838 Exam 2

mostly sun review questions

what is the number of cells produced daily by the bone marrow

100 billion

what is the ratio of red blood cells to white blood cells in the blood stream

1/700th

what are the different formed elements of blood

red cells, white cells, platelets

how can the types of formed elements of blood be distinguished

white blood cells have granulocytes (neutrophils, eosinophils, basophils) which are are segmented and monocytes and lymphocytes

what are the two major complexes found on the surface of activated platelets that are important to the surge in thrombin production?

intrinsic tenase complex and prothrombinase

describe the coagulation factors that form the intrinsic tenase complex and what it activates

formed by coagulation factors VIIIa-IXa

activate thrombin generation in the propagation phase of coagulation

describe the coagulation factors that from the prothrombinase complex and what it activates

formed by coagulation factors Va-Xa

activate thrombin generation in the propagation phase of coagulation

Name the vitamin K dependent clotting factors and the organ in which they are synthesized

factors II (prothrombin), VII, IX, and X whoch are all synthesized in the liver

what is the catalytic enzyme in fibrinolysis

Plasmin

what are two inhibitors of fibrinolysis

⍺2-antiplasmin and ⍺2-macroglobulin (inhibit plasmin)

PAI-1 and PAI-2 which are plasminogen activator inhibitors that stop the conversion of plasminogen to plasmin

what are the three types of anemia

iron-deficiency anemia, pernicious anemia, hemolytic anemia

define anemia

a condition where the blood doesn’t have enough healthy red blood cells resulting from a lack of red blood cells or dysfunctional red blood cells in the body

what are the major causes of macrocytic anemia

deficiency in vitamin B12 or folic acid or drugs that interfere with DNA synthesis

what are the major causes of microcytic anemia

abnormalities in hemoglobin production or iron deficiency

what is the most common form of anemia

iron deficiency anemia

what is the most likely cause of iron deficiency anemia in premenopausal women

heavy period

what is the most likely cause of iron deficient anemia in men

peptic ulcers or GI cancer

what are some disorders associated with iron deficiency anemia

rapid or irregular heartbeat, heart failure or and enlarged heart, pregnancy complications or delayed growth in infants and children

what are the physiologic adaptations to slowly developing iron deficiency anemia

physiologic compensatory mechanisms (increase cardiac output, diverting blood flow)

biochemical adaptation (increase unloading of oxygen in the tissues)

in what situations might the serum ferritin level be normal or elevated in a patient with iron deficiency

in patients with inflammatory conditions

ferritin levels are elevated in response to inflammation

what neurologic defects are observed in prolonged pernicious anemia

nerve damage and memory loss

what symptoms of pernicious anemia are usually relatively mild

diarrhea constipation nausea vomiting fatigue lack of energy or lightheadedness

are changes in the peripheral blood smear necessary for neurologic effects of vitamin B 12 deficiency

no (im only pretty sure about this answer)

name two crucial cofactors in DNA synthesis whose deficiency results in pernicious anemia

cobalamin and folic acid

in what specific biochemical pathways do cobalamin and folic acid participate

enzyme catalyzed methylation reaction in DNA synthesis

what are conditions that can lead to hemolytic anemia

sickle cell disease, autoimmune disorders, bone marrow failure, infections

what drugs can induce hemolytic anemia

cephalosporins, penicillin, dapsone, levodopa and methyldopa, levofloxacin, nitrofurantoin, NSAIDs, and quinidine

*what does lymphocytosis mean*

elevated lymphocyte counts often triggered by viral infections, but consistently elevated levels indicate malignancies like leukemia

at what level of neutropenia dose the incidence of infection dramatically increase

1,500 neutrophils per microliter is neutropenia while lower than 500 per microliter is severe case

what are the most common sites and types of infections observed in neutropenic patients

skin infections like folliculitis and boils

cellulitis = bacterial invasion of the dermis or epidermis

gum disease and chronic gingivitis

what is the probable underlying abnormality in cyclic neutropenia

mutations of nuetrophil elastase (ELANE) whihc is a decrease in neutrophil production or an increase in apoptosis that causes a deficiency of neutrophils in the bloodw

what is cyclic neutropenia

an inherited or acquired blood disorder characterized by recurrent episodes of abnormally low levels of neutrophils making the individual highly susceptible to infection

what is the most common category of thrombocytopenia

immune causes such as autoantibodies directed against the platelet membrane antigen GpIIb/IIIa

what are the three general mechanisms of thrombocytopenia

immune or non-immune mediated destruction of platelets caused by drugs or auto-antibodies directed against the platelet membrane antigen GpIIb/IIIa

increase in spleen size or activity

platelet consumption as a result of ongoing clotting

name the platelet protein antibodies implicated in the pathogenesis of heparin induced thrombocytopenia

heparin can bind to PF4 (platelet factor four) which promotes blood aggregation and then IgG is produced agains the heparin-PF4 complex

by what mechanism can heparin induced thrombocytopenia actually increase clot formation

platelets bind to each other during the IgG-Fc receptor or PF4-PF4 receptor interactions which initiates the formation of blood clots

what constitutes the Virchow triad of factors predisposing to the formation of intravascular clots

hyper coagulability, venous stasis, endothelial injury

Deficiencies in which proteins can result in clinically significant thromboses

Proteins C and S

what is the basis for activated protein C resistance

APC resistance is caused by a point mutation in the factor V gene that is resistant to inactivation by APC that causes a longer duration of thrombin generation that leads to a hyper coagulable state

what is the most common site for deep vein thrombosis

the legs (because of sluggish blood flow or higher likelihood of blood vessel compression injury)

what is the nature of the defects in hemophilia A and B

both are x chromosome linked recessive traits

A = deficiency of coag factor VIII

B = deficiency of coag factor IX

what are the parts of the respiratory zone

the conducting zone - passage for air to move in and out of the lungs

the respiratory zone - allows inhaled oxygen to diffuse into the capillaries

what part in the lungs does allow gas exchange between the lungs and the blood

the alveoli

what are the two principal physiologic roles of the lungs

to make oxygen available to tissues for metabolism

to remove the main byproduct of that metabolism

what mechanism do the pulmonary arteries have for matching alveolar perfusion with ventilation

hypoxic pulmonary vasoconstriction (HPV) = homeostatic mechanism for said matching

what does decreased alveolar PO2 cause in the lung? increased?

vasoconstriction of the pulmonary arteries

vasodilation of the pulmonary arteries

what are the roles of the connective tissue and surfactant systems in lung function

connective tissue fibers maintain the anatomic integrity of visceral pleura

surfactant enhances the anatomic stability of the alveoli and reducing surface tension to prevent the collapse of alveoli

what are the major sites of resistance to airflow in the lungs

trachea and bronchus

what does visceral pleura do

covers the outer surface of the lung

what are the different roles of the pulmonary and bronchial arteries

pulmonary arteries supply deoxygenated blood from the heart and participate in gas exchange at the alveolar capillary membrane

bronchial arteries carry oxygenated blood to the lungs

what are the humoral and cellular components of the specific immune defense system of the lungs

mobile phagocytic cells secrete cytokines

B and T lymphocytes of the mucosa associated system

white blood cells from alveolar capillaries

list the components of the nonspecific defense system of the lungs

mechanical barrier, mucus, mucocilary clearance

what is the role of the ciliary action of the respiratory epithelium

removing inhaled particles including pathogens before they can reach the lung tissue

what are the requirements for successful lung function

healthy airway and healthy pulmonary parenchyma

what are the six general categories of lung disease

obstructive lung disease

pulmonary vascular disease

pulmonary edema

restrictive lung disease

infectious disease

neoplastic disease

abnormalities of the FEV1 and FEV1/FVC are the result of a decrease in the airflow through the lungs that may be caused by what

obstructive lung diseases

what is the major characteristic of obstructive lung disease

hard to exhale (asthma, COPD, bronchiectasis, acute bronchitis)

what is the major characteristic of restrictive lung disease

limited ability of the lungs to expand during inhalation (interstitial lung disease, pulmonary sarcoidosis, idiopathic pulmonary fibrosis)

what is the major characteristic of pulmonary vascular diseases

affects the blood vessels along the route between the heart and lungs

what is the major characteristic of pulmonary edema

watery fluid in the lungs inhibiting oxygen and carbon exchange

what is the fundamental physiologic problem in obstructive lung disease and give examples of each of the three principal sources

increased resistance to expiratory airflow caused by:

inhaled secretions in within the lumen

airway wall thickening and airway narrowing

loss of surrounding supporting structure

which acute-acting mediators contribute to asthmatic airway responses

leukotrienes, prostaglandins, histamine

what are the three categories of provocative agents that can trigger asthma

physiologic or pharmacologic mediators

allergens

exogenous physicochemical agents or stimuli that produces airway hyperactivity

what are some of the common symptoms and signs of acute asthma

wheezing, chest tightness, SOB, cough

what are some histopathologic features of asthma

inflammatory cells (lymphocytes, eosinophils, mast cells), damaged bronchial and bronchiolar epithelial cells

what are the pathologic events that contribute to chronically abnormal airway architecture in asthma

acute and chronic inflammatory processes, mucus hyper-secretion, damaged airway epithelium

name three reasons for increased airway resistance and obstruction in asthma

bronchospasm, mucus plugging, edema in the peripheral airways

what is the leading cause of COPD

long term exposure to irritants that damage the lungs and airways

name eight symptoms and signs of chronic bronchitis

wheezing and cough with sputum production

ronchi are continuous low pitched rattling lunch sounds that often resemble snoring

typical chest radiographic findings with increased lung volumes with relatively depressed diaphragms

ventilation/perfusion mismatching

tachycardia, hypoxemia, pulmonary hypertension

polycythemia increases the hematocrit may increase to over 50%

pulmonary function abnormalities reduce all flows; reduced REV1 and FVC and the FEV1/FVC ratio

name six signs and symptoms of emphysema

breath sounds are decreased in intensity, reflecting decreased airflow and prolonged expiry time

hyperinflation of lung

hypercapnia, respiratory acidosis, and a compensatory metabolic acidosis

tachycardia, hypoxemia, pulmonary hypertension

polycythemia increases the hematocrit may increase to over 50%

pulmonary function abnormalities reduce all flows; reduced REV1 and FVC and the FEV1/FVC ratio

describe the protein related to an increased risk of emphysema

deficiency in α1-protease inhibitor (α1-antitrypsin)

what are the pathophysiologic changes in emphysema

destruction of the airspaces distal to the terminal bronchioles

loss of alveolar surface area and the accompanying capillary bed for gas exchange

loss of the supporting structures: elastin containing connective tissue and surrounding lung parenchyma

what is a vicious cycle theory of the pathogenesis of bronchiectasis

1: an infectious insult and impaired drainage obstruction or defect in host defense

2: activation of a host immune response

3: progressive destruction of normal lung architecture

4: permanent abnormal dilation and destruction of the major bronchi and bronchiole walls

what are some examples of pulmonary vascular disease

pulmonary:

-arterial hypertension

-venous hypertension

-embolsim

what are the main causes of pulmonary arterial hypertension

lung disease

autoimmune disease

heart failure

idiopathic

how does pulmonary venous hypertension cause increased pulmonary vascular resistance

increased blood pressure in the pulmonary veins (carrying blood away from the lungs to the heart)

what is the most common source of pulmonary embolism

a blood clot that forms in a deep vein in the leg and travels to the lungs where it becomes lodged in a smaller lung artery. Almost all blood clots that cause pulmonary embolism are formed in the deep leg veins

what is the pathophysiology of pulmonary embolism

hemodynamic changes

changes in ventilation

changes in oxygenation

bronchoconstriction

pulmonary infarction

describe hemodynamic changes in relation to the pathophysiology of pulmonary embolism

mechanical obstruction of the pulmonary arterial circulation increasing the right ventricular afterload

describe changes in ventilation in relation to the pathophysiology of pulmonary embolism

ventilation and perfusion become mismatched with blood flow from obstructed pulmonary arteries redirected to other gas exchange untis

describe changes in oxygenation in relation to the pathophysiology of pulmonary embolism

mild to moderate hypoxemia with a low PaCO2 is the most common finding in acute pulmonary thromboembolism

describe the role of bronchoconstriction in relation to the pathophysiology of pulmonary embolism

causes wheexing and increased work of breathing

describe pulmonary infarction in relation to the pathophysiology of pulmonary embolism

obstruction of small pulmonary arterial branches that act as end arteries leads to pulmonary infarction in about 10% of cases

what is the difference between pulmonary edema and pleural effusion

pulmonary edema is a broad term that is an abnormal accumulation of fluid in the extravascular compartments of the lungs

pleural effusion is when fluid builds up in the layers of tissue that line the outside of the lungs and the inside of the chest due to poor pumping by the heart of by inflammation

what is the most common cause of pulmonary edema

left heart failure (congestive heart failure)

(right heart failure is found with cor pulmonale)

what causes a non-cardiogenic pulmonary edema

acute respiratory distress syndrome (ARDS)

adverse drug reaction

blood clot in the lungs

exposure to certain toxins, high altitudes, near drowning etc

viral infections

what is the pathophysiologic process of edema formation

a direct of an indirect pathologic insult → increased capillary permeability due to disrupted endothelial barrier → abnormal accumulation of fluid in the extravascular compartments of the lungs

what are common symptoms of pulmonary edema

dyspnea or extreme SOB that worsens with activity or lying down

a feeling of suffocating or drowning that worsens when lying down

a cough that produces frothy sputum that may be tinged with blood

wheezing or gasping for breath

cold clammy skin

how does interstitial lung disease affect lung function

causes progressive scarring (lung fibrosis) between the air sacs which causes lung stiffness and eventually reducing the ability to breathe and get enough oxygen into the blood stream

what medication is known to cause pulmonary fibrosis

bleomycin

name the five events in the pathophysiology of idiopathic pulmonary fibrosis

1: repetitive micro-injury to susceptible type 2 alveolar epithelium

2: injury induced imflammatory response including t cell activation causing increased production or activation of pro-fibrotic mediators like TGF-B

3: accumulation and activation of contractile myofibroblasts

4: deposition of stiff cross-linked extracellular matrix with tissue destruction

5: failure of type 2 alveolar epithelial cell reconstruction leading to bronchiolization (abnormal proliferation of bronchiolar epithelial cells) with the formation of honeycomb cysts

name eight symptoms and signs of idiopathic pulmonary fibrosis

cough

dyspnea

tachypnea

inspiratory crackles

nail clubbing

hypoxemia

pulmonary hypertension (with prominent pulmonary valve closure sound)

what are the major functions of the GI tract

motility: movement of intralunminal contents along tract

secretion: release of ion, water, enzymes and bile to aid digestion

digestion: intraluminal breakdown of indegested substances

absorption: uptake of molecules across mucosal surface into epithelial cells

metabolism: intracellular biotransformation

excretion: removal of waste substances

defense: protection against ingested toxins, bacteria, and viruses

what are the four major layers of a cross-section through the GI tract

mucosa: epithelium, lamina propria, muscularis mucosae

submucosa: loose connective tissue to support the epithelium

serosa: mesothelium and connective tissues

what volumes of fluid are transferred into and out of the GI tract each day

9 in 9 out

ingest 2 secrete 7

absorb 7.5 into small intestine 1.4 in large intestine

excrete 0.1 in feces

how are molecules absorbed into cells

passive transport: diffusion and facilitate diffusion

active transport

pinocytosis

filtration (most prominent in kidneys)

what is the consequence of drug biotransformation

active drug is converted into inactive metabolites

active drug is changed to other active product

inactive drug changed to product with activity (prodrug)

nontoxic or less toxic drug is changed to toxic metabolites

what are the defense mechansism of the GI tract

defense from acid

-mucus production

-bicarbonate production

-prostaglandin production (attenuates acid production)

-tight junctions (prevents breach of epithelium)

-bicarbonate from pancreas (neutralizes acid leaving stomach)

defense from infection

-stomach acid (kills pathogens)

-rapid epithelial cell turnover (limit consequences of infection)

-microbiota

-secretory immune system

drug metabolism pathways and biotransformation enzymes

phase one metabolism = functionalization

-oxidation, reduction, hydrolisis

-alcohol dehydrogenases, aldehyde dehydrogenases, carboxylesterases, CYP, epoxide hydrolases, flavin containing monooxygenases

phase two metabolism = conjugation

-glucuronidation, sulfation, glutathionylation, methylation, acylation

-glutathione transferases, sulfotransferases, UDP glucuronosyltransferases