Kaplan Flashcards
Describe the time landmarks for embryologic hematopoiesis
Yolk sac (third week), liver (1 month), spleen and lymphatic organs (2-4 months), and bone marrow (after 4 months)
Beginning at 1 month of development and continuing until the 7th month, blood elements are formed in the liver and the liver is the dominant source of hematopoiesis. In the last month before birth, bone marrow becomes the dominant site of hematopoiesis.
What is TdT and where is it present
Terminal deoxynucleotidyl transferase (TdT) is present only in extremely primitive cells of the lymphocyte lineages. It is the enzyme that is active when VDJ rearrangement of the heavy chain (or both chains of the T-cell receptor) variable domain genes is occurring, and it is responsible for mediating N-nucleotide addition to the junctions of the gene segments.
What is the mnemonic for remembering DiGeorge Syndrome
“CATCH 22” - Cardiac abnormality, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia, resulting from a deletion on chromosome 22.
How do patients with DiGeorge Syndrome present
- Present with tetany (usually first noted in the facial muscles) due to hypocalcemia secondary to hypoparathyroidism.
- Thymus is absent, as are the parathyroid glands, due to failure of development of the 3rd and 4th pharyngeal pouches. Since patients without a thymus are unable to complete normal T-lymphocyte development, these patients will have deficiencies in all immunologic reactions dependent on T cells (Type IV HSR, which is totally dependent on T lymphocytes and their cytokines, would be absent from these patients).
- Recurrent infections due to defective cellular immunity, and abnormal facies are additional features.
Etiology and pathophysiology of Infectious Mononucleosis
Caused by EBV (herpesviridae; dsDNA, nuclear membrane envelope), which infects B lymphocytes by attaching to the CD21 receptor (CD21+ lymphocytes are the cells infected and destroyed by the virus; the proliferation of these cells are the cause of the LAD and splenomegaly and are thus found in lymph nodes and spleen, but will not be found circulating in the blood). However, the cells that will predominate in a blood film will be reactive T cells, which would be CD8+ T lymphocytes (Downey cells)
Presentation and diagnosis of a patient with Infectious Mononucleosis
Presents with sore throat, HA, fever, malaise, tender LAD (vs. lymphoma which would likely be painless), pharyngitis, tonsillitis, HSM, periorbital edema, rash, and a palatal enanthem.
Diagnosis is made by heterophile antibody testing (monospot), EBV antibody titers, and the finding of lymphocytosis with atypical lymphocytes.
What is the treatment of Infectious Mononucleosis
Treatment includes rest, fluids, and analgesics. Administration of penicillin derivatives (ampicillin) can lead to a maculopapular rash. Physician should advise the patient to restrict physical activity because the hepatosplenomegaly places the patient at increased risk of splenic rupture with physical contact.
What does CMV cause and what type of inclusions
CMV is responsible for heterophile-negative mononucleosis and would have owl-eye inclusions
Is there a link between chronic EBV infection and tumors
Links between chronic EBV infection and tumors have been most strongly established with nasopharyngeal carcinoma, the African form of Burkitt lymphoma, and B-cell lymphomas in immunosuppressed individuals.
How do RBCs appear in malaria
Schuffner’s dots - appear as multiple brick-red dots in infected erythrocytes. Only found in RBCs infected by Plasmodium vivax or P. ovale. Both P. vivax and P. ovale are capable of causing relapses following recovery from the primary infection because both organisms leave dormant forms (hypnozoites) in the liver.
What is the treatment for malaria
Chloroquine therapy is considered to be the treatment of choice for uncomplicated malaria provided there are no contraindicates for its use. Chloroquine is associated with reactivation of psoriasis as well as chloroquine-induced retinopathy. The combination of atovaquone and proguanil is used in patients unable to tolerate chloroquine therapy, as well as for the treatment of chloroquine-resistant malaria
What causes Lymphogranuloma Venerum (LGV)
Caused by chlamydia trachomatis (also an important cause of blindness in developing countries)
Describe the primary lesion in LGV and compare with granuloma inguinale
Primary lesion is usually a self-healing papule or shallow ulcer, and is painless. Once LAD develops however, the swollen, draining lymph nodes are quiet painful. Histologically, the buboes of LGV are enlarged lymph nodes with stellate abscesses.
