Ultimate Block 6 Deck
effect of coughing in RHF
Tussive or effort-related syncope because of the inability of the RV to deliver blood adequately to the left side of the heart Coughing inc thoracic pressure>dec CO
What type of collagen is present in fibrosis?
Type I
What type of hypersensitivity reaction is allergic rhinitis?
Type I
What type of sensitivity reaction is atopic asthma?
Type I Hypersensitivity
keratin is marker for what type of tissue
epithelium
What is sudden death in PE caused by?
electromechanical dissociation (Aka heart pumping but no blood supply); right heart failure 2/2 both left and right pulm arteries significant occlusion
Kawasaki Disease
Medium vessel vasculitis; typical in *Asian children*; vasculitis of *coronary arteries*, leading to potential *aneurysms*; tx w/ *aspirin* and IVIG -Flare ups can show ST segment elevations
Why does mesothelioma present with recurrent pleural effusions?
Mesothelial cells normally make fluid!
How much of the lung in the air is normally blown out in the first second?
80%
metastasis and prognosis of adenocarcinoma
80% present with metastases Higher propensity for brain Prognosis: poor; 5 year overall survival for stage IV 8%
What percentage of lung cancer occurs in smokers?
85%
Name the four valves of the heart
Mitral, pulmonic, tricuspid, aortic
What pneumocytes are damaged in ARDS?
I and II
3 mechanisms of group III
hypoxic-induced vasoconstriction mechanical stress due to hyperinflated lungs destruction of pulmonary capillaries by emphysema/fibrosis
What disease end-stage has honeycombing of lung?
idiopathic pulmonary fibrosis
how does a pulmonary infarction occur?
if a large or medium sized artery is obstructed usually in pt with pre-existing cardiopulm compromise 10% of PE cause infarction
minimal residual disease
if any disease is left after chemo goal is zero- must give more chemo if any residual disease is left
What causes acute rheumatic fever
Molecular mimicry by bacterial M protein that resembles human tissue
How can you look for lesions on valves in endocarditis?
Transesophageal echocardiogram
Septal Defects are Best Heard at Which Listening Post?
Tricuspid
What valve does Staphylococcus aureus endocarditis affect?
Tricuspid (normal)
Tricuspid atresia
Tricuspid valve orifice fails to develop
3 phases of CML
Triphasic clinical course: Chronic phase, present at the time of diagnosis in approximately 85 percent of patients Accelerated phase, neutrophil differentiation becomes progressively impaired and leukocyte counts are more difficult to control with myelosuppressive medications Blast crisis, resembling acute leukemia in which myeloid or lymphoid blasts fail to differentiate
Single large vessel arising from both ventricles
Truncus arteriosus
Cause of Persistent Truncus Arteriosis
Truncus arteriosus fails to divide into pulmonary trunk and aorta due to lack of aorticopulmonary septum formation
Truncus arteriosus cause
Truncus fails to divide
Where is erythemia marginatum in acute rheumatic fever classically located?
Trunk and limbs
What is Rhabdomyoma associated with?
Tuberous sclerosis
Plexiform lesions pulmonary hypertension
Tufts of capillaries
markers in mycosis fungoides/Sezary syndrome
Tumor cells express adhesion molecule cutaneous leukocyte antigen (CLA) and CCR4 and CCR10 (contribute to homing of CD4+ T cells to skin)
How many carcinogens are there in cigarette smoke?
over 60
Acute monocytic leukemia
proliferation of monoblasts usually *lacking MPO* -characteristically infiltrate gums - swells gums
what ANA is characteristic of drug-induced lupus? what are common drugs to cause? how tx?
*antihistone antibody* procainamide, hydralazine, isoniazid rarely see CNS or renal involvement remove drug -> remission
Transposition of great vessels
Aorta arises from right ventricle and pulmonary artery arises from left ventricle- creates two separate shunts that do not mix
Heart Valve Development
Aortic/Pulmonary valves: derived from endocardial cushion of outflow tract Mitral/Tricuspid: derived from fused endocardial cushions of the AV canal
Where does secondary TB arise, and why?
Apex of the lung where there is poor lymphatic drainage and high oxygen tension
platelets
Apheresis unit- Contains >3 x 10^11 platelets We exclusively use apheresis platelets at MU Volume 200-300 mL or more (plasma or PAS) Expected response to 1 apheresis unit: 30-50K Stored with continuous gentle, horizontal agitation at 20-24 C for up to 5 days (likely become contaminated with bacteria if later than this) One bag comes from a single donor PAS- platelet aggregate solution (salt and sugar solution) Platelets are very high-maintenance and are often in short supply- don't give them too liberally
Ejection Fraction Calculation
EF= SV/EDV = EDV - ESV / EDV
2 common mutations in adenocarcinoma and significance
EGFR, EML-ALK4 fusion indicate better prognosis b/c they have targeted treatments erlotinib- EGFR TKI crizotinib- EML-ALK4 TKI
How does Eisenmenger syndrome cause polycthemia?
EPO is released in response to hypoxia, leading to polycythemia
subset of breast carcinomas assoc. oncogene
ERBB2 (HER2/neu) - epidermal growth factor receptor amplification of receptor cause increased growth
How does tricuspid atresia present?
Early cyanosis
Presentation of transposition of great vessels
Early cyanosis
How does truncus arteriosus present?
Early cyanosis, with deoxygenated blood from the RV mixing into the aorta and LV blood
PE finding in aortic regurgitation
Early, blowing diastolic murmur
What do the macrophages do when they come in 4-7 days post MI?
Eat up dead and necrotic debris
Vitamin D
D2 = ergocalciferol—ingested from plants. D3 = cholecalciferol—consumed in milk, formed in sun-exposed skin (stratum basale). 25-OH D3 = storage form. 1,25-(OH)2 D3 (calcitriol) = active form. Function: Increase intestinal absorption of calcium and phosphate, Increase bone mineralization at low levels, bone resorption at higher levels. Deficiency: Rickets in children (deformity, such as genu varum "bow legs"), osteomalacia in adults (bone pain and muscle weakness), hypocalcemic tetany. Breastfed infants should receive oral vitamin D. Deficiency is exacerbated by low sun exposure, pigmented skin, prematurity. Excess: Hypercalcemia, hypercalciuria, loss of appetite, stupor. Seen in granulomatous disease ( activation of vitamin D by epithelioid macrophages).
Name the HACEK organisms and what they cause
Haemophilus, actinobacillus, cardiobacterium, eikenella, kingella; endocarditis with negative blood cultures
hard cervical nodes suggest
Hard cervical nodes, particularly in older patients and in smokers, suggest metastatic cancer.
lymph node consistency
Hard nodes are found in cancers that induce fibrosis (desmoplastic response) and when previous inflammation has left fibrosis. Firm, rubbery nodes are found in lymphomas and; nodes in acute leukemia tend to be softer.
What do we use to determine clonality of B lymphocyte?
Ig light chain - B cell expresses either kappa or lambda kappa/lambda ratio normally 3:1 ratio >6:1 or inverted indicates monoclonality (lymphoma)
Class III Antiarrhythmics
K+ channel blockers AIDS Amiodarone Ibutilide Dofetilide Sotolol
GI stromal tumor assoc. oncogene
KIT (stem cell growth factor receptor) point mutation
HHV-8 as oncogenic virus
Kaposi sarcoma eastern european males, AIDs pt, transplant pt all susceptible
What is the intermediate filament of epithelial cells?
Keratin
What is the most common site of systemic spread of secondary TB, and what does it cause there?
Kidney, causes sterile pyuria
Cause of lobar pneumonia that presents with "red sputum jelly"
Klebsiella pneumonia
Lung carcinoma assoc. oncogene
L-MYC (transcription factor) amplification
How do you screen for lung maturity in neonates?
L:S ratio (lecithin to sphingomyelin ratio) Lecithin should increase with gestational age; sphingomyelin should remain constant
What are the three most commonly involved coronary arteries in MI and what areas of the heart do they affect?
LAD: affects anterior LV wall and anterior septum Right Circumflex: affects posterior LV wall and posterio septum and LV papillary muscles Left Circumflex: affects lateral wall of LV
what are the 4 key mediators which attract neutrophils to acute inflammation site?
LTB4 C5a IL-8 bacterial products
What does aortic regurgitation cause in LV, and why?
LV hypertrophy and eccentric hypertrophy due to volume overload
What ventricle is usually involved in MI and what ventricles are usually spared?
LV involved usually RV and both atria are generally spared
Why is Mycoplasma pneumoniae not visible on gram stain?
Lack of cell wall
Lung cancer defined by poorly differentiated large cells, but not other features of non-small cell carcinoma
Large cell carcinoma
Pathogenesis of Staphylococcus aureus endocarditis (acute endocarditis)
Large vegetations destroy the valve
Giant Cell Arteritis
Large vessel vasculitis; mostly temporal artery; can lead to irreversible blindness due to ophthalmic artery occlusion; tx w/ steroids -Most commonly affects *branches of carotids* w/ *granulomatous vasculitis* -Linked to *polymyalgia rheumatica* (flu-like symptoms + joint pain)
Takayasu Arteritis
Large vessel vasculitis; usually younger *Asian* females; *granulomatous thickening/narrowing of aortic arch and great vessels* -> called *pulseless disease* due to weak upper extremity pulses; tx w/ steroids
Squamous cell carcinoma arising from the epithelial lining of the vocal cord (usually)
Laryngeal carcinoma
Benign papillary tumor of the vocal cord
Laryngeal papilloma
What's another name for croup
Laryngotracheobronchitis
Inflammation of the upper airway
Laryngotracheobronchitis (croup)
When does dilated cardiomyopathy occur in progression of myocarditis?
Late complication
Mitral Valve Prolapse
Late systolic crescendo murmur with *midsystolic click*; most frequent valvular lesion; best heard over *apex* -Can predispose to infective endocarditis -Can be caused by myxomatous degeneration (1° or 2° to connective tissue disease such as Marfan or Ehlers-Danlos syndrome), rheumatic fever, chordae rupture
When do you see dilated cardiomyopathy in pregnancy?
Late third trimester or soon (weeks to month) after birth)
cardiogenic pulmonary edema
Left heart failure - inc pulmonary venous pressure>pulmonary venous distention and transudation of fluid. Presence of hemosiderin-laden macrophages ("HF" cells) in lungs. (PCWP >18) Causes include ischemia, myocardial infarction, dilated cardiomyopathy, restrictive cardiomyopathy, and HTN. Clinical features are due to decreased forward perfusion and pulmonary congestion Pulmonary Edema - Results in dyspnea, paroxysmal nocturnal dyspnea (due to increased venous return when lying flat), orthopnea, and crackles (pulmonary edema) Small, congested capillaries may burst, leading to intraalveolar hemorrhage marked by hemosiderin-laded macrophages ('heart-failure" cells) Decreased flow to kidneys leads to activation of renin-angiotensin system (fluid retention exacerbates CHF; mainstay of treatment is ACE inhibitor) Myocardial infarction complications - Can occur 2° to LV infarction, VSD, free wall rupture, papillary muscle rupture with mitral regurgitation. Valvular Disorder - Especially Mitral Stenosis/Mitral Regurgitation (volume overload in LA>Left CHF)
Intracellular organism that is best visualized by silver stain
Legionella pneumophilia
Pneumonia transmitted from water source
Legionella pneumophilia
Name the six microscopic changes during/after MI and when the occur
Less than 4 hours: none 4-24 hours: coagulative necrosis 1-3 days: neutrophils 4-7 days: macrophages 1-3 weeks: granulation tissue with plump fibroblasts, collagen, and blood vessels Months: fibrosis
What is the difference between lymphoma and leukemia?
Leukemias: The neoplastic cells originate in the bone marrow and the neoplastic cells are found predominantly in the bone marrow and, usually, the peripheral blood. Lymphomas: The neoplastic cells USUALLY originate in the lymph nodes or spleen and cause the development of a solid tumor.
Endocarditis associated with SLE
Libman-Sacks endocarditis
What causes angina and syncope with exercise in aortic stenosis
Limited ability to push blood across the stenotic valve decreases perfusion of myocardium and brain
What does aspirin/heparin do in MI treatment?
Limits thrombosis
Corneal Arcus
Lipid deposition into the corneas; can *suggest hypercholesterolemia*; *arcus senilis* is normal aging causing corneal lipid deposition
What often can accompany emphysema due to alpha-1 antitrypsin deficiency?
Liver cirrhosis
Diagnosis of biopsy of pink, PAS positive globules in hepatocytes
Liver cirrhosis due to accumulation of A1AT accumulation in ER of hepatocytes
What are the three classical patterns of pneumonia on CXR, and which ones are caused by bacteria vs. virus?
Lobar (bacterial) Bronchopneumonia (bacterial) Interstitial (viral)
Pneumonia characterized by consolidation of an entire lobe
Lobar pneumonia
Salmeterol/formoterol
Long acting beta2 agonist agents for prophylaxis. Adverse effects are tremor and arrhythmia
Lesions in asbestosis
Long, golden brown fibers with associated iron; called asbestos bodies or ferruginous bodies
How does emphysema result in obstructive disease?
Loss of elastic recoil in alveolar air sacs and subsequent collapse of airways during exhalation results in obstruction and air trapping
Laboratory findings associated with anemia of chronic disease
Low Hb, Low MCV, increased ferritin, decreased TIBC, decreased serum iron, decreased % saturation
Is carcinoid tumor high or low grade malignancy?
Low grade
how pulmonary circulation is different from systemic circulation
Low resistance, high compliance vascular bed Only organ to receive entire CO Changes in CO as well as pleural/alveolar pressure affect pulmonary blood flow Different reactions compared to the systemic circulation: pulmonary vascular tone increases in response to hypoxia (Unlike in systemic circulation, hypoxia results in constriction in pulmonary circulation) Hypoxic pulmonary vasoconstriction (HPVC) occurs in response to both alveolar hypoxia and pulmonary arterial hypoxemia
IgA deficiency
Low serum and mucosal IgA *MOST COMMON IG Deficiency* inc. risk for mucosal infection, especially viral - *but most pt asymptomatic*
Streptococcus viridans: low or high virulence?
Low virulence
classic EKG of restrictive cardiomyopathy
Low voltage EKG with diminished QRS
EKG Finding in Restrictive Cardiomyopathy
Low voltage w/ diminished QRS amplitude
Amniotic fluid emboli
can lead to DIC in the mother, especially post partum
Clinical Findings in Aortic Dissection
Presents w/ tearing chest pain, of sudden onset, radiating to the back *+/− markedly unequal BP in arms* -CXR shows *mediastinal widening*
What is the purpose of the valves?
Prevent backflow
positional therapy
Prevents patient from sleeping on back Option as primary treatment for mild OSA Adjunctive in moderate or severe OSA
should blood be given liberally or restrictively?
Previously taught to give blood liberally, but it was found that there is either the same or a better outcome with restrictive transfusions (give less blood)
What are the two types of TB?
Primary and secondary
jejunal resection
Primary digestive & absorptive site for most nutrients Ileal Adaptation (increases absorptive area by growth in length and function of villi to be more similar to jejunum) Ileum normally just absorbs water, sodium, B9, and bile acids Starts 24-48 hrs after resection
primary vs. secondary follicles
Primary follicles are unstimulated, while secondary follicles have been stimulated by Ag and have germinal centers
What are the two types of pulmonary hypertension?
Primary or secondary
Why do those with chronic bronchitis have cyanosis?
Trapped air increases PaCO2, which decreases PAO2 and subsequently PaO2
Antiphospholipid antibody syndrome
hypercoaguable state d/t antiphospholipid antibodies (esp. lupus anticoagulant) require lifelong anticoagulation associated with SLE, but *more common as primary disorder*
What is pigeon breeder's lung?
hypersensitivity pneumonitis
transudate characteristics
hypocellular (clear) low protein (<2.5 g/dL) d/t: inc. hydrostatic pressure (HF, Na retention); dec. oncotic pressure (cirrhosis, nephrotic syndrome)
Anti-NMDA receptorencephalitis as a paraneoplastic syndrome happens in ?
ovarian teratoma psych disturbance, mem deficits, seizures, dyskinesias, autonomic isntability, language dysfunction
squamous cell carcinoma is often positive for which immunohistochemical markers?
p63+, CK (cytokeratin) 5/6+
obstructive vs. restrictive lung disease
page 611
Wiskott-Aldrich syndrome
thrombocytopenia, eczema, recurrent infections-defective humoral and cellular immunity (WATER) major cause of death *bleeding* d/t WASP gene mutation (Xlinked)
Lung volumes vital capacity
tidal volume + inspiratory reserve volume + expiratory reserve volume
most common indication for FFP
to reverse INR on warfarin
mitochondrial inheritance
transmitted only through mother - Variable expression in population and even in families d/t *heteroplasmy*
Pleural effusions
transudate, exudate, lymphatic Excess accumulation of fluid between pleural layers leading to restricted lung expansion during inspiration. Can be treated with thoracentesis to remove fluid.
multiple myeloma treatments
treated with thalidomide or lenalidomide (newer version) + corticosteroid but inc risk of thrombosis with these drugs- so also put the patients on aspirin newer- bortezomib- proteasome inhibitor
What are the types of single-gene disorders with nonclassic inheritance?
trinucleotide-repeat mutations (fragile X) mitochondrial gene mutations genomic imprinting (PWS and Angelman) gonadal mosaicism
how do you tx DIC?
tx underlying cause and transfusing blood products and cryoprecipitate (coag factors) if necessary
Gas embolus
typically 2/2 decompression sickness (the bends and the chokes) -> nitrogen gas precipitates out of blood d/t rapid ascent by a diver a chronic form is known as *Caisson dz* -> characterized by *multifocal ischemic necrosis of bone* also assoc. w/ laparoscopic surgery
what disorders affect primary hemostasis?
typically d/t platelet abnormalities (qualitative or quantitative) -Immune thrombocytopenic purpura -MAHA (seen in TTP and HUS) qualitative: Bernard-soulier, glanzmann thromboasthenia, aspirin, uremia
Ubiquitin-proteosome degradation
ubiquitin tags intermediate filaments of cytoskeleton and proteosomes then degrade
BMI categories
underweight <18.5 normal 18.5-24.9 overweight 25.0-29.9 obesity I 30.0-34.9 obesity II 35.0-39.9 obesity III 40.0 and above
retinoblastoma
unilateral occurs when both Rb are sporadic germline mutation causes familial Rb (2nd hit somatic) -> bilateral Rb and osteosarcoma retina is a field just ready to be mutated by nonionizing radiation (UVB)
where is the highest density of breast tissue located?
upper outer quadrant of breast
naphthylamine
urothelial carcinoma of bladder from cigarette smoke
Risk factors for breast cancer
1. gender (males 1/100 cases) 2. age - usu post-menopausal 3. early menarche/late menopause 4. obesity 5. atypical hyperplasia (5x incr risk) 6. first-degree relative with breast cancer
what epithelium lines lobules and ducts of breast?
