohemalytic anemia b. Non-immune mediated hemolytic anemia 2. Intrinsic (intra-corpuscular) abnormalities of red cells: a. Red cell membranes disorders -Hereditary spherocytosis** - Paroxysmal nocturnal hemoglobunuria (PNH) b. Red cell enzyme deficiencies - G6PD deficiency c. Disorders of hemoglobin synthesis - Hemoglobinopathies and thalassemias**

What is aneurysm?

Aneurysm-localized abnormal dilatation of vessel or heart • May be after trauma, congenital(ie berry aneurysm), infection(ie syphilis, mycotic), or relating to systemic diseases aneurysms --> turbulent blood flow --> risk of thrombi forming --> risk of Pulmonary embolizism (or infarct caused by paradoxical embolization if you have a septal defect)

What is abestosis? What are 3 abestosis-related diseases?

Asbestos is a family of proinflammatory crystalline hydrated silicates Asbestos-related diseases include: 1. Parenchymal interstitial fibrosis (asbestosis) 2. Lung carcinoma 3. Mesotheliomas***** Others: -Localized fibrous plaques or, rarely, diffuse pleural fibrosis -Pleural effusions, recurrent

Eisenmenger syndrome

At birth, shunts flow in a left to right direction; Includes ASD's,VSD's, and PDA. Shunting results in right-sided volume overload that eventually causes pulmonary hypertension and with reversal of flow and right to left shunting, cyanosis

What is atopic asthma usually caused by and how does it work?

Atopic asthma is caused by Th2 and Ig-E mediated immune reactions to environmental allergens and is characterized by early-phase and late phase reactions TH2 cytokines IL-3,4,5 are all important mediators *In type 1 hypersensitivity, B-cells are stimulated (by CD4+TH2 cells) to produce IgE antibodies specific to an antigen.

What is the consequence of aneurysm formation?

Atrophy of the media and loss of elastic tissue leads to weakness, dilatation rupture, thrombosis.

What is daily intake of iron in western world?

Average daily dietary intake in the Western world is 15 to 20 mg

What is Thrombophlebitis & Phlebothrombosis

Blood clots in the veins as opposed to arteries 90% of them occur deep leg veins vs varicositis which occur in superficial veins -can break off and enter the IVC • Risk factors cardiac failure, neoplasia, pregnancy, obesity, postoperative status, prolonged bedrest or immobilization, genetic hypercoagulability • Trousseau sign-migratory thrombophlebitis as a paraneoplastic syndrome, esp w/pancreas, colon, lung cancer -paraneoplastic-doesnt occur directly caused by cancer but related to it Signs: • Early, none • Edema, cyanosis, dilated superficial veins, heat, redness, tenderness, swelling, pain, possible • Homan sign; pain on forced dorsiflexion of foot • Phlegmasia alba dolens-iliofemoral thrombosis w/pregnancy -->Phlegmasia alba dolens-iliofemoral (AKA milk plague) the only thing you need to know about this is that pregnancy makes you hypercoagulability • Risk of PE

What are 2 kinds of non-immune mediated hemolytic anemias?

Both are Extrinsic abnormalities of RBCs 1. Microangiopathic hemolytic anemia: small vessels become partially obstructed or narrowed by lesions that predispose passing red cells to mechanical damage. -Thrombotic thrombocytopenia purpura (TTP) -Hemolytic-uremic syndrome (HUS) -Disseminated intravascular coagulation (DIC) -Other causes: malignant hypertension, systemic lupus erythematosus 2. Traumatic hemolysis -Physical blows or their equivalent: e.g. marathon racing -Defective cardiac valve prostheses (the blender effect)

What is the difference between emphysema and chronic bronchitis in terms of -Age -Dyspnea -Cough -Infection -Respiratory insufficiency -Cors pulmonale -Airway resistance -Elastic Recoil -Chest Radiograph -Appearance

Bronchitis -Age: 40-45 -Dyspnea: Mild, late -Cough: Early, copious sputum** -Infection: common** -Respiratory insufficiency: repeated -Cors pulmonale: common** -Airway resistance: increased -Elastic Recoil: normal -Chest Radiograph: prominant vessels; large heart -Appearance: Blue bloater Emphysema -Age: 50-75 -Dyspnea: severe, early -Cough: late, scanty sputum -Infection: occasional** -Respiratory insufficiency: terminal -Cors pulmonale: rare; terminal** -Airway resistance: normal, slightly increased -Elastic Recoil: low** -Chest Radiograph: Hyperinflation; small heart -Appearance: Pink puffer Pure emphysema -acinus (respiratory bronchioles, alveolar ducts, and alveoli) -loss of elastic recoil -emphysema Pure Bronchitis -large airways (traechea, bronchi) -mucus hypersecretion -chronic bronchitis Blue boater = pure bronchitis doesn't effect the alveoli at the beginning which is why they don't have a problem breathing like the pink puffer does

What 2 diseases is COPD a combination of

COPD = a combo of 2 separate types of obstructive diseases (emphysema and bronchitis)

What are some causative organisms for infective endocarditis? name the 2 main ones

Causative organisms differ in the major high-risk groups. 1. Streptococcus viridans - in Previously damaged or abnormal valves • 50% to 60% of cases. 2. Staph. aureus organisms - infect either healthy or deformed valves. • 10% to 20% of cases overall • IV drug abusers Enterococci and HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella) • Prosthetic valve endocarditis - coagulase-negative staphylococci. • Gram-negative bacilli and fungi. • Culture-negative endocarditis -10% to 15% of all cases. Aortic and mitral valves most common sites. - May erode into the underlying myocardium and form ring abscess.

What is the most common cause of myocarditis?

Cause, not response to myocardial injury (ie in MI) •Coxackieviruses A and B and other enteroviruses probably account for most of the cases. Coxackieviruses A and B and other enteroviruses probably account for most of the cases.

Describe community-acquired viral pneumonias

Causes **Interstitial pneumonitis - inflammation of walls rather than alveolar spaces (like in bacteria acquired pneumonias) Affect alveolar septae with alv spaces less involved Prevents oxidation of blood so marked respiratory distress Septae widened by chronic inflamm. cell infiltrate. Less sputum than in bacterial pneumonias. Patchy or diffuse areas of lung affected Prognosis usually good But alv damage with hyaline membranes in severe cases. Epidemics→ greater mortality Damage to pul defenses → 2nd bacterial superinfections

What occurs in Hyperplastic Arteriolosclerosis

Chronic hemodynamic stress -endothelial cells leak plasma proteins -smooth muscle cells matrix synthesis Severe hypertension • Smooth muscle proliferation, basement membrane and fibrin deposition. Microscopic: "Onion-skin lesions" • Concentric, layered thickening with luminal narrowing.

What is asthma? what is the difference between atopic vs topic athma?

Chronic inflam disorder causing recurrent wheezing, breathlessness & cough other words: characterized by reversible bronchoconstriction caused by airway hyperresponsiveness to a variety of stimuli Hallmarks: -Intermittent and reversible airway obstruction -Chronic bronchial inflammation -Smooth muscle hypertrophy & hyperactivity -Increased mucus secretion. Expiration is main difficulty. So lungs become hyperinflated. Atopic (evidence of allergen sensitization and immune activation, often in a patient with allergic rhinitis or eczema) Non-atopic (no evidence of allergen sensitization). In either type, episodes of bronchospasm can have diverse triggers, such as: -Respiratory infections (especially viral infectns) -Exposure to irritants (e.g. smoke, fumes, cold air, stress, and exercise).

What are 4 types of pulmonary infections? Describe pulmonary infections in general

Classified on basis of clinical setting and/or etiologic agent bacteria, viruses, mycoplasma & fungi Most cases, micro-organisms enter by inhalation Hematogenous origin occasionally 1. Community-acquired bacterial pneumonias -Lobar pneumonia -Lobular bronchopneumonia 2. Community-acquired viral pneumonias 3. Nosocomial pneumonia Aspiration pneumonia 4. Chronic pneumonia Granulomatous: TB; fungi

What occurs in Anthracosis? What 3 conditions is it related to? What occurs in Asymptomatic Anthracosis?

Coal (a form of carbon) → spectrum of lung changes in coal workers. Silica in coal dust → progressive disease 1. Asymptomatic anthracosis: Also seen in urban dwellers and tobacco smokers -Inhaled carbon pigment is engulfed by alveolar or interstitial macrophages -Then accumulates in connective tissue along lymphatics, including the pleural lymphatics, or in organized lymphoid tissue along the bronchi or in the lung hilus. 2. Simple coal workers pneumoconiosis 3. Complicated coal workers' pneumoconiosis?

What is coarctation of the aorta highly associated with?

Coarctation of aorta is Highly associated w/ turners syndrome --> complete monosomy of genes on the short arm of the x chromosome, most commonly caused by the absence of X chromosome left to right shunt also non-cyanotic

What occurs in a AV canal? what is it associated with?

Combination of ASD and VSD- one big canal combined ventricle and atriums Highly associated with trisomy 21 (aka down syndrome)

Describe the Rheumatic Heart Disease Pathogenesis

Combination of antibody and T cell mediated immune reactions Strep M proteins antibodies cross-react with heart antigens CD4+ T cell specific for streptococcal peptides corss react with heart proteins produces cytokine-activated marcrophages called ashoff bodies

What conditions are associated with the development of ARDS? Acute Resp. Distress Syndrome

Complication of diverse conditions, including both direct injuries to the lungs and systemic disorders. In many cases, a combination of predisposing conditions is responsible (e.g., shock, oxygen therapy, and sepsis).

What is the purpose of the conducting region within the lungs?

Conducting region: protects fragile alveoli and ensures delivery of inspired air to them.

What occurs in congenital heart disease? what 2 categories is it sorted in to?

Congential- you're born with it Congenital heart disease: flow of blood is often the wrong direction Abnormalities of the heart/great vessels present at birth. • Most common heart disease in children • May be associated with genetic syndromes such as trisomy 13,18, 21, XO • May be caused by a genetic abnormality • May be environmental, ex Rubell syndrome Separated in to 2 categories: -shunts -obstructions

What occurs in Pulmonary or right sided HHD?

Cor pulmonale: Isolated pulmonary Hypertensive Heart Disease Acute cor pulmonale • Following massive pulmonary embolism. • Right ventricular dilation. Chronic cor pulmonale • Right ventricular hypertrophy and dilation

What 4 disorders predispose one to Cors Pulmonale?

Cors Pulmonale= pulmonary/ right sided HHD 1. Disease of the pulmonary parenchyma 2. disorders of chest movement 3. Diseases of the pulmonary vessels 4. Pulmonary arterial constriction

What can occur due to a aortic dissection (can occur de novo or as consequence of aneurysm)? where does it usually start?

Creation of a false channel within the muscular wall of the aorta. May not have aneurysmal dilatation • Expanding hematoma • Often starts near ascending aorta, near valve Aortic dissection can cause chest pain like a heart attack but does not show the same blood indicators as a heart attack when you do the test in the hospital.

What occurs in Rheumatic Aortic Stenosis

Cusps thickened and distorted. • Commissures fused. • Less than 10% of cases of acquired aortic stenosis.

What occurs in a right to left shunt? what are the 3 most common types

Cyanotic(R-L) • Tetralogy of Fallot • Transposition of the great vessels • Truncus arteriosus all begin with T* Deoxygenated blood from right bypasses lungs, goes to left, hence early cyanosis Most common: • Tetralogy of Fallot • Transposition of Great Vessels • Also Tricuspid atresia, TAPVR, Truncus arteriosus *TAPVR = Total anomalous pulmonary venous return : o2 rich blood does NOT return from the lungs to the left atrium --> o2 rich blood returns to the right heart instead--> mixes with o2 poor blood.

What are the risk factors of Abdominal Aortic Aneurysm What occurs if it ruptures?

Cystic medial degeneration (sometimes w/Marfan's, sometimes independent) Atherosclerosis Connective tissue abnormality (ie Marfan's) Hypertension -HTN is a risk factor b/c you are overloading your blood vessels, thereby weakening them higher risk of bursting If it ruptures: - Rupture into peritoneal cavity or retroperitoneum (ascities) - Obstruction w/ischemiausually w/smaller vessels -Embolism of atheroma or mural thrombus-Stroke, loss of limb possible • Impingement on adjacent structure, ie ureter or vertebra • Abdominal "tumor"

Name some functional changes in renal failure Whats different in early vs late

Decreased GFR Decrease tubular secretion and absorption Failure to detoxify blood and ECF Failure to regulate volume and solutes Edema, metabolic acidosis and hypocalcemia Overt uremia in terminal stages Early: -loss of ability to concetrate urine (isothenuria) and conserve water, massive Na losss, polyuria, nocturia, dehydration Late: -loss of ability to dilate urine...massive salt and water overload, hypertension, CHF...oliguria and anuria

In accordance with iron def. anemia how are the following affected: Serum iron ferritin TIBC transferrin saturation BM

Decreased hemoglobin/hematocrit Iron studies: decrease in Serum iron, decrease in Ferritin Increase in TIBC ( Total Iron Binding Capacity) Decrease in Transferrin saturation BM: decreased stainable iron (Prussian blue stain ) in macrophages

What occurs in Cystic fibrosis?

Defect due to abnormal function of an epithelial chloride channel protein Encoded by the CFTR cystic fibrosis transmembrane conductance regulator gene cAMP-dependent Cl- channels are defective in exocrine gland epithelium Affects ALL exocrine glans in the body (Pancreas, sweat salivary glands)*** -->Abnormally viscid mucous secretions → obstruction of other organ passages and → clinical problems. Pancreatic insufficiency ↓ exocrine secretions Impaired intestinal digestion and absorption. Reduced Cl - secretion into resp tract lumen → increased reabsorption of Na+ ions and water. So concentrated, more viscid mucus→obstruction clinical features -Chronic bronchitis -Bronchiolitis obliterans -Bronchiectasis -Lung abscesses -Cor pulmonale

What occurs in atherosclerosis? What are some risk factors? (nonmodifiable vs modifiable)

Degenerative disease of large and medium sized arteries. Atherosclerotic plaques. • Intimal lesions protrude into and narrow the vessel lumen Risk factors: Nonmodifiable: -increasing age -male gender (premenopausal women are relatively protected against atherosclerosis) -family history** -genetic abnorm. *family history is the most significant independent risk factor for atherosclerosis. However, these genetic diseases account for only a small percentage of cases. Modifiable: -hyperlipidimia/ hypercholestrolemia -hypertension -cigg smoking (2x) -diabetes (2x) -inflammation due to C reactive protein

Describe a berry aneurysm

Develop at branch points of Circle of Willis • Can rupture. Most common cause of significant subarachnoid hemorrhage • 25-50% mortality with rupture • SEVERE SUDDEN headache

Describe chronic interstitial lung diseases

Diffuse interstitial fibrosis of the lung gives rise to restrictive lung diseases characterized by reduced lung compliance and reduced forced vital capacity (FVC) The ratio of FVC to FEV is normal. Bilateral, often patchy, involvement of pulmonary CT -->Mainly delicate alveolar wall interstitium Stiffness → ↑ effort of breathing (dyspnea). -->Reduced compliance -Damaged alv walls (epith & endoth) → hypoxia -Diffuse small nodules or "ground-glass" shadows. -Often resp failure, with pul HT and cor pulmonale. -Later stages difficult to differentiate b/c scarring & gross destructn → end-stage "honeycomb" lung

caput medusae

Dilated veins around the umbilicus, associated with cirrhosis of the liver.

What is Reynaud's phenomenon

Exaggerated vasoconstriction of arteries and arterioles in the extremities, particularly the fingers and toes, but also occasionally the nose, earlobes, or lips • Primary exaggerated central and local vasomotor responses to cold or emotion; it affects 3% to 5% of the general population and has a predilection for young women.

what is extravascular hemolysis

Extravascular hemolysis : opsonization of red cells by the autoantibodies leads to erythrophagocytosis in the spleen. Macrophages start to engulf RBC's. this prevents RBC's from entering spleen through the splenic sinusoids in cases of herditary spherocytosis

20% of all females suffer from infections of_______________________

Urinary tract or kidney

what occurs in hemolytic anemias?

Extrinisic abnormality of the RBC's anemias caused by accelerated red cell destruction Features shared by all uncomplicated hemolytic anemias include: -Premature destruction of red cells and a shortened red cell life span below the normal 120 days. -Elevated erythropoietin levels and a compensatory increase in erythropoiesis. -Accumulation of hemoglobin degradation products released by red cell breakdown, such as bilirubin.

what are immunohemolytic anemias? what are 2 types?

Extrinsic abnormality of RBCs Premature destruction of red blood cells caused by antibodies binding to red cells. 2 types: Warm antibody type Cold antibody type

Describe Fatty streaks

FATTY STREAKS = gross appearance : •EARLIEST LESIONS IN ATHEROSCLEROSIS. •composed of lipid-filled foamy macrophages. •BEGIN AS MULTIPLE MINUTE FLAT YELLOW SPOTS -------------> COALESCE INTO ELONGATED STREAKS 1 CM OR MORE IN LENGTH. •NOT SIGNIFICANTLY RAISED AND DO NOT CAUSE ANY FLOW DISTURBANCE. •AORTAS LESS THAN 1 YEAR OLD CAN EXHIBIT FATTY STREAKS. •Seen in virtually ALL CHILDREN OLDER THAN 10 YEARS, regardless of geography, race, sex, or environment. •THE RELATIONSHIP OF FATTY STREAKS TO ATHEROSCLEROTIC PLAQUES IS UNCERTAIN. •MAY EVOLVE INTO PRECURSORS OF PLAQUES • NOT ALL FATTY STREAKS ARE DESTINED TO BECOME ADVANCED LESIONS.

T/f Cells producing keratin when they normally do not is a definitive sign of cancer

False Keratin production does NOT mean you have a cancer - all it means is that you have a cells capable of producing keratin

T/f cigarette smoking is a risk factor for bronchitis, but not emphysema

False it is for both

Describe the main functions of ferritin and transferrin

Ferritin is a protein-iron complex found in all tissues but particularly in liver, spleen, bone marrow and skeletal muscle. Very small amounts of ferritin normally circulated in the plasma. Plasma ferritin correlates with total body iron stores. Transferrin - iron-binding glycoprotein synthesized in the liver, its major function is to deliver iron to erythroid precursors. Measured by Total Iron Binding Capacity (TIBC): TIBC - range 300 to 350 ug/dL. Transferrin Saturation- a value of serum iron divided by TIBC. 15-50% (males), 12-45% (females)

What is ferritin and transferrin?

Ferritin is a protein-iron complex found in all tissues but particularly in liver, spleen, bone marrow and skeletal muscle. -->Very small amounts of ferritin normally circulated in the plasma. -->Plasma ferritin correlates with total body iron stores. Transferrin - iron-binding glycoprotein synthesized in the liver, its major function is to deliver iron to erythroid precursors. -->Measured by Total Iron Binding Capacity (TIBC): TIBC - range 300 to 350 ug/dL. --> Transferrin Saturation- a value of serum iron divided by TIBC. 15-50% (males), 12-45% (females)

Describe the etiology of Adenocarcinoma

Gain-of-function mutations** in multiple genes encoding receptor tyrosine kinases, including: EGFR (epidermoid growth factor receptor) ALK (anaplastic lymphoma kinase) ROS MET RET (rearranged during transfection) which are all also mutated in other forms of cancer. only one which is GOF, rather than LOF

What is honeycomb lung?

Gross appearance of end stage lung Gross + radiologic appearance due to dense fibrosis → collapse of alveolar walls --> formation of "cystic" spaces. Seen in Chronic Interstitial lung diseases

Where would Endocarditis of SLE - Libman-Sacks Endocarditis be found?

Gross findings: Mitral and tricuspid valves - 1-4 mm, sterile vegetations. - Foumd on Undersurfaces of the AV valves, endocardium; chordae. Histologically: Microcopic findings: • Fibrinous vegetations. • +/- Valvulitis with fibrinoid necrosis of the valve substance • +/- Hematoxylin bodies** • Fibrosis and deformities can resemble CRHD and require surgery. CRHD = chronic rheumatic heart disease

List who is most susceptible to the following pneumonia causing bacteria: H. influenza M. catarrhalis S. aureus K. pnuemoniae P. aureginosa L. pneumophilia

H. influenza M. catarrhalis -both seen in people with COPD S. aureus -secondary to viral resp. infections K. pnuemoniae -seen in chronic alcoholics P. aureginosa -seen in people with burns, Cystic fibrosis, and neutropenia L. pneumophilia -seen in organ transplant recipients

What are sites of turbulence in endothelial injuries?

Hemodynamic turbulence = blood that is not flowing well - aka NOT in a laminar fashion - smashing against the wall at branch points --> can cause damage to endothelial layers (this can be caused by aneurysms) Sites of turbulence - Ostia - Branch points - Posterior wall of abdominal aorta

What occurs in a truncus arteriosus?

Lack of separation of the aorta and pulmonary artery, resulting in a SINGLE ARTERIAL VESSEL one vessel coming off the heart which branches in to aorta and pulmonary this always comes with a VSD!! (left to right shunt) Need to know that this alwaysss alwayssss comes with a VSD or else its fatal shortly after birth This is cyanotic

What are anorectal venous plexus? whats the difference between an internal and external plexus?

Hemorrhoids internal: origin above denate line external: origin below denate line If its both above and below its both external and internal

Describe the morphology of a small cell carcinoma

Highly malignant tumor with a strong relationship to cigarette smoking only about 1% occur in nonsmokers. May arise in major bronchi or periphery of lung. No known preinvasive phase. Most aggressive of lung tumors Metastasize widely and virtually always fatal. Usually metastatic at presentation. Cells small, fusiform ("oat cell") or spherical -Large dark-staining nucleus and scanty cytoplasm -Nuclear "molding"; chromatin finely granular Dense-core granules, NE markers and secrete hormones (paraneoplastic syndromes). Untreated small cell carcinoma: 6 - 17 weeks survival period -Very sensitive to RT & chemotx -Even with treatment: mean survival is ~ one year

What is the most common glomerular disease?

IgA nephropathy/ Berger disease affects children and young children frequent cause of gross hematuria Many patients maintain renal function Deposition of circulating IgA immune complexes in mesangium...mesenagial proliferation and matrix increase (immune type gomerular injury)***

Describe megaloblastic anemias What are 2 major types

Impairment of DNA synthesis that leads to abnormally large blood cells and their precursors. Ineffective hematopoiesis: defective cell maturation and division; apoptosis of precursor cells. -Marrow hyperplasia -Peripheral blood: pancytopenia Two major types: Vitamin B12 deficiency (most common: pernicious anemia). Folate deficiency vitamine b12 def. causes neurological complications!

Who is at risk of PNEUMOCYSTIS JIROVECI PNEUMONIA what occurs in it?

In almost 100% AIDS sufferers at some time during disease and common cause of death. Infection correlates with CD4 cell count < 200 /ml. Cup-shaped organisms 5 mm diam Diffuse or patchy pneumonia. Alveolar spaces filled with foamy material consisting of organisms and cell debris. Also interstitial inflammation with hyaline membrane formation. Often, other bacterial, fungal and viral infections

What is a Infarct extension

Infarct extends beyond original borders. • simple Infarcts heals from margins to center. Most advanced peripherally. • Infarct extension - More advanced healing centrally. Causes of Infarct extension : • Retrograde propagation of a thrombus. • Proximal vasospasm. • Impaired contractility causes insufficient flow trough stenoses. • Microemboli. • Arrhythmia.

Describe what occurs in chronic endothelial cell injury in terms of the -endothelial cells -smooth muscle cells -macrophages -plaque formation

Injured endothelial cells: -Change shape and causing increased permeability. -Allow cell migration and lipid into the intimal space. -Make cell surface adhesion molecule VCAM-1 causing leukocyte adhesion and emigration. -Produce chemotactic factors to attract leukocytes. Smooth muscle cell (SMC) recruitment and Macrophage activation -Growth factors stimulate SMC proliferation and extracellular matrix synthesis. MPGs and SMCs engulf lipid -LDL is oxidized in the arterial wall by free radicals produced by inflammatory cells. -Activated macrophages and smooth muscle cells ingest LDLox and become foam cells. -fatty streak on luminal surface forms (represents what is going on underneath the endothelium) SMC proliferation, collagen, matrix and extracellular lipid deposition -- Recruited SMCs synthesize collagen stabilizing atherosclerotic plaques. - Activated inflammatory cells --> SMC apoptosis --> increase ECM catabolism --> unstable plaques. - Macrophage undergo apoptosis and liberate lipid adding to the lipid core.

Whats the difference between hemoglobinathy and thalassemias?

Intrinsic (intra-corpuscular) Intrinsic (intra-corpuscular) abnormalities of red cells Hemolytic anemias Hemoglobinopathy- abnormal structure of one of the globin chains. Thalassemias - underproduction of normal globin proteins. The two conditions may overlap - some conditions causing abnormalities in globin proteins also affect their production (e.g. sickle-thalassemia).

What is a adenocarcinoma

Invasive malignant epithelial tumor with glandular differentiation or mucin production by tumor cells. Grow in various patterns. Compared with SCC, they are usually more peripherally located and tend to be smaller. Most express thyroid transcription factor-1 At periphery of tumor there is often a lepidic pattern of spread, in which the tumor cells "crawl" along normal-appearing alveolar septa. ***Gland formations are pretty characteristic of adenocarcinomas. Lung adenocarcinoma: -Usually peripheral (some closer to hilum) -Grow slowly and form small masses but metastasize widely at early stage.

what does the osmotic fragility test for?

It is a measure of the resistance of erythrocytes to hemolysis by osmotic stress in a hypotonic saline solution. A normal RBC is able to swell because of its volume to surface ratio. Spherocyte lost its stretch-ability. Once the limit is reached lysis occurs.

What is the most common site of a myocardial rupture?

LAD midventricular level

Myocardiac infarctions are most likely to occur at

Left anterior descending LAD= widow maker

What are some symptoms of Systemic HHD? (Hypertensive Heart Disease)

Left ventricular hypertrophy Increase in LV wall thickness Increase in heart weight Increase in LV wall stiffness =impaired diastolic filling +/- left atrial enlargement microscopic feature Early - Increased myocyte diameter Later - Nuclear enlargement +/- interstitial fibrosis.

Describe Calcific Stenosis of Congenitally Bicuspid Aortic Valve

Most frequent congenital cardiovascular malformation - 1% of population affected • Structural abnormalities of the aorta common. • Mitral valve is generally normal • Late complications: AS or AR; infective endocarditis; aortic dilation and/or dissection; cusp prolapse. The raphe is a major site of calcific deposits. • Less frequently-cusps of equal size and raphe is absent

Describe Restrictive Cardiomyopathy

Lest common; most rare Ventricles are fine, systolic are fine, atrium is the only thing that's disrupted due to stiff ventricles • Reduced ventricular compliance due to stiffening of wall and failure of relaxation leads to resistance to diastolic filling. (a stiff heart basically) • Systolic function unaffected, hence no hypertrophy**** • Radiation injury/fibrosis, amyloidosis, sarcoidosis, idiopathic, inborn errors of metabolism, metastatic tumors • Essentially normal sized heart, dilated atria*** huge atria- the only cardiomyopathy that affects the atria • If not idiopathic, see specific pathology of the causative disease no change in size of ventricles, they just get stiff aka stenosis. (amyloids are a common cause of this) Stiff ventricles don't contract like they should --> so blood is in the atria. Congo red is used to stain amyloids which is what is found in this disorder

What is the primary feature of obstructive lung diseases?

Limitation of airflow due to partial or complete obstruction. Primary feature: decreased expiratory flow rate Expiratory airflow obstruction due to: -Anatomic airway narrowing, as in asthma or -loss of elastic recoil of lung, as in emphysema.

Difference between lobar pneumonia and bronchopneumonia (lobULAR pneumonia)

Lobular: -Patchy involvement of parenchyma -Neutrophil-rich exudate fills bronchi, bronchioles and alveoli. -In very young, old & debilitated Lobar -Acute bacterial infection of large part of a lobe or an entire lobe. -4 classical stages rare today in U.S.A. b/c it is altered by antibiotics. 4 stages: Congestion, Red hepatization, Gray hepatization, Resolution -This type of pneumonia is more common in Young healthier people with more virulent organism Whole lobe is radiopaque in lobar pneumonia, but focal opacities in bronchopneumonia

what are carcinoid tumors? what do they cause? who do they affect most?

Low-grade malignant epithelial neoplasms Subclassified into typical and atypical carcinoids. Some produce vasoactive amines. Carcinoid syndrome: intermittent attacks of diarrhea, flushing, & cyanosis. Most patients < 40 years of age Many are nonsmokers. Histology: small, round, uniform nuclei and moderate cytoplasm

What is the most frequently diagnosed cancer in the world? What is the most common cause of cancer mortality in the world?

Lung cancer is the most frequently diagnosed major cancer in the world and the most common cause of cancer mortality worldwide It is the most common cause of cancer death for both men & women in U.S.

Describe metastasis to the lungs

Lung is most common site of metastatic neoplasms -b/c so much blood from different parts of the body pass thru the lungs to become o2 rich Lung metastases occur in 30 to 55 percent of advanced cancers Usually multiple discrete nodules (cannonball lesions) scattered throughout all lobes, more at periphery. Other patterns include solitary nodule, endobronchial, pleural, pneumonic consolidation, and combinations of these.

Describe the pathogenesis of Tuberculosis why is there a worry of resistane and hypersensitivity?

M. tuberculosis enters m'phages by endocytosis and replicates within phagosomes. Virulence partially due to ability to impair endosome maturation & phagolysosome formation Bacteria proliferate in alv m'phages in earliest stage of primary tuberculosis (< 3 weeks) -Results in bacteremia and seeding of multiple sites but most patients are asymptomatic or mildly ill. After 3 wks, mycobact Ags (attached to Ag-presenting cells) which stimulate TH1 cells → IFN-y. -This activates m'phages to be bactericidal. TH1 cells also orchestrate formation of epithelioid granulomas and caseous necrosis: -Activated m'phages (due to IFN-y from TH1 cells) are stimulated to release TNF -TNF recruits monocytes and they → epithelioid cells TH1 cells activate m'phages: immunity (bactericidal activity) hypersensitivity (with tissue destruction - caseation) Process triggers both resistance to the organism and hypersensitivity to tubercular antigens Immunity confers resistance and comes at cost of hypersensitivity and accompanying tissue destruction

What is MYCOBACTERIUM AVIUM-INTRACELLULARE COMPLEX (MAC) caused by?

MYCOBACTERIUM AVIUM-INTRACELLULARE COMPLEX (MAC) Caused by M. avium and M. intracellulare Clinically significant disease mostly occurs in late stages of AIDS (CD4+ T-cell counts < 60 cells/mm3) Organisms prolif in many organs, including lungs. M'phages contain abundant acid-fast bacilli.

What occurs in infective endocarditis?

Organisms colonize or invade heart valves or endocardium. • Vegetations of thrombotic debris and organisms often with destruction of the underlying cardiac tissues. • Bacterial infections in most cases. • Fungi and other microorganism classes less commonly. • The aorta, aneurysm sacs, other blood vessels, and prosthetic devices can also become infected.

What are the major targets and Consequences of atherosclerotic disease? What does the outcome depend on?

Major targets • Large elastic arteries - aorta, carotid, and iliac arteries. • Large and medium-sized muscular arteries - coronary and popliteal. Major consequences - Myocardial Infarct , cerebral infarct, aortic aneurysms, and peripheral vascular disease. Outcome will depend on: • Size of the involved vessels. • Stability of the plaque. • Degree of degeneration of arterial wall.

Describe pernicious anemia

Most frequent cause of vitamin B12 deficiency. The median age at diagnosis is 60 years. Occurs in all racial groups. Results from an autoimmune attack on the gastric mucosa and intrinsic factor itself. Histology: chronic atrophic gastritis: -Loss of parietal cells, which are responsible for secretion of intrinsic factor. -A prominent infiltrate of lymphocytes and plasma cells, - Megaloblastic changes in mucosal cells similar to those found in erythroid precursors. Demyelination of the dorsal and lateral tracts of spinal cord. -Found in about ¾ of all cases of florid pernicious anemia. Leads to: -Sensory ataxia (loss of sense of position, loss of coordination) and abnormal gait. -Peripheral neuropathy. -Numbness and paresthesia (burning or prickling sensation that is usually felt in the hands, arms, legs, or feet).

Describe some key things seen in Chronic Rhumatic Heart Disease

Mitral valve - Virtually always involved. • Alone 70%; With aortic valve 25%. • Pulmonary valve - rare Gross Findings: Leaflet thickening; Commissural fusion. Shortening, thickening and fusion of chorde.

What occurs in a VSD? Ventricular septal defect whats the worst VSD?

Most common congenital heart lesion • If small may be asymptomatic and close spontaneously • If large, generally presents from birth membranous VSD is the worst muscular VSD is not as bad since it wont get much bigger once it forms

What is Centriacinar (Centrilobular) Emphysema?

Most common form-smoking related Respiratory bronchioles (central or proximal part of lobule) destroyed and enlarged. "Holes" rimmed by spared tissue This emphysema Start in resp. bronchioles (as opposed to the terminal bronchioles) --> Gradual spread down system to involve alveolar ducts (spread more distally)

Describe a renal cell carcinoma

Most common malignant renal tumor (85% of renal cancers in adults) --> 2-3% of all cancer in adults and classified in to 3 main types 1. Clear cell carcinomas (most common) 2. Papillary renal cell carcinomas 3. Chromophobe renal cell carcinomas Often seen in older patients arise from kidney tubular epithelium Tabacco is the most prominent risk factor (2x) Treated by nephrectomy

What is dilated cardiomyopathy? What are some symptoms?

Most common pattern (90%) SYSTOLIC (CONTRACTILE) DYSFUNCTION • Poor contractility (systolic) leads to increased endsystolic, and diastolic volumes, leading to dilatation and failure. Symptoms: • Slow onset CHF • Poor ejection fraction • Mitral regurgitation • Arrhythmias • Embolism • Death within 5 years not rare Histology: Neatly fibrotic within the dilated cardiomyopathy Histology demonstrates variable myocyte hypertrophy and interstitial fibrosis flappy, thinned out walls but large cavity. ***DCM makes up 90% of the cardiomyopathies ****Scoop shaped ventricles (characteristic of DCM) Dilated Cardiomyopathy-Heavy, flabby heart w/dilated chambers.

What is the most common site for metastases from lung carcinomas to go to

Most common site of METS from lungs is the Lymph nodes Liver is the 2nd most common site for METS (45%) Adrenal is 35% on chart but may be as high as 50% now (we don't know why lung cancer goes here)

What occurs in left sided heart failure?

Most commonly secondary to ischemic heart disease, systemic hypertension, valve disease, myocardium disease, symptoms are mainly a consequence of pulmonary congestion and edema Heart can't keep up w/venous return from lungs • Increase back pressure into lungs leads to pulmonary congestion and edema • Lungs heavy/wet(Rales) • Micro-Lungs show congestion, edema, and hemosiderin-laden alveolar macrophages in alveoli "heart failure cells" • Decreased renal perfusion activates --> renin-angiotensin-aldosterone system, leads to retention of salt and water, worsening pulmonary edema • Hypoxic encephalopathy (lack of O2 to brain)

What is Silicosis? what is its hallmark lesion?

Most prevalent chronic occupational disease in the world . Occupational exposures include: -->Mining -->Stone cutting -->Ceramics production Crystalline forms of silica, especially quartz AA's more susceptible > whites Silica also → acute silicosis Lipoproteinaceous material within alveoli M"phages phagocytose silica crystals Activates inflammasome Release of inflam mediators Early stages of silicosis: tiny nodules. Coalesce into hard, collagenous scars*** Some nodules may → central softening and cavitation due to superimposed TB or to ischemia. Expansion & coalescence of lesions may → progressive massive fibrosis. -Most patients do not develop shortness of breath until this stage. -May progress even after exposure has ceased. Hallmark lesion: central area of whorled collagen fibers with a more peripheral zone of dust-laden m'phages

What is sarcoidosis? what 2 glands does it affect the most? Histology? Prognosis?

Multisystem disease characterized by non-necrotizing granulomas in many organs. Course unpredictable: Inexorably progressive, or periods of activity with remissions, sometimes permanent High levels of CD4 TH1 T cells in the lungs secreting cytokines such as IFN-y Bilateral hilar lymphadenopathy or lung involvement in 90% In U.S., most affects A-As (F > M) 20-40 yrs old. Parotid and major salivary glands are often affected UNKNOWN ETIOLOGY -No definitive diagnostic test -Usually diagnosed by exclusion Histology Regardless of the tissue, involved tissues contain well- formed nonnecrotizing granulomas composed of aggregates of tightly clustered epithelioid macrophages, often with giant cells. Laminated concretions composed of calcium and proteins known as Schaumann bodies and stellate inclusions known as asteroid bodies are found within giant cells in approximately 60% of the granulomas. --> however these are also found in other granulomatous diseases and are not diagnostic of sarcoidosis Prognosis: 65-70% recover with little residual effect. 20% permanent lung or visual dysfunction 15% get progressive fibrosis & cor pulmonale

What can occur in instances of myocardial rupture?

Necrotic myocardium - soft and weak - Usually rapidly fatal. - 3 to 7 days after MI ; mean 4 to 5 days. -Risk factors > 60, female, hypertension. You can get a Ventricular free wall (blown out hole due to heart pumping while walls are not strong) - called hemopericardium and cardiac tamponade - Most common site - antero-lateral wall - midventricular level --> you can die instantly from this Rupture of the ventricular septum acute VSD and L-R shunt

What occurs in Superior vena cava syndrome

Neoplasms that compress or invade the superior vena cava • Bronchogenic carcinoma or mediastinal lymphoma. • Other space occupying lesions in the mediastinum such as aortic aneurysms • Marked dilation of the veins of the head, neck, and arms with cyanosis . • Pulmonary vessels can also be compressed, inducing respiratory distress.

What occurs in vascular ectasias?

Nevus flammeus (a "birthmark"), the most common form of vascular ectasia, is a light pink to deep purple flat lesion on the head or neck composed of dilated vessels. Most ultimately regress spontaneously. The so-called port wine stain is a special form of nevus flammeus. These lesions tend to grow during childhood, thicken the skin surface, and do not fade with time. Babies face gets darker when they cry because vessels get congested

Describe how Erythrocytes (RBC's) look and function

No nucleus. Size: 6-8 micron (normal). Shape: biconcave disc. Hemoglobin content: normochromic (central pallor ~ 1/3 of RBC diameter). Function: transportation of oxygen.

What is the treatment for ALI and ARDS?

No proven specific treatment Improvements in therapy has cut annual mortality rate in U.S. from 60% to ~ 40%. Most deaths attributable to sepsis or multiorgan failure and, in some cases, direct lung injury. *** Most survivors recover pulmonary function but many have persistent impairment. In a minority of patients, the exudate and diffuse tissue destruction result in scarring, interstitial fibrosis, and chronic pulmonary disease.

In a left to right shunt what occurs? What are the 3 most common types?

Non-cyanotic(L-R): (not cyanotic at first but CAN become so later) • Atrial septal defect (ASD) • Ventricular septal defect (VSD) • Atrioventricular canal (endocardial cushion defect) • Patent ductus arteriosus (PDA) • Coarctation of the aorta Increased pulmonary flow --> increased pulmonary pressure/volume --> pulmonary hypertension --> RV Hypertrophy --> heart failure Normally Systemic is 125 and Pulmonary is 15-18 mmHg • Not initially cyanotic, but can become later • When pulmonary pressure equals systemic, can have reversal of shunt from right to left, leading to cyanosis 3 most common: • Atrial septal defect (ASD) • Ventricular septal defect (VSD) • Patent ductus arteriosus (PDA) Other 2: Atrioventricularcanal (endocardialcushion defect) Coarctation of the aorta

What is Pneumoconioses?

Nonneoplastic lung reaction to inhaled mineral dusts in workplaces, including those induced by chemical fumes and vapors. Ambient air pollution also has deleterious effects on the general population, especially in urban areas It increases risk of asthma, especially in children -->Inner city children are more likely to get asthma due to ambient pollution

Describe the active phase of myocarditis whats the most common type of myocarditis?

Normal or dilated •some hypertrophy may be present. •The lesions may be diffuse or patchy. •The ventricular myocardium is typically flabby and often mottled by either pale foci or minute hemorrhagic lesions. •Mural thrombi may be present in any chamber. •Interstitial inflammatory infiltrate and focal necrosis of myocytes adjacent to the inflammatory cells You have to see 2 histologic traits together: 1. interstitial inflammation (between the myocytes) 2. focal necrosis of the myocytes in the area ***Both of these things together are needed to confirm myocarditis!!! microabscesses are associated with this Lymphocytic myocarditis = most common type of myocarditis b/c viruses (specifically coxsackie) is the most common cause of myocarditis and viruses elicit lymphocytic response clinically myocarditis might be asymptomatic give rise to acute heart failure or evolve to DCM

Describe nosocomial or hospital-acquired pneumonia which bacteria usually cause them?

Nosocomial infections often life-threatening Gram-positive cocci (mainly S. aureus and S. pneumonia) and gram-negative rods (Enterobacteriaceae and Pseudomonas species) are the most common isolates. Common in patients with: -Severe underlying disease -Immunosuppression -Prolonged antibiotics -Invasive devices -Intravascular catheters -Patients on mechanical ventilation are at particularly high risk.

What are 6 Obstructive lung diseases?

OBSTRUCTIVE: COPD Emphysema Chronic bronchitis Asthma Bronchiectasis Cystic fibrosis thiCCC BAE

What are the 4 steps of Lobar pneumonia

ONE (congestion): vascular dilatation and intra-alveolar fluid exudate. TWO (red hepatization): obliteration of alveolar spaces by rbc's, pmn's & fibrin. THREE (grey hepatization): fibrinosuppurative exudate persists while rbc's disintegrate. FOUR (resolution): exudate is digested.

What is the difference between obstructive and restrictive lung diseases?

Obstructive lung diseases are characterized by an increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchioles. Restrictive diseases are characterized by reduced expansion of lung parenchyma and decreased total lung capacity.

Quick Run Down: Difference between occlusion and regurgitation + what typically causes each Inflammatory valve diseases causes __________ Describe: Rheumatic heart disease Infective endocarditis Nonbacterial thrombotic endocarditis

Occlusion (stenosis) --> caused typically by valve calcification Regurgitation (insuffieciency) --> caused by abormal matrix synthesis and turnover causing myxomatous degeneration inflammatory valve diseases cause post inflammatory neovascul. an scarring. Rheumatic heart disease results form anti-strep. antibodies that cross-react with cardiac tissues; it is most commonly affects the mitral valve and is responsible for almost all cases of acquired mitral stenosis infective endocarditis rapidly destroys normal valves and can affect previously abnormal valves. Systemic embolization can produce septic infacts. Non bacaterial t.e. occurs on previously normal valves as a result of hypercoaguable states; embolization is an important consideration

What occurs in Hyaline Arteriolosclerosis

Occurs in small vessels Chronic hemodynamic stress AKA chronic stress on the walls of vessel: - Endothelial cells leak plasma proteins. - Smooth muscle cell matrix synthesis Microscopically: -pink hyaline thickening -narrow lumen Causes: - Hypertension - Elderly persons - Diabetic microangiopathy -Stress on the walls of the vessels- causes endothelial walls to leak fluid and proteins

Describe squamous cell carcinoma Growth patterns? Histology?

Often preceded by squamous metaplasia or dysplasia Then transforms to CIS - that may last years (CIS= carcinoma in situ) Eventually, invasive SCC may appear. In the past, most SCCs arose centrally from the segmental or subsegmental bronchi. Incidence of SCC of peripheral lung is increasing Marker of early change = increase in # of goblet cells aka goblet cell hyperplasia Growth patterns: 1. Exophytic growth into bronchial lumen -Produces an intraluminal mass. -Further enlargement → bronchial obstruction, -Leading to distal atelectasis and infection. 2. Growth along broad front → cauliflower-like intraparenchymal mass that pushes lung sub ahead of it. The neoplastic tissue is gray-white & firm to hard As in almost all types of lung cancer,. Focal areas of hemorrhage or necrosis may show red or yellow-white mottling and softenin -Sometimes these necrotic foci cavitate. Histology: Well-differentiated SCC with keratinization and pearls/Well-diff tumors: sheets of paving stone-like epith cells with intercellular bridges & keratin (pearls).

What enzyme is responsible for converting chemicals found within cigarettes/tobacco smoke in to their ultimate carcinogenic forms

P-450 monooxygenase enzyme converts chemicals to ultimate carcinogens Polymorphisms in P-450 genes may increase activation of procarcinogens in tobacco smoke

Difference between the type types of cardiac overload hypertrophies

PRESSURE-OVERLOAD HYPERTROPHY. Concentric increase in wall thickness. New sarcomeres added in parallel Increased cross-sectional area VOLUME-OVERLOAD HYPERTROPHY Ventricular dilation. New sarcomeres added in series Wall thickness may be increased, normal, or less than normal; Heart weight, rather than wall thickness, best measure of hypertrophy in VO hearts.

What is the difference between primary and secondary TB?

PRIMARY TUBERCULOSIS -In previously unexposed people -usually asymptomatic -Almost always involves lungs. - Ghon focus at initial site of involvement (Typically in subpleural parenchyma) Ghon complex: focus and regional lymph nodes which drain the focus. Organisms disseminate widely to other organs. Granulomas don't form in immunosuppression Histologically Tubercle (tuberculous granuloma) is microscopic aggregation of: -Plump round (epithelioid) histiocytes -Multinucleate giant cells surrounded by lymphocytes and fibroblasts. Central caseous necrosis usually present. SECONDARY (REACTIVATION) TUBERCULOSIS -affects previously infected people -manifests as cavitary lesion in the lung apices -Reactivation of bacilli in dormant lesions (rarely exogenous reinfection) following reduced host resistance. -Apical lesion enlarges with expansion of area of caseation -Erosion into a bronchus and discharge of caseous material produces cavity. -Dissemination through lymphatics and vena cava: miliary lung lesions --> Multiple "bird seed" lesions -->productive cough seen Dissemination via blood stream (due to erosion of pulmonary veins): systemic miliary tuberculosis in entire organs (bone marrow, liver, spleen etc.) Both primary and secondary result in H. seeding or spreading through blood

What is the metaplastic change seen in SCC?

PSEUDOSTRATIFIED COLUMNAR EPITHELIUM --> STRATIFIED SQUAMOUS EPITHELIUM --> Dysplasia ---> Carcinoma in Site ---> Invasive SCC

What is a paradoxical embolization?

Paradoxical embolization: Normally if you have a thrombus form it goes to the right side of heart and it will go to the lungs (pulmonary embolism). But If you have an ASD there is a hole b/w the 2 atria, so the blood and the thrombus crosses over into the left heart --> this can cause an infarct stroke (paradoxical embolization = left sided embolism) commonly seen in a ASD

List 3 pathogenic fungi List 3 opportunistic fungi

Pathogenic fungi: Limited pulmonary involvement in immunocompetent people but disseminated disease in immunosuppression Opportunistic fungi are low virulence. Cause disease in immunosuppression PATHOGENIC Histoplasmosis capsulatum Blastomycosis dermatidis Coccidioides immitis OPPORTUNISTIC Pneumocystis jiroveci Aspergillus species Cryptococcus neoformans Candidiasis species

What are pencil cells? where are they seen?

Peripheral blood smear: microcytic, hypochromic anemia with poikilocytosis (variation in shape) and anisocytosis (variation in size). *Pencil cells (small, elongated red blood cells)

What is bronchiectasis?

Permanent abnormal dilatation of bronchi & bronchioles Caused by destruction of muscle & elastic tissue 2nd to persistent infection &/or obstruction. Tumors, mucus plug, FB Necrotizing pneumonia Cystic fibrosis Symptoms: Symptoms are often episodic -Severe persistent cough -Mucopurulent sputum -Dyspnea and cyanosis

Describe what occurs during the acute stage of ARDS

Pneumocyte injury ↓ Marcrophage ↓ Pro-inflam cytokines (IL-1, TNF, chemokines) ↓ Neutrophils chemotaxis & activation ↓ Leukotrienes, RoS, proteases, PAF ↓ Local tissue damage (alv epith & endothelium) ↓ Edema fluid accumulation, Surfactant inactivation and Hyaline membrane (fibrin + necrotic epith) ARDS is a clinical syndrome of profressive respiratory insufficiency cauused by diffuse alveolar damage in the setting of sepsis, severe trauma, or diffuse pulmonary infection Neutrophils play a crucial role in ARDS as they are they cause of endothelial and epithelial damage Histologically: -alveolar edema -epithelial necrosis -PMN accumulation -Hyaline membranes lining alveolar ducts and walls

what are some consequences of neglecting atherosclerosis while it is in its 1. pre-clinical phase 2. clinical phage

Pre-clinical phase -usually young children a normally artery can progress from a 1. normal artery to fatty streak 2. Normal artery to a fibrofatty plaque 3. Fatty streak to fibrofatty plaque -all the above occur at lesion-prone areas and are accelerated by risk factors 4. Fibrofatty plaque to advanced/vulnerable plaque -this entails cell death and degeneration and remodeling of plaque and wall ECM as well as calcification clinical phase -usually middle age to elderly 1. advanced plaque to a aneurysm and rupture 2. advanced plaque to occlusion by thrombus 3. advanced plaque to a critical stenosis

What are some predisposing factors to infective endocarditis? What is the source of the organisms that cause this?

Predisposing factors: Cardiac and vascular abnormalities • Mitral valve prolapse • Calcific valvular stenosis • Bicuspid AV • Artificial valves • Congenital defects • Rheumatic HD Risk can be lowered with antibiotic prophylaxis source: • Infection elsewhere • Dental or surgical procedure • Contaminated needle (IVD) • Trivial breaks in the epithelial barriers of the gut, oral cavity, or skin.

What occurs in valvular heart disease?

Presentations - Stenosis, insufficiency or both can occur Clinical consequences vary depending on: • Valve involved • Degree of impairment • Rate of development • Rate and quality of compensatory mechanisms Infective endocarditis - sudden destruction of an aortic valve cusp can cause acute, massive regurgitation - rapidly fatal Rheumatic mitral stenosis usually develops indolently over years, and clinical effects often well tolerated.

what are cardiomyopathies?

Primary abnormality of myocardium -->Also NOT a end stage disease only thing that is end stage is CHF • Wide array of etiologies: inflammation, immune, genetic, metabolic, idiopathic • Dilated, hypertrophic, restrictive based on morphology and function • Traditionally, exclude ischemic, although "ischemic cardiomyopathy" is a term used by some for CHF associated w/CAD Cardiomyopathies manifests as 3 different physical manifestations (aka 3 different types of CM) 1. Dilated CM (DCM) (most common) 2. Hypertrophic (HCM) 3. Restrictive (least common) *** we are not talking about ischemic cardiomyopathy

What occurs in Histoplasmosis

Primary lung disease: self-limited, often latent primary disease with granulomas (like TB) May undergo caseation necrosis and coalesce to produce areas of consolidation But may liquefy → cavities Resolution: fibrosis and calcification Histoplasma capsulatum infection by inhalation of soil particles contaminated by bird droppings Pathogenic fungi -macrophages have a capsule around them hence capsulatum Causes chronic disease in previously healthy people

What are some Consequences of Atherosclerotic Stenosis How do vasodilators effect them in cases of severe A.S?

Severe concentric lesions will no longer respond to vasodilators .• Small arteries - occlude vessel lumina compromise blood flow and causing ischemic injury. • Critical stenosis - significantly limits flow, and demand begins exceeding supply. 70% fixed occlusion • Patients develop chest pain on exertion (stable angina). • Bowel ischemia; ischemic encephalopathy; intermittent claudication.

What can Progressive atherosclerotic narrowing lead to?

Progressive atherosclerotic narrowing which can lead to: 1. Acute plaque change 2. Increased demand for blood 3. Vasospasm This can lead to: Insufficient coronary perfusion relative to myocardial demand.

What is typical pulmonary artery pressure? What does it rise to in cases of hypertension?

Pulmonary artery pressure - 9 - 18 mmHg Pulmonary hypertension - > 25mmHg

What are some signs of left sided heart failure? What are some symptoms?

Signs: •Hypoxic encephalopathy • Renal underperfusion causes Renin aldosterone to kick in, worsening pulmonary edema • Azotemia (urea in blood) Symptoms • Dypnea on exertion (Dyspnea = shortness of breath) • Paroxysmal nocturnal dyspnea • Orthopnea (can't lay flat at night b/c laying flat makes them cough and gasp (uses lots of pillows to sleep) • Hemoptysis (Hemoptysis = coughing up blood) • Rales

What left ventricular area is in danger if the following coronary artery get occluded 1. Right coronary artery 2. Left anterior descending coronary artery 3. left circumflex coronary artery which MOST often results in MI's? what are 2 other non-transmural infarcts?

RCA -30-40% of MI's -inferior/posterior left ventricular wall -posterior portion of the septum LAD -40-50% of MI's*** -anterior left ventricular portion of the wall -anterior portion of setpum -apex circumferential LCX -15-20% of MI's -Lateral wall of Left ventricle EXCEPT apex 2 other non-transmural infacts 1. global hypotension (circumferential subendocardial) 2. Small intramural vessel occlusions (microinfarcts)

What is the Reid index?

Reid index: ratio of thickness of mucous gland layer to thickness of wall betwn epithelium & cartilage Normally less than 0.4. Increased in chronic bronchitis

What are renal calculi?

Renal Calculi are common and more frequent in males. Eighty percent of renal stones are unilateral. Most stones arise in the kidney and may be composed of Ca oxalate, uric acid, cystine, etc. High urinary concentration of stone's constituents exceeding urinary solubility promotes stone formation which is also influenced by urinary PH, volume, bacteria & inhibitors of crystal formation. Small stones may enter ureters and cause colic pain, gross hematuria & increased risk of infection; larger stones are asymptomatic often diagnosed radiologically.

what is the most common pneumoconiosis in the world?

Silicosis

What does resolution of a cell injury usually entail?

Resolution is impeded due to epithelial necrosis and inflammatory damage that impairs the ability of remaining cells to assist with edema resorption. If the inflammatory stimulus lessens, macrophages remove intraalveolar debris and release fibrogen cytokines TGF-β and PDGF. These factors stimulate fibroblast growth and collagen deposition, leading to fibrosis of alveolar walls. Examples: Bronchiolar stem cells proliferate to replace pneumocytes. Endothelial restoration occurs through proliferation of uninjured capillary endothelium.

Describe idiopathic pulmonary fibrosis Describe its pathogenesis

Restrictive disease Radiologic & histologic pattern of fibrosis is UIP Usual interstitial pneumonia= UIP Other diseases also show UIP therefor it is NOT diagnostic of IPF So must be excluded (before "idiopathic"). Pathog. Fibrosis in genetically predisposed individuals. Not much inflammation is seen, just fibrosis. Genetic mutations: -Telomerase - maintains telomeres (ends of chromosomes) so prevents cell senescence -Surfactant -MUC5B (Mucins) Environmental factors. -Cigarette smoking is the most important agent. Abnormal repair Rx to recurrent alv epith injuries: Epith TGFb → f'blasts → myof'blasts → collagen Symptoms and treatment: -Dry cough and progressive dyspnea -Most patients deteriorate. Mean survival only 2-4 yrs. -Lung transplant is only definitive Tx

What are some symptoms of right sided heart failure?

Right heart can't keep up w/systemic return • Systemic & portal venous congestion and edema • Chronic passive congestion of the liver ( nutmeg liver) -->central lobular congestion!!! Congestion is w/in the blood vessel and you see more blood vessels around the central vein than around portal track • Splenomegaly (big spleen) • Distended neck veins (only on right sided) • Deep leg vein thrombosis, stasis dermatitis • Pedal and pretibial edema, +/- pitting of the skin • Anasarca (total body edema- in nearly all body cavities) • Pericardial, pleural effusions, ascites ***pulmonary edema is NOT associated w/ right sided failure/cor pulmonale signs and symptoms are related chiefly to peripheral edema and visceral congestion

What occurs in an atheroembolism?

Ruptured plaque can embolize atherosclerotic debris - Distal vessel obstruction and acute thrombosis leads to microemboli formation

What clinical symptoms are seen in ALI?

Severe dyspnea & tachypnea at start of ALI, followed by increasing cyanosis and hypoxemia, respiratory failure, and diffuse bilateral infiltrates on radiographs Hypoxemia may be refractory to oxygen therapy due to ventilation perfusion mismatching (described below), and respiratory acidosis can develop. Early in the course, lungs become stiff due to loss of functional surfactant. Tachypnea = abnormal rapid breathing -Dyspnea = difficulty breathing on exertion

what is atelectasis? is it reversible? 3 types

Shrunken, relatively airless pulmonary parenchyma Due to incomplete expansion or collapse of previously inflated parenchyma. Reduces oxygenation of blood Predisposes to infection. Often reversible. 1. Resorption Atelectasis 2. Compression Atlectasis 3. Contraction Atlectasis

What is the physical differences between systemic HHD and pulmonary HHD

SYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEART DISEASE. •Marked concentric thickening of the left ventricular wall •Reduction in lumen size. PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEART DISEASE (COR PULMONALE). •Right ventricle dilated •Thickened free wall •Hypertrophied trabeculae

What is the ultimate result of forward failure?

Systolic dysfunction leads to tissue hypoxia

What is the difference between simple and obstructive chronic bronchitis?

Simple chronic bronchitis: productive cough, with mucoid sputum, but no physiologic evidence of airflow obstruction. Obstructive chronic bronchitis: chronic outflow obstruction Bronchitis in general: -Persistent cough with sputum production for at least 3 months in 2 consecutive years -Coexistent emphysema almost always

What occurs in Simple coal workers pneumoconiosis? what occurs in Complicated coal workers' pneumoconiosis?

Simple coal workers pneumoconiosis -Coal macules and nodules -Carbon-laden macrophages; nodules also contain a delicate network of collagen fibers. -Eventually → early emphysema Complicated coal workers' pneumoconiosis --> Progressive massive fibrosis; black lung disease -10% of cases Nodules coalesce → PMF -Large black scars cause: Progressive resp dysfunctn Pulmonary hypertension Cor pulmonale Once progressive massive fibrosis develops, it may continue to worsen even if further exposure to dust is prevented. Domestic indoor use of "smoky coal" (bituminous) for cooking and heating is associated with an increased risk of lung cancer death No convincing evidence that coal dust increases susceptibility to tuberculosis or to cancer in absence of smoking.

What are some small blood vessel diseases? Large blood vessel diseases?

Small blood vessel disease • Hyaline arteriolosclerosis • Hyperplastic arteriolosclerosis Large blood vessel disease • Atherosclerosis

why are particles size 1-5 micrometers in diameter so dangerous? what disease do they put you at risk for? what disease do larger particles put you at risk for?

Small highly soluble particles → A L I they are the perfect size to slip past the immune system and cause damage. Any bigger and won't be able to travel down to the alveoli, they will get blocked higher up and removed. Larger particles→fibrosing collagenous pneumoconiosis In most cases, they stimulate resident innate immune cells in the lung, leading to diseases Some cross the epithelial cell lining and interact directly with fibroblasts and interstitial macrophages Some activate the inflammasome when phagocytosed

Best test to diagnose TB?

Solid agar media: growth at 3-6 weeks provides drug sensitivity so its the gold standard

Describe Hypertensive Heart Disease (HHD)

Split into left side or right sided Systemic hypertension --> caused by left heart HHD Pulmonary Hypertension --> caused by right sided HHD HHD means you are having Cardiac Hypertrophy: Response to pressure overload -Myocardial dysfunction -Cardiac dilation -CHF -Sudden death common disorder affecting 25% of the population major risk factor for atherosclerosis, congestive heart failure, and renal failure May be primary or essential -idiopathic Secondary -primarily due to renal failure

whats the difference between stable plaques and unstable plaques?

Stable -tend to have dense fibrous cap -minimal lipid accumulation -little inflammation Unstable -"vulnerable" -thin caps -large lipid cords -relatively dense inflammatory infiltrates

which bacteria is the most common etiologic agent for community acquired bacterial pneumonia lung infections?

Streptococcus pneumoniae is most common etiologic agent

Describe the etiology of small cell carcinoma

Strongest association with smoking Shares many molecular features with SquamousCC Includes frequent loss-of-function aberrations TP53 (75% to 90% of tumors) RB (close to 100% of tumors) Chromosome 3p deletions. Amplification of genes of he MYC family. Worst type of cancer in terms of prognosis

transmural infarcts occur in what 3 arteries?

The following branches of the coronary arteries 1. LAD 2. LCX (left circumflex) 3. RCA

What causes acute coronary syndrome?

acute plaque changes Stable plaque abruptly becomes an unstable athero-thrombotic lesion. • Acute plaque change • Thrombus occludes the artery. • Often associated with plaque inflammation.

What occurs in RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN

Surfactant insufficiency is primary in RDS. It is 2nd in ARDS******* Most common cause of respiratory distress in newborn. Premature infants Type II cells not mature enough to produce surfactant Surfactant reduces Surface tension and decreases pressure needed to keep alveoli open. Atelectesis occurs without surfactant Hypoxia → epithelial & endothelial damage Hyaline membranes (necrotic cells & fibrin) on luminal aspect of alveolar walls. Treatment: -Antenatal corticosteroids (stimulate surfactant synthesis) -Exogenous surfactant and O2 at birth.

What are paraneoplastic syndromes? which cancer is associated with these?

Symptom complexes in patients with cancer which cannot be readily explained by local or distant spread of the cancer or by the secretion of hormones indigenous to the site of origin of the tumor. Lung carcinoma may be associated with paraneoplastic syndromes Examples: -PTHrP (PTH-related protein)→ hypercalcemia (SCC) -ACTH → Cushing syndrome -Elevated ADH -Neuromuscular syndromes (SCLC) -Finger clubbing & hypertrophic pulmonary osteoarthropathy -Coagulation abnormalities (adenocarcinomas)

What is the leading killer of HIV-positive people?

TB

Describe Oral TB

Usually 2nd to pulmonary disease via infected sputum, although hematogenous is possible. Oral mucosal nodules: irregular, indurated, red or ulcerated, often painful Osteomyelitis: hematogenous or entry via tooth, → periapical tissues → bone

What occurs in ischemic heart disease?

The heart is getting insufficient blood. Results in: • Insufficient oxygen. • Insufficient nutrients. • Insufficient removal of metabolites. • Aggravated by increased in cardiac energy demand. • > 90% Coronary atherosclerosis.

what occurs in anemia of chronic disease?

The most common cause of anemia in hospitalized patients in the U.S. Associated with reduced erythroid proliferation and impaired iron utilization. Certain inflammatory mediators, particularly interleukin-6 (IL-6), stimulate an increase in the hepatic production of hepcidin, which blocks the transfer of iron from macrophages to erythroid precursors. Etiology: Chronic infections: e.g. chronic osteomyelitis, lung abscess Chronic immune disorders: e.g. rheumatoid arthritis and regional enteritis. Neoplasms: e.g. Hodgkin lymphoma, lung and breast carcinomas. Lab findings: Decreased serum iron Normal or increased serum ferritin

In heart failure what often occurs to the heart cells?

They Hypertrophy due to adaptive molecular and cellular remodelling distinct sign: distended neck veins

Nutmeg Liver Picture

This is nutmeg liver . It is caused by right sided heart failure. *** Nutmeg liver = central lobular congestion!!! Congestion is w/in the blood vessel and you see more blood vessels around the central vein than around portal track

Leukocytoclastic vasculitis

This is the 3rd example of small-medium vasculitis This is a Skin disease that looks like a rash Biopsy shows breaking down white blood cells coming out of small vessels

T/F Progressive ischemia leads to collateral vessels that protect against ischemia

True

Difference between true and fake aneurysm?

True Aneurysm involves all 3 layers of blood vessel False aneurysm aka hematoma = defect in wall that has perforated thru, but the adventitia is the only bulging more likely to rupture b/c it has a thinner wall (1 layer instead of thing --> this type all 3).

What is sudden cardiac death?

Unexpected cardiac death without symptomatic heart disease or early after symptom onset. Ischemic heart disease/ischemia caused by coronary artery disease is the most common cause other usual causes: -Lethal arrhythmia - Usual cause- asystole, V- fibrillation. - Acute myocardial ischemia - Causes electromechanical cardiac instability of myocardium distant from the conduction system. - Arrythmogenic foci are often adjacent to scars left by old MIs Myocardial infaction at this point has left permanent damage to parenchyma of the heart SCD is also less often due to plaque rupture with thrombosis that induced fatal rapid arrythymias

what layers of blood vessels is responsible for vasodilation and vasoconstriction?

Tunica Media

Describe a typical emphysema patient

Typical patient is middle-aged, barrel-chested********, heavy-smoker. Productive cough depends upon extent of associated chronic bronchitis. -pure emphysema is NOT associated with a productive cough; it is instead assosicated with a alpha-1-AT def. Early, progressive dyspnea, with expiratory airflow limitation (key to diagnosis) Uncomplicated emphysema: relatively normal blood oxygenation at rest (hence "pink puffers") Usually loss of weight.

Describe the morphology of Large cell carcinomas

Undifferentiated malignant epithelium -Large nuclei -Prominent nucleoli -Moderate amount of cytoplasm Dx of exclusion Lack features of other types: Cytological I H markers

Describe varicose veins of the legs

Upper & lower superficial veins • Most common location • Increase w/age, obesity, female, pregnancy • Venous dilatation...valve incompetence...stasis...congestion/ edema...thrombosis...stasis dermatitis and varicose ulcers • Resultant impaired circulation leads to risk of infection and impaired wound healing

Describe what occurs in CHF (Chronic Heart Failure) (2 types of failure)?

Usually chronic inability to deliver needs associated with congestion of organs • Can be acute after fluid overload, MI, acute valvular function, eg • CHF is characterized by diminished cardiac output , systolic dysfunction(sometimes called forward failure,) • or damming back of blood in the venous system, diastolic failure with insufficient filling (so-called backward failure), or both. Not a disease**** • End stage of many processes • May be left or right sided, or both • Degree if dysfunction and whether compensated or not best evaluated outside of heart. pic: All of these 3 medical conditions cause increase in cardiac work, cellular stress, and all eventually lead to CHF

What occurs in Bacillary angiomatosis

Vascular proliferation in immunocompromised hosts (e.g., patients with AIDS) caused by opportunistic gram-negative bacilli of the Bartonella family. • Lesions can involve the skin, bone, brain, and other organs. • Two species are implicated: • Bartonella henselae, whose principal reservoir is the domestic cat; this organism causes cat scratch disease (a necrotizing granulomatous disorder of lymph nodes) in immunocompetent hosts. • Bartonella quintana, which is transmitted by human body lice; this microbe was the cause of "trench fever" in World War I.

Summarize Vasculitis

Vasculitis is inflammation of vessel walls; it is frequently associated with systemic manifestations (including fever, malaise, myalgias, and arthralgias) and organ dysfunction that depends on the pattern of vascular involvement. ▪ Vasculitis can result from infections, but more commonly has an immunologic basis, including immune complex deposition, formation of antineutrophil antibodies (ANCA), or T cell responses to vascular wall antigens. ▪ Different forms of vasculitis tend to specifically affect vessels of a particular caliber and location, and the clinical manifestations depend on the pattern of vessel involvement.

Angiosarcoma Hepatic angiosarcoma

Very high grade and aggressive • Older adults • May occur at any site, but most often involves skin, soft tissue, breast, and liver. • Hepatic angiosarcoma is associated with carcinogenic exposures, including arsenic (e.g., in pesticides), Thorotrast (a radioactive contrast agent formerly used for radiologic imaging), and polyvinyl chloride (a widely used plastic). Long latency. • Angiosarcoma can also arise in the setting of lymphedema, classically in the ipsilateral upper extremity several years after radical mastectomy (i.e., with lymph node resection) for breast cancer; the tumor presumably arises from lymphatic vessels (lymphangiosarcoma). • Angiosarcoma has also been induced by radiation • Angiosarcomas are locally invasive and can readily metastasize; 5-year survival rates approach 30%

what are vibrissae?

Vibrissae: long hairs in nasal vestibule filter foreign particles Large venous blood vessels in nose warm inspired air

Describe the structure of Influenza what variations cause epidemics? what variations can cause pandemics?

Viral genome composed of 8 single-stranded RNAs RNA virus bound by nucleoproteins that determine virus type A, B, C -Type A infect humans, pigs, horses, and birds Viral surface lipid bilayer contains factors that determine subtype Hemagglutinin (H) Neuraminidase (N). Epidemics: mutations of H and N antigens allow virus to escape most host antibodies Pandemics: Both H & N replaced by recombination of RNA segments with those of animal viruses 3 known subtypes of human flu viruses: H1N1, H1N2, & H3N2.

What are podocytes and where are they found?

Visceral epithelial cells found within the glommerular capillary wall

What is hematocrit?

Volume of packed red blood cells per unit of blood. --> Expressed as a percentage, e.g: 42 ml packed red blood cells/100 ml of blood, Hct = 42% it is 3x the hemoglobin, used to calculate amount either way**

Restoring blood flow in how many mins can prevent necrosis?

Within 20-30 minutes of the onset of ischemia may prevent necrosis.

Describe the ultrastructural changes due to ischemia

Within minutes of the onset of ischemia: • Myofibrillar relaxation • Glycogen depletion • Cell and mitochondrial swelling • Potentially reversible Severe ischemia > 20 to 30 minutes causes irreversible damage. • Necrosis of cardiac myocytes. • Disruption of sarcolemmal membrane. • Intracellular macromolecules leak out of cells.

What occurs in Lymphedema?

You block your lymphatic system • Primary lymphedema can occur as an isolated congenital defect (simple congenital lymphedema) or as the familial Milroy disease (heredofamilial congenital lymphedema), which results in lymphatic agenesis or hypoplasia. • Secondary or obstructive lymphedema stems from blockage of a previously normal lymphatic; by tumors, surgery that removes nodes, radiation, filariasis, postinflammatory. • Lymphedema increases the hydrostatic pressure in the lymphatics distal to the obstruction and causes increased interstitial fluid accumulation. • Persistent edema and subsequent deposition of interstitial connective tissue leads to a peau d'orange (orange peel) appearance of the overlying skin, • Seen typically in skin overlying breast cancers after the draining lymphatics are clogged with tumor cells; • Ulcers may develop due to inadequate tissue perfusion. Rupture of dilated lymphatics (e.g., secondary to obstruction from a tumor) leads to milky accumulations of lymph designated as chylous ascites (abdomen), chylothorax, and chylopericardium. "elephantiasis" also lymphedema - from parasitic worms

patent ductus arteriosus

a blood vessel in a fetus that bypasses pulmonary circulation by connecting the pulmonary artery directly to the ascending aorta in adult life this can be problematic if it doesnt close off -->long term risk of CHF

Describe an acute nephritic syndrome

a glomerular syndrome Acute onset of severe hematuria, mild to moderate proteinuria, oliguria/anuria and hypertension (fluid retention and increased renin release from ischemic kidney) Pathogen: -Proliferation of cells within glomeruli, WBC infiltrate, capillary wall damage and low GFR

What occur in nephrotic syndrome?

a glomerular syndrome a complex of -severe proteinuria -hypoalbuimemia -generalized edema -hyperlipidemia -lipiduria Pathogen: -Glomerular capillary wall damage... increased permeability to plasma proteins... massive proteinuria -Highly selective proteinuria (albumin only) -Poorly selective proteinuria (globulins and albumin) -Low blood albumin, low colloid osmotic pressure, interstitial Na and water retention

saccular aneurysm

a sac-like bulge on one side layered on top of one another

fusiform aneurysm

a spindle-shaped bulge grows as a fusiform on both sides

Describe the morphology of an adenocarcinoma in situ

a type of morphologic precursor (preinvasive) epithelial lesions Adenocarcinoma in situ formerly called bronchioloalveolar carcinoma Less than 3 cm Composed entirely of dysplastic cells growing along preexisting alveolar septae. The cells have more dysplasia than atypical adenomatous hyperplasia

Describe the morphology of an atypical adenomatous hyperplasia

a type of morphologic precursor (preinvasive) epithelial lesions Small lesion (≤5 mm) characterized by dysplastic pneumocytes lining alveolar walls that are mildly fibrotic It can be single or multiple and can be in the lung adjacent to invasive tumor or away from it.

What are varicose veins?

abnormally dilated, elongated, tortuous veins often from increased intraluminal presssure such as long periods of standing Can occur anywhere, but there are 3 important clinical sites being discussed: Superficial veins of legs, anorectal venous plexus, esophagus

What occurs in Rheumatic fever?

acute, immunologically mediated, multisystem inflammatory disease that occurs a few weeks post group A streptococcal pharyngitis. RF rarely follows streptococci infections other sites. • Acute rheumatic carditis is common during the active phase of RF and may progress to chronic rheumatic heart disease (RHD), and deforming fibrotic valvular disease. • Mitral stenosis -only cause.

What adds the irreversible component of asthma?

air-way remodeling which results in sub-basement thickening and hypertrophy of bronchial glands and smooth muscle

What is papillary muscle rupture? what does it result in? What is pericarditis? 2 types? What is a mural thrombi? What is a Ventricular aneurysm?

all are other complications of surviving a MI PMR: Results in severe acute mitral regurgitation. Peri: 2 types- early and late Early: Underlying myocardial inflammation leads to fibrinous pericarditis. Late: Dressler's syndrome - Several weeks or months p MI. • Believed autoimmune. fever, chest pain (usually pleuritic in nature), a pericardial friction rub, and /or a pericardial effusion. -circumferential inflammation MT: Abnormal contractility and endocardial damage --> thrombus and potential embolism. VA True aneurysms bounded by scarred myocardium • Large transmural infarcts with early expansion. • Paradoxically bulges during systole. • Complications - mural thrombus; arrhythmias; heart failure.

difference between angina pectoris and unstable angina?

angina pectoris --> chest pain due to inadequate perfusion - commonly due to atherscletoric disease causing >70% stenosis unstable angina --> increasingly frequent pain following less exertion and even occuring as rest --> results from erosion or rupture of atherosclerotic plaque triggering platelet aggregat., vasocontriction, formation of a mural thrombus that need not be occlusive

aschoff bodies

anitschkow cells with wavy ribbon-like chromatin; lymphocytes, plasma cells, and MPGs anitschkow cells- "caterpillar" cells seen in acute rheumatic carditis.

Transposition of Great Vessels (TGA)

aorta is now coming out of the right ventricle pulmonary artery coming out of the left ventricle Aorta and pulmonary artery are switched You have Two closed systems. • Need communication to survive • ASD, VSD, PDA (patent ductus arterious- still that connection between pulmonary artery and aorta skipping the lungs) TGA = 2 completely closed circuits!!!! Instead of the normal open blood circuit You will die b/c you're not delivering o2 to the body unless you have an ASD or VSD or patent ductus arteriosus

What is the role of lipids and lipoproteins in atherosclerosis?

arterial injury causes endotheilial dysfunction --> modification of apoB containing lipoporteins and infiltration of monocytes into the sub-endothelial space. Internalization of the apoB containing lipoproteins by macrophages promote foam cell formation, which is the hallmark of the fatty streak phase of atherosclerosis

what occurs in atrophic glossitis?

atrophy of lingual papillae, leaving a smooth/bald and erythematous (reddened) surface. Hyper-sensitivity to hot foods, acidic foods, spicy foods. Damaged nerve endings in the tongue. seen in megoblastic anemias

How to tell if a urinary tract obstruction is bilateral or unilateral?

bilateral if its below the ureters unilateral if above

What is the difference between warm antibody type vs cold antibody type immunohemolytic anemias?

both are Extrinsic abnormalities of RBCs Warm antibody type Activate at 37°C (body temp) Most common immunohemolytic anemia (48-70%)*** Mostly of the IgG type, or rarely Ig A type. Etiology: Primary (idiopathic= no cause): 50% Secondary to pre-existing condition: 50% - Neoplasms: e.g. lymphomas, leukemias - Autoimmune disorders (e.g. SLE) - Drugs: e.g. penicillin, -methyldopa Extravascular hemolysis : opsonization of red cells by the autoantibodies leads to erythrophagocytosis in the spleen. Macrophages start to engulf RBC's. Variable clinical severity. Treatment: Steroid medications, such as prednisone. Intravenous immunoglobulin (IVIG) Removal of the spleen (splenectomy) Cold antibody type (cold agglutinin): Less common than the warm antibody immunohemolytic anemia (16-32% of the cases). Occurs in peripheral cool parts of the body, e.g. fingers, ears, toes in cold whether. IgM antibodies bind and agglutinate red blood cells at low temperatures (0-4 oC). Most cells with bound IgM pick up some C3b but are not lysed intravascularly. When these cells travel to warmer areas, the weakly bound IgM antibody is released, but the coating of C3b remains. The cells are phagocytosed by macrophages in the spleen and liver Acute cases are often associated with infectious agents Mycoplasma pneumonia Infectious mononucleosis Self-limited Chronic: Idiopathic Associated with lymphoma

t/f Women more susceptible than men to get lung cancer Only 11% heavy smokers get lung cancer

both true

Describe the pathogenesis of a mitral valve prolapse

cause unknown in most cases MVP is associated with heritbale disorders of the connective tissue -MARFAN SYNDROME -defects in FBN-1 alter cell-matrix interactions and dysregulate TGF-beta signaling --> excessive TGF-beta can cause laxity and myxomatous changes can be prevented with inhibitors of TGF-beta

what are the Biochemical Functions of Vitamin B12 and Folate?

coenzymes in DNA synthesis Methylmalonic acid --> Methylmalonylcoenzyme A --(vitamine b12)---> Succinyl coenzyme A A deficiency of vitamin B12 leads to increased plasma and urine levels of methylmalonic acid --> Formation and incorporation of abnormal fatty acids into neuronal lipids --> cause a demyelinating disorder of the peripheral nerves and the spinal cord (neurologic complications of vitamin B12 deficiency).

in terms of the heart what is a "dominant artery" what is the dominant artery for the right side and the dominant one for the left side

dominant artery= the coronary artery that perfuse the posterior 1/3 of the setpum Right dominant -right coronary artery (RCA) 80% of individuals are dominant this way Left dominant -Left circumflex artery (LCX) 20% are left dominant LAD is always anterior 2/3 of septum for both Left and Right coronary artery for left and right ventricular free wall resp.

which disease do patients who often present with "silent" Mitral infarctions have?

entirely asymptomatic MI's commonly seen in the setting of diabetes mellitus

The primary or initiating factor in the genesis of chronic bronchitis is.....

exposure to noxious or irritating inhaled substances such as: -tobacco smoke (90% of the time) -dust -grain -cotton -silica

T/f Area must susceptible to risk of necrosis after coronary artery occlusion = areas closes to the blood supply

false Area must susceptible to risk = areas furthers away from blood supply --> endocardium dies first Endocardium dies first --> areas of necrosis spread backwards toward the occluded vessel

t/f myocardial infarction risk is three times as high in diabetics as in nondiabetics.

false myocardial infarction risk is twice as high in diabetics as in nondiabetics.

When are verrucae seen?

fibrinoid necrosis within cusps or along chodae seen in cases of Acute Rhumatic Fever

what is generally the ultimate result of insult or injury to the lung parenchyma?

fibrosis

what is the morphology of infective endocarditis?

gross findings: friable, bulky, destructive vegetations on the heart valves, single or multiple, one or more valves SBE vegetations- less valve destruction than ABE vegetation- fibrin, inflammatory cells, and organisms Emboli containing bacteria can cause abscesses to develop at sites where the emboli lodge --> septic infarcts or mycotic aneuysms

What are the 2 most importance causes of endothelial dysfunction

hemodynamic disturbances and hypercholestrolemia

What is the glomerular filtratrion barrier permeable to?

high permeable to water and small solutes impermeable to large, negatively charged proteins Maintained by visceral epithelial cells- podocytes

Where is hydronephrosis seen?

hydronephrosis: dilation of the renal pelsvis and calyces assocaited with profressive atrophy of the kidney due to outflow obstruction of urine seen in cases of urinary tract obstruction even in cases of complete obstruction, GFR initially persists due to back diffusion of filtrate into renal interstitum...renal atrophy and compression of medullary renal vasculature

What initially occurs in heart failure?

initially heart can compensate by release of catecholamines, myocyte hypertrophy. Get hypertrophic heart • Hypertrophy due to adaptive molecular and cellular remodelling • Enlargement later pathologic w/ineffective function/structure. May have arrhythmias • Later when compensation fails see dilatation (Dilatation = walls thin out again --> muscle gets floppy and hear gives up)

What is the immediate threat of acute blood loss? what happens when a patient survives this?

immediate threat- hypovolemic shock rather than anemia if patient survive- hemodilution begins, blood volume replenishes in 2-3 days normocytic and normochromic anemia is due to hemodiluation

Describe athersclerotic changes

impinges on the lumen Gross: • Yellow to grey plaques. • 0.3 to 1.5 cm in diameter - coalesce into masses. • Patchy, usually involving only a portion of arterial wall. • Thrombus over ulcerated plaques is red-brown.

What occurs to blood vessels during injury?

injury (of almost any type) to the vessel wall results in a stereotyped healing response involving smooth muscle cell proliferation, extracellular matrix deposition, and intimal expansion. Excessive thickening of the intima may result in luminal stenosis and vascular obstruction.

threat of chronic blood loss?

iron def. anemia

What are arrhythmias caused by?

ischemic or structural changes in the conduction system or by myocyte electrical instability in structurally normal hearts arrythmias more often are due to mutations in ion channels that cause aberrant repolirization or depolirization

Intrinsic pathway of coagulation vs extrinsic pathway

killikrenin converts factor 12 to 12a 12a converts 11 to 11a 11a converts 9 to 9 a 9a along with with factor 8 convert 10 to 10a 10a along with 5a convert prothrombin to thrombin thrombin converts fibrinogen to fibrin 13a is involved in the covalent cross-linking of fibrin allowing a clot to form extrinsic pathway 7a + TAF (tissue activating factor) converts 10 to 10a rest is the same

what cell is the most important defense mechanism in the alveoli?

macrophages; Alveolar macrophages phagocytose particles which reach alveoli surfactant produced by type 2 alveolar cells Lymphoid tissue immune defense mechanisms: secretory IgA, serum IgM & IgG, and T lymphocytes. Surfactant reduces surface tension

What occurs in Acute tubular injury? ATI

most common cause of acute kidney causes -electrolyte abnormalities -acidosis -uremia -signs of fluid overload Results from ischemic or toxic injury to renal tubules and associated with renal intrarenal vasoconstriction -->results in reduced GFR --> diminished delivery of oxygen and nutrients to tubular epithelial cells Characterized by: -necrosis of tubular segments -interstitial edema

What is myocardial hibernation?

myocardium that is subjected to chronic, sub-lethal ischemia may also enter in to a state of lowered metabolism and function that is referred to as hibernation the function of hibernating myocardium may be restored by revascularization paradoxially, repetitive short lived transient severe ischemia may protect the myocardium against infarction by mechanisms that are not understood

where are boxcar nuclei seen

myocyte (cardiac muscle cell) having a boxcar nuclei is symptomatic of hypertrophy and CHF

What occurs to nuclear cell size in erythropoiesis?

nuclei become smaller and small and nuclear:cytoplasmic ratio decreases

Name 3 instances of MI in absense of coronary atherosclerosis How common are these?

occurs in 10% of cases 1. Vasospasm with or without coronary atherosclerosis. -cocaine abuse can cause this -also caused by platelet aggregation 2. Emboli from the left atrium -atrial fibrillilation -Mural thrombi -vegetations of infective endocarditis -prosthetic material 3. Emboli from the right atrium -Paradoxical emboli via patent foramen ovale What else can cause MI in the absence of coronary AS plaques? - Vasculitis = vessel occluded by acute and chronic inflammation and fibrosis - Amyloids - Shock = decrease BP enough (ie. hemorrhage / bacterial infection) --> shock --> decrease BP --> poor perfusion --> MI

Where does glomular injury often result from?

often caused by deposition of antibodies and immune complexes, activation of complement, and leukocytes recruitment and activation Glomerulonephritis are caused by the formation of immune complexes

What occurs in pyelonephritis?

one of the most common kidney diseases 85% of gram negative bacilli -colonize distal urethra -bladder dysfunction or outflow obstruction

What is the dominant feature of nephrotic syndrome?

proteinuria (along with hematuria with functional impairment)

What occurs in community acquired bacterial pneumonia lung infections? whats elevated?

pulmonary infection; Abrupt onset of high fever, shaking chills, and cough-producting mucopurulent sputum Bacterial invasion of lungs → intra-alveolar fluid exudate → solidification (consolidation) of parenchyma Streptococcus pneumoniae is most common etiologic agent. Alveoli filled with pmn's, fibrin & edema fluid Walls intact So complete recovery possible with proper tx C-reactive protein and procalcitonin (acute-phase reactants produced primarily in liver) are significantly elevated in bacterial more than in viral infections. Traditionally, bronchopneumonia was separated from lobar pneumonia but they overlap in the modern era <10% of patients die from this, death is usually from complications such as empyema and bacteremic dissemination

Empyema Bacteremic

pus in the pleural cavity bacteria arriving from a distant source via the bloodstream such as heart valves, brain, kidney, and joints causing metastatic abscesses

Describe rapidly progressive glomerulonephritis

rapid loss of renal function and severe oliguria which results in death if not treated Also known as Crescentric glomerulonephritis Distinctive crescents formed by cellular proliferation and WBC migration of cells, collection of fibrin strands internal to bowman capsule -->Good response to steroid and cytotoxic agents but many require dialysis or transplantation Subepithelial humps and BM ruptures

What is hereditary spherocytosis?

red cell membranes disorders Inherited (intrinsic) defects in the red cells membrane--> formation of spherocytosis --> sequesteration and destruction in the spleen -decreases membrane stability eventually leading to membrane loss - decreases surface to volume ratio via spherocytosis -decreases deformability -Causes erythrostasis which decreases glucose and pH Eventually causes phagocytosis by extravasular hemolysis treatment- splenectomy

When is renin secreted by the kidneys?

released in response to decreased blood pressure in afferent arterioles renin -->>>angiotensin II which regulated blood pressure by increasing vascular smooth muscle cell tone and by increased aldosterone secretion which consequently increases renal sodium resorption

whats is cors pulmonale

right heart failure due to pulmonary hypertension. Pulmonary edema not prominent

Where do chronic endothelial injuries begin at?

sites of intact or non-dividing endothelium

What are Curschmann's spirals? Where are they seen? Where are charcot-leyden crystals seen?

strips of shed epithelium seen in cases of asthma Inflam cells including eosinophils and macrophages and their Charcot-Leyden crystals (derived from eosinophil proteins)

T/f premenopausal women are relatively protected against atherosclerosis

true

t/f Diuretics are the treatment to get rid of edema

true

t/f Hypertension is the most important cause of left ventricular hypertrophy

true

t/f Leg stasis from right sided heart failure can lead to deep vein thrombosis and pulmonary embolism

true

What 2 things determine blood pressure?

vascular resistance and cardiac output vascular resistance = regulated at the level of the arterioles, influenced by neural and hormonal inputs cardiac output= determined by heart rate and stroke volume (strong influenced by blood volume). -blood volume is in turn regulated mainly by renal sodium excretion or resorption

Describe the histology of kaposi sarcoma

vascular tumor of adults occurring around medium- and large-sized veins with NO endothelial lining

Epithelioid hemangioendothelioma

vascular tumor of adults occurring around medium- and large-sized veins. The clinical behavior is extremely variable; most are cured by excision, but up to 40% recur, 20% to 30% eventually metastasize, and perhaps 15% of patients die of their tumor.

What occurs in Lymphangiomas? Specifically cavernous lymphangiomas

• Capillary • Cavernous lymphangiomas (cystic hygromas) are typically found in the neck or axilla of children, and more rarely in the retroperitoneum. • Cavernous lymphangiomas can occasionally be enormous (up to 15 cm in diameter) and may fill the axilla or produce gross deformities about the neck. Of note, cavernous lymphangiomas of the neck are common in Turner syndrome. • The tumor margins are indistinct and unencapsulated, making definitive resection difficult.

What are some complications following acute MI?

• Contractile dysfunction - Heart failure - shock • Arrhythmias • Right ventricular infarction - Acute right-sided heart failure • Infarct extension • Infarct expansion - like a balloon -Weakening of necrotic muscle allows stretching, thinning, and dilation of the infarct region. • Papillary muscle dysfunction - Post infarct mitral regurg. • Progressive late heart failure • Myocardial rupture

What are some predisposing conditions to Nonbacterial Thrombotic Endocarditis / Marantic endocarditis? Describe this condition as well

• Debilitated patients; cancer or sepsis - marantic endocarditis. • Systemic hypercoagulable state. • Trousseau syndrome of migratory thrombophlebitis • Procoagulant effects • Endocardial trauma: Indwelling catheter • Track along Swan-Ganz PA catheters • small sterile thrombi on the leaflets of the cardiac valves. Found along the lines of closure of leaflets or cusps • NOT INVASIVE; NO INFLAMMATION • local effects usually unimportant • +/- SYSTEMIC THROMBI -prodouces infarcts in the brain , heart, or elsewhere Heparin therapy is recommended to prevent future clots. The Trousseau sign of malignancy should not be confused with the Trousseau sign of latent tetany caused by low levels of calcium in the blood.

What occurs in relaxation failure?

• Diastolic dysfunction • leading to Congestion and stasis of systemic organs Essentially blood can not move

What occurs in mitral stenosis?

• Diffuse fibrous thickening and distortion of valve leaflets. • Fusion of commissures. • Fish mouth or buttonhole stenoses. • Calcification • Left atrium progressively dilates. • May harbor mural thrombi in appendage or on the wall which can then embolize. • Long-standing pulmonary congestion leads to: -Pulmonary hypertension. -RV hypertrophy

What are the 2 most common causes of vasculitis? what is it mainly classified by?

• Direct injury to vessels by infectious organisms • Immune-related inflammation mainly classified by size of the vessel

What occurs in a glomus tumor?

• Exquisitely painful tumors arising from modified smooth muscle cells of the glomus bodies, arteriovenous structures involved in thermoregulation. • Most commonly found in the distal portion of the digits, especially under the fingernails. Excision is curative.

What are 2 large cell vasculitis?

• Giant cell arteritis • Takayasu arteritis

What occurs in Takayasu's Arteritis

• Granulomatous inflammation of large arteries branching from aortic arch • Luminal occlusion • Blindness, neurological impairment, undetectable upper extremity pulses • Young females NO UPPER EXTREMITY PULSE*********** Seen in the large vessels coming off the aorta, not the temporal arteries as in GCA

What are some Vasculitis associated systemic disorders?

• Henoch Schönlein purpura (big bruises) • Purpura of extensor surfaces of arms, legs, buttocks • Abdominal pain, vomitting, intestinal bleeding • Nonmigratory arthralgia • Renal abnormalities • Necrotizing vasculitis of small dermal vessels

Describe some immune-related vasculitis mechanisms main cause? 2 types?

• Immune complex formation with damage • Anti-neutrophil cytoplasmic autoantibodies(ANCAs) directed against enzymes in neutrophil granules** ANCA's are the main cause of vasculitis • p-ANCA against myeloperoxidase(p=perinuclear) • c-ANCA against proteinase(c=cytoplasmic) • Antiendothelial cell antibodies • Autoreactive T-cells

Describe Kaposi's sarcoma

• Intermediate grade vascular neoplasm caused by human herpesvirus 8 (HHV8) that is highly associated with acquired immunodeficiency syndrome (AIDS). • Classic KS is a disorder of older men of Mediterranean, Middle Eastern, or Eastern European descent (especially Ashkenazic Jews); it is uncommon in the United States. It can be associated with malignancy or altered immunity, but is not associated with HIV infection. • Endemic African KS typically occurs in HIVseronegative individuals • Transplant-associated KS • AIDS-associated (epidemic) KS is an AIDS-defining illness, and worldwide, it represents the most common HIV-related malignancy This is a low grade malignancy Kaposi sarcoma = a Vascular tumor but what is unique is that there is NO endothelial lining (looks like spindle cell tumor with extravesated red cells in between)

What occurs in Kawasaki disease (mucocutaneous lymph node disease)?

• Involves coronary arteries • Systemic symptoms, fever, eye and mouth mucous membrane redness/erosion, red palms, soles, skin rash, cervical adenopathy • Usually children under 4 • Coronary aneurysms and death possible This is a baby disease **TIP: this is the ONLY time you give a child Aspirin

Location, size, and morphology of Myocardial Necrosis depends on

• Location, severity, and rate of obstruction. • Size of perfused vascular bed • Duration • Metabolic/oxygen needs • Collateral blood vessels • Coronary arterial spasm • Other factors - heart rate, cardiac rhythm, oxygenation.

What occurs in hypertrophic cardiomyopathy? What are some symptoms?

• Marked Left Ventricle Hypertrophy without dilatation leads to resistence to diastolic filling with hypercontracted heart and contracted slit like ventricle("banana-like") DIASTOLIC (RELAXATION) DYSFUNCTION 100% genetic: • 50% familial(autosomal dominant),50% sporadic • Asymmetrical thickening, often in subaortic region of septum HCM has Very specific histology *****Total disorganization of the myocytes (Like pick up sticks) fibers not going parallel like normal, instead they go every which way Symptoms: • Angina • Atrial fibrillation w/possible thromboembolism • Mitral infective endocarditis • Ventricular arrhythmias • Sudden death --> seen in student athletes

Describe some important morphologies in Sudden cardiac death

• Marked coronary atherosclerosis - 80% to 90% (majority ***) • Nonatherosclerotic origin - 10% to 20% • Acute plaque disruption - 50% (****) • Acute MI - diagnostic changes 25% • Myocardial ischemia induced irritability thought to initiate most malignant ventricular arrhythmias. • Scars of previous infarcts and subendocardial myocyte vacuolization indicate severe chronic ischemia is common

What are vulnerable plaques?

• More likely to rupture • Large areas of foam cells and extracellular lipid • Fibrous caps are thin or contain few smooth muscle cells. - Clusters of inflammatory cells. • Fibrous cap - continuously remodeled. • Collagen - Synthesis versus degradation affects cap stability. • Plaque inflammation increases degradation and reduces synthesis of collagen, destabilizing the fibrous cap. • Healing plays role in the growth of atheromata

Describe calcific aortic stenosis Morphology? what is the prognosis without valve replacement for people with -angina -CHF

• Most common of all valvular abnormalities. -Normal valves -70-90 y/o -Bicuspid valves- 50-70 y/o • Wear and tear degeneration causes dystrophic and passive accumulation of calcium salt hydroxyapatite* - Hyperlipidemia, hypertension, inflammation play a role. - Valve injury in CAS differs from atherosclerosis You get • Heaped-up calcified masses on cusps prevent opening. • Begins in fibrosa layer; protrudes into the sinuses of Valsalva. • Commissures usually not fused Gradual narrowing of the valve orifice --> Valve area: Severe AS - 0.5 to 1 cm2 (normal - 4 cm2) • Concentric LVH due to increasing pressure gradient.** --> Hypertrophied myocardium tends to be ischemic. • Onset of symptoms heralds decompensation and poor prognosis. Without valve replacement: • 50% with angina will die within 5 years. • 50% with CHF will die within 2 years.

What are 4 clinical syndromes due to ischemic heart disease?

• Myocardial infarction • Angina pectoris • Chronic IHD with heart failure. • Sudden Cardiac Death.

What do acute plaque changes cause?

• Platelets adhere to subendothelial collagen and necrotic plaque. -Activate and release granules. -Aggregate to form microthrombi. -Vasospasm stimulated by released platelets mediators. • Tissue factors activate coagulation pathway, adding to thrombus. • Thrombus evolves to complete occlusion within minutes. Some occlusions fibrinolysisresolve due to fibrinolysis, or relaxation of spasm: • 4 hours of onset of MI - 90% thrombosed • 12 to 24 hours after onset, 60% thrombosed

What are 3 examples of Medium-sized vessel vasculitis

• Polyarteritis nodosa (PAN) • Kawasaki disease • Thromboangiitis obliterans(Buerger disease) "Medium BK Pepsi"

What is the Role of hypercholesterolemia in HHD?

• Predominant lipids in plaques. • Hyperlipoproteinemia and hypercholesterolemia --> premature atherosclerosis. • Plasma cholesterol and LDL levels correlate with severity. • Lowering serum cholesterol - slows progression, some regression, and reduces CV risk. • Increases local O2 free radicals

What are the 4 parts of TOF (Tetralogy of Fallot)?

• Right ventricular outlet obstruction(subpulmonic stenosis) • VSD • Overriding aorta • Right ventricular hypertrophy Net result: you're cyanotic I = interventricular septal defect (VSD) (usually caused from L-->R shunts) H = hypertrophy of RV O = overriding aorta P = pulmonary stenosis (skinny pulmonary artery) IHOP ** net effect = a CYANOTIC shunt (R-->L shunt) away from the lungs

What are some consequences of acute plaque changes?

• Rupture; fissuring; erosion; ulceration; thrombosis • Plaque hemorrhage - Further plaque disruption. • Probably common, repetitive, and often clinically silent.

What occurs in Polyarteritis nodosa? what is the main worry about it?

• Segmental necrotizing inflammation of vessels, most often of kidney, heart, liver. Lungs spared!! • Acute inflammation, necrosis and thickening of vessels • Can get aneurysms, ruptures • Young adults • Fever, ischemia of involved organs. • Can die of acute renal failure** main worry

What is right sided heart failure caused by?

• Usually due to left sided failure. • Backup from left into lungs overloads right heart, -less commonly: primary pulmonary disorders • "cor pulmonale"-right heart failure due to pulmonary hypertension. Pulmonary edema not prominent • Heart cannot accept normal systemic return signs and symptoms are related chiefly to peripheral edema and visceral congestion

What are 3 examples of small vessel vasculitis?

• Wegner's granulomatosis • Churg Strauss syndrome(allergic granulomatous angiitis) • Leukocytoclastic vasculitis

What are 2 Intermediate Grade Neoplasms What are 2 malignant ones?

•Kaposi sarcoma • Hemangioendothelioma Malignant: • Angiosarcoma • Hemangiopericytoma

What are some results/symptoms of left sided heart failure?

•ischemia due to MI • Hypertension • Aortic stenosis • Mitral regurgitation Symptoms: • Dypnea on exertion • Paroxysmal nocturnal dyspnea • Orthopnea • Hemoptysis • Rales

Describe RBC morphology in accordance to size, Hb content, and shape

■ Red cell size: Normocytic (normal size) Microcytic (small) Macrocytic (large) ■ Hemoglobin content Normochromic (normal Hb per RBC) Hypochromic (decreased Hb per RBC) Hyperchromic (increased Hb per RBC) ■ Shape: normal or abnormal (e.g. sickle cells)

Summarize vascular tumors

▪ Vascular ectasias are not neoplasms, but rather dilations of existing vessels. ▪ Vessel neoplasms can derive from either blood vessels or lymphatics, and can be composed of endothelial cells (hemangioma, lymphangioma, angiosarcoma) or other components of vascular wall cells ▪ Most vascular tumors are benign (e.g., hemangiomas), some have an intermediate, locally aggressive behavior (e.g., Kaposi sarcoma), and others are highly malignant (e.g., angiosarcoma). ▪ Benign tumors typically form obvious vascular channels lined by normal-appearing endothelial cells. Malignant tumors are more often solid and cellular, exhibit cytologic atypia, and lack welldefined vessels.