In contrast, granuloma inguinale (caused by Klebsiella granulomatis) is characterized by primary painless genital ulcers that develop into red, granulomatous ulcers that bleed easily.
Which immunoglobulins are low in splenectomized patients and what does that put them at risk for
May have low levels of IgG2 and IgM because splenic lymphocytes are the major producers of these antibodies, which provide protection against encapsulated organisms.
Splenectomy therefore renders patients extremely susceptible to infections with encapsulated organisms; immunization against S. pneumoniae is therefore recommended.
What is the mnemonic for the causes of DIC
Causes (STOP Making New Thrombi)
Sepsis (gram-negative), Trauma, Obestric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion.
Describe the pathophysiology of DICe
Endothelial cell damage triggers a massive activation of both the prothrombotic and antithrombotic pathways. There is consumption of the coagulation factors with a resulting increase in both the PT and PTT. Platelets are consumed, leading to an increase in the template bleeding time. The degradation of fibrin leads to increased split products appearing in the circulation and a decrease in fibrinogen. The D-dimer assay measures cross-linked fibrin derivatives and is a specific test for fibrin degradation products (FDP) that confirms the diagnosis of DIC.
How do fibrin degradation products (FDPs) differ from D-dimer
FDPs can result from degradation of either fibrin or fibrinogen. D-dimer differs from FDPs in that it is formed only from fibrin. Therefore D-dimer is a more specific indicator of both thrombin and plasmin activity (signifies simultaneous activity of both thrombin and plasmin)
When are helmet cells and schistocytes seen
Helmet cells and schistocytes are seen on peripheral blood smear in any condition that causes mechanical damage to blood vessels, producing hemolysis (e.g. HUS, TTP, DIC, trauma from mechanical heart valves)
Etiology of vWD
AD bleeding disorder caused by either a deficiency or qualitative defect in wWF, a protein that is required for platelet adhesion by binding to platelet G1b.
An abnormal wWF causes a defect in the initial adhesion of normal platelets to a damaged vessel wall. vWF also carries factor VIII in the blood, so factor VIII levels are consequently low, and the PTT is prolonged.
Describe the clinical features and lab studies for a patient with vWD
Clinical Features - spontaneous bleeding from mucus membranes, prolonged bleeding from wounds, and menorrhagia in young females; bleeding into joints is uncommon.
Lab studies - normal platelet count, prolonged bleeding time (indicated platelet pathology), normal PT and often a prolonged PTT. There will be an abnormal response to Ristocetin, as Ristocetin will only cause platelet agglutination in the presence of vWF.
Treatment for vWD
Desmopressin (DDAVP) in type I vWD (deficiency of vWF) which releases vWF from Weibel-Palade bodies of endothelial cells.
Pathophysiology of anemia of chronic disease
Seen in the settings of chronic infection, systemic inflammation, or malignancy
Hepcidin - principal mediator of anemia of chronic disease; acute phase reactant that plays a key role in iron regulation. Produced in the liver and its key function is to internalize iron and decrease iron release from macrophages and enterocytes. Inflammatory cytokines such as IL-6 increase hepcidin expression, leading to a decrease in absorption of iron from intestines, and the block of iron release from macrophages. In the context of inflammation, macrophages express hepcidin in response to microbial stimulation. In Hodgkin lymphoma, high levels of cytokines such as IL-6 are present, resulting in systemic symptoms and anemia.
Labs of anemia of chronic disease
Initially presents as a normochromic normocytic anemia (normal MCV, normal serum iron, normal ferritin). Once iron becomes low/inaccessible (due to chronic inflammation), there is a shift to a hypochromic, microcytic anemia (low MCV, low serum iron) with increased ferritin and low TIBC.
NOTE: TIBC reflects transferrin, which responds to the ferritin level (i.e. body’s iron stores). When ferritin level is high, transferrin is low and vice versa.
What is one association with Vitamin B12 deficiency
associated with infection (via undercooked or raw fish) with the fish tapeworm Diphyllobothrium latum
What does Ixodes tick transmit
implicated in transmission of Babesia microti as well as Borrelia burgdorferi and Anaplasma (formerly Ehrlichia) phagocytophila.
Blood smear, geography, and presentation in Babesia
Intraerythrocytic protozoan parasites and causes the clinical disease babesiosis.
The most common appearance in blood smears is ring forms inside RBC, typically in combination with one or two chromatic dots.
Geography includes East coast (e.g. MA) and Midwest (co-exists with Lyme disease and ehrlichiosis).
Most patients are asymptomatic; symptomatic cases in reasonably healthy individuals develop fever, HA, chills and fatigue. Causes hemolytic anemia that is severe in splenectomized or severely debilitated patients; rarely can be fatal.
What are the two reasons for the development of neonatal jaundice
(1) bilirubin production in increased because of hemolysis of fetal RBCs as they are replaced with newly formed hemoglobin A-containing RBCs; the porphyrin of heme liberated by hemolysis is converted to bilirubin
(2) hepatic excretory capacity of bilirubin is low at birth, in part because of low UDP-glucuronyl transferase in the perinatal period.
What patients are more commonly affected with neonatal jaundice and what is the treatment
Neonatal hyperbilirubienmia occurs more frequently in boys and those of East Asian descent
Treatment is with phototherapy because light decomposes bilirubin into water-soluble substances that are excreted in the urine. Another molecule that absorbs light is riboflavin (vitamin B2), which also degrades with phototherapy and thus must be supplemented to prevent deficiency.
What is kernicterus
If serum bilirubin levels increase too much, the unconjugated bilirubin can cause kernicterus (deposition of unconjugated bilirubin in basal ganglia), which can produce lifelong neurologic complications in surviving infants.
Describe immune cell responses of extracellular bacterium
Increased total WBC count with a granulocytosis (including both the mature neutrophils and the immature band form neutrophils) with a left shift (meaning disproportionately large numbers of the immature neutrophil forms compared to the mature neutrophil forms).
Persistence of neutrophils at high levels is almost always indicative of an infection with an extracellular bacterium because the primary mechanism of immune defense against extracellular bacteria is the production of antibodies and complement activation to cause opsonization, or enhancement of phagocytosis and killing by phagocytic cells such as neutrophils. Anemia is likely to be observed since most bacteria have extremely high nutritional requirements of iron, which they must scavenge from the host.
Describe immune cell responses of fungus
seen in immunocompromised; mononuclear response
Describe immune cell responses of intracellular bacterium
monocytosis; principal immune response to intracellular organisms is TH1 cell, which secretes cytokines to stimulate the effector cells of cell-mediated immunity
Describe immune cell responses of parasite
eosinophilia; eosinophils act in concert with antiparasitic antibodies to promote antibody-dependent cell-mediated cytotoxicity (ADCC) against parasites.
Describe immune cell responses of virus
intracellular parasites that would elicit a TH1 response and a monocytosis (granulocytes are increased in response to extracellular organisms)
What is benign reactive lymphadenitis
Features include palpable tender LAD, preserved lymph node architecture, multiple large germinal centers, recognizable light and dark zones, frequent mitoses, tingible body macrophages (macrophage containing debris from ingested lymphocytes)
When do pathologic fractures occur. Describe causes of lytic and blastic bone lesions.
Occur when there is bony weakening due to another disease processes.
Lytic bone lesions - multiple myeloma, lung carcinoma, or breast carcinoma
Blastic bone lesions - prostate carcinoma or breast carcinoma
What does streptokinase cause
Causes thromobolysis through formation of an activator complex with plasminogen to cleave the arginine-valine bond of plasminogen, resulting in the formation of plasmin. Plasmin degrades fibrin and fibrinogen as well as the procoagulant factors V and VIII. The activator complex also diffuses into the thrombus, thereby activating preplasmin-2, which lyses fibrin, thus breaking up thrombi and potentially restoring blood flow to ischemic cardiac muscle.
Acetaminophen
analgesic and antipyretic indicated for the treatment of mild pain associated with muscle pain associated with arthritis, HA, and menstrual cramps as well as the treatment of fever; ineffective at reducing inflammation. Not associated with gastric distress and does not have the CV risk warning associated with NSAIDs and COX-2 inhibitors (also note that the COX-2 inhibitor celecoxib is contraindicated in patients with sulfonamide allergies)
How is warfarin metabolized and which drugs are inhibitors of P450
metabolized by hepatic CYP450. Ketoconazole is an azole antifungal drug and a potent inhibitor of P450 enzymes, which will cause an increased warfarin effect and thus increased INR. Other antimicrobials that are P50 inhibitors are erythromycin, clarithromycin, ciprofloxacin, and the protease inhibitors used in treating HIV. Additional potent hepatic enzyme inhibitors include amiodarone, diltiazem, isoniazid, and fluoxetine. Conversely, potent hepatic enzyme inducers are carbamazepine, phenytoin, phenobarbital, rifampin, and St. John’s wart.
How can you prevent hyperuricemia
Patients with leukemia are prone to develop uric acid kidney stones due to increased uric acid production due to increased purine breakdown, particularly during chemotherapy. Prevention of hyperuricemia and/or uric acid stone development in ALL patients is typically instituted with a xanthine oxidase inhibitor, such as febuxostat or allopurinol
What are the two types of plasminogen activators
urokinase-like PA (uPA), such as urokinase and streptokinase, and tissue PA (tPA), such as alteplase, reteplase, and tenecteplase
How is native tPA produced
Native tPA is produced by endothelial cells and recombinant forms have been used extensively in the early treatment of MI to promote lysis of newly formed thrombi. Specifically, these agents bind to fibrin in a thrombus and convert the entrapped plasminogen to plasmin, resulting in fibrinolysis. Since thrombolytics like tPA, when given in pharmacologic doses, lead to the direct degradation of some fibrinogen as well as fibrin, the available fibrinogen for the common part of the pathway will be decreased, and both the intrinsic and extrinsic pathways will be partially blocked, leading to prolongation of both PT and PTT.
Describe blood flow of compensated aortic coarctation
blood flow above and below the coarctation is normal despite a large difference in BP because the resistance above the coarctation has increased sufficiently to maintain the flow of blood at a normal level required to satisfy the metabolic requirements of the tissues. The pressure and resistance below the coarctation are normal
Where does coarctation usually occur and what are the clinical features
- > 95% of coarctation occurs just distal to the left subclavian artery in the region of the ductus arteriosus. The descending thoracic aorta is supplied via reverse collateral flow in the intercostal arteries. These arteries, the major branch of which runs in the costal groove on the underside of the rib, expand and cause erosion of the inferior aspect of the rib (rib notching).
- Disparity in pressure between upper and lower extremities
Describe transposition of great vessels and treatment
Failure of truncoconal septum to spiral. This is fatal if a shunt (e.g., PDA, VSD, ASD, PFO) is not present to mix the venous and systemic blood.
Indomethacin closes PDA and Prostaglandin E1 (e.g. alprostadil or misoprostol) keeps PDA open
Endocardial Cushion Defect
caused by failure of neural crest cells to migrate and are commonly seen in Down Syndrome (can present with characteristic physical findings including flat facial profile, prominent epicanthal folds, and a simian crease and duodenal atresia with the characteristic “double bubble” sign on x-ray.
What is the pericardial cavity
potential space between the two layers of pericardium, the epicardium (also known as the visceral pericardium) and the parietal pericardium. Accumulation of blood in the pericardial space causes increased pressure on the heart, which restricts filling of the heart during diastole (cardiac tamponade). This reduced filling results in reduced CO and reduced BP.
What is the most common cause of sudden cardiac death
the most common underlying cause is ischemic heart disease (IHD), which is most frequently related to atherosclerosis of the coronary arteries. Occlusion of a coronary artery can cause electrical instability, and can thereby cause an arrhythmia, leading to sudden cardiac death.
Pathophysiology of Familial Hypercholesterolemia
AD disease caused by defective or absent LDL receptors on liver cells. As a result, patients develop high levels of LDL cholesterol, leading to the early formation of atherosclerotic plaques, coronary artery disease, and MI and the appearance of xanthomas on the skin.
Prognosis of patients with Familial Hypercholesterolemia
These patients often die in their twenties or thirties because of myocardial or cerebral infarction
Describe the normal process of cholesterol transport
Normally, the LDL-R is a cell surface receptor that recognizes apoprotein B 100 that is present in the cholesterol-rich LDL. The LDL-R is present in clathrin-coated pits, and when activated, leads to invagination and formation of clarithrin-coated vesicles intracellularly. This process is called receptor-mediated endocytosis.
Once internalized, the vesicle will shed its clathrin coat and fuse with an endosome, where the low pH cause release of the LDL particles from the receptors. The LDL particles are delivered to a lysosome, where they are degraded, releasing free cholesterol within hepatocytes.
Describe the relationship between BUN and creatinine
Most disease processes that affect BUN and creatinine cause both to rise together. An exception to this rule is early CHF (low BP, cardiac enlargement, and perihilar infiltrates seen on CXR), in which the BUN can rise selectively.
Describe the arterial supply to the heart
provided by R/L coronary arteries, which are branches of the ascending aorta
What do the RCA and LCA supply
- Right Coronary Artery - supplies the RA, RB, the SA and AV nodes, and parts of the LA and LV. The distal branch of the right coronary arterial (in 70% of subjects) is the posterior interventricular artery that supplies, in part, the posterior aspect of the interventricular septum.
- Left Coronary Artery - supplies most of the LV, LA, and the anterior part of the interventricular septum., The two main branches are the anterior interventricular artery (LAD, and circumflex artery.
What artery is obstructed in MI
In MI, the LAD is obstructed in 50% of cases, the right coronary in 30%, and the circumflex in 20% of cases.
What do you think when you hear that the LV wall moves paradoxically
When the left ventricular wall moves paradoxically (i.e. bulges outward during systole and inward during diastole), think of MI secondary to occlusion of the LAD.
Describe EKG in AFib
irregularly irregular ventricular rhythm without discrete P waves. The QRS complex is often narrow, but may be widened if aberrant conduction or bundle branch block is present. Medications that slow ventricular rate include digoxin, CCBs, and BBs.
What is the treatment of choice for AFIb
Beta-blockers such as esmolol and metoprolol, and CCBs such as verapamil and diltiazem, are generally considered to be the treatment of choice for atrial fibrillation in patients without evidence of heart failure. Digoxin can also be used; it decreases conduction through the AV node and can be used for AFib with rapid ventricular rate.
Describe the specificity of Beta Blockers
Beta 1 selective blockers include “A-BEAM” = acebutalol, betaxolol, esmolol, atenolol, metoprolol; can also remember that A-M are cardioselective (beta 1) vs. N-Z are non-selective (beta 1 and 2) and the exceptions include carvedilol and labetalol (block both alpha 1 and beta receptors)
- Remember that B1 receptors predominate in the heart, while B2 receptors predominate in the lungs
- Beta-adrenergic blockers prevent angina by decreasing myocardial oxygen requirements during exertion and distress through the reduction of HR, myocardial contractility and BP. Beta-blockers are considered first-line agents in the treatment of chronic angina.
- The beta-1 selective agents are most commonly used in the treatment of stable angina. However, beta-blockers with intrinsic sympathomimetic activity (e.g. acebutolol and pindolol) are not recommended for patients with angina because they may exacerbate the angina in some patients.
- In addition to BBs, exertional angina can be treated with CCBs (amlodipine, felodipine, nifedipine) and/or isosorbide mononitrate or transdermal nitroglycerine.
What does AFib commonly cause
Common cause of thrombus formation (mainly when it has not been appropriately treated).
Premortem thrombi are characterized by thin, white laminations (lines of Zahn) composed mostly of platelets, whereas postmortem clots do not show lines of Zahn but instead resemble chicken fat.
Describe EKG in common heart block
no correlation of P waves and QRS complexes. The combination of increased pulse pressure (systolic - diastolic; normally is 40mmHg) and a decreased HR (30-45/min) should suggest this diagnosis.
What causes complete heart block
Most commonly caused by coronary artery disease or degeneration of the cardiac conduction system with agents known to cause AV block (i.e. atenolol at high doses may cause different degrees of heart block). The initial management can be with atropine, isoproterenol, and dopamine.
Clinical features and EKG changes in acute pericarditis
sharp, stabbing pain that worsens with inspiration and is improved when sitting up and leaning forward. Diffuse ST elevations are a characteristic finding early in acute pericarditis. Generally is preceded by a viral upper respiratory illness, although patients often cannot recall any preceding illness.
Clinical features and EKG changes of premature ventricular contractions (PVCs)
Some patients can have palpitations or even syncopal episodes, while others may be completely asymptomatic
Can present after MI in which tissue damage in ventricular tissue produces ectopic (non-SA node) sites of electrical activation. When these sites depolarize, the ventricles contract independently of the SA node and the atypical activation patterns generate the premature and abnormal QRS patterns seen on ECG. Typically, p waves do NOT precede a PVC since the electrical impulse originates in the ventricles, rather than the atria.
Describe filling in PVCs
Do not allow sufficient time for normal ventricular filling to take place. As a result, preload (left ventricular end-diastolic volume) is reduced.
Occurs independently of atrial contraction. Reduced filling time generates reduced SV during this contraction. The ventricular contraction closes the AV valves, so the atria eventually contract against closed AV valves, producing an abnormally high atrial pressure and “cannon a waves” on jugular vein pressure tracing.
What is JVD a reflection of
indicates elevated jugular venous pressure, a classic sign of venous HTN, which can be caused by right-sided HF. JVD is a reflection of RA pressure adn can be used to estimate central venous pressure, which is normally less than 8.
Describe the pathophysiology of JVD
In CHF there is activation of the RAAS, casuing salt and water retention. If the heart is not damaged too badly, the increase in blood volume caused by the fluid retention can increase venous return sufficiently to totally compsenate for the diminished pumping capacity of te heart. The increase in venous return causes the right atrial pressure to rise, which elevates venous pressure throughout the body. This increase in venous pressure can cause both excessive fluid loss from microcirculation and the development of peripheral edema.
o This excess fluid, combined with decreased cardiac contractility, causes an increase in hydrostatic pressure.
o Consequently, there is passage of fluid from the microcirculation to the interstitialspace, leading to edema.
o The presence of S3, heard best over the apex, is evidence of CHF.
How does the body try to maintain mean systemic filling pressure (MSFP) after a major hemorrhage
The body tries to maintain mean systemic filling pressure (MSFP) after a major hemorrhage by constricting veins and venules
What is a pleural effusion
accumulation fo fluid in the pleural cavity; may be a transudate or exudate
Describe chylorus (exudative) effusions
Exudative effusions with high lipid content, thus giving it a milky-white appearance, and originate from the lymphatic channels. They are most commonly related to disruption or obstruction by trauma or malignancy (lymphoma, knife stabbing near lymphatic channels)
Exudative effusions have a pleural fluid to serum protein ratio of >0.5 and a pleural fluid to serum LDH ratio of >0.6, or pleural fluid LDH > 2/3 the upper limit of normal serum value.
Lymphoma or a large tumor in the chest can damage the thoracic duct, allowing the chylomicron-rich lymphatic fluid to drain into the pleural cavity (chylothorax).
What causes an exudative vs. transudative pleural effusion
Bacterial pneumonia can lead to empyema and cause an exudative effusion and purulent pleural fluid with a yellow-green appearance (pus) on throacentesis.
CHF (back-up of blood flow within lung capillaries and increased hydrostatic pressure) and neprhortic syndrome (loss of albumin and decreased oncotic pressure) contribute to transudative pleural effusions. Fluid will be clear yellow, ressembling serum.
Describe the pressure and oxygen consumption in aortic stenosis
severe cases are associated with increased LV pressure and increased LV work, increased LV oxygen consumption and decreased cardiac tissue oxygen concentration, and increased adenosine in cardiac tissue.
Describe blood flow through the coronary circulation
Blood flow through the coronary circulation is regulated almost entirely by the metabolic requirements of the cardiac muscle. When oxygen consumption of the heart increases, a larger-than-normal proportion of the ATP in the heart-muscle cells degrades to adenosine. The adenosine then dilates the coronary blood vessels, increased O2 delivery to an adequate level. In this way, the coronary blood flow increases in direct proportion to the oxygen consumption of the heart.
Cause of infective endocarditis
Staph aureus – gram+ coagulase + cocci in clusters; classically results from IV drug abuse, and since the pathogen is mostly introduced via venous access, bacterial vegetations most commonly form on the right side of the heart, especially the tricuspid valve.
Complications of endocarditis
Septic emboli thrown off from the tricuspid valve will mostly affect the pulmonary circulation rather than the systemic circulation. As a result, a pulmonary abscess can occur.
Prerenal azotemia, splenic abscess and stroke are typically produced with left-sided involvement of endocarditis. They occur as a result of septic emboli released into the systemic circulation that can lodge in renal vasculature (renal infarcts), in the spleen (abscess), or in the cerebral vessels (stroke).
Oxygen Consumption Equation
Oxygen Consumption Equation = CO (arterial O2 content - venous O2 content)
MAP Equation
MAP = CO * TPR. However, if venous pressure (or right atrial pressure) is severely increased, it must be taken into account when estimating TPR such that the equation becomes MAP - RA pressure = CO * TPR
What does trypanosoma cruzi
Cause of Chagas disease (endemic in vast areas of South America), spread by triatomids called reduviid bugs (“kissing bugs”). Intracellular protozoan that localizes mainly in the heart and nerve cells of the myenteric plexus, leading to myocarditis and dismotility of hollow organs, such as the esophagus (producing achalasia), colon and ureter.
What is the most common cause of ARDS
Sepsis
Describe the pathophysiology of ARDS
ARDS results from alveolar injury, which causes the release of pro-inflammatory cytokines (TNF, IL-1, IL-6). Neutrophils are recruited to the lungs by these cytokines, where they become activated and release toxic mediators that damage alveolar epithelium and capillary endothelium (increasing microvascular permeability). This then allows protein to escape from the vascular space, producing an oncotic gradient, and fluid enters the interstitium, overwhelming the lymphatics. Alveolar spaces become filled with bloody, proteinaceous edema fluid and cellular debris from cells undergoing necrosis. Functional surfactant is lost causing alveolar collapse. These processes cause impaired gas exchange, decreased lung compliance, and pulmonary HTN.
What is the equation for the net fluid movement
Qf = k [(HPc + OPi) - (HPi + OPc)].
A positive Qf (net fluid movement between compartments) indicates net filtration and a negative value indicates net reabsorption. Sepsis can cause a generalized increase in vascular permeability, which can in turn lead to increased interstitial colloid osmotic pressure, increased interstitial fluid hydrostatic pressure, and increased lymph flow
Describe the functions of carotid and arterial baroreceptors
- A decrease in systemic arterial pressure leads to a compensatory increase in BP and CO (secondary to an increase in sympathetic outflow and decrease in parasympathetic outflow).
- Increased sympathetic activity at arterioles causes greater NE release, leading to enhanced alpha-1-adrenergic receptor stimulation, which are linked to Gq causing PIP2 hydrolysis forming IP3 and DAG. DAG travels to the membrane to activate PKC. IP3 is water-soluble and diffuses in the cytoplasm to internal storage vesicles to release calcium. Calcium then binds calmodulin to form a complex that activates MLCK which phosphorylates myosin light chains, leading to the interaction of myosin with actin to cause smooth muscle contraction, increasing BP. Vasopressin and ATII would also increase IP3.
- An increase in systemic arterial pressure leads to a compensatory dilation of the arterioles and decreases CO (secondary to a decrease in sympathetic outflow and increase in parasympathetic outflow)
What is the effect of the baroreceptors after major hemorrhage
Arterial barorecerptors located in the carotid sinus (innervated by CN IX) and aortic arch (innervated by CN X) respond to stretching of the arterial wall. Information is sent to the nucleus tractus solitarius (NTS) in the medulla
Trigger of the baroreceptor reflex, which increases sympathetic activity and decreases parasympathetic (vagal) activity causing an increase in HR and TPR (via stimulation of alpha-1 adrenergic receptors with NE from sympathetic outflow. Decreased blood flow to the kidney activates the RAAS.
What is the consequence of severe cell damage on K+
Severe cell damage can release K+ into the bloodstream, producing hyperkalemia. On EKG, hyperkalemia is associated with abnormally tall, tented T waves because K+ is responsible for repolarization of cardiac cells
Cardiogenic Shock values
decreased SV, decreased CO, increased SVR, increased preload
Hypovolemic Shock values
decreased SV, unchanged CO, increased SVR; similar to cardiogenic shock, but with decreased cardiac preload instead of increased preload.
Septic Shock values
increased SV, increased CO, decreased PVR
Exercise values
increased SV, increased CO, unchanged SVR
Describe phase 3 of the cardiac cycle
During each cardiac cycle, the walls of the ventricle undergo both isometric (muscle length does not change) and isotonic (muscle length does change with a constant tension on the muscle) contraction and relaxation
Phase 3 corresponds to a period of isometric contraction, referred to as the period of isovolumetric/isovolumic/isometric contraction. The ventricle is contracting and the pressure is rising rapidly, but the volume of the ventricle remains constant; thus, muscle length is relatively constant. During this phase, the rate of rise of the LV pressure reaches its maximum value, the +dP/dt max.
AV fistula on return curve
An AV fistula can shift the venous return curve to the right and rotate it upward with no change in the CO curve
Exercise on return curve
Exercise can shift the venous return curve right and the CO curve upward
HF on return curve
HF due to impaired contractility and narcotic overdose can shift the CO curve downward without directly affecting the venous return curve.
Hemorrhage on return curve
• Hemorrhage shifts the venous return curve left and shifts the cardiac output curve downward
Doxorubicin Usage and MOA
antibiotic antineoplastic agent commonly used in the treatment of Hodgkin lymphoma, breast, endometerial, lung, and ovarian cancers. It intercalates DNA, forms free radicals, and inhibits topoisomerase
AE of Doxorubicin
Both doxorubicin and daunomycin are associated with the development of congestive cardiomyopathy/CHF (classic S/Sx including orthopenia, paroxysmal nocturnal dyspnea, nocturia, tachycardia, pitting edema, pulmonary rales, S3 sound).
Doxorubicin cardiotoxicity can be acute, occurring during and within 2-3 days of administration. Dexrazoxane is an iron-chelating agent that is used to prevent cardiotoxicity.
Describe the pupillary light reflex
Afferent CN II, efferent CN III
Light shined in eye → impulses carried in CN II to pretectal nuclei which innervate the Edinger-Westphal nulcei (preganglionic parasympathetic CN III neurons) bilaterally → innervate ciliary ganglia (postganglionic parasympathetic neurons) → sphincter pupillae muscle of iris → pupillary constriction
Because shinning light in one eye causes bilateral stimulation of EW nuclei, it leads to constriction of the ipsilateral pupil (direct light reflex) and contralateral eye (consensual light reflex)
If you have a lesion of right CN II how will this affect the pupillary light reflex
If you have lesion right CN II, right eye will not transmit light information to elicit either a direct or consensual response. However, when light is shined in healthy left eye, light information is transmitted fine and constriction occurs in both eyes
What is a marcus-gunn pupil
Relative afferent pupillary defect; decreased sensitivity of the affected eye to light, which results from lesions of the retina, optic nerve, or eye.
Swinging flashlight test – shine light in Marcus Gunn pupil (pupils do not constrict fully), shine light in normal eye (pupils constrict fully), shine light in affected pupil again (apparent dilation of both pupils because the stimulus carried by the optic nerve [CN II] of the affected eye is weaker than the normal eye)
What is age-related macular degeneration (AMD)
slow or sudden loss of central visual fields; peripheral fields are preserved, as is some useful color vision.
What are the two forms of age-related macular degeneration (AMD)
Dry (atrophic) macular degeneration (80%) – alterations in the retinal epithelium are seen, as are drusen deposits in the maculae
Wet (exudative) macular degeneration – network of new vessel formation behind the retina that can be a source of intraretinal hemorrhage and subretinal fluid. This type can eventually contract with scar formation. Accounts for >80% of patients with AMD who have severe visual loss or legal blindness.