2 layers of epithelium 1. inner luminal layer (columnar) - makes milk 2. outer myoepithelial layer - contractile fxn to eject milk towards nipple
fibrocystic change cancer risk: ductal hyperplasia and sclerosing adenosis
2x increased risk for invasive carcinoma -risk increased for both breasts sclerosing adenosis - can show up calcified on mammogram increase in glands in lobule with collagen deposition
fibrocystic change cancer risk: atypical hyperplasia
5x increased risk for invasive carcinoma -risk increased for both breasts depending on location can be atypical ductal hyperplasia or atypical lobular hyperplasia
Fat Soluble Vitamins
A, D, E, K. Absorption dependent on gut and pancreas. Toxicity more common than for water-soluble vitamins because fat-soluble accumulate in fat. Malabsorption syndromen with steatorrhea (CF and celiac disease), or mineral oil intake can cause fat-soluble deficiencies.
drugs used in heart failure and which ones affect mortality
ACE inhibitors or angiotensin II receptor blockers, β-blockers (except in acute decompensated HF), and spironolactone dec mortality. Thiazide or loop diuretics are used mainly for symptomatic relief. Hydralazine with nitrate therapy improves both symptoms and mortality in select patients.
Water soluble vitamins
B1 (thiamine: TPP) B2 (riboflavin: FAD, FMN) B3 (niacin: NAD+) B5 (pantothenic acid: CoA) B6 (pyridoxine: PLP) B7 (biotin) B9 (folate) B12 (cobalamin) C (ascorbic acid) All wash out easily from body except B12 and B9 (folate). B12 stored in liver for ~ 3-4 years. B9 stored in liver for ~ 3-4 months. B-complex deficiencies often result in dermatitis, glossitis, and diarrhea. Can be coenzymes (eg, ascorbic acid) or precursors to organic cofactors (eg, FAD, NAD+).
lyme disease
Caused by Borrelia burgdorferi, which is transmitted by the Ixodes deer tick (also vector for Anaplasma spp. and protozoa Babesia) Natural reservoir is the mouse (and important to tick life cycle). Common in northeastern United States. Stage 1 - Early localized: erythema migrans (typical "bulls-eye" configuration is pathognomonic but not always present), flu-like symptoms. Stage 2 - Early disseminated: secondary lesions, carditis, AV block, facial nerve (Bell) palsy, migratory myalgias/transient arthritis. Stage 3 - Late disseminated: encephalopathies, chronic arthritis
heart conduction pathway
Conduction pathway—SA node>atria>AV node>bundle of His>right and left bundle branches>Purkinje fibers>ventricles; left bundle branch divides into left anterior and posterior fascicles. SA node "pacemaker" inherent dominance with slow phase of upstroke. AV node—located in posteroinferior part of interatrial septum. Blood supply usually from RCA. 100-msec delay allows time for ventricular filling. Pacemaker rates—SA > AV > bundle of His/ Purkinje/ventricles. Speed of conduction—Purkinje > atria > ventricles > AV node.
Wernicke-Korsakoff syndrome
Confusion, ophthalmoplegia, ataxia (classic triad) + confabulation, personality change, memory loss (permanent). Damage to medial dorsal nucleus of thalamus, mammillary bodies
ductal carcinoma in situ can present how?
-calcification on mammography -usu doesn't form a mass no invasion of basement membrane
what are the benign breast lesions that can have calcification on mammography?
-fat necrosis -sclerosing adenosis of fibrocystic change
causes of galactorrhea
-nipple stimulation -prolactinoma -drugs
Vitamin E (tocopherol/tocotrienol)
Function: Antioxidant (protects RBCs and membranes from free radical damage).High-dose supplementation may alter metabolism of vitamin K enhanced anticoagulant effects of warfarin. Deficiency: Hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination. Neurologic presentation may appear similar to vitamin B12 deficiency, but without megaloblastic anemia, hypersegmented neutrophils, or increase serum methylmalonic acid levels.
Vitamin B7 (biotin)
Function: Cofactor for carboxylation enzymes -pyruvate carboxylase: pyruvate (3C) --> oxaloacetate (4C) -Acetyl-CoA carboxylase: acetyl-CoA (2C) --> malonyl-CoA (3C) -Propionyl-CoA carboxylase: propionyl-CoA (3C) --> methymalonyl-CoA (4C) Deficiency: rare. Dermatitis, alopecia, enteritis. Caused by Abx use or excessive ingestion of raw egg whites
Vitamin B2 (riboflavin)
Function: Component of flavors FAD and FMN, used as cofactors in redox reactions, eg, the succinate dehydrogenase reaction in TCA cycle FAD and FMN are derived from riboFlavin Deficiency: Cheilosis (inflammation of lips, scaling and fissures at the corners of mouth), Corneal vascularization
Marasmus
Malnutrition not causing edema. Diet is deficient in calories but no nutrients are absent. Marasmus results in muscle wasting.
second degree AV block includes
Mobitz type I and II
dilated cardiomyopathy
Most common cardiomyopathy (90% of cases). Often idiopathic or familial. Dilation of all four chambers of the heart Systolic dysfunction (ventricles cannot pump), leading to ventricular CHF; complications include mitral and tricuspid valve regurgitation and arrhythmia Causes - Alcohol abuse, wet Beriberi, Coxsackie B viral myocarditis, chronic Cocaine use, Chagas disease, Doxorubicin toxicity, hemochromatosis, sarcoidosis, peripartum cardiomyopathy. ABCCCD. Findings: HF, S3, systolic regurgitant murmur, dilated heart on echo, balloon appearance of heart on CXR
central sleep apnea
No respiratory effort due to CNS injury/toxicity, HF, opioids. May be associated with Cheyne- Stokes respiration. Treat with positive airway pressure
nipple ulceration and erythema (not infxs)
Paget Disease of the Breast -DCIS that has crept up to involve skin of nipple -always associated with underlying carcinoma
fibroadenoma-like tumor with overgrowth of fibrous component, forming "leaf-like" projections
Phyllodes tumor -post-menopausal females -can be malignant
Mobitz Type I (Wenckebach)
Progressive lengthening of PR interval until a beat is "dropped" (a P wave not followed by a QRS complex). Usually asymptomatic. Variable RR interval with a pattern (regularly irregular). Sinus rhythm (P before every QRS and positive P in lead II) with 2nd degree AV block, Type I (Wenckebach). PR progressively prolongs and then P fails to conduct Every 3rd P wave is not conducted (3 P waves for every 2 QRS or 3:2 conduction). The shortest PR is following the nonconducted P wave. Commonly seen in vagal states or drugs that affect AV conduction.
sleep apnea
Repeated cessation of breathing > 10 seconds during sleep>disrupted sleep>daytime somnolence. Diagnosis confirmed by sleep study. Normal Pao2 during the day. Nocturnal hypoxia>systemic/pulmonary hypertension, arrhythmias (atrial fibrillation/flutter), sudden death. Hypoxia>inc EPO release>inc erythropoiesis
obstructive sleep apnea
Respiratory effort against airway obstruction. Associated with obesity, loud snoring. Caused by excess parapharyngeal tissue in adults, adenotonsillar hypertrophy in children. inc pulse pressure (inc sympathetic tone); Pulsus paradoxus | Treatment: weight loss, CPAP, surgery.
first degree AV block
The PR interval is prolonged (> 200 msec). Benign and asymptomatic. No treatment required. Sinus rhythm (P before every QRS and positive P in lead II) with first degree AV block (PR > 0.21 sec) Commonly seen in vagal states (e.g. sleep) and with drugs that affect AV conduction (e.g., beta-blockers, Ca2+ channel blockers such as diltiazem or verapamil, digoxin) Drug Causes: Type II (beta) and IV (Ca2+) Anti-arrhythmics; Digoxin
Duchenne muscular dystrophy
X-linked disorder typically due to frameshift or nonsense mutations>truncated or absent dystrophin protein>progressive myofiber damage. Weakness begins in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle. Waddling gait. <5 years of age. Dilated cardiomyopathy common death cause
breast feeding + fissures?
acute mastitis (staph aureus)
erythematous breast with purulent nipple discharge, may progress to abscess formation
acute mastitis (staph aureus)
atrial stunning
cardioversion of atrial fibrillation/flutter to sinus rhythm is associated with a cardioversion related transient mechanical dysfunction of the left atrium and left atrial appendage Result is paradoxical dec left atrial appendage blood flow velocities despite reversion to sinus rhythm Leads to increased risk of developing thromboembolic events hours to weeks after cardioversion of atrial fibrillation to sinus rhythm Causes postcardioversion thromboembolism despite restoration of sinus rhythm
high-grade ductal cells with central necrosis and dystrophic calcification later? cancer risk?
comedo type of DCIS. precancerous.
well-differentiated tubules that lack myoepithelial cells -good prognosis
ductal carcinoma: tubular carcinoma
fibroadenoma features that demonstrate hormone sensitivity
estrogen sensitive mass -grows during pregnancy -painful during menstrual cycle -shrinks with menopause
S1
mitral and tricuspid valve closure
fibrocystic change cancer risk: fibrosis, cysts, apocrine metaplasia
no increased risk
invasion of nipple by large cells with clear cyto
pagets disease
nipple ulceration + erythema + excematous scaling
pagets disease (underlying carcinoma)
diastolic dysfunction
preserved EF, normal EDV; dec compliance often 2° to myocardial hypertrophy. In diastolic heart failure, there is impaired cardiac relaxation and abnormal ventricular filling. Hypertrophic/Restrictive cardiomyopathy
systolic dysfunction
reduced EF, inc EDV; dec contractility often 2° to ischemia/MI or dilated cardiomyopathy. In systolic heart failure, there is reduced cardiac contractility.
why do smokers get periductal mastitis?
relative vitamin A deficiency -results in squamous metaplasia of lactiferous ducts -causes duct blockage and inflammation (myofibroblasts cause nipple retraction)
central acinar compression by fibrosis + peripheral duct dilation
sclerosing adenosis
cardioversion
tachycardia/arrhythmia is converted to a normal rhythm using electricity or drugs
what is the functional unit of the breast?
terminal duct lobular unit (consists of lobules that make milk and duct that drains milk)
Paget Disease of Breast associated with?
underlying carcinoma (usu DCIS)
Mobitz Type II
Dropped beats that are not preceded by a change in the length of the PR interval (as in type I). May progress to 3rd-degree block. Often treated with pacemaker.
Beriberi
Dry- polyneuritis, symmetrical muscle wasting Wet- high-output cardiac failure (dilated cardiomyopathy), edema
What is normal mean arterial pressure in pulmonary circuit?
10 mmHg
What percentage of asthmatic adults have aspirin-intolerant asthma?
10%
what percentage of breast cancer is hereditary?
10%
What percentage of adults have mitral valve prolapse?
2-3%
pathophys of BCR-ABL
ABL kinase uses same pro-growth and pro-survival pathways turned on by hematopoietic growth factors (RAS and JAK/STAT). Preferentially drives the proliferation of granulocytic and megakaryoytic progenitors and causes abnormal release of immature granulocytic forms from the marrow into the blood
myotonic type 1 muscular dystrophy
AD -> CTG repeat in DMPK gene -> abnormal expression of myotonin protein kinase -> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia *C*ataracts, *T*oupee, *G*onadal atrophy
neurofibromatosis 2
AD, NF2 gene on Chr 22 -> makes *merlin* which is cell membrane-related protein that acts as a tumor suppressor via *contact-inhibition method* manifestations: bilateral vestibular schwannomas (tinnitus, hearing loss, balance problems), meningnomas, ependymomas, eye lesions (cataracts, retinal hemorrhages), skin lesions (cutaneous tumors, skin plaques) affects 2 ears, 2 eyes, and 2 parts of brain
protein C or S deficiency
AD, decreases negative feedback on coag cascade normally deactivate factors 5 and 8 this is associated with increased risk of *warfarin skin necrosis* (initially dec. C and S before procoags -> high risk of thrombosis esp. in skin)
what is ADA deficiency SCID
ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products build up of these is toxic to lymphocytes
What are the paraneoplastic syndromes small cell carcinoma can cause?
ADH, ACTH, or Eaton-Lambert syndrome
Autoimmune polyendocrine syndrome
AIRE (autoimmune regulator enzyme) mutation so cannot produce enough self antigens in thymus to see if self reactive T cells are present -> problem with central tolerance triad includes: hypoparathyroid, adrenal failure, chronic candida infxn
What disease is common in Down syndrome arising after 5 years of age?
ALL
Hallmarks of cancer
ALL CANCERS display these d/t darwinian pressure: evasion of apoptosis growth signal self sufficiency (oncogenes) anti-growth signal insensitivity (inactive tumor suppressors) Warburg effect (glucose metabolism from mitochondria to glycolysis) sustained angiogenesis limitless replicative potential tissue evasion metastasis *all accelerated by genomic instability and cancer-promoting inflammation*
2 main types of acute leukemia
ALL and AML (each has subtypes)
ionizing radiation
AML, CML, papillary carcinoma of thyroid generates OH free radical
Diagnosing and complications of Sjogren?
ANA and anti RNP (SSA/Ro or SSB/La) lymphocytic sialadenitis on lip biopsy (minor salivary gland) addition diagnostic criterion complications: inc. risk of B-cell (marginal) lymphoma -> unilateral enlargement of the parotid gland late in disease
pancreatitis treatment
Aggressive IV fluids and early enteral nutrition will save pancreatitis patient's life
Causes of reactivation of mycobacterium tuberculosis
Aging; AIDS is common cause
When does aortic stenosis present?
Over 60 (wear and tear)
"Machine like murmur" at birth
PDA
What is infantile coarctation of the aorta associated with?
PDA
astrocytoma associated oncogene
PDGFB (overexpression, autocrine loop)
What are crackles
PE finding, hearing edema in interstitium of the lung
What keeps ductus arteriosus open?
PGE
What can squamous cell carcinoma produce, and what does it cause?
PTHrP, causing hypercalcemia
"Monday Disease"
PTs who have industrial exposure to nitrates develop tolerance to the nitrates throughout the week, lose it on the weekend, and return Monday symptomatic
PV vs reactive polycythemia
PV = *EPO low, SaO2 nl* Reactive polycythemia d/t high altitude or lung dz -> *SaO2 low, EPO high* or Renal Cell carcinoma causing *high EPO and thus reactive polycythemia, SaO2 nl*
Hypoxemia definition
PaO2 < 60
Osler nodes
Painful, associated with endocarditis
What are PiZZ homozygotes at risk for?
Panacinar emphysema and cirrhosis
Where is alpha-1 antitrypsin deficiency emphysema most severe in the lung?
Panacinar emphysema that is most severe in lower lobes
Out of all the Jones criteria, which is the only one that does not resolve?
Pancarditis
Name a complication of ASD
Paradoxial emboli (emboli that arise from the right side of the body and cross over to the left side of the heart, resulting in brain or distal extremity lodging)
What is the most common cause of Laryngotracheobronchitis (croup)
Parainfluenza virus
What is eaton-lambert syndrome?
Paraneoplastic syndrome often present with small cell carcinoma in which there are Abs against presynaptic Ca channels that can result in muscle weakness
Failure of the ductus arteriosus to close
Patent ductus arteriosus
microangiopathic hemolytic anemia
Pathogenesis: RBCs are damaged when passing through obstructed or narrowed vessel lumina. Seen in DIC, TTP/HUS, SLE, HELLP syndrome, and malignant hypertension. Schistocytes (eg, "helmet cells") are seen on peripheral blood smear due to mechanical destruction (schisto = to split) of RBCs. HELLP Syndrome - Hemolysis, Elevated Liver enzymes, Low Platelets. A manifestation of severe preeclampsia. Blood smear shows schistocytes. Can lead to hepatic subcapsular hematomas>rupture>severe hypotension. Treatment is immediate delivery
CT-guided biopsy
Pathological diagnosis of lung nodule Quite invasive: risk of pneumothorax (upto 30%) Better used for peripheral lesions
Why do you include ventilation with positive end expiratory pressure in treatment of ARDS?
Patients have collapse of air sacs due to increased surface tension, so leaving some pressure in the lungs at the end of expiration will help keep the sacs open to be filled on inhalation
niacin (B3) deficiency
Pellagra: Triad of D's: Diarrhea Dermatitis Dementia Death Very distinct dermatitis only in sun-exposed areas
Tension pneumothorax is caused by?
Penetrating chest wall injury
What is Dressler Syndrome?
Pericarditis that arises 6-8 weeks after infarction due to autoimmune production of antibodies against your own pericardium
What surrounds the epicardium?
Pericardium
Causes of Right to Left Shunts
Presents as *blue babies*; know the "*5 T's*": Truncus arteriosus Transposition Tricuspid atresia Tetralogy of Fallot TAPVR
adenocarcinoma is often positive for what immunohistochemical marker?
TTF1
Name the two types of pneumothorax
1. Spontaneous 2. Tension
Name the four phases of lobar pneumonia
1. Congestion 2. Red hepatization 3. Gray hepatization 4. Resolution
What are two complications of fibrinolysis/angioplasty?
1. Contraction band necrosis caused by Ca re-entering dead tissue 2. Reperfusion injury caused by oxygen re-entering tissue and generating free radicals
How do you treat transposition of great vessels
1. Creation of a shunt to allow the two circuits to mix after birth 2. PGE to keep PDA open
Three clinical features of hypertrophic cardiomyopathy
1. Decreased CO 2. Sudden death due to ventricular arrhythmias 3. Syncope with exercise
Clinical features of sarcoidosis
1. Dyspnea or cough (cough most common presentation) 2. Elevated serum ACE 3. Hypercalcemia
Clinical features of emphysema
1. Dyspnea, cough (with minimal sputum) 2. Prolonged expiration with pursed lips 3. Weight loss 4. Barrel chest 5. Hypoxemia and cor pulmonale as complications
Name three clinical features of aortic regurgitation
1. Early blowing diastolic murmur 2. Hyperdynamic circulation 3. Bounding pulses, pulsating nail beds, head bobbing
Two Unique Findings of Cardiac Tamponade
1. Electrical alternans (due to "swinging" movement of heart in effusion fluid) 2. Pulsus paradoxus: *decrease in amplitude of systolic BP by > 10 mm Hg during inspiration*
Hemoglobin modifications: carboxyhemoglobin
CO binds competitively to Hb and with 200x grater affinity than O2. Treat with 100% oxygen and hyperbaric oxygen.
most common mutation in CLL
13q- also has best prognosis
5 year survival of lung cancer, and why so low?
15%; presents late due to no effective screenings
high risk HPV?
16, 18, 31, 33 squamous cell carcinoma of vulva, vagina, anus, cervix, adenocarcinoma of cervix
AV Blocks
1st= prolonged PR 2nd T1= Weinkebach 2nd T2= dropped beats w/o length change 3rd= atria + ventricles independent of each other
When should a hyperbaric chamber be used?
CO poisoning gas gangrene decompression sickness arterial gas emboli
MAP=
CO x TPR or 2/3 diastolic pressure + 1/3 systolic pressure -*MAP approximates afterload*
Fick Principle
CO= rate of O2 consumption/ (arterial O2 content - venous O2 content)
How do you make diagnosis of pneumonia (3 ways)
CXR, sputum gram stain and culture, blood cultures
indications for plasma transfusions
Coagulation factor replacement in patients with a deficiency of multiple clotting factors Decreased production (liver disease) IF actively bleeding or planned procedure Consumption (DIC) Dilution (massive blood loss, repeated plasma exchange procedures) Replacement of a single coagulation factor when individual factor concentrates are not available Replacement fluid during therapeutic plasma exchange for thrombotic thrombocytopenic purpura (TTP)—contains ADAMTS13 Factor VII has a short in vivo half life (3-5 hours), so transfuse right before planned procedures (not the day before!)
Black lung
Coal worker's pneumoconioses that is caused by carbon dust that leads to diffuse fibrosis (and shrunken lung)
Pneumoconioses
Coal workers' pneumoconiosis, silicosis, and asbestosis leads to increased risk of cor pulmonale and Caplan syndrome (rheumatoid arthritis and pneumoconioses with intrapulmonary nodules)
Where does coarcation lie in infantile coarctation of the aorta in relation to ductus arteriosus and aortic arch?
Coarctation is distal to aortic arch but proximal to ductus arteriosus
What does imaging of lung cancer often reveal?
Coin lesion, or solitary nodule
Clinical features of bronchiectasis
Cough, dyspnea, foul-smelling sputum
JAK2 mutation associated with
PV, ET, and myelofibrosis (50% of myelofibrosis cases)
Cause of aortic regurgitation that is not aortic root dilation
Valve damage (due to infectious endocarditis)
Treatment of mitral valve prolapse
Valve replacement
later onset of asthma indicates
non-atopic asthma Especially in females, likely due to hormonal changes
Club (clara) Cells
nonciliated; low-columnar/cuboidal with secretory granules. Secrete component of surfactant; degrade toxins; act as reserve cells
drugs that can cause gynecomastia?
spironolactone, digoxin, cimetidine, alcohol, ketoconazole (some drugs cause awesome knockers)
cavitation is pathognomonic for which type of lung cancer?
squamous cell
hypoxia and causes
-low oxygen delivery to tissue ischemia, hypoxemia, decreased o2 carrying capacity
what two pathologies are characteristic of fibrinoid necrosis?
-malignant htn and vasculitis
Hand-schuller-christian dz
-malignant langerhans cells scalp rash, lytic skull defects, Diabetes insipidus, exophtahlmos in child
angiosarcoma. what is the liver form associated with?
-malignant proliferation of *endothelial cells* -- highly aggressive common sites = *skin, breast, liver* Liver angiosarcoma associated with exposure to *PVC*, arsenic, Thorotrast
Multiple myeloma
-malignant proliferation of plasma cells in bone marrow -*most common primary bone malignancy* - metastatic is most common bone CA -*high IL-6 possible* - stimulate plasma cell growth and Ig production clinical features: +bone pain with hypercalcemia* - activate RANK receptor on clasts -> bone destruction (lytic punchout lesions on xray, esp in *skull and vertebrae*) *elevated serum protein* - neoplastic plasma cells make *alot of Ig* (M spike on serum protein electrophoresis) -usually IgG or IgA *increased infxn risk* - lack antigenic diversity 2/2 monoclonoal ab *Rouleaux formation of RBCs* - high serum protein decreases charge b/w RBCs *Primary AL amyloidosis* - free light chains circulate and deposit in tissue *Proteinuria* - light chain excreted as *Bence Jones protein* -> can lead to kidney failure (myeloma kidney)
HbS/B-thal heterozygote
-may or may not see mild to moderate sickle cell dz depending on B-globin production
Buerger disease
-medium vessel necrotizing vasculitis involving digits -presents with *ulceration, gangrene, and autoamputations of fingers and toes* - Raynaud also -*High assoc. with Heavy Smoking* tx: smoking cessation
Kawasaki disease
-medium vessel vasculitis normally affecting Asian children <4yo presents with nonspecific sx *fever, conjunctivitis, erythematous rash on palms/soles, cervical LAD* *Coronary artery involvement common -> thrombosis and MI or aneurysm* (most common cause of cardiac dz in children) Tx: aspirin! or IVIG - dz self limitied
Besides epithelium, what other tissues can undergo metaplasia classically?
-mesenchymal (connective) tissues ex. myositis ossificans where CT in muscle -> bone during healing after trauma
Lymphocyte depleted HL
-most aggressive HL, seen in elderly or HIV pt
causes of increased ESR?
-most anemias, -infections, -inflammation (giant cell arteritis, polymyalgia rheumatica) -cancer -renal dz (ESRD or nephrotic synd) -pregnancy
nodular sclerosis HL
-most common type (70%) of HL -enlargening cervical or mediastinal LN in a young adult, usually female LN have bands of sclerosis w/ RS cells in *lacunae*
B-ALL
-most common type of ALL TdT+ with CD10, CD19, CD20 -excellent responose to chemo -> prophylaxis for scrotum and CSF (chemo can't pass into, so inject) -t(12;21) = *good prognosis* - seen in kids -t(9;22) = *poor prognosis* - in adults (Ph+ ALL)
Tricuspid Atresia
Absence of tricuspid valve and hypoplastic RV; requires both ASD and VSD for viability
How do bronchioles stay open?
Air sacs on bronchioles have elastic recoil, which pull open walls
Lung volumes tidal volume (TV)
Air that moves into lung with each quiet inspiration, typically 500 ml
What is the main risk of acute epiglottitis?
Airway obstruction (medical emergency!)
What are the risk factors (2 main, 3rd rare) for laryngeal carcinoma?
Alcohol and tobacco; rarely arises from laryngeal papilloma
Pancarditis in acute rheumatic fever can involves...
All layers of the heart (endocarditis, myocarditis, pericarditis)
How does the allergen that incites asthma affect mast cells- what does it do to surface IgE?
Allergen crosslinks surface IgE on mast cells
Subtype of rhinitis
Allergic rhinitis (Type I Hypersensitivity)
What is the most common stimulator for asthma?
Allergic stimuli (atopic asthma)
alloimmunization
Alloantibodies=antibodies against foreign rbc antigens that the patient doesn't express Clinically significant=the antibody is capable of causing hemolytic transfusion reactions, hemolytic disease of the fetus and newborn, and/or decreased survival of transfused red blood cells
What is a rare cause of emphysema?
Alpha-1 Anti Trypsin Deficiency
what inactivates plasmin?
Alpha-2 Antiplasmin
lymphatic pleural effusion
Also known as chylothorax. due to thoracic duct injury from trauma or malignancy. Milky-appearing fluid; increased TAGs
What is the main defense mechanism at the very bottom of the lung?
Alveolar macrophage (eat things that escape mucus defense of upper lung and get to bottom of lung)
What causes normal inflammation in the lungs?
Alveolar macrophages eating "bad" particles that have made it to the bottom of the lung
What induces fibrosis in pneumoconioses?
Alveolar macrophages, which engulf the foreign particles and induce fibrosis
A-a gradient
Alveolar-arterial gradient A-a gradient = PAO2 - PaO2 Difference between the partial pressure of O2 in the (A) alveoli and that in the (a) artery ARE THE LUNGS TRANSFERRING OXYGEN PROPERLY? Useful information about the state of GAS EXCHANGE (V/Q imbalance or diffusion impairment) see Goljan noes for more specific equation clinical usefulness: Confirm hypoventilation as the cause of hypoxemia Unmask a problem with gas exchange in a hyperventilating patient.
What is damaged in acute respiratory distress syndrome?
Alveolar-capillary interface (diffuse alveolar damage within the air sac)
what inhibits tPA?
Aminocaproic acid
Causes of restrictive cardiomyopathy
Amyloidosis, sarcoidosis, endocardial fibroelastosis, Loeffler syndrome
Blood Complication due to Endocarditis
Anemia of chronic disease
Benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue
Angiofibroma
BMI cutoff for anorexia vs. bulimia
Anorexics usually below 17.5 BMI, bulimics usually at or above 17.5
What does mild exposure to carbon (pollution) result in, and where?
Anthracosis (collection of carbon-laden macrophages) in lungs and hilar lymph nodes
mepolizumab and reslizumab
Anti-IL5 Reduces exacerbations Possible increase in FEV1 Possible decrease in steroids use
omalizumab
Anti-IgE To reduce/discontinue treatment with oral corticosteroids in severe asthma. In patients with severe allergic symptoms of asthma, rhinitis, dermatitis and high circulating IgE levels
What neutralizes proteases released by normal inflammation in the lung?
Anti-proteases, typically alpha-1 antitrypsin
B cell activation
Antigen binding by surface IgM or IgD, results in maturation to IgM or IgD secreting plasma cells. No second signal needed if enough antigen present to activate and cross link Ig's or antigen activates TLR. Alternate Pathway B-cell presents antigen to Th2 T-cell via MHC II -- CD40 receptor on B cell binds CD40L on Th2 as 2nd signal -- Th2 secretes IL-4 and IL-5 to mediate isotype switching, hypermutation and plasma cell maturation.
Dextromethorphan
Antitussive (antagonizes NMDA glutamate receptors). Synthetic codeine analog. Mild opioid effect when used in excess. Naloxone can be given for overdose. May cause serotonin syndrome if combined with other serotonergic agents
Transfusion Associated Circulatory Overload (TACO)
Any blood product except cryoprecipitate (low volume) Usually occurs at extremes of age Symptoms include respiratory distress, new/increasing O2 requirement, peripheral edema Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, chest xray, BNP, diuretics Patient may receive additional transfusions, but consider slowing rate of infusion and giving additional diuretics common commonly occurs when transfusion is given too quickly
transfusion-associated circulatory/volume overload (TACO)
Any blood product except cryoprecipitate (low volume) and usually occurs at extremes of age Clinical Presentation - Respiratory distress, new/increasing O2 requirement, peripheral edema Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, chest xray, BNP, diuretics Patient may receive additional transfusions, but consider slowing rate of infusion and giving diuretics
causes of inc DLCO
Anything that increases transit (carriers or flow) Polycythemia Alveolar hemorrhage Left to right shunt Early CHF Asthma - acutely air trapped regions result in increased alveolo-capillary surface area and diffusion across membrane Exercise - b/c increase in capillary size
What is adult coarctation of the aorta associated with?
Bicuspid aortic valve
Is vocal cord nodule usually bilateral or unilater?
Bilateral
How do you confirm diagnosis of lung cancer?
Biopsy of lesion (coin lesion)
Montelukast, zafilukast
Block leukotriene receptors (CystLT1). Especially good for aspirin induced asthma,
anticholinergics for asthma
Block vagal pathways Block reflex bronchconstriction Inhaled Ipratropium/Tiotropium Slower onset of action (30 min)
BODE index
Body mass index (BMI) Airflow Obstruction (FEV1) Dyspnea (mMRC dyspnea score) Exercise capacity (6MWT) Better prognosticator than FEV1 alone and can be used to assess therapeutic response
pulmonary hypertension drugs Endothelin receptor antagonists
Bosentan; ambtisentan Competitively antagonize endothelin-1 receptors to decrease pulmonary vascular resistance. Hepatotoxic (monitor LFTs)
Water-hammer pulse
Bounding pulses commonly seen in aortic regurgitation
What are the main two mediators of pain?
Bradykinin and PGE2
What sensitizes the pleura of the lung causing pleuritic chest pain?
Bradykinin and PGE2 (mediators of pain!!)
What are the most common metastasis to the lung?
Breast and colon
Name common mets to the heart
Breast and lung carcinoma, melanoma, lymphoma
PTEN (negatively regulates PI3k/AKT pathway) tumor suppressor gene associated with what cancer
Breast, prostate, and endometrial cancer cowden syndrome
Benign tumor composed of lung tissue and cartilage that is often calcified on imaging
Bronchial hamartoma
Asthma
Bronchial hyperresponsiveness causes reversible bronchoconstriction. Smooth muscle hypertrophy, Curschmann spirals (shed epithelium forms whorled mucus plugs), and charcot-leyden crystals (eosinophilic, hexagonal, double-pointed, needle-like crystals formed from breakdown of eosinophils in sputum) Can be triggered by viral URI, allergens, stress. Test with methacholine challenge. Findings: cough, wheezing, tachypnea, dyspnea, hypoxemia, decreased inspiratory/expiratory ratio, pulsus paradoxus, mucus plugging
What is the difference between bronchus and bronchioles?
Bronchioles do not have cartilage to help them stay open, but bronchus do
Lung cancer characterized by columnar cells that grow along preexisting bronchioles and alveoli
Bronchioloalveolar carcinoma
Asthma drugs
Bronchoconstriction is mediated by inflammatory processes and parasympathetic tone; therapy is directed at both of these pathways
What does histamine and leukotrines C4, D4, and E4 cause when they are released by mast cells in asthmatic?
Bronchoconstriction, inflammation, edema (early phase reaction)
Pneumonia characterized by scattered patchy conoslidation centered around bronchioles
Bronchopneumonia
Pneumonia that is often multifocal and bilateral
Bronchopneumonia
4 myeloproliferative disorders
CML, polycythemia vera, essential thrombocythemia, myelofibrosis
Atypical pneumonia with posttransplant immunosuppressive therapy
CMV
How do metastasis to the lung appear on imaging?
Cannon ball nodules
Capillary Resistance
Capillaries have highest total cross-sectional area and lowest flow velocity
transudate
Capillary permeability to protein is normal Conditions associated LV dysfunction Ascites due to cirrhosis Hypoproteinemia Renal Failure No further work up is necessary for a diagnosis of transudate Treat the underlying cause
What paraneoplastic syndrome can carcinoid tumor sometimes cause?
Carcinoid syndrome
Lung cancer defined by well differentiated neuroendocrine cells that are chromogranin positive
Carcinoid tumor
What causes laryngeal papilloma?
HPV 6 and 11 (associated with koilocytic change in biopsy)
Common cause of secondary pneumonia and pneumonia superimposed on COPD (COPD exacerbation)
Haemophilus influenzae
Characteristic features of ARDS on pathology
Hyaline membranes
Tiny regions of TB all over lung
Miliary TB
What can secondary TB lead to?
Miliary TB or tuberculous bronchopneumonia
Who is at risk for berylliosis?
Miners and workers in aerospace industry
What does supplemental O2 do in MI treatment?
Minimizes ischemia
What valve is most involved in endocarditis in acute rheumatic fever
Mitral (aortic is next most common)
What valve is most commonly involved in chronic rheumatic heart disease/
Mitral (second most involves aortic)
Complications of dilated cardiomyopathy
Mitral and tricuspid valve regurgitation (valves stretch) and arrhythmia
Where are vegetations in nonbacterial thrombotic endocarditis, and what do they cause as a result of their location
Mitral valve along lines of closure; result in mitral regurgitation
What does mitral regurgitation usually arise as a complication of? Also name some other causes
Mitral valve prolapse Other causes: LV dilation (in left sided CHF), infective endocarditis, acute rheumatic heart disease, papillary muscle rupture after MI
hypersensitivity pneumonitis
Mixed III/IV hypersensitivity reaction to environmental antigen leading to dyspnea, cough, chest tightness, headache. Often seen in farmers and those exposed to birds.
IgM vs. IgG Ab's involved in alloimmunization
Most IgM antibodies against red blood cell antigens are naturally occurring (carbohydrate antigens): ABO antibodies, Anti-M Most IgG antibodies are acquired through exposure to foreign antigens from transfusion or pregnancy (protein antigens): Rh blood group system is most immunogenic (D, C/c, E/c) followed by Kell blood group system
What is the cause of most congenital heart defects?
Most are sporadic
Atrial Myxomas
Most common 1° cardiac tumor in adults; 90% occur in the atria (mostly left atrium); associated w/ multiple syncopal episodes due to obstruction -May have *"plopping" sound on ausculation
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Most common enzymatic disorder of RBCs. Causes extravascular and intravascular hemolysis (mostly intravascular). X-linked recessive. Defect in G6PD glutathione RBC susceptibility to oxidant stress. Hemolytic anemia following oxidant stress (eg, sulfa drugs, antimalarials, infections, fava beans). NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides. NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents (eg, fava beans, sulfonamides, primaquine, antituberculosis drugs). Infection (most common cause) can also precipitate hemolysis; inflammatory response produces free radicals that diffuse into RBCs, causing oxidative damage. Findings: Back pain, hemoglobinuria a few days after oxidant stress. Labs: blood smear shows RBCs with Heinz bodies (denatured Hemoglobin precipitates within RBCs due to oxidative stress) and bite cells (result from the phagocytic removal of Heinz bodies by splenic macrophages). "Stress makes me eat bites of fava beans with Heinz ketchup."
What is the most common type of ASD, and what is another type
Most common is ostium secundum type Another type is ostium primum, which is associated with Down's Syndrome
What is the most common cause of restrictive lung disease and a secondary cause?
Most common: interstitial diseases of the lung Another cause: chest wall abnormalities (obesity)
Septic Transfusion Reaction/Bacterial Contamination of the Product
Most commonly platelets (room temp storage), then RBCs (fridge), uncommonly plasma (freezer) Caused by bacteria (+/- endotoxin) in stored units Gram positives in platelets and Gram negatives in rbcs Generally abrupt and severe onset of symptoms including fever/chills, hypotension/shock, nausea/vomiting, respiratory distress Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, start broad spectrum antibiotics, supportive care No contraindication to additional transfusion, incidence reduced with Psoralen/UV treated platelets
Rhabdomyomas
Most frequent 1° cardiac tumor in children; shows *hamartomatous growths*
inhaled corticosteroids
Most potent and effective anti-inflammatory Reduce acute and chronic inflammation Fewer symptoms Improved pulmonary function Decreased airway hyperresponsiveness Reduced exacerbation frequency and severity Reduced airway remodeling Reduced mortality Inhaled route reduces side effects
fine needle aspiration of node
Most useful when searching for recurrence of cancer False-positive results are uncommon, but there is a substantial false-negative rate due to sampling error and difficulty recognizing well-differentiated lymphomas Don't cut out a piece of tissue, take out individual cells (architecture not maintained, sampling error is an issue) These issues make it difficult to identify which type of lymphoma, but you can likely still tell if it's a lymphoma
oral corticosteroids
Mostly used to treat acute exacerbations Maintenance therapy needed in ~1% Patients should be maintained on the lowest possible dose Side-effects are a significant problem Monitor bone density and perform regular eye check up for cataracts
What glands hypertrophy in chronic bronchitis?
Mucinous glands (bronchial)
Expectorants: n-acetylcysteine
Mucolytic (CF) - disrupts disulfide bonds Antidote for acetaminophen overdose
What does atrial fibrillation increase risk for, and how?
Mural thrombus; wall isn't moving as well, resulting in stasis and increasing risk for thrombosis
rhabdomyolysis
Muscle cell death which can be triggered by numerous etiologies. The common factor is the disruption of the sarcolemma (muscle cell membrane) and release of intracellular myocyte components. Most often, cell injury is caused by depletion in ATP Also caused by membrane injury, muscle cell hypoxia, electrolyte disturbances, and generation of ROS Substances which leak into the plasma include potassium, phosphate, CK, urate, and myoglobin Massive release of myoglobin after muscle cell injury exceeds haptoglobin binding capacity and may precipitate in the glomerular filtrate This may cause renal tubular obstruction, nephrotoxicity, intrarenal vasoconstriction, and acute kidney injury Clinical Manifestations: Myalgias; Weakness; Red to brown urine due to myoglobinuria
When can you get pericarditis after MI?
Must be transmural MI
Amiodarone Considerations
Must check PFTs, LFTs, and TFTs when using; also keep in mind it has multiple Class effects
What causes liver cirrhosis in emphysema due to alpha-1 antitrypsin deficiency?
Mutant A1AT misfolded protein accumulates in the ER of hepatocytes, causing liver damage
Common cause of atypical pneumonia that affecst young adults (military recruits or those in dorms); complicatiosn include autoimmune hemolytic anemia (IgM against I antigen on RBCS causes cold hemolytic anemia) and erythema multiforme
Mycoplasma pneumoniae
Name six causes of interstitial (atypical) pneumonia
Mycoplasma pneumoniae Chlamydia pneumoniae Respriatory syncytial virus (RSV) Cytomegalovirus Influenza virus Coxiella burnetti
markers in APL
Myeloid antigen expression, CD34, HLA-DR usually absent or weak; CD56 positive
What is the most common cause of death during the acute phase of acute rheumatic fever
Myocarditis
Heart problem characterized by a lymphocytic infiltrate in the myocardium that results in chest pain, arrhythmia with sudden death, or heart failure
Myocarditis (caused by Coxsackie A or B)
Why is a tumor of mesenchyme most common in adults?
Myocytes are permanent cells!
Hypertrophic cardiomyopathy biopsy
Myofiber hypertrophy with disarray
What does a biopsy of hypertrophic cardiomyopathy show?
Myofiber hypertrophy with disarray
What is vocal cord nodule composed of histologically?
Myxoid (degenerative) connective tissue
What causes mitral valve prolapse
Myxoid degeneration of the valve (accumulation of ground substance) makes it floppy
Benign mesenchymal tumor of the heart with a gelatinous appearance and abundant ground substance on histology
Myxoma
Tumor that usually forms pedunculated mass in left atrium and causes syncope due to obstruction of mitral valve
Myxoma
What is the most common primary cardiac tumor in adult?
Myxoma
Neuroblastoma assoc. oncogene
N-MYC (transcription factor) amplification
Mitral stenosis
Narrowing of mitral valve orifice
Coarctation of the aorta definition
Narrowing of the aorta
Protrusion of edematous, inflamed mucosa
Nasal polyp
What is the consequence of repeated bouts of rhinitis?
Nasal polyp
Biopsy of pleomorphic keratin-positive epithelial cells in a background of lymphocytes is typical of what disease?
Nasopharyngeal carcinoma
Malignant tumor of nasopharyngeal epithelium
Nasopharyngeal carcinoma
What is the cause of bronchiectasis?
Necrotizing inflammation with damage to airway walls
CML vs leukemoid reaction
Negative LAP stain (leukemoid have + stain) increased basophils (not in leukemoid rxn) t(9;22) present
Tetralogy of Fallot on x-ray finding
Boot shaped heart
MEN2A, MEN 2B and sporadic medullary carcinoma of thyroid associ. oncogene
RET - neural growth factor receptor point mutation
Eisenmenger Syndrome
RV compensation for L->R shunts causes hypertrophy of RV -> L-R shunt becomes R-L due to increased RV contractility -Also shows *polycythemia and clubbing*
What happens to the RV in tricuspid atresia?
RV is hypoplastic
How is radon, which is a risk of lung cancer apart from cigarette smoke, formed
Radioactive decay of uranium, which is present in the soil
What is responsible for most of the public's exposure to ionizing radiation?
Radon
What is the second most frequent cause of lung carcinoma in US?
Radon
Sydenham's chorea
Rapid involuntary muscle movements
What causes secondary TB?
Reactivation of mycobacterium tuberculosis
What nerves can be involved in lung cancer?
Recurrent laryngeal (hoarseness) Phrenic (diaphragmatic paralysis)
Chronic thromboembolic PH
Recurrent microthrombi leads to decreased cross-sectional area of pulmonary vascular
How does meothelioma present?
Recurrent pleural effusions, dyspnea, chest pain
What is the gross change during the granulation phase 1-3 weeks after MI?
Red border emerging as granulation tissue enters from edge of infarct
restrictive lung disease
Reduced lung volumes, TLC by definition TLC<80% The flow volume loop often maintains a nearly normal shape with reduced size curve shifted to right
Mitral regurgitation
Reflux of blood from left ventricle into left atrium during systole
How does lobar pneumonia heal?
Regeneration of tissue via type II pneumocytes
Reid Index; what is it and how does it change in chronic bronchitis?
Reid index: thickness of mucinous glands relative to the thickness of the entire wall Increases from under 40% to 50% in chronic bronchitis
How does Interstitial (atypical) pneumonia present?
Relatively mild upper respiratory symptoms, with minimal sputum and low fever (hence atypical presentation)
What is the immediate response of mast cells to IgE linkage by allergen?
Release of preformed histamine granules Generation of leukotrienes C4, D4, E4
What does inflammation of the lung as caused by alveolar macrophages lead to?
Release of proteases by neutrophils and macrophages
Hallmark of dead cell
Removal of nucleus (sign of coagulative necrosis)
Uvulopalatopharyngoplasty
Removing tonsils and uvula, part of posterior rim of soft palate Scarring, sore throat, dysphagia, velopharyngeal reflux (liquid coming out of nose when drinking) Only in certain patients (poor success rate, significant morbidity) previously the main OSA treatment before CPAP
What leads to chronic rheumatic heart disease?
Repeat exposure to group A beta hemolytic streptococci
What causes nasal polyps (3 things)?
Repeated rhinitis, CF, aspirin-intolerant asthma
Contraction Band Necrosis
Reperfusion of irreversibly damaged myocytes leads to Ca2+ influx -> hypercontraction of myofibrils
obstructive sleep apnea (OSA)
Repetitive cessation (apnea), reduction (hypopnea) of airflow, or RERA's during sleep despite the presence of respiratory efforts Due to partial or complete upper airway occlusion during sleep RERA- respiratory effort related arousal
How do you treat aortic stenosis?
Replacement of the valve once complications have occurred
How centroblasts become centrocytes
Rescued centroblasts become centrocytes by retrieving Ag from FDC and bind to CD4 cells. Activated CD4+ T cells produce IL4 and IL10 which induces clonal expansion and isotype switching of these high-affinity centrocytes.
Lung volumes funcional residual capacity
Residual volume + expiratory reserve volume volume of gas after normal expiration
How do you treat hypersensitivity pneumonitis?
Resolves with removal of exposure
Respiratory zone
Respiratory bronchioles, alveolar ducts, and alveoli. Participates in gas exchange.
Winter's formula
Respiratory compensation for metabolic acidosis Expected PaCO₂ = 1.5 (HCO₃) + 8 +/- 2 If the CO₂ is above this expected number, you have a respiratory acidosis, likewise if CO2 is below this number you have a respiratory alkalosis (aspirin toxicity)
Neonatal respiratory distress syndrome definition
Respiratory distress in neonates due to inadequate surfactant levels
What lines the nasal mucosa?
Respiratory epithelium
What is Kartagener syndrome associated with? 3 things
Sinusitis, infertility, situs inversus
What determines the age of presentation of VSD?
Size of defect
What do beta blockers do in MI treatment?
Slow heart rate, decrease oxygen demand, decrease arrythmia risk
Class I Antiarrhythmics Primary MOA
Slow or block conduction speed thru *decreasing the slope of phase 0 polarization*
What are the two categories of lung carcinoma?
Small cell and non-small cell
Poorly differentiated small cell lung cancer that arises from neuroendocrine cells
Small cell carcinoma
What percentage of lung cancer is small cell, and what percentage is non-small cell
Small cell: 15% Non small cell: 85%
Name the two neuroendocrine lung cancers and what differentiates them
Small cell: poorly differentiated Carcinoid: well differentiated Both chromogranin positive
U Waves
Seen in hypokalemia and bradycardia
Superior vena cava syndrome
Seen in lung cancer that obstructs the SVC and causes distended head and neck veins with edema, blue discoloration of arms and face
Ghon complex
Seen in primary TB; area of fibrosis/calcification indicating primary TB; typically subpleural
What are the two results of valvular lesions?
Stenosis or regurgitation
Treatment for sarcoidosis
Steroids; will often resolve without treatment
What is the most common cause of community acquired pneumonia
Streptococcus pneumoniae
Burkitt lymphoma assoc. oncogene
c-MYC (transcription factor) t(8;14) involving IgH c-MYC on ch 8 IgH ch 14
ANP and BNP Work via _____
cGMP (as do other vasodilators!); BMP has longer half-life
3 microscopic patterns of chronic lymphadenitis
follicular hyerplasia, paracortical, sinus histiocytosis
Sturge-Weber syndrome (encephalotrigeminal angiomatosis)
genetic defect: congenital, noninherited (sporadic) developmental problem of *neural crest derivatives* d/t *somatic mosaicism for activating mutation in one copy of GNAQ gene* patho: affects small blood vessels -> port wine stain face (on upper/lower eyelid esp.) features: ipsilateral leptomeningeal angioma -> seizures/epilepsy; intelectual disability, episcleral hemangioma -> increased IOP -> early onset glaucoma Screen w/ CT/MRI for brain lesions *STURGE*= Sporadic, port wine Stain, Tram track calcifications, Unilateral; Retardation, Glaucoma, GNAQ gene, Epilepsy
Niemann-Pick Disease Type C
genetic defect: defect in NPC1 or NPC2 -> leads to defective transport of cholesterol from lysosomes to cytoplasm inheritance: AR Features: can present as hydrops fetalis/still birth, neonatal hepatitis, or *most commonly chronic form with progressive neurologic damage (ataxia, dystonia, dyarthria) presenting in childhood*
Hepatic type GSD - von Gierke dz (type 1)
genetic defect: deficiency in Glucose-6-Phosphatase inheritance: AR Features: hepatomegaly, FTT, stunted growth, hypoglycemia d/t glucose mobilization failure
Hunter syndrome (a type of mucopolysaccharidoses)
genetic defect: deficiency of lysosomal enzyme a-1-iduronidase -> dermtan, heparan, kertan, chondroitin build up in lysosome inheritance: X linked recessive (only MPS with this inheritance) Features: mild developmental delay, gargoylism, airway obstruction, HSM, *aggressive behavior* Hunters see clearly and aggressively aim for the X
Niemann-Pick type A and B
genetic defect: lysosomal accumulation of sphingomyelin d/t *deficiency of sphingomyelinase* inheritance: AR Features: *type A*: HSM, FTT, vomiting, fever, severe mental deterioration and death by 3yo; *Type B:* organomegaly but no CNS involvement common in Ashkenazic Jews type B is paternally imprinted on Chr 11 No man Picks his nose with is Sphinger
generalized glycogenosis - Pompe dz (type 2)
genetic defect: lysosomal glucosidase deficiency inheritance: AR Features: mild HSM, massive cardiomegaly, cardiorespiratory failure w/in 2 yrs
myopathic type GSD - McArdle dz (type 5)
genetic defect: muscle phosphorylase inheritance: AR Features: painful cramps assoc. w/ strenuous exercise; myoglobinuria in 50% cases; onset in adulthood; exercise fails to raise lactate in blood
Gaucher dz
genetic defect: mutations in gene encoding *glucocerebrosidase* -> cannot cleave glucose from ceramide -> glucocerebroside accumulates in phagocytes after ingesting cell membranes of senescent cells inheritance: AR Features: type 1 most common: macrophages throughout body except brain accumulate -> splenic and skeletal involvement -> *pancytopenia or thrombocytopenia 2/2 hypersplenism* along with *pathologic fx and bone pain from expansion of marrow space* type 2 and 3 affect CNS -> *Most common lysosomal storage disorder* Tx: recombinant enzymes -> nl life expectancy; or HSC transplant can cure
What causes increase in allergies (type 1 HSR)?
genetic susceptibility (atopy pt have more IgE and IL-4 producing Th2 cells) hygeine hypothesis, dietary fat hypothesis, vitamin D hypothesis, food processing hypothesis
Polycythemia as a paraneoplastic syndrome
happens from production of EPO (high hematocrit) assoc. w/ Pheo, renal cell carcinoma, HCC, hemangioblastoma, leiomyoma
wound healing basics
healing begins when inflammation begins combination of regeneration and repair
What are the master regulators of the immune response?
helper T cells
CD34+
hematopoietic stem cell All CD34 positive cells are blasts But not all blasts are CD34 positive
what role does Rb have in cell cycle?
holds E2F transcription factor, which is necessary for transition to S phase from G1 E2F is released when this is phosphorylated by cyclinD/CDK4 complex without this protein, free E2F would roam and allow cell cycle in uncontrolled growth
what paraneoplastic syndromes are associated with small cell lung cancer
hypercalcemia (PTHrP or high calcitriol) cushing (high ACTH) SIADH (high ADH)
ventilatory respiratory failure
hypercapnic respiratory failure Alveolar hypoventilation (dec RR): Decreased respiratory drive - stroke, CNS disease, neuromuscular weakness, obesity, drugs Increased mechanical load- pleural effusion Excessive dead space (inc RR) - COPD, PE, pulmonary fibrosis Increased CO2 production E.g. Sepsis/SIRS, major surgery, overfeeding, anxiety/pain Symptoms: Somnolence Prognosis based on baseline function A-a gradient will be normal If high CO2 production is the cause of hypercapnia, pt is usually tachypneic
what cancers are assoc. w/ trousseau and NBTE paraneoplastic syndromes
lung, pancreatic, and gastric adenocarcinomas
Heart sounds for mitral stenosis
opening snap followed by diastolic rumble
Dilation of all four chambers of the heart
Dilated cardiomyopathy
What is nasopharyngeal carcinoma associated with?
EBV
DDX of caseating granulomas
Fungal or TB
Where are granulomas in sarcoidosis most commonly located?
Hilar lymph nodes and lung, leading to restrictive lung disease
what is an example of dysplasia?
Cervical intraepithelial neoplasia (CIN) in which dysplasia of cervix has occurred and is precursor of cervical cancer
What lymph nodes does nasopharyngeal carcinoma typically involve/present with?
Cervical lymph nodes
atrial fibrillation
Chaotic and erratic baseline with no discrete P waves in between irregularly spaced QRS complexes. Irregularly irregular heartbeat. Most common risk factors include hypertension and coronary artery disease (CAD). Can lead to thromboembolic events, particularly stroke. Causes: Hypertension, hyperthyroidism, CAD, rheumatic heart/valve disease, binge drinking, and heart failure; Isolated atrial amyloidosis of ANP (deposited in the atrium w/normal aging and increases the risk of atrial fibrillation); Sleep Apnea; Anything that inc Atrial Pressure (eg, hypertension/mitral stenosis) Treatment includes anticoagulation, rate control, rhythm control, and/or cardioversion. Absent a wave on Jugular Venous Pulse.
What is allergic rhinitis characterized by?
Characterized by inflammatory infiltrate with eosinophils
Horner syndrome in lung cancer- what causes it, and what are symptoms
Compression of sympathetic chain, leading to ptosis, miosis (pinpoint pupil), anhidrosis (no sweating)
Is it complete or incomplete occlusion of a coronary artery in MI?
Complete
Compliance
Compliance: change in lung volume for a given change in pressure. Compliance decreases in pulmonary fibrosis, pneumonia, pulmonary edema. Compliance increases in emphysema and normal aging.
What is the main complication of MI within the first 24 hours, the microscopic change, and the gross change?
Complication: Arrhythmia Microscopic: coagulative necrosis Gross: dark
What is PDA associated with?
Congenital rubella
What causes the clinical features of R CHF?
Congestion
Heart fails to pump appropriately
Congestive heart failure
What does chronic ischemic heart disease lead to?
Congestive heart failure
What is the interstitium of the lung?
Connective tissue of the alveolar air sacs
Who is at risk for asbestosis
Construction workers, plumbers, shipyard workers
Anitschkow cells
Contained in Aschoff bodies in myocarditis of acute rheumatic fever
seeding of body cavities with cancer is characteristic of what?
ovarian carcinoma, which involves peritoneum (omental caking)
What is severity of emphysema due to alpha-1 antitrypsin based on?
Degree of A1AT deficiency
What determines the degree of shunting in Tetralogy of Fallot
Degree of stenosis in RV outflow tract
Endocardial fibroelastosis
Dense layer of fibrosis and elastic tissue in the endocardium; cause of restrictive cardiomyopathy in children
Where are coxiella spores present?
Deposited on cattle by ticks; present in cattle placentas
What is amyloidosis?
Deposition of a misfolded protein that can be localized or systemic; if systemic, can be primary (AL deposited due to plasma cell issue) or secondary (AA deposited due to chronic inflammation and overproduction of SAA which becomes AA)
What normally connects squamous cells?
Desmosomes
Emphysema definition
Destruction of alveolar air sacs
What causes late complication of hypoxemia in emphysema?
Destruction of capillaries in alveolar air sac
PH due to lung diseases or hypoxia
Destruction of lung parenchyma (COPD), hypoxemic vasoconstriction (obstructive sleep apnea, living in high altitude)
characteristics of RV
thin walled, compliant better suited for high volumes than high pressure preload tolerant, afterload vulnerable
causes of dec DLCO
things that block conduction pus, water (edema), emphysema, interstitial lung disease, pulmonary hypertension, PE, anemia, MI
Expectorants: Guafenesin
thins respiratory secretions does not suppress cough reflex
red infarction
this is if blood re-enters: 1. loosely organized tissue *testes and pulmonary*
fibrinoid necrosis
this is necrotic damage to a blood vessel wall in which leaking of proteins (including fibrin) enter vessel wall resulting in bright pink staining of the wall microscopically
HUS (hemolytic uremic syndrome)
this occurs secondary to endothelial damage by drugs or infxn classically associated with *E coli O157:H7* dysentery in children (from exposure to undercooked beef) *E coli verotoxin* damages endothelial cells -> platelet microthrombi form
What is the XIST gene responsible for?
this produces a long noncoding RNA which is kept in the nucleus and coats most of one of the X chromosomes and silences it = X inactivation
C1 inhibitor deficiency
this results in hereditary angioedema -characterized by edema of skin (esp. periorbital) and mucosal surfaces C1 is not regulated and can activate complement leading to acute inflammation
how is G6PD enzyme isoform used to distinguish clonality?
this technique only usefully in females several isoforms exist and found on X chromosome hyperplasia should have relative 1:1 ratio d/t polyclonality neoplasia is monoclonal so one isoform will predominate
how do arachidonic acid metabolites mediate acute inflammation?
AA chopped off PM via PLA2 -> AA into prostaglandins (COX) or leukotreines (5-lipoxygenase)
universal donor for plasma
AB plasma is the universal donor (given in trauma cases when there's no time to match donor, but A often given b/c there isn't enough AB plasma available- rarest blood type)
Causes of Dilated Cardiomyopathy
ABCCCD Alcohol abuse wet Beriberi Cocaine Chagas (which causes myocarditis) Coxsackie B Doxorubicin (chemotherapy)
CML and some types of ALL assoc. oncogene
ABL (tyrosine kinase) t(9;22) with BCR (Philadelphia chr)
What is the main treatment for left sided CHF?
ACE-inhibitor
How are genetic mutations causing dilated cardiomyopathy passed down?
AD
How are type I and II pneumocytes damaged in ARDS?
Activation of neutrophils induce protease and free-radical mediated damage of Type I and II pneumocytes
How do unmeasured electrolytes affect anion gap?
Actual gap is actually about 0, but there are many electrolytes that we don't measure
acute vs. chronic cor pulmonale
Acute Cor Pulmonale occurs after a sudden and severe stimulus resulting in a sudden increase in pulmonary resistance with RV dilatation and failure but no RV hypertrophy e.g massive pulmonary embolus, ARDS Chronic Cor pulmonale more slowly evolving and slowly progressive pulmonary hypertension that leads to RV dilation and hypertrophy (RV adapting to inc afterload)
What is another name for Staphylococcus aureus endocarditis?
Acute endocarditis
eosinophilic lung diseases
Acute eosinophilic pneumonia (usually in smokers who stop and start) Chronic eosinophilic pneumonia Eosinophilic granulomatosis with Polyangiitis (Churg-Strauss) Hyper eosinophilic syndromes (clonal disorder of eosinophils) ABPA- allergic rxn to aspergillus Ag's- usually in CF or asthmatics Parasitic infections in the lung Most common cause of eosinophilic lung disease, especially pneumonia
Inflammation of the epiglottis
Acute epiglottitis (medical emergency)
What always follow necrosis?
Acute inflammation (neutrophils and macrophages)
What is the most common etiology of sudden cardiac death?
Acute ischemia
Name the most common cause and three other less common causes of sudden cardiac death
Acute ischemia (most common) Less common: mitral valve prolapse, cardiomyopathy, cocaine abuse
What do acute and chronic rheumatic valve disease cause in mitral valve?
Acute: creates mitral regurgitation Chronic: creates mitral stenosis
Lung cancer defined histologically by glands or mucin
Adenocarcinoma
What is the most common congenital heart defect?
VSD
Measurement of MIP and MEP
Values <50% of predicted are considered low Normal values: MIP -60 cm H20 and MEP +120 cmH2O Reduction in MIP ~ diaphragm muscle weakness Reduction in both ~ global muscle weakness
Nodule that arises on the true vocal cord
Vocal cord nodule (singer's nodule)
Alveolar ventilation (VA)
Volume of gas per unit time that reaches the alveoli VA = (VT-VD)(RR)
What does mitral regurgitation cause?
Volume overload and left-sided heart failure
When does pneumonia occur?
When normal defenses are impaired
cryoprecipitate
When plasma is being thawed, the slushy part is removed and this is cryo Generally used to treat fibrinogen deficiency Cold insoluble portion of fresh frozen plasma Stored at -18 °C for up to 1 year Thaw at 30-37 °C, expires 6 hours after thawing Volume: 5 to 15 mL Each unit contains a minimum of 150 mg fibrinogen and 80 IU of factor VIII Also contains vWF, factor XIII, and fibronectin Standard adult dose is 10 units One bag of cryo raises fibrinogen level by 7 mg/dL in 70 kg adult One bag of cryo contains the equivalent fibrinogen of ½ bag of FFP no cross-matching required
When does patent ductus arteriosus close?
When there is good oxygenation of the blood
when would platelets in PAS solution be given?
for patients who have allergic rxns to the plasma in platelet solution
What does secondary TB look like in lungs?
forms cavitary foci of caseous necrosis
milk production outisde of lactation?
galactorrhea -not a sign of breast cancer
Bernard-Soulier syndrome
genetic GPIB deficiency; platelet ADHESION impaired, blood smear shows thrombocytopenia with enlarged platelets. enlarged because they are slightly more immature
hemophila B (christmas dz)
genetic factor 9 deficiency presents same as hemophila A
Milrinone
*PDE-3 inhibitor* leading to c*A*MP accumulation -> Ca2+ influx -> increased ionotropy and chronotropy + vasodilation -Used for *acute decompensated HF*
What is the most common cause of secondary htn? what are 2 high yield causes of this? how common is secondary htn?
*Renal artery stenosis* most common cause - Atherosclerosis (elderly men) and Fibromuscular dysplasia (young females) 5% of htn is secondary
Myocardial Action Potential
*Seen in bundle of His and Purkinje fibers*: Phase 0 (rapid upstoke and depolarization): Na+ channels open Phase 1 (initial repolarization): inactivation of Na+ channels w/ opening of K+ channels Phase 2 (plateau): Ca2+ influx -> Ca2+ release from SR -> contraction Phase 3 (rapid repolarization): massive K+ efflux due to opening of voltage gated K+ channels and closure of Ca2+ channels Phase 4: restores resting potential thru K+ channels
EKG Findings in Prinzmetal Angina
*Transient ST segment elevation*
Fat embolus
2/2 bone fx (esp. long bones) and soft tissue trauma *->* typically associated with pulmonary vessels *->* dyspnea and petechiae on skin overlying chest
cancer epidemiology
2nd leading cause of death for children and adults most common cancers in adults: 1. breast/prostate 2. lung 3. colorectal most common cancer by mortality: 1. lung, 2. breast/prostate 3. colorectal
multiple myeloma non-secretors
3% have no detectable M protein on both serum and urine IFE (nonsecretory) Need bone marrow biopsy
What is a bronchial hamartoma?
Benign tumor composed of lung tissue and cartilage that is often calcified on imaging
Takotsubo Cardiomyopathy
"broken heart syndrome"; ventricular apical ballooning due to increased sympathetic stimulation
Splinter hemorrhages
Associated with endocarditis
Homan sign
Dorsiflexion of foot leads to calf pain indicates DVT
SV=
EDV - ESV
what are the normal types of hgb?
HbF (a2y2) HbA (a2b2) HbA2 (a2d2)
Normal Reid Index
Less than 40%
Myocardial infarction definition
Necrosis of cardiac myocytes
Atrial Repolarization on ECG
Not visualized due to it being masked by the QRS complex
Tender lesions on fingers or toes associated with endocarditis
Osler nodes
What is another name for lecithin that is the major component of surfactant?
Phosphatidylcholine
lymphocytic rich HL
best prognosis of all HL
chromogranin is marker for what type of tissue
neuroendocrine cells (small cell carcinoma of lung and carcinoid tumors)
primary myelofibrosis
panmyelosis and fibrosis Megakaryocytic proliferation and atypia with reticulin or collagen fibrosis
upper airway obstruction
trachea and higher
How do you treat small cell lung cancer versus non small cell lung cancer?
Small cell: chemo, not usually surgical resection Non-small-cell: surgical resection, not chemo
How does PDA present at birth?
"machine like murmur"
what characteristics do thromboses have?
-lines of zahn (layers of platelet/fibrin and then RBCs) -attachment to vessel wall
What is tricuspid atresia associated with?
ASD, causing a right to left shunt
mantle cell lymphoma assoc. oncogene
CCND1 (cyclin D1) t(11;14) involving IgH
Infectious Cause of PDA
Congenital rubella
What is ACE level in sarcoidosis
Elevated
Prognosis of bronchioloalveolar carcinoma?
Excellent
MHCII deficiency
SCID cause; necessary for CD4 activation and cytokine production
what does protein C do?
inactivates factors 5 and 8
plasmapheresis (plasma exchange)
removes autoantibodies and provides functional ADAMTS13
treatment for lobular carcinoma in situ?
tamoxifen with close follow up -low risk of progression to invasive carcinoma
Tx for HTN in Pregnancy
"Hypertensive Mom's Love Nifedipine" 1. Hydralazine 2. Methyldopa 3. Labetalol 4. Nifedipine -Most other HTN meds are teratogenic!
What are the 7 steps of neutrophil arrival and function?
#1 - margination (vasodilation slows BF in post cap venule so cells move from center of flow to periphery d/t dec. laminar flow) #2 - rolling (selectin speed bumps upregulated via endothelial cells - P selectin from WP bodies via histamine - E selectin induced via TNF and IL-1) selectins bind Sialyl lewis X on leukocytes resulting in rolling #3 adhesion (CAMs (I and V) upregulated on endothelium via TNF and IL-1) and integrins upregulated on leukocytes via C5a and LTB4 -> firm adhesion between endothelium and leukocytes #4 transmigration and chemotaxis via *PECAM-1* (postcap venules toward IL8, C5a, LTB4, bacterial products) #5 phagocytosis (consumption of pathogens/necrotic tissue; enhanced by IgG and C3b opsonization) - also, pseudopods from leukocytes form phagosomes internalized and join lysosomes #6 destruction of phagocytosed material (o2 dependent killing=most effective mech) HOCL oxidative burst in phagolysosomes destroy microbes # 7 resolution (neuts undergo apoptosis and disappear 24 hr after resolution and inflammatory stimulus ends) omega 3 FA derivatives used for cessation of leukocyte influx
Percentage of expected/ideal body weight
% EBW = Weightpt / Expected weight for ht & gender x 100% Expected wt for ht Females = 100 pounds + 5 pounds/inch above 5 ft Males = 106 pounds + 6 pounds/inch above 5 ft
Name the three ways coxiella burnetii is different from most rickettsiae
(1) Causes pneumonia (2) does not require arthropod vector for transmission (because it survives as heat resistant endospores) (3) does not produce a skin rash
most common cytogenetic abnormality in ALL
(9,22)
short-acting beta-2 agonists
(albuterol, salbutamol) Rapid onset of action, duration 4 to 6 h Most effective on "as-needed basis" Relieves symptoms but do not control inflammation
long-acting beta-2 agonists
(salmeterol, formoterol) Not indicated for relief of acute asthma symptoms Long-term prevention of symptoms/nocturnal symptoms Prevent exercise-induced bronchoconstriction ICS + LABA very effective Should NOT be used as monotherapy
respiratory disturbance index
(total of all respiratory events)/hours of sleep Mild OSA: RDI - 5 to 14.9 Moderate OSA: RDI - 15 to 30 Severe OSA: RDI - more than 30
Brugada Syndrome
*AD* disorder most common in *Asian males*; ECG pattern of *pseudo-RBBB* and *ST elevations in V1-V3* -Increased risk of ventricular tachyarrhythmias and SCD -Prevent SCD with *implantable cardioverter-defibrillator (ICD)*
Most Common Sites of Atherosclerosis
*Abdominal aorta* > coronary artery > popliteal artery > carotid artery
Histologic Findings in Rheumatic Heart Disease
*Aschoff bodies* (granulomas w/ giant cells) and *Anitschkow cells* (enlarged macrophages w/ ovoid/wavy rod-like nuclei) in the *myocardium* -Explains why MYOCARDITIS IS THE MOST COMMON CAUSE OF DEATH IN ACUTE RHD
Neutropenia causes? tx?
*Drug toxicity* (chemo or alkylating agents) - damage stem cells especially affects neuts *Severe infection* (gram - sepsis) - neuts out of blood, into tissue Tx: GM-CSF or G-CSF
Signaling Molecule for Heart Looping
*Dynein*; hence if dynein is dysfunctional you get Kartagener syndrome -> dextrocardia
Four Carcinomas Route Hematogenously
*F*ollicular thyroid carcinoma, *C*horiocarcinoma, *R*enal cell carcinoma, *H*epatocellular Carcinoma
Electrolyte Disturbances Causing Torsades du Pointes
*Hypomagnemia, hypokalemia*; tx w/ *Mg Sulfate*
Hydralazine
*Increases cGMP* -> arteriolar smooth muscle *relaxation*; also causes vasodilation -> *afterload reduction* -Admin w/ beta-blocker to prevent *reflex tachycardia* -Used for emergency severe HTN reduction
Leber hereditary optic neuropathy
*Mitochondrial disorder* creates a defective enzyme responsible for converting oxygen, fats, and simple sugars to energy. Characterized by vision loss. subacute bilateral vision loss in teens/young adults, 90% male
JVP
*a* wave= *a*trial contraction; absent in A fib! *c* wave= RV *c*ontraction x decent *v* wave= increase RA pressure due to *v*illing (filling) against closed tricuspid valve *y* descent= RA empt*y*ing in RV; absent in cardiac tamponade, enhanced in constrictive pericarditis
protoporphyrin synthesis
*aminolevulinic acid synthetase (ALAS)* converts succinyl CoA to aminolevulinic acid w/ *vit. B6 cofactor* - RLS last step occurs in mitochondria of RBC where Fe+2 is added to protoporphyrin *lead* - inhibits ALAD and ferrochelatase enzymes (denature them) *etoh* - poison to mitochondria *vit. B6* needed as cofactor (*isoniazid* most common cause of this def.)
Tx for Hypertensive Emergency
1. Clevidipine 2. Fenoldopam (D1 receptor agonist -> vasodilation) 3. Labetalol 4. Nicardipine 5. Nitroprusside (short acting cCMP agonist)
in SCD, extensive sickling leads to vaso-occlusion, presenting how?
*dactylitis* - swollen hands and feet 2/2 infarcts of bones (classic to see in 6 month old AA baby) *autosplenectomy* - spleen shrinks and fibrosed -> *low antibody production intravascularly* -> increased risk of infxn of *encapsulated organisms* (S pna, H. influenzae) *most common cause of death in children so vaccinate for H. influenzae* *Acute chest syndrome* - vasoocclusion in chest microcirculation (CP, SOB, lung infiltrates) - often assoc. with *pna* (inflammation->vasodilation->slow blood flow->deoxygenated RBCs->sickling) *most common cause of death in adults* *pain crisis* vasoocclusion of bones and organs *renal papillary necrosis* (vasocclusion causing hematuria and proteinuria)
virchow triad
*disruption of blood flow* (turbulence or stasis - laminar flow disrupted) *endothelial cell damage* (bacterial endotoxins, radiation injury, metabolic abn. like homocystinuria, toxins from cigs) *hypercoaguable state*
Fragile X Tremor/Ataxia
*genetic defect*: CGG premutations in FMR1 gene -> forms toxic gain of function mRNA d/t having more CGGs -> accumulate in nucleus and form intracellular inclusions *features*: premature ovarian failure (<40yo) in female and progressive neurodegenerative syndrome in males in 50s (intention tremor and cerebellar ataxia)
Lymphopenia causes?
*immunodeficiency* (HIV, DiGeorge syndrome) *high cortisol state* (steroids or Cushings) - induce apoptosis of lymphs *autoimmune destruction* (SLE) *Whole body radiation* - lymphs *most sensitive cell to radiation* indicating earliest changes s/p radiation
aortic dissection causes
*most common is htn (older adults) -> hyaline arteriolosclerosis to vasovasorum -> atrophy of aortic media also assoc. w inherited defects in CT (younger adults) -> marfans or EDS cause weakness of CT in media
name 6 disease processes that are associated with causing DIC.
*obstetric complications* (placental thromboplastin released into mother blood) *sepsis*, esp. N meningitidis and E coli (endotoxins from bacteria + cytokines induce endothelial cell -> TF released) *adenocarcinoma* (mucin activates coagulation) *acute promyelocytic leukemia* (primary granules activate coag) *rattlesnake bite* (venom activates coag) *trauma*
other important features of tumor development
*telomerase* -> cell immortality *angiogenesis* (via FGF and VEGF produced by tumor) *avoiding immune surveillance* (downregulating MHC1)
Pulmonary arterial hypertension (PAH)
- Idiopathic PAH - heritable (often BMPR2 gene inactivation which normally inhibits vascular smooth muscle proliferation) - poor prognosis - Includes pulmonary venous occlusive disease and persistent PH of newborn. - Other causes include drugs, CT disease, HIV infection, portal hypertension, congenital heart disease, schistosomiasis
what are causes of polycythemia?
- Relative, Appropriate absolute, Inappropriate absolute, PV
vit b12 labs
- low serum b12 -high serum homocysteine (inc. risk of thrombosis) - high methylmalonic acid
Polyarteritis Nodosa
- medium vessel Necrotizing vasculitis involving multiorgans - *lungs spared* -presents in young adult as *hypertension (renal involvement), abdominal pain w/ melena (mesenteric artery involvement), neuro sx, and skin lesions.* associated with *HBsAg* (type 3 HSR) -Lesions varying stages are present. *Early=transmural inflammation with fibrinoid necrosis* -> healing leads to fibrosis and *string of pearls* appearance. tx: corticosteroids + cyclophosphamide -> *fatal if not tx*
Neutrophilic leukocytosis causes?
-*Bacterial infxn or tissue necrosis* - marginated pool released and bone marrow increased production of immature cells (left shift) which have *decreased Fc receptors (CD16)* -*high cortisol state* - impairs leukocyte adhesion -> margination of neuts
iron deficient anemia causes.
-*dietary lack or blood loss* (infants-human milk low iron; children-poor diet; *PUD* in males, *menorrhagia or preg* in females; elderly *colon polyps/carcinoma* and *hookworm* in developing world) other causes *malnutrition, malabsorption, and gastrectomy* - acids help iron absorption maintaining Fe+2 state (better absorbed)
Fragile X Syndrome (Martin-Bell Syndrome)
-*most common cause of inherited intellectual disability and 2nd most genetically associated (behind Down)* -X linked Dominant -Women who carry long expansion can produce oocytes with CGG expansion during oogenesis -> pass onto son or daughter -*Sx: 90% get post pubertal macroorchidism*, long face, large everted ears, autism, hyperextensible joints, *mitral prolapse* -*Patho: Trinucleotide repeats CGG (230 repeats) in FMR1 gene -> hypermethylation -> transcription silencing -> affects brain and testes most to shuttle mRNAs which regulate synaptic function to suppress protein synthesis ie abnormal protein synthesis* -*dx: PCR to detect repeats or Karyotype looking for "break in X"
Factor V Leiden
-*mutated form of factor 5 which lacks cleavage so resistant to degradation by protein C* (G -> A point mutation; Arg506Gln near cleavage site) -most common hypercoaguability in caucasians -DVTs, cerebral vein thromboses, recurrent pregnancy loss
3 Ps of parietal cells?
-*p*roton pump -highly *P*ink cytoplasm -*p*ernicious anemia
Lymphocytic leukocytosis causes?
-*viral infections*- T lymphs undergo hyperplasia in response to virally infected cells -*Bordetella pertussis infection*- produces *lymphocytosis-promoting factor*, blocking circulating lymphocytes from leaving the blood to enter the LN
name 2 causes of high homocysteine levels.
-*vitamin b12 or folate deficiency* (methyl group is transferred to homocysteine from cobalamin to make methionine) cobalamin gets methyl group from methyl THF. -*cystathionine beta synthase deficiency*(convert homocysteine to cystathionine -> leads to thrombosis, mental retardation, lens dislocation, long slender fingers)
AD
-AB amyloid (from B amyloid precursor protein) deposits in brain forming amyloid plaques gene for B-APP present on Chr 21 -> most down syndrome pt develop this dz by age 40
anemia of chronic dz
-anemia 2/2 prolonged inflammation with APR (hepcidin) being continually produced (SLE, RA, cancer, CKD) initially normocytic but can become microcytic *most common anemia of hospitalized pt* labs: *high ferritin*, low TIBC, low serum iron, low %sat, high FEP tx underlying cause - *exogenous EPO* useful esp. in cancer pt or CKD
Tuberous Sclerosis
-AD - 100% penetrant -proteins affected normally forms complex that inhibits mTOR kinase - not found in pt (*Hamartin chr9 and Tuberin protein, chr16* - tumor suppressor genes) -Sx: *Cortical tubers, Mental retardation, seizures, cysts (liver, kidney), Hamartomas, Benign neoplasms (renal angiomyolipomas), Rhabdomyomas, Subependymal astrocytoma* -Tx:*symptom based, surgical resection of cortical tubers -> dec. seizure activity, possible mTOR inhibtors
Eosinophilia causes?
-Allergic rxn (type 1 HSR) -parasitic infections -*Hodgkin lymphoma* (Reed Sternberg cells produce IL-5) - common finding
Waldenstrom's macroglobulinemia
-B cell lymphoma w/ monoclonal IgM production features: -*generalized LAD* -*M spike* -*visual or neuro defects* - d/t IgM causing serum hyperviscosity -*Bleeding* - viscous serum = defective platelet aggregation tx acute complications w/ *plasmapheresis to remove IgM
B-thal major
-Bo/Bo which is most severe form of disease and presents w/ severe anemia a few months post birth (HbF temporarily protective) -alpha chains precipitate and damage RBC (extrvascular hemolysis) -*Massive erythroid hyperplasia* -> expansion of hematopoiesis in skull (crew cut) and facial bones (chipmunk facies) + *extramedullary hematopoiesis and HSM* + risk of *aplastic crisis w/ parvovirus B19 of erythroid precursors* tx: chronic transfusions -> complication *hemochromatosis* electrophoresis: HbA2 HbF and little or no HbA
Digoxin ADEs
-Cholinergic: nausea, vomiting, diarrhea, *blurry yellow vision (think van Gogh)*, arrhythmias, AV block -Can lead to *hyperkalemia*, which indicates poor prognosis -Factors predisposing to toxicity: renal failure (excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na+/K+ ATPase), drugs that displace digoxin from tissue-binding sites, and decrease clearance (eg, verapamil, amiodarone, quinidine)
von Hippel-Lindau disease
-Deletion of VHL gene on Chr3 -AD -pVHL ubiquinates hypoxia inducible factor -> numerous tumors since VHL not there -sx=*HARP* -> Hemangioblastomas of retina, brain stem, cerebellum, spine; Angiomatosis of skin, mucosa organs; bilateral Renal cell carcinomas; Pheochromocytomas -Tx: *Sx based w/ surveillance of possible sx*
infectious mononucleosis cause and CD8+ response?
-EBV infection causing lymphocytic leukocytosis of CD8+ cells; CMV can cause too -EBV transmitted via kissing -Infects oropharynx (pharyngitis), liver (hepatitis w/ inc. LFTs), B cells CD8+ cause generalized LAD d/t T cell hyperplasia in *LN paracortex* - *Splenomegaly* d/t hyperplasia of T cells in *PALS* - High WBC w/ *reactive CD8+ cells in blood
Basophilia causes?
-HY association = *CML*
Name the four restrictive diseases
-Idiopathic pulmonary fibrosis -Pneumoconioses -Sarcoidosis -Hypersensitivity pneumonitis
familial amyloid cardiomyopathy
-Mutated serum transthyretin deposits in heart leading to constrictive cardiomyopathy 5% AA pt carry mutation
Burkitt Lymphoma
-Neoplastic proliferation of intermediate-sized B cells (CD20+) - *associated with EBV* -Classical presentation is *extranodal mass in a child or young adult* two forms: *african form* affects jaw; *sporadic* affects abdomen *t(8;14) most common, c-myc moves to IgH on chr 14* c-myc is oncogene -*high mitotic index and "starry sky" appearance microscopy* (tingible body macros are white)
Adult T-Cell Leukemia/Lymphoma (ATLL)
-Neoplastic proliferation of mature CD4+ T cells -Associated with *HTLV-1* - seen in Japan and Caribbean most commonly and *IV drug abuse* -Features: *cutaneous lesions, generalized LAD with HSM, and lytic (punched out) bone lesions w/ hypercalcemia*
malaria
-RBC rupture d/t life cycle of plasmodium -> cyclic fevers with hemolytic anemia spleen also consumes some RBCs -> mild extravascular hemolysis w/ splenomegaly
What is nystagmus and what causes it?
-Rhythmic oscillations of eyes from vestibular or optokinetic stimulation -some causes: *medial cerebellum lesion, MLF lesion, mamillary body lesion, vertigo (BPPV), PCP, phenytoin*
Takayasu arteritis
-Same dz as Temporal arteritis but affects *aortic arch at branch points* -presents in pt *<50 yo usually young asian females* -> have *visual and neurologic sx w/ weak or absent pulse in upper extremity* *ESR elevated* Tx: corticosteroids
T-ALL
-TdT+ with CD2 through CD8 -*Do not have CD10* -blood and marrow have high lymphoblasts -very responsive to tx -Presents in *Teenagers* as mediastinal *thymic* mass (aka acute lymphoblastic lymphoma d/t mass) - *presents as SVC-like syndrome* -can spread to *CNS or testes*
What and how do you grade a tumor?
-This is a way to express level of differentiation in a malignancy: based on architecutral pattern, nuclear/cellular pleomorphism, and mitotic rate grades 1-4 (4 is undifferentiated)
SLE epidemiology
-Women of childbearing age -often affected during puberty -African American or Hispanic decent estrogen may play role
complications of atherosclerosis
-account for >50% of dz in western countries Stenosis of medium vessels -> PVD, Angina, Ischemic bowel dz (mesenteric arteries) Plaque rupture w/ thrombosis -> MI and stroke (MCA) plaque rupture w/ embolization = atherosclerotic emobolus (*cholesterol crystals w/in embolus*) weakening of vessel wall -> aneurysm
Coagulation factor inhibitor
-acquired antibody against a coagulation factor resulting in impaired function (most common factor 8) clinical and lab findings similar to hemophilia A HY: PTT *does not* correct when you mix pt blood with normal plasma d/t inhibitor - in hemophilia A, PTT does correct
direct coombs test
-add anti-IgG/complement antibodies to pt blood -> if agglutination occurs, confirms RBC coated with IgG or complement *most important test for IHA*
how does B12 get into body?
-amylase liberate B12 from proteins it is bound to in saliva -> then bound to *R binder* -*pancreatic proteases* in duodenum detach B12 from R binder -> binds *intrinsic factor* from gastric parietal cells -*IF-B12* complex absorbed in *ileum*
Macroangiopathic hemolytic anemia
-hemolytic anemia 2/2 mechanical destruction of RBCs -causes: prosthetic heart valves and aortic stenosis schistocytes present
iron deficient anemia labs, clinical features, tx.
-anemia, koilonychia (spoon shaped nails), and pica -increased RDW, micro, hypo RBCs, low ferritin, high TIBC, low serum iron and %saturation *initially normocytic, then to microcytic* HY: *high free erythrocyte protoporphyrin* tx: give iron - also, do not forget to figure out cause!
Small vessel vasculitis affects what vessels? what are 4 high yield dz?
-arterioles, capillaries, venules -Wegener Granulomatosis, Microscopic Polyangiitis, Churg-Strauss Syndrome, and Henoch-Schonlein Purpura
What can vitamin A deficiency result in?
-associated with night blindness and deficient immune system -metaplasia can result from this b/c needed to differentiate specialized epithelium of conjunctiva -> thin squamous conjunctiva can become stratified keratinizing squamous epithelium (keratomalacia)
name 3 common cuases of endothelial cell damage.
-atherosclerosis -vasculitis -high levels of homocysteine
mixed CT dz
-autoimmune dz causing tissue damage with mixed features of SLE, scleroderma, and polymyositis HY: speckled ANA with serum ab to *U1 RNP*
Abdominal aortic aneurysm
-ballon dilation of abd aorta - usually *below renal arteries, above aortic bifurcation* -2/2 atherosclerosis - seen in *male smokers >60yo w/ htn* atherosclerosis *increases diffusion barrier to media -> atrophy and weakness of vessel wall* -pulsatile mass in abdomen that grows w/ time -*Rupture=major complication* esp when >5cm diameter -> *Triad of hypotension, pulsatile mass, flank pain* can compress local struc. (ureters) and thrombosis
Thoracic aneurysm
-ballon dilation of thoracic aorta -d/t *weakness of aortic wall* *classically seen in tertiary syphilis* -> endarteritis of vasovasorum -> luminal narrowing -> decreased flow -> atrophy of vessel wall -> causes *tree bark appearance to aorta* Major complication: *dilation of aortic valve root -> aortic valve insufficiency* others include compression in mediastinum or thrombosis
Eosinophilic granuloma
-benign proliferation of langerhans cells *in bone* pathologic fx in adolescent - skin not involved biopsy = langerhan cells w/ mixed inflammatory cells including *numerous eosinophils*
E cadherin tumor suppressor
-binds to B catenin and keeps it near cell membrane if cell damage, cadherin damaged lets B catenin go and can cause proliferation for repair mutation of this can lead to metastasis as well as cancers (colone, breast, gastric and other carcinomas)
Monckeberg medial calcific sclerosis
-calcification of media of arteries (muscle), *nonobstructive* -*not clinically significant* - incidental finding on breast mammography or xray
Immune hemolytic anemia
-caused by antibody mediated destruction via IgG or IgM dx w/ *coombs test*: either direct or indirect test
what are the morphologic changes of cells undergoing apoptosis?
-cell shrinks, causing cytoplasm to become more eosinophilic -nucleus condenses and fragments in organized order -apoptotic bodies fall from cells and macrophages remove IT IS NOT FOLLOWED BY INFLAMMATION
how are TLRs mediators in acute inflammation?
-cells of innate immunity have TLRs that bind PAMPs (CD14 a coreceptor of TLR4 on macrophages recognize LPS on gram- bacteria) TLR activation -> increased NF-kB -> many immune mediator genes activated TLRs on adaptive immune cells so play role in chronic too
self tolerance mechanisms
-central tolerance in thymus or bone marrow (apoptosis or in B cells, receptor editing via RAG genes) -peripheral tolerance -> anergy (CD4 bind self antigen w/o 2nd signal) or apoptosis (Fas aka CD95 expressed by T cell if bind but no second signal) Regulatory T cells -> block T cell activation and produce antiinflammatory cytokines (IL10 TGFB) IL10 down regulates MHCII
chronic inflammation basics
-characterized by lymphocytes and plasma cells in tissue (mononuclear infiltrate) delayed but more specific than acute tissue destruction and repair occur simultaneously (causing angiogenesis and fibrosis)
acute inflammation basics
-characterized by presence of *edema and neutrophils* -occurs in response to *infection or tissue necrosis* -immediated response with limited specificity (innate immunity) -peaks in 24 hr at site
Monocytosis causes?
-chronic inflammatory states -malignancy
How are NHLs classified and what are the 6 HY NHLs?
-classified based on: Cell type (B vs T), cell size, pattern of growth, expression of surface markers, cytogenetic translocations -will focus on cell size Small B cells = *follicular lymphoma, mantle cell, marginal, and small lymphocytic lymphoma* (CLL that involve tissue) Intermediate B cells = *Burkitt Lymphoma* Large B cells - *diffuse large B-cell lymphoma*
gangrenous necrosis
-coagulative necrosis resembling mummified tissue characteristic of ischemia LE and ischemia of GI tract -if superimposed infxn = wet
Autosomal recessive
-commonly more severe than dominant disorders -INcreased risk in consanguineous families
X-linked agammaglobulinemia
-complete lack of immunoglobulin d/t disorder B cell maturation (pre and pro B cells cannot mature) mutation of bruton tyrosine kinase (X linked) presentation: after 6 months when mother Ig gone -> bacterial infxn, enterovirus (IgA not in intestines), GIARDIA lamblia (HY) avoid live vaccines (polio)
indirect coombs test
-confirms presence of abx in pt serum -anti-IgG/complement added to pt serum -> agglutination occurs if antibodies are present
physiologic generation of free radicals
-cytochrome C oxidase sends electrons to O2 in mitochondria to make H2O -if partially reduced, can yield O2 -> O2- -> H2O2 -> OH -> H2O
decreased O2-carrying capacity
-d/t Hb loss or dysfunction -anemia (nl PaO2 and SaO2) -CO poisoning (PaO2 normal; SaO2 decreased) -Methemoglobinemia (Fe+3 b/c oxidized)
name the 3 high yield causes of normocytic anemia with predominant *extravascular* hemolysis
-hereditary spherocytosis -Sickle cell dz -hemoglobin C
aplastic anemia
-damage to HSC resulting in pancytopenia (anemia, thrombocytopenia, leukopenia) with *low RC* and *high EPO* causes: *drugs/chemicals* (benzene, antimetabolites, alkylating agents), *viral infxn* (EBV, HIV, hepatitis), autoimmune damage biopsy shows empty fatty marrow tx: cessation of causative drug, supportive care w/ transfusion and marrow stimulating factors (EPO and GMCSF) also possible to use immunosuppression or bone marrow transplant
necrosis
-death of large groups of cells followed by acute inflammation; allows via pathologic process morphology: increased eosinophilia, nuclear changes (pyknosis, karyorrhexis) dead cells can be replaced by *myelin figures* from damaged cell membranes
anemia d/t underproduction basics
-decrasaed production of RBC by bone marrow -low RC etiologies: macro and microcytic anemia, renal failure (low EPO), damage to bone marrow precursor cells
what are the two ways an organ can atrophy?
-decrease # cells via apoptosis -decrease size cell via Ubiquitin-proteosome degradation of cytoskeleton and autophagy of cellular components
hypoplasia
-decrease in cell production during embryogenesis, resulting in a relatively small organ (eg streak ovary in Turner syndrome)
ischemia causes
-decreased arterial perfusion -decreased venous drainage (Budd chiari-thrombosed hepatic vein) -shock aka generalized hypotension -> poor tissue perfusion
alpha-thallasemia
-decreased production of globin chains for hgb d/t *gene deletion* from chromosome 16 (2 genes per = 4 total) one gene deleted = asymptomatic 2 deleted = mild anemia w/ higher RBC count (*cis deletion* is assoc. w/ increased risk of severe thal. in offspring - seen in asians; *trans* seen in AA) 3 deleted: severe anemia; beta chains form tetramers called *HbH which damage RBCs* 4 deleted: hydrops fetalis in utero; *y chains form tetramers called Hb Barts* that damage RBCs
how does chronic granulomatous dz occur, how do you screen, and what does it lead to?
-defect in NADPH oxidase (AR or Xlink) -> poor O2 dependent killing recurrent infxn and granuloma formation of cat + organisms (b/c they can rid their H2O2 to H2O vs cat - which have H2O2 so neuts can use to make HOCL) S. aureus, P. cepacia (HY), Serratia marcescens, Nocardia, Aspergillus, H pylori, Candida, E coli *Cats* *N*eed *PLACESS* to *B*elch their *H*airballs screen via nitroblue tetrazolium test: leukocytes incubated with NBT dye -> turns blue if NADPH oxidase present to convert o2 to o2-; if not, colorless
fanconi anemia
-defective DNA repair mechanism where *homologous end joining* is not working (used to repair double-strand breaks) -causes *megaloblastic anemia*, short stature, inc. incidence of tumors/leukemia, cafe-au-lait spots, and thumb/radial defects
Severe Combined Immunodeficiency (SCID)
-defective cell and humoral mediated immunity causes: cytokine receptor defects, ADA deficiency, MHC class II deficiency susceptible to fungal, viral, bacterial, protozoal infxn along with live vaccines tx: sterile isolation and stem cell transplant
What is fibromuscular dysplasia?
-developmental defect of the blood vessel wall resulting in irregular thickening of large/medium arteries, especially *renal artery*
Vitamin B12 deficiency
-dietary vitamin B12 is complexed to animal-derived proteins less common than folate def. b/c stored in liver for years most common cause: *pernicious anemia* other causes: pancreatic insufficiency (need enzymes to liberate from R binder) and *damage to terminal ileum* (crohn dz or fish tapeworm), *dietary def. rare* clinical features: -megaloblastic anemia, glossitis, *subacute combined degeneration of spinal cord* (2/2 methylmalonic acid buildup b/c b12 needed to turn into succinyl CoA-needed to myelinate neurons) *SCD*-poor proprioception+vibration (post. column) sensation and spastic paresis (Lat. CST)
dysplasia
-disordered cellular growth and structure often referred to as proliferation of precancerous cells theoretically reversible if inciting stress is eliminated - if not, becomes carcinoma (irreversible)
Follicular lymphoma vs reactive follicular hyperplasia
-disruption of nl LN architecture -lack of tingible body macrophages in germinal centers -Bcl2 expression in follicles (shouldn't be here) -Monoclonality (kappa vs lambda light chain 20:1 ratio)
atherosclerosis pathogenesis
-endothelial damage -> endothelial dysfunction -> LDLs leak into intima -> lipids oxidized then macrophages consume via scavenger receptors -> Foam cells -> Fatty streak -> inflammation and healing leads to deposition of ECM and proliferation of SM (PDGF and FGF) -> fibrous plaque
what is the cause of a hypercoaguable state?
-excessive procoagulant proteins or defective anticoagulant proteins (inherited or acquired) presents: recurrent DVTs or DVT at young age
aplasia
-failure of cell production during embryogenesis (eg unilateral renal agenesis)
roles of folate and vit. b12 in DNA synthesis?
-folate circulates in serum as methylTHF - removal of methyl group allows to participate in synthesis of DNA precursors -methyl group transferred to B12 -B12 transfers to homocysteine->making methionine
trinucleotide repeat mutation characteristics
-generally expand with G and C creating an unstable DNA region -at a threshold point, impaired gene function occurs -proclivity to expand depends strongly on sex of transmitting parent 3 mechs which unstable repeats cause dz: *loss of function from transcription silencing* (Fragile X), *toxic gain of function in protein*(huntington or SCAs), or *toxic gain of function via mRNA* (fragile X tremor-ataxia syndrome)
Autophagy of cellular components
-generation of autophagic vacuoles -these will go on to fuse with lysosomes whose enzymes will break down components adaptive response to respond to nutrient deprivation, cell cannibalize itself to survive
cell death
-hallmark is loss of the nucleus occurring via: condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis) occurs either necrosis or apoptosis
irreversible cellular injury
-hallmark is membrane damage (plasma and mitochondrial) -cytosolic enzymes leak out and calcium comes in (activate lysosomal enzymes) -ETC disrupted and cytochrome c into cytosol -> apoptosis
hypoxemia (PaO2<60mmhg, SaO2<90%) causes
-high altitude -hypoventilation - increasing PaCO2 decreases PaO2 -diffusion defect - thicker diffusion barrier (pulm fibrosis) -V/Q mismatch (circulation or ventilation problem)
protein misfolding and apoptosis
-if a cell cannot cause proper folding of protein, can lead to increase in chaperones to help -> if not helpful apoptosis -ex CJD, AD other dz of misfolded proteins: CF, a1-antitrypsin
what roles does Hageman factor (XII) play in acute inflammation?
-if exposed to SEC or tissue collagen, can activate complement, kinin system (kinin cleaves HMWK to bradykinin -> vasodilation, increased vas. perm, pain) severe gram - bacterial infections activate -> DIC
predictive factors: ER and PR positivity? rec located where?
-if positive, increased response to anti-estrogen tx -tamoxifen -both receptors located in nucleus
orotic aciduria
-inability to convert orotic acid to UMP (de novo pyrmidine synthesis pathway) b/c *defective UMP synthase* AR presentation: children FTT, developmental delay, *megaloblastic anemia refractory to folate and B12* orotic acid in urine tx: uridine monophosphate or uridine tracetate to bypass mutated enzyme
Monoclonal gammopathy of undetermined significance (MGUS)
-increased serum protein with M spike on SPEP but other features of multiple myeloma absent -common in elderly (5% of 70yo) - 1% of MGUS pt develop myeloma
how does estrogen induce a hypercoagulable state?
-induces increased production of coag factors -> higher risk of thrombosis
parvovirus B19
-infected progenitor red cells temporarily halts erythropoiesis - *significant anemia in setting of preexisting marrow stress* (sickle cell) tx is supportive (w/ 7-10 days infxn resolves) -decreased correct retic count
delayed wound healing happens in?
-infection (most common cause; S aureus most common) -vitamin C deficiency, copper, or zinc -FB, ischemia, DM, malnutrition
Vasculitis basics
-inflammation of the blood vessel wall -vessel wall has 3 layers: endothelial intima, smooth muscle media, CT adventitia -etiology is typically unknown - mostly non-infectious sx: fever, fatigue, wt loss, myalgias - *sx of organ ischemia* large, medium, and small vessel vasculitides
hereditary spherocytosis
-inherited defect of RBC cytoskeleton-membrane tethering proteins (*ankyrin, spectrin, band 3*) mostly *AD inheritance* -membrane blebs form and lost over time -> disc shaped RBCs d/t loss of membrane (low surface area:volume ratio) aka *spherocytes* -> less able to *migrate through splenic sinusoids* -> consumed by *splenic macrophages* findings: spherocytes, increased RDW, increased MCHC, splenomegaly (hypertrophic macrophages), jaundice, bili gallstone risk risk for aplastic crisis (parvovirus B19) dx: *osmotic fragility test* (shows fragile in hypotonic solution - spherocytes burst) tx: *splenectomy* - Howellojolly bodies on smear after (frags of nuclear material)
Li-Fraumeni syndrome
-inherited mutation in one p53 with second p53 mutated somatically high propensity to develop multiple types of carcinomas and sarcomas and leukemias
Atherosclerosis definition and common arteries
-intimal plaque which obstructs blood flow -contains *necrotic lipid core (cholesterol) w/ fibromuscular cap* often with *dystrophic calcification* 4 most common arteries: *Abdominal aorta > coronary > popliteal > carotid*
Plummer-Vinson syndrome
-iron def. anemia that has *esophageal webs, atrophic glossitis* presents w/ anemia, dysphagia, beefy-red tongue middle aged women most affected - cause is unknown but genetics and nutritional defs. are thought to play role -risk of progressing to esophageal squamous cell carcinoma
Temporal (Giant cell) arteritis
-large vessel granulomatous vasculitis classically involves *branches of carotid artery* -Most common vasculitis in older adults - usually affect females presents: *HA (temporal artery), visual disturbances (ophthalmic artery), Jaw claudication (Facial artery)* -Has joint and muscle pain (polymyalgia rheumatica) and *ESR elevated* -Dx:*biopsy of long segment of vessel d/t segmental inflammation* - should have *giant cells and intimal fibrosis* Tx with *corticosteroids* - tx quickly to avoid *blindness*
IgM mediated IHA
-leads to *intravascular hemolysis (fixes complement - can form MAC*) -> occurs in relatively cold temperature (extremities) -> splenic macrophages consume membrane to form spherocytes too associated with: *M pna and mononucleosis infxn*
What is O2-independent killing?
-less effective method to kill microbes and occurs via enzymes present in leukocyte secondary granules lysozyme in macros; major basic protein in Eosinophils
how does liver failure and large volume transfusion cause abnormal secondary hemostasis?
-liver failure: dec. production of coag factors and dec. activation of vitamin K (followed using PT) -dilution of coag factors
What are the two patterns that AD mutations fall into?
-loss of function in: -ones affecting proteins involved in regulating complex metabolic pathways subject to feedback inhibition (ex LDL receptor) -key structural proteins like collagen or cytoskeletal elements of RBC (Eg spectrin) -or gain of function (huntington)
reversible cellular injury
-low ATP leads to disrupted Na/K pump, Ca pump, and aerobic glycolysis low pH denatures proteins and precipitates DNA -hallmark is cellular swelling 2/2 Na and Ca in cell -> membrane blebbing and RER dissociates from ribosomes leading to decreased protein synthesis Also *fatty change* shoing lipid vacuoles in cytoplasm of cells dependent on fat metabolism
Common variable immunodeficiency
-low Ig d/t B cell or helper T cell defects risk for bacterial, enterovirus (lack of IgA), giardia lamblia in late childhood increased risk of lymphoma and autoimmune dz
Kaposi sarcoma
-low grade malignant proliferation of *endothelial cells* -- associated with HHV-8 which drives tumor -*purple patches, plaques, and nodules on skin*; can occur on visceral organs seen in: -*older eastern european males* - tumor is local, remove surgically -*AIDS* - tumor spreads - tx with *antiretrovirals* -*transplant pt* - tumor spreads - tx by *decreasing immunosuppression*
What is leukocyte adhesion deficiency and describe clinical features?
-most commonly d/t AR defect of *integrins* (CD18 subunit) or decreased *Sialyl-Lewis* (type 2) clinical: delayed separation of umbilical cord (relies on inflammation 2/2 necrosis), increased circulating neutrophils (margination b/c cant hold onto BV, mainly in lung) and recurrent bacterial infxn lacking pus neutrophils cant get to site of inflammation
Arteriolosclerosis
-narrowing of small arterioles - divided into hyalin and hyperplastic types
Fat necrosis
-necrosis of adipose -> white chalky appearance d/t deposition of calcium (fatty acids + calcium = saponification) characteristic of trauma (breast) or lipase (pancreatitis) appears dark blue on HandE around fat cells
Liquefactive necrosis
-necrotic tissue that becomes liquefied 2/2 enzymes destroying cells and protein Brain infarction (microglial cell enzymes), abscess (neutrophil enzymes), pancreatitis (enzymes)
coagulative necrosis
-necrotic tissue that remains firm with cell shape and organ structure presevered via coagulation of proteins -nucleus disappears; increased cytoplasmic binding of eosin -d/t ischemic infarction except in brain (often wedge shaped based on downstream tissue feed)
Dystrophic calcification (a pathologic calcification)
-necrotic tissues act as a nidus for calcification (ABNORMAL tissue) in the setting of NORMAL serum calcium and phosphate associated with: TB and granulomatous dz, fat necrosis, infarcts, crest syndrome, aging heart valves can form psammoma bodies
triple-negative carcinoma of breast
-negative for ER, PR and Her2-neu -higher incidence in African-American females
Acute myeloid leukemia
-neoplastic accumulation of immature myeloid cells (>20%) in bone marrow -*myeloblasts characterized via positive cytoplasmic staining of MPO* -> these aggregates are seen as *Auer Rods* -most commonly arises in older adults (50-60yo) -subclassify based on *cytogenetic abnormalities, lineage of immature myeloid cells, and surface markers* -can arise from pre-existing dysplasia (*myelodysplastic syndromes), esp w/ prior exposure to *alkylating agents or radiotherapy*
Acute lymphoblastic leukemia
-neoplastic accumulation of lymphoblasts (>20%) in bone marrow - *positive nuclear staining for TdT (dna polymerase)* -commonly arises in *children*; assoc. w/ *Downs syndrome (after age 5)
Hodgkin lymphoma basics
-neoplastic formation of Reed-Sternberg (RS) cells, *large B cells w/ multilobed nuclei and prominent nucleoli* (owl eyed) w/ *CD15 and CD30* -RS secrete cytokines -> B symptoms (fever, chills, wt loss, night sweats) -Also, attracts lymphs, plasma cells, macrophages, and eosinophils -Bulk of tumor = reactive inflammatory cells (basis of classification of HL) Nodular sclerosis, lymphocyte rich, mixed cellularity, lymphocyte depleted
Mycosis fungoides/Sezary syndrome
-neoplastic prolferation of mature CD4+ T cells that infiltrate the skin, producing *localized skin rash, plaques, and nodules* -*Pautrier microabscesses* = aggregates of neoplastic cells of epidermis -if spread to blood = *Sezary syndrome* w/ characteristic lymphocytes with *cerebriform nuclei (sezary cells)* on smear
Hairy cell leukemia
-neoplastic proliferation of *mature B cells* characterized by *hairy cytoplasmic processes* -positive for *tartrate-resistant acid phosphatase* (TRAP) clinical features: splenomegaly (*hairy cells accumulate in red pulp*) and "dry tap" on bone marrow d/t *marrow fibrosis* -LAD usually absent -Adult male most common -*Excellent response to 2-CDA (Cladribine), an adenosine deaminase inhibitor* -> adenosine accumulates to toxic levels in neoplastic B cells
Diffuse large B cell lymphoma
-neoplastic proliferation of large B cells (CD20+) that grow *diffusely in sheets* *most common NHL* *clinically aggressive* - poor differentiation -either sporadic or transfomration of low grade lymphoma (*Bcl-2 or Bcl-6 alterations*) -*late adulthood w/ LAD or an extranodal mass*
Lymphoma basics
-neoplastic proliferation of lymphoid cells that form a mass; may originate in *lymph node or in extranodal tissue* -divided into: NHL (60%) and HL (40%)
Myeloproliferative disorders (MPD)
-neoplastic proliferation of mature cells of myeloid lineage; typically dz of *late adulthood (50-60yo avg) -*high WBC w/ hypercellular bone marrow* - all myeloid lineage cells high, but classified based on predominant -includes *PV, ET, myelofibrosis, and CML* -increased risk for *hyperuricemia and gout* -*marrow fibrosis or transformation to acute leukemia possible*
Myelofibrosis
-neoplastic proliferation of mature myeloid cells, esp. *megakaryocytes* - V617F JAK2 kinase mutations (50% cases) -Megakaryocytes make high amt *PDGF* -> marrow fibrosis features: splenomegaly (extramedullary hematopoiesis), *leukoerythroblastic smear* (tear-drop RBCs, nucleated RBCs, immature granulocytes) tear drop b/c RBC stretched as leaving fibrotic marrow -increased risk for *infection, thrombosis, bleeding
Essential thrombocythemia
-neoplastic proliferation of mature myeloid cells, esp. *platelets* -RBCs and granulocytes also higher *V617F JAK2 kinase mutation* Sx: d/t increased bleeding and/or thrombosis (under or over fn platelets) -low hyperuricemia/gout risk nor marrow fibrosis or acute leukemia
Polycythemia vera
-neoplastic proliferation of mature myeloid cells, especially *RBCs* -granulocytes + platelets also higher *V617F JAK2 kinase mutation* Sx: *mostly d/t hyperviscous blood* -blurry vision and HA -venous thrombosis (hepatic, portal, dural sinus veins) -flushed face 2/2 congestion -itching esp after bath (d/t increased mast cells -> histamine) *classic sx = erythromelalgia* - severe burning pain and red-blue coloration from *episodic clots in extremities tx: phlebotomy; 2nd line hydroxyurea or *Ruxolitinib* (JAK1/2 inhibitor) w/o tx, death w/in 1 yr
Chronic lymphocytic leukemia
-neoplastic proliferation of naive B cells which *co-express CD5 and CD20 and CD23* *Most common leukemia overall* - >60yo, progresses slowly, commonly asymptomatic -increased lymphocytes and *smudge cells* seen on smear -LN involvement -> generalized LAD aka *small lymphocytic lymphoma* complications: hypogammaglobulinemia - no desire to make Igs (*most common cause of death = infxn*) -*autoimmune hemolytic anemia* - if Igs made, can be against RBCs -*Richter transformation* - transforming into *diffuse large B cell lymphoma* = enlarging LN or spleen
Mantle cell lymphoma
-neoplastic proliferation of small B cells (CD20+) and CD5+ that *expand mantle zone* -late adulthood w/ painless LAD -*t(11;14) Cyclin D1 gene on chr 11 translocates to IgH locus on chr 14* -> high cyclin D1 drives G1->S transition -Very aggressive, pt typically presents w/ late-stage dz
Marginal zone lymphoma
-neoplastic proliferation of small B cells (CD20+) expanding *into marginal zone* -associated with *chronic inflammatory states* like *Hashimoto thyroiditis, Sjogren syndrome, and H pylori gastritis -marginal zone formed by *post-germinal center B cells* which are activated when LN being stimulated
Follicular lymphoma
-neoplastic proliferation of small B cells (CD20+) that form *follicle-like nodules* *late adulthood w/ painless LAD* *t(14;18) = BCL2 on *chr 18* -> Ig heavy chain locus on *chr 14* -> increased Bcl2 (inhibits apoptosis by stabilizing mito. membrane - nl want apoptosis going on at follicle) tx: for symptomatic pt use *low dose chemo or rituximab (anti CD20 ab)* -*can progress to diffuse large B cell lymphoma*
senile cardiac amyloidosis
-non-mutated serum transthyretin (2nd most common protein in blood) deposits in heart overtime -usually asymptomatic - found in 25% of pt >80yo
Folate deficiency
-obtained from green veggies and some fruits - absorbed in *jejunum* -develops w/in months d/t body storage being minimal causes: *poor diet* (alcoholics and elderly), *increased demand* (preg, cancer, hemolytic anemia), *folate antagonists* (MTX) clinical and lab findings: -megaloblastic anemia w/ hypersegmented neuts -glossitis (poor turnover of cells -> inflammation occurs) - dec. folate, inc. homocysteine (inc. risk of thrombosis) -*nl methylmalonic acid*
cellular injury
-occurs when stress exceeds cells ability to adapt -dependent upon type of stress, severity, and type of cell affected (eg. neurons vs skeletal muscle for ischemic injury) eg of timing: slow ischemia to kidney -> atrophy -abrupt ischemia -> kidney injury
Autosomal dominant
-often pleiotropic and variable expressivity Fhx: crucial for dx
reticulocytes
-on smear, larger cells w/ bluish cytoplasm (residual RNA) nl - 1-2% (everyday, 1-2% RBC removed from circulation) >3% retic is proper response to anemia (beware of false elevation) correct RC by multiplying count by Hct/45 -proper Retic production = peripheral destruction -improper = underproduction
what are the 5 high yield causes of normocytic anemia with predominant *intravascular* hemolysis
-paroxysmal nocturnal hemoglobinuria (PNH) -G6PD deficiency -Immune hemolytic anemia (IHA) -microangiopathic hemolytic anemia (MAHA) -Malaria
myelophthisic process
-pathologic process (mets) that replace bone marrow -> hematopoiesis impaired -> pancytopenia
sickle cell trait
-presence of one mutated Beta chain and one normal -> <50% HbS (HbA slightly more efficiently produced) -typically *asymptomatic* b/c RBCs w/ <50% HbS will not sickle except in *renal medulla* -main complication is renal medulla microinfarctions in presence of *extreme hypoxia and hypertonicity of medulla* -> microscopic hematuria and cant concentrate urine
Acute megakaryoblastic leukemia
-prolif of megakaryoblasts; *lack MPO* -associated with Down syndrome (*usually before age 5)
cancer-enabling inflammation
-provoke a chronic inflammatory rxn leads to: anemia of chronic dz, fatigue, cachexia 2/2 systemic inflammation *effects of inflammatory cells*: -release of factors promote proliferation (EGF) -removal of growth suppressors (proteases degrade adhesion moleculeS) -enhance resistance to cell death (macroph can attach to cancer cells to avoid lack of adhesion) -induce angiogenesis (VEGF) -activate invasion and mets (proteases, TNF and EGF)
diamond-Blackfan anemia
-rapid onset anemia w/in 1st yr of life d/t *intrinsic defect in erythroid progenitor cells* findings: high % HbF (low total Hgb) -short stature, craniofacial abnormalities, upper extremity malformations (triphalangeal thumbs) in up to 50% cases
CD4 t cell roles
-secrete cytokines to help inflammation Th1 subset: produce IFN-y (activate macros, promote B cell class switching, produce IL-2 to provide 2nd signal for CD8 cells) Th2: secrete IL-4 and IL13 (class switch of b cell to IgE) IL 5 (eosinphil chemotactic and activator + IgA class switch) Th17: secrete Il-17 -> neutrophils
What is the role of FMRP protein?
-selectively binds mRNAs associated with polysomes and regulates their intracellular transport in dendrites -it suppresses mRNAs in dendrites - if not present then abnormal translation of proteins in synaptic junctions occurs -> abnormal synaptic activity -> MR
what role does hepcidin play in anemia of chronic dz?
-sequesters iron by binding to *ferroportin* in intestinal mucosal cells and macrophages so decreases macrophages transferring to erythroid precursors -suppresses EPO production -*attempting to prevent bacteria from accessing iron*
BRAF
-serine threonine kinase Hairy cell leukemia oncogene -melanoma
Lab finds in sickle cell dz and trait
-sickle and target cells on blood smear (not in trait) -*Metabisulfite screen* - cause any cells with any HbS to sickle -> + in SCD and trait electrophoresis confirms presents of HbS dz- 90% HbS, 8% HbF, 2% HbA2 trait- 55%HbA, 43%HbS, 2%HbA2
Limited systemic sclerosis
-skin is limited to hands and face; late visceral involvement CREST syndrome prototype ( calcinosis/anti-*C*entromere ab, *R*aynauds, *E*sophageal dysmotility, *S*clerodactyly, *T*elangiectasias of skin)
Paraneoplastic cerebellar degeneration
-small cell lung cancer (anti Hu -gynecologic and breast cancers (anti Yo) -hodgkin lymphoma (anti Tr) antibodies against antigens in purkinje cells
Churg-Strauss Syndrome
-small vessel *necrotizing granulomatous inflammation w/ eosinophils involving multiorgans, esp. heart and lung* -asthma and peripheral eosinophilia often present *p-ANCA* correlate w/ dz activity
What drugs (2) can cause dilated cardiomyopathy
1. Cocaine 2. Doxorubicin
Wegener Granulomatosis
-small vessel necrotizing granulomatous vasculitis involving nasopharynx, lungs, kidneys -presents in *middle-aged man with sinusitis or nasopharyngeal ulceration, hemoptysis with bilateral nodular lung infiltrates, and hematuria* (d/t rapidly progressive glomerulonephritis) *c-ANCA levels correlate w/ dz activity* (anti-proteinase 3) -Biopsy reveals *large necrotizing granulomas w/ adjacent necrotizing vasculitis* tx: *cyclophosphamide* and steroids
Microscopic polyangiitis
-small vessel necrotizing vasculitis involving multiple organs, especially *lung and kidney* -presents similar to Wegener, but *w/o nasopharyngeal involvement or granulomas* -Serum *p-ANCA levels* (anti-MPO) correlate with dz activity tx: cyclophosphamide and steroids
Henoch-Schonlein Purpura
-small vessel vasculitis *d/t IgA immune complex deposition* (type 3 HSR) *most common vasculitis in children* -presents with *palpable purpura on buttocks and legs, GI pain and bleeding, and hematuria* (IgA nephropathy) -typically occurs s/p *URI* dz self limited, but may recur - *if severe, tx w/ steroids*
caseous necrosis
-soft friable necrotic tissue with 'cottage cheese" appearance combo of coagulative and liquefactive characteristic of granulomatous inflammation d/t TB or fungal infxn or nocardia
langerhans cell histiocytosis basics
-specialized dendritic cells found in skin - derived from monocytes -APC to naive T cell -neoplastic proliferation of langerhan cells *Birbeck (tennis racket) granules seen on EM* also *CD1a+ and S-100+ by immunohistochemisty*
Acute promyelocytic leukemia (APL)
-t(15;17) = retinoic acid receptor (RAR) on chr 17 -> chr 15; *RAR disruption blocks maturation of promyelocytes* -promyelocytes contain many primary granules -> *increased risk for DIC* -Tx; *all-trans-retinoic acid (ATRA, vitamin A derivative)* -> binds altered receptor and causes *blasts to mature, and eventually die*
PATCHED tumor suppressor
-these are negative regulators of hedgehog signaling pathway -mutations can lead to overexpression of NMYC and D cyclins -Gorlin syndrome is assoc. with this (nevoid basal cell carcinoma)
how do mast cells mediate acute inflammation?
-they are found widely throughout connective tissue activated by: tissue trauma, C3a C5a, cross-linking of cell-surface IgE by antigen *Response*: immediately release preformed histamine -> vasodilation of arterioles and increased vascular permeability delayed production of AA metabolites, particularly *leukotrienes*
What are macrophages responsible for in inflammation?
-they are manager of process - *dominant cell in chronic inflammation* peak after neuts around 2-3 days after inflam begins get to tissue same way as neuts -utilize o2 independent killing (lysozyme) *manage* next step in inflam process: -*resolution+healing* - antiinflammatory cytokines (IL10 TGFB) made by macros -*continued acute inflam*- persistent pus formation via IL8 from macros recruiting neuts -*abscess*- macros stim. fibrosis around inflam via cytokines and fibrogenic GFs *chronic inflammation*: weeks or months of inflammation, tissue injury
hyperplastic ateriolosclerosis
-thickening of vessel wall by *hyperplasia of smooth muscle* (onion skin appearance) -2/2 *malignant htn* -reduced vessel caliber w/ end-organ ischemia -can lead to *fibrinoid necrosis* of vessel wall w/ hemorrhage -classically causing *ARF with 'flea-bitten' appearance*
ATIII deficiency
-this hypercoaguability decreases the protective effect of *heparin-like molecules* produced by the endothelium, increasing risk for thrombus heparin-like molecules normally activate this protein which then *inactivates thrombin and coag factors* PTT does not change in these pt if you give then *normal heparin doses* -> high doses will activate limited ATIII -> you then give coumadin to maintain an anticoagulated state
Lead poisoning
-this inhibits ferrochelatase and ALA dehydratase -> low heme syn. high RBC protoporphyrin sx: *LEAD* poisoning *L*ead *L*ines on gingivae (burton lines) and on metaphyses of long bones *E*ncephalopathy and *E*rythrocyte basophilic stippling *A*bdominal colic and sideroblastic *A*nemia *D*rops-wrist and foot drop. *D*imercaprol and E*D*TA are 1st line *treatment*
What is Chediak Higashi syndrome and what step in neutrophil arrival/function is it defective)
-this is a protein trafficking defect (AR) and characterized by impaired phagolysosome formation problem with railroad in cell to carry proteins around clinical features: inc. risk of pyogenic infxn, neutropenia (intramedullary death of neuts), giant granules in leukocytes (d/t fusion after budding from golgi), defective primary hemostasis (d/t abnormal dense granules of platelets), albinism (relies on melanocytes to send melanosomes to keratinocytes), peripheral neuropathy (NTs can't move down to axon terminal)
carbon monoxide poisoning
-this is classically seen from exposure to fires and exhaust from cars -classic finding is cherry-red appearance of skin (causes Fe to reflect better by light) and severe HA
TGF-B pathway
-this normally activates its receptor to activate SMAD -> antiproliferative genes turned on and proliferative genes turned off mutations in this pathway can lead to colon, stomach, endometrial cancer SMAD4 = pancreatic cancer
what lab findings do you see in MAHA
-thrombocytopenia with higher bleed time -normal PT/PTT -anemia w/ schistocytes -increased megakaryocytes in bone marrow
granulomatous inflammation
-type of chronic inflammation d/t FB, infection, self antigen defining feature of granuloma = epitheliod histiocyte (macrophage with abundant pink cytoplasm) surrounded by giant cells and rim of lymphocytes noncaseating (lack central necrosis) caseating ( central necrosis)
Trinucleotide expansion disorders affecting coding regions
-typically code for CAG which causes polyglutamine proteins leading to toxic gain of function -> leads to aggregation -progressive neurodegeneration striking midlife -morphologic hallmark: accumulation of mutant protein in large intranuclear inclusions
Name three complications of aortic stenosis
1. Concentric left ventricular hypertrophy 2. Angina and syncope with exercise 3. Microangiopathic hemolytic anemia
IgG mediated IHA
-typically involves *extravascular hemolysis (opsonizes RBC)* -> ab binds in warm central part of body -> splenic macrophages remove membrane -> spherocytes associated with SLE, CLL, drugs (penicillin and cephalosporins) drugs can attach RBC membrane with Ig binding to drug-membrane complex *or* cause autoantibodies to form against self-antigens on RBC (methyldopa) tx: cessation of drug, steroids, IVIG, or splenectomy (*rids place that destroys RBC and where Ig are being produced*)
T lymphocytes in chronic inflammation
-use TCR (with CD3) for antigen surveillance CD4 can be activated by APC presenting antigen -> need B7 on APC bind to CD28 on CD4 t cell (2nd signal) CD8 can be activated via host cell presenting foreign material on MHC1 -> IL-2 from CD4 Th1 provide 2nd signal
what important molecules for thrombogenesis are synthesized and stored in endothelial cells?
-vWF -Factor 8 -thromboplastin (Tissue factor) -tPA -PGI2
how do tumors invade and spread?
-when mutations continue to accumulate in tumor -> cell-cell adhesion molecules downregulated (E *cadherin*) -> tumor cells can dissociated -> attach to *laminin* and destroy basement membrane (collagen type 4) via *collagenase* -> attach to *fibronectin* in ECM and spread locally via autocrine chemokines then enter circulation (lymphs or blood) to first capillary bed available but some cancers prefer certain regions more d/t adhesion molecules on cancer and region deposited
Lipofuscin
-yellow-brown "wear and tear" pigment associated with normal aging d/t oxidation and polymerization of autophagocytosed organellar membranes - or lipid peroxidation in autopsy of elderly, heart, colon, liver, kidney, eye, and other organs will show this
What percent of live births have congenital heart defect?
1%
Why is there hypercalcemia in sarcoidosis?
1-alpha hydroxylase activity of epithelioid histiocytes in granulomas composing noncaseating granulomas converts Vitamin D to its active form
Contractility Decreases w/ ______
1. Acidosis 2. Hypoxia 3. Hypercapnea 4. Meds 5. Decreased intracellular Na+ (decreases activity of Na+/Ca2+ exchanger)
Name the two respiratory distress syndromes
1. Acute respiratory distress syndrome 2. Neonatal respiratory distress syndrome
Name the four subtypes of non-small cell lung carcinoma
1. Adenocarcinoma 2. Squamous cell 3. Large cell 4. Carcinoid tumor
Pathogenesis of Asthma
1. Allergens induce Th2 phenotype in CD4+ T cells in genetically susceptible individuals 2. Th2 cells secrete IL4, IL5, and IL10 3. Reexposure to allergen leads to IgE mediated activation of mast cells
Name three things asthma is associated with
1. Allergic rhinitis 2. Eczema 3. Family history of atopy (hyperallergic)
Name six treatments for MI
1. Aspirin/heparin 2. Supplemental O2 3. Nitrates 4. Beta Blocker 5. ACE inhibitor 6. Fibrinolysis or angioplasty
Triad of aspirin-intolerant asthma
1. Asthma 2. Aspirin-induced bronchospasms 3. Nasal polyps
Triad of aspirin intolerant asthma
1. Asthma 2. Bronchospasm with aspirin 3. Nasal polyps
What are the four symptoms/outcomes of PE?
1. Asymptomatic (most) 2. Pulmonary infarction 3. Sudden death (saddle embolus) 4. Chronic PE can become reorganized and lead to thickening of vascular wall and ultimately pulmonary HTN
Name things that characterize pulmonary hypertension (4)
1. Atherosclerosis of pulmonary trunk 2. Smooth muscle hypertrophy of pulmonary arteries 3. Intimal fibrosis 4. Plexiform lesions with severe, long standing disease
Two restrictive lung disease characterized by non-caseating granulomas
1. Berylliosis (pneumoconiosis) 2. Sarcoidosis
What is the most common incidence of cancer (top 3) in the US?
1. Breast/prostate 2. Lung 3. Colorectal
Name causes of necrotizing inflammation that lead to damage in airway walls and ultimately bronchiectasis (5)
1. CF 2. Kartagener syndrome 3. Tumor/foreign body 4. Necrotizing infection 5. Allergic bronchopulmonary aspergillosis
What is the triad of symptoms associated with Sjogren Syndrome?
1. Can't chew a cracker 2. Dust in eye 3. Increased risk for dental cavities
Name four entities that can cause pneumoconioses
1. Carbon dust 2. Silica 3. Beryllium 4. Asbestos
Name the four chronic obstructive pulmonary diseases
1. Chronic bronchitis 2. Emphysema 3. Asthma 4. Bronchiectasis
Clinical features of asthma
1. Episodic and related to allergen exposure 2. Dyspnea and wheezing 3. Productive cough with spiral shaped mucus plugs (Curschmann spirals) and eosinophil derived crystals (Charcto-Leyden crystals) 4. Severe, unrelenting attack can cause status asthmaticus and death
Name four nonallergic asthmatic causes (non-atopic asthma)
1. Exercise 2. viral infection 3. Aspirin (aspirin intolerant asthma) 4. Occupational exposures
Name four clinical features of endocarditis
1. Fever 2. Murmur 3. Janeway lesions, Osler nodes (hurt), splinter hemorrhages in nail bed, Roth spots 4. Anemia of chronic disease
Main Causes of Secondary HTN
1. Fibromuscular dysplasia: muscular hypertrophy blocking renal artery; shows *string of beads* sign on angiography 2. 1o hyperadlosteronism 3. Atherosclerosis of the renal arteries
What can asbestosis lead to?
1. Fibrosis of lung and/or pleura 2. Cancer of lung and/or pleura
Name two late complications of emphysema
1. Hypoxemia 2. Cor pulmonale
Name three causes of secondary pulmonary hypertension
1. Hypoxemia (as in COPD or interstitial lung disease) 2. Increased volume in pulmonary circuit (i.e. congenital heart disease) 3. Chronic recurrent PE
Name complications of neonatal respiratory distress syndrome
1. Hypoxemia increases risk of persistent PDA (which closes when there is good oxygenation of the blood) and necrotizing enterocolitis 2. Supplemental oxygen increases risk for free radical injury (blindness, bronchopulmonary dysplasi)
What are the interleukins that Th2 cells secrete, and what does each do?
1. IL4 (mediates class switch to IgE) 2. IL5 (attracts eosinophils) 3. IL10 (stimulates Th2 cells and inhibits Th1 cells)
What is the most common cause and then other causes of dilated cardiomyopathy
1. Idiopathic 2. Other: genetic mutation, myocarditis, alcohol abuse, drugs, pregnancy, hemochromatosis
What are the normal defenses that when impaired can contribute to pneumonia development (3)?
1. Impaired cough reflex 2. damage to mucociliary escalator 3. mucus plugging
Clinical features of neonatal respiratory distress syndrome
1. Increased respiratory effort after birth, tachypnea with use of accessory muscles, grunting 2. Hypoxemia with cyanosis 3. Diffuse granularity of lung on x-ray (ground glass appearance)
Name three complications of mitral valve prolapse
1. Infectious endocarditis 2. Arrhythmia 3. Severe mitral regurgitation All are relatively rare
Name three clinical features of right CHF
1. JVD 2. Hepatosplenomegaly with "nutmeg" liver that may lead to cardiac cirrhosis (cirrhosis of the liver in CHF) 3. Pitting edema
Name the major JONES criteria
1. Joints (migratory polyarthritis) 2. Pancarditis 3. Subcutaneous Nodules 4. Erythema marginatum 5. Sydenham's chorea
Name tissue commonly involved in sarcoidosis
1. Lungs/hilar lymph nodes 2. Uvea (uveitis) 3. Skin (cutaneous nodules or erythema nodosum) 4. Salivary and lacrimal glands (mimics Sjogren Syndrome)
Name two general clinical features of mitral stenosis
1. Opening snap followed by diastolic rumble 2. Volume overload leading to dilation of left atrium
Name three laboratory findings of endocarditis
1. Positive blood cultures (except HACEK) 2. Anemia of chronic disease 3. Transesophageal echocardiogram- use to look for lesions on valves
Name three things neonatal respiratory distress syndrome is associated with
1. Prematurity 2. C-section 3. Maternal diabetes
Clinical features of chronic bronchitis
1. Productive cough 2. Cyanosis 3. Increased infection and cor pulmonale risk
Clinical features of idiopathic pulmonary fibrosis
1. Progressive dyspnea and cough 2. Fibrosis on lung CT
Complications of volume overload and dilation of left atrium result in what three complications
1. Pulmonary congestion with edema and alveolar hemorrhage 2. Pulmonary hypertension and right-sided heart failure 3. Atrial fibrillation with associated risk for mural thrombosis
What are the risks of giving supplemental oxygen in neonatal respiratory distress syndrome due to free radical formation
1. Retinal injury leading to blindness 2. Lung damage leading to bronchopulmonary dysplasia
What are the two roles of type II pneumocytes?
1. Stem cell 2. Produce surfactant
Treatment of ARDS
1. Treat underlying cause 2. Ventilation with PEEP (positive end-expiratory pressure)
Four features of Tetralogy of Fallot
1. VSD 2. Aorta that overrides VSD 3. RV outflow tract stenosis 4. RV Hypertrophy
What is the general model of induction of autoimmune dz?
1. genetic deficiencies (AIRE, MHC-DR2, etc) 2. leads to loss of self tolerance 3. self-reactive lymphocytes in periphery -> initiation event activates and recruited to tissue that they can damage
What is the most common cause and then other less common causes of right sided congestive heart failure?
1. left CHF is most common cause Other important causes include left to right shunt and chronic lung disease (cor pulmonale)
most common cancers in children 0-14? and highest morality too in this order.
1. leukemia 2. CNS 3. Neuroblastoma
features that suggest hereditary nature of breast cancer
1. multiple 1st degree relatives affected 2. tumor at early age (pre-menopausal) 3. multiple tumors in single patient
what are the primary hemostasis steps?
1. transient vasoconstriction (neural + endothelin) 2. Platelet adhesion (Platelet via GP1b - vWF - SEC) vWF from a-granules (platelets) and WP bodies (endothelium) 3. platelet degranulation (ADP, TXA2) 4. Platelet aggregation (ADP binds receptor -> GP2b/3a comes to surface and binds other platelets via fibrinogen)
daily energy requirement for typical person
30 kcal/kg/day
Syphilitic Heat Disease
3o syphilis disrupts the *vasa vasorum* of the aorta -> atrophy of the wall -> dilation of aorta -> *tree bark appearance*
modified Mallampati scale
4 classes based on how much of uvula, soft palate, and fauces are visible vs. how much airway is visible class IV- soft palate not visible at all
Leukotriene Modifying Agents
5-Lipoxygenase Inhibitors Leukotriene receptor antagonists Oral agents Prevent allergen-induced asthma, exercise-induced asthma, and aspirin-induced asthma Reduce corticosteroid requirements Generally safe More effective in children and those with sinus disease, less effective in adults
Zileuton
5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes. Hepatotoxic.
What is the average age of lung cancer presentation?
60
Why are many Ab's located in gut?
60-70% of Ab's are in gut b/c it is exposed to many new Ag's
hypertrophic cardiomyopathy
60-70% of cases are familial, autosomal dominant (most commonly due to mutations in genes encoding sarcomeric proteins, such as myosin binding protein C and β-myosin heavy chain). Can be associated with Friedreich ataxia. Causes syncope during exercise and may lead to sudden death in young athletes due to ventricular arrhythmia. Pompe Disease (Type II GSD). Findings: S4, systolic murmur. May see mitral regurgitation due to impaired mitral valve closure Diastolic dysfunction ensues. Marked ventricular concentric hypertrophy (sarcomeres added in parallel), often septal predominance. Myofibrillar disarray and fibrosