PBL exam 3 .txt

• 1. Etiology or cause- genetic or aquired
• 2. Pathogenesis- sequence of events in the response of cells or tissues to the etiologic event
• 3. Morphologic change - structural alteration in cells or tissues that are either characteristic of the disease or diagnostic of the etiologic event.
• 4. Clinical manifestation - The nature of the morphologic changes and their distribution in different organs or tissues influence normal function and determine the clinical features, course, and prognosis of the disease.

Hyperplasia

Hypertrophy

Atrophy

During times of stress and increased demand the cell adapts, if there is an inability to adapt the cell will die. If the stimulus is injurious the cell will die. Cell injury is reversible up to a certain point but if the stimulus persists the cell reaches the point of no return and suffers irreversible cell injury and death.

• 1. Necrosis - Response to abnormal stresses such as ischemia and chemical injury. Always pathologic.
• 2. Apoptosis - Cell dies through activation of an internally controlled suicide program. Eliminates unwanted cells in embryogenisis and also occurs in some pathologic events.

Calcium

The intercellular accumulation of a number of substances.

Hyperplasia, hypertrophy

Atrophy

Metaplasia

Acute reversible injury

Irreversible injury leading to cell death- necrosis or apoptosis

Subcellular alterations in various organelles

• factors produced by the cell or surrounding cells
• activation of cell surface receptors and downstream signaling molecules

Capable of DNA synthesis and cell division

• hormonal - increase of the female breast at puberty and uterus during pregnancy
• compensatory - increase tissue mass after damage or resection. The liver can regenerate. After nephrectomy the other kidney enlarges and makes up for the lose.

• Increase in local production of growth factors, increase in the number of growth factor receptors, or activation of intercellular signaling pathways.
• -All lead to in increase production of transcription factors leading to cellular proliferation.

excessive hormonal stimulation or growth factors acting on a target.

Synthesis of more structural components.

Increase do to the arrest of the cell cycle without undergoing mitosis

Increased functional demand or by specific hormonal stimulation.

• Induction of embryonic genes - Beta myosin in place of alpha myosin.
• Transcription factors -
• Growth factors - TGF-B, IGF-1, FGF
• Vasoactive agents- alpha adrenergic agonists, endothelin-1, angiotensin II.

• Secreted by the fetal atrium and ventricle and then by the adult atrium, response to pressure and volume change by regulating salt excretion to regulate volume and pressure.
• ex. increased atrial pressure due to excess venous return leads to higher levels of ANF excretion and an increase in urine production by the kidneys.

• 1. mechanical - stretch
• 2. trophic- growth factors and vasoactive agents secreted by non myocytes.

when the muscle reaches it limit for enlargement and is no longer able to compensate.

• 1. Decreased workload
• 2. Loss of innervation
• 3. Diminished blood supply
• 4. Inadequate nutrition- use of muscle for energy after fat stores are used up.
• 5. Loss of endocrine stimulation- loss of estrogen after menopause results in atrophy of the endometrium, breast, and vaginal epithelium.
• 6. aging
• 7. pressure - enlarged benign tumor can compress and cause atrophy of surrounding tissue.

can die if blood supply is inadequate for even the atrophied cell.

• degradation of cytosolic and nuclear proteins.
• Proteins are first conjugated to ubiquin then degraded within protease's.
• Stimulated by glucocorticoids and thyroid hormones
• Inhibited by insulin.
• Cytokines such ad TNF are capable of increasing muscle proteolysis in this way.

• reversible change from one cell type to another. May represent an adaptive substitution where one cell type is better suited to withstand an adverse environment.
• -most common is columnar to squamous, in the respiratory tract in response to chronic irritation. The new cells can survive but the special feature of mucus secretion is lost.

Esophageal squamous cells are changed to columnar under the influence of refluxed gastric acid.

Bone formation in muscle after bone fracture

• Not a change in the phenotype but reprogramming of the stem cells in the tissue or of undifferentiated mesenchymal cells in connective tissue.
• BMP's induce chondrogenic or osteogenic expression of stem cells while repressing differentiation to muscle of fat.

1. oxygen deprivation-

BMP-2 receptor mutation,

• Healthy- large bronchi
• Disease - bronchioles

• -cleave surface gp of Va and VIIIa
• -stimulates the release of t-PA
• -inactivates inhibitors of t-PA

• -can not bind clot bound plasmin
• -allows the destruction of a fibrin clot without the destruction of fibrinogen in circulation

not an enzyme but an allosteric modifier of human plasminogen that allows plasminogen to autocatylitically activate itself

after stress

• -x linked
• - bleeding into soft tissues (hematomas)

• cofactor in the gamma carboxilation of factors 2,7,9,10
• the carboxilation is of the glutamate side chain
• carboxilated side chains bin to calcium and then to activates platelets

mostly thrombin but has some activity on 8,9,10,11

Will bind to other plasma protein then AT3, this can cause the active amount in the blood to be reduced and spontaneous thrombi can be generated

• heparin binds to platelet factor four
• induces a conformational change in PF4 causing the immune system to not recognize it
• antibodies are made against heparin PF4 complex
• when antibodies bind the platelets become activated

• bines vit K reductase enzyme needes to regenerate vit K
• reduced gamma carboxilation, factors can not bind calcium or form complexes after coagulation is initiated
• also blocks protein S and C

• pentasaccharide that enhances AT3 interaction with Xa
• HIT is not a complication since fondaparinux does not bind for PF4

• Hirudin- discovered in leeches
• irreversible reaction
• bivalrudin, high binding aftinity for thrombin with a transient affect

Thromoxin A2

• 1. vascular constriction
• 2. platelet plug
• 3. blood coagulation
• 4. growth of fibrous tissue

actin, myosin, thombosthenin

Calcium, dence granual

causes vascular smooth muscle, vascular endothelial cells, and fibroblasts to grow and multiply

phospholipids

8-12 days, tissue macrophages, mainly spleen

contraction

platelets, endothelium, circulation

ADP, thromboxan A2

platelets only

platelts

platelets

• 1. can be invaded by fibroblasts and form connective tissue, promoted by PDGF, 1-2 weeks
• 2. dissolve

• 1. formation of a complex of activated substances called prothrombin activator, rate limiting step in blood coagulation
• 2. The activator catalyzes prothrombin to thrombin in the presence of calcium
• 3. Thrombin convers fibrinogen to fibrin

• vascular damage
• damage to special substances in the blood

prothrombin receptor, on the cell membrane of platelets already bound to damaged tissues

prothrombin and bradykinin

• no, it is too large.
• During pathological conditions vascular permeability can increase enough to let it out

Long fibrin chain attached to clot

released by activated platelets and cross links fibrin monomers by covalent bonds

• after a clot is formed the platelets contract and squeeze out all the fluid, this fluid is serum.
• does not contain clotting factors

low platelet level

ATP and calcium to activate actin/myosin and thrombosthenin

2, 8, 9, 10,11, and 12

• 1. trauma to vascular wall
• 2. trauma to blood
• 3. contact of blood with collagen

• Intrinsic- damage to blood
• Extrinsic-damage to vascular wall

Xa

tissue factor, tissue throboplastin

• X and V and calcium
• factor X is the protease in this complex, V accelerates the action
• thrombin itself has posotive feedback on factor V

• blood trauma, release of factor XII (activated when it contacts collagen surface or glass)
• exposure of of blood to collagen

HMW kininogen, accelerated by prekallikrein

VIII and IX

XII activating XI and XI activating IX

De-ionize calcium to stop coagulation in collected blood

precipitate calcium out of solution to prevent clotting

extrinsic is much faster then intrinsic

• 1. smoothness of endothelium
• 2. layer of glycocalyx, mucopolysacharide
• 3. thrombomodulin and heparin on surface

• binds thrombin and removes it from circulation
• complex activates protein C which cleaves V and VIII and causes the release of t-PA

ATIII and fibrin mesh (prevents the spread of clot)

mast cells, large amounts in lung and liver to stop the coagulation of slow moving venous blood

I, V, VIII, XII

liver

II, VII, IX, X, protein c

liver fails to secrete bile into the GI tract, obstruction of the bile duct or liver disease, prevents adqauate fat absorption

x linked

factor VIII and von willebrands factor (protects factor 8 in circulation)

thrombocytopenia is small vessels and hemophilia in large

spleenectomy and whole blood transfusion are helpful

• widespread clotting in the circulation
• usually occurs with large amounts of traumatized or dying tissue that releases tissue factor into the blood
• can remove many clotting factors and eventually cause bleeding

DIC, caused by bacteria or endotoxins, part of the reason septic shock is lethal.

• 12 hours 50%
• 24 hours 20% clotting power

yes the liver will convert the citrate to glucose within a couple minutes

increased blood flow to activated tissues

concentration of prothrombin in the blood

Toll like receptor

secondary hyperparathyroidism due to phosphate retention.

partial pressure difference

PSA/d(mx^1/2)

104 and 40 and 95

• increase in open pulmonary capillaries, more ideal retaliation perfusion ratio
• blood is fully oxygenated about 1/3 of the way through the capillary

• left ejects 2-3% more volume due to addition of bronchial circulation
• shunt flow

vita B deficiency that affects cell oxygen utilization

disables cytochrome oxidase activity, cell can not utilize oxygen

delivery and use of oxygen

46, 45, 40, 45

increase

1.34 ml

amount of O2 (ml) in 100ml of blood

5ml, can increase to 15ml during heavy exercise

• increase in cardiac output
• decrease in affinity for Hb, raise in temp CO2, 2.3DPG and decrease in pH

percentage of blood that gives up its oxygen as it passes through the capillaries

2,3, DPG (poor tissue blood flow)

ADP

brain convolutions and death

CO, partial pressure of 0.4 will allow CO to equally compete with O2 for binding to Hb. 0.6 is lethal

• normal, no obvious signs of hypoxia
• since pO2 is not depressed there is no low O2 feedback mechanism to increase respiration
• can treat with pure oxygen and CO2 in the blood to increase breathing

4ml

• CO2 is higher in the venous blood causing an increase in production of H2CO3, this then dissociates and the H is buffered by Hb and the bicarb is exchanged for Cl. The chloride content of venous blood is less then arterial blood
• Water moves into the cell to maintain the osmotic equilibrium and causes the cell to swell.

carbonic anhydrase inhibitor, can cause tissue pCO2 to reach 80

• CO2 bound to the terminal amine group of Hb
• pKa is around 7 so 50% is available at blood pH

52in venous blood to 48 in arterial, 4ml/100ml blood

• the binding of oxygen to Hb displaces CO2 from the blood in the lungs
• The combination of oxygen with Hb causes Hb to become a stronger acid
• The more acidic Hb has less affinity for CO2 at the terminal amine group
• The increased acidity of Hb causes it to release more H that in turn bind with bicarb and form water and CO2, the CO2 is released from the lungs
• This effect doubles the amount of CO2 released from the blood in the lungs and double the amount picked up in the tissues. from 2ml to 4ml.

7.41 and 7.37

• volume percent of CO2 over the volume percent of O2
• Usually in the range of 82 %
• using mainly carbohydrates for metabolism increases
• using fates for metabolism decreases
• Decreases in the fasting and starved states

hypertension, pulmonary atherosclerosis, heart failure

Pulmonary embolism

oral contraceptives, recent surgery, obesity, cancer, pregnancy

• respiratory compromise, non perfused but ventilated portion of the lung.
• cardiac compromise, increased pulmonary resistance

Failure of the right heart due to pulmonary hypertension

not usually in an individual with normal heart function

An infarct will cause damage to the lung parenchyma

• PE that is infected, leads to more intense neutrophile exudation and more intense inflammatory response
• Some convert to abscesses.

ECG shows a rhythm but there is no pulse.

chest pain, fever, dyspnea, shock, increased serum lactic dehydrogenase

D-dimer

early ambulation, elastic stockings, anti coagulation

air, fat, amniotic fluid, sickle cells, foreign bodies during IV drug use

1/4 systemic

alveolar hypoxia causes vasoconstriction of its bronchioles

• 1. COPD, vasoconstriction due to hypoxia
• 2. left heard failure of mitral stenosus
• 3. PE
• 4. Autoimmune, sclerosis, attach of collagen leading to inflammation

idiopathic primary p hypertenstion

mutation in the BMOR2 signaling pathway

• cell surface protein of the TGF-beta family
• binds TGF, BMP, activin, inhibin
• in vascular smooth muscle BMPR2 causes inhibition of proliferation and favors apoptosis
• Two hit model where a person with BMP2 mutation needs additional genetic or environmental insult to develop the disease

prostacyclin, NO

• crotalaria spectabilis, bush tea
• aminorex, appetite suppressant
• olive oil
• fenfluramine and phentermine, anti obesity drugs

tuft of capillaries that form producing a network that spans the lumens of dilated thin walled vessels.

hemoptysis

sclerosis

• atheromas
• intimal fibrosis
• medial muscular hypertrophy
• plexogenic arteriopathy
• organized thrombi, recanulization

• autoimmune disease of circulating antibodies targeted to collagen IV
• Initiate an inflammatory destruction of the basement membrane in the lungs and kidney glomeruli
• Causes rapid progressive glomerulonephritis and necrotizing hemorrhagic interstitial pneumonitis
• may be unmasked by some environmental insult
• Deposits of immunoglobins on the BM
• Treat with plasma replacement and immunosuppresive therapy

Uremia

• Intermittent diffuse alveolar hemorrhage
• Presents with cough, hemoptysis, anemia, weight loss
• longs have areas of consolidation

• There is hemorrhage into the alveolar space and hemosiderosis in the alveolar space and free macrophages in the alveoli
• No inflammation

hemociderosis, iron overload disorder.

• autoimmune, upper respritory tract and lungs
• Diagnostic features are capillarities and scattered poorly formed granulomas

pneumonia

respiratory, viral

• immunosupressive theropy
• chronic disease
• leukopenia

• Loss of cough reflex; anesthesia, coma, drugs, chest pain
• Injury to ciliary apparatus; smoking, genetic, corrosive gases
• Loss of alveolar macrophages; smoking, drinking, anoxia, oxygen intoxication
• pulmonary congestion or edema
• accumulation of secretions; CF

Nosocomial infaction

• 1. community acquired
• 2. community acquired atypical
• 3. nosocomial
• 4. aspiration
• 5. chronic
• 6. necrotizing and lung abcess
• 7. pneumonia in the immune compromised host

filled with an inflammatory exudate, thus causing consolidation of the tissue.

alginate

• Most common community acquired
• Diagnosis with gram positive filled macrophages
• responds to PCN
• 20% of the population have this as normal flora, can then check for blood culture

• pleomorphis, gram negative
• major cause of life threatening lower repritroy infections and meningitis in children
• community acquired acute pneumiae
• colonizes the pharynx
• two forms incapsulated and un-incapsulated, the encapsulated secretes haemocin that kills the un-cap
• can produce otitis media, sinusitis, and bronchopneumonia
• secretes a factor that disorganizes ciliary beating and a protease that that degrades IgA
• can cause acute pink eye in children
• Most common bacterial cause of acute COPD

community acquired, one of the top causes of otitis media in children

• community and nosocomial
• secondary bacterial pneumonia following a viral infection
• lung abscess and empyema

• community acquired
• most frequent cause of gram negative pneumonia
• Thick and gelatinous sputum
• commonly affects malnourished and debilitated people, alcoholics

most common cause of nosocomial pneumonia but also community acquired with cystic fibrosis patients

• Legionnaires disease
• pontiac fever
• lives in artificial aquatic environments, water cooling tower, portable water supplies
• predisposed by chronic organ disease
• diagnose by culture, antigens in the urine

• bronchial, patchy consolidation
• lobular consolidation
• four stages; congestion, red hepatization, grey hepatization, resolution
• red stages is blood filled exudate and when when blood is digested just fibrin exudate is left behind

• tissue distraction with necrosis and abcsess formation
• spread of infection to the pleural cavity known as empyema
• organization of the exudate
• bacterial dissemination to the heart valves, brain kindness spleen and joints

• abrupt onset of fever, shaking chills, cough with mucopurulent sputum, hemptysis
• radio-opaque appearance of lobe or broncials

empyema

• modorate amount of sputum , no physical findings of consolidation, small elevation of white cells, lack of exudate and afebrile
• most common cause is mycoplasma pneumonia
• viral causes are; influenza, synctial, adenovirus, rhinovirus, herpis simplex, cytomeglovirus)
• most of the time identified as the common cold
• attaches to upper respritory tract and causes inflammation

• trasidate edema in the alveoli
• Patchy or lobar ares of congestion without consolidation

• viral envolope contains hemagglutinin and neuraminidase
• cleared by cytotoxic t cells
• pandemics occur when there are mutation in the hemaggluinin and neuraminidase; can be with the animal forms

• Incubation period of 2-4 days
• dry cough, malaise, myalgias, fever and chills
• caused by a coronavirus, infects the lower respiratory tract and spreads throughout the body

myalgias

malaise

• hospital acquired
• common in patients with severe underlying disease, immunosuppressed, prolonged antibiotic therapy, pt with IV catheters
• Gram negative rods of enterobacteria and staphylococcus aureus

• can aspire while unconscious or during repeated vomiting
• typically recover more then one organism from culture, aerobes are more common

• a local suppurative process within the lungs
• common organisms are streptococci, staphylococcus auras and a host of gram negative

• 1. aspiration of infected material; in acute alcoholism, coma, anestesia, dental sepsis depressed cough reflex,
• 2. primary bacterial infection
• 3. septic emobolism
• 4. neoplasia, from a malignancy
• 5. miscellaneous; direct trauma, spread of infection,
• 6. no known cause, primary cryogenic lung abscesses

• very in size
• if due to inspiration, more common on right
• scattered if due to infection
• can lead to gangrene of the lung
• CARDINAL CHANGE; suppurative destruction of the lung parenchyma within the central area of cavitation
• must rule out carcinoma

• usually a localized lesion in the immunocompetent patient
• granulomatous inflammation
• Bacterial (tb)
• fungal ( histooplasmosis, blastomycosis, coodioidomycosis); granulomatous that resemble TB, thermally dimorphic,
• geographic distrabution

grow as hyphae and produce spores at environmental temps but grow as yeasts at body temp

• Histoplasma capsulatum is acquired by inhalation of dust particles for soil contaminated by bird or bat droppings
• ohio, mississippi river, and caribbean
• intercellular parasite of macrophages
• self limited primary pulmonary
• expresses a heat shock protein that binds to macrophage B2-integrin
• multiple in the phagasome and multiple in the macrophage before lysing it
• T cells recognize the fungal cell wall antigens and secrete interferon which activates the macrophage to kill the yeast
• Histoplasma induces macrophages to secrete TNF to recrouit more macrophages
• Disseminates in the immunecompromised patient
• seen in apices of the lungs

• Blastomyces dermatidis
• central and southeast US, canada, middle east, and africa
• can come through the skin
• abrupt illness with productive cough, headache, chest pain, fever, and pain
• pulmonary infiltrates
• suppurative granulomas in which macrophages can not digest, the prolonged precense of yeast cells keeps recruiting neutrophils
• skin can be involved and may be mis diagnosed as squamous cell cancer

• coccidioides immitis
• almost 100% infection rate if inhaled
• southwest and far west US
• positive skin test reaction
• when ingested by the macrophage the fusion of the phagosome and lysosome is blocked to resist killing
• mostly asymptomatic

• infected by opportunistic bacteria
• in AIDs patients it is usually P. carinii
• Bacteria; pseudomonas aeruginosa, mycobacterium, legionella pneumophilia, listeria monocytogenes
• Viral; CMV and herpes
• Fungi; pneumocysetes caranii canidida, aspergillus, phycomycetes, cryptococcus neoformes

• leading cause of disease in HIV patients
• oppurtunistic organisms
• Kaosi sarcoma and non hogkins lymphoma, both non infectious agents
• CD4 count; bacterial and tubrical infections with a count over 200, pneumocystis usually below 200, mycobacterium below 50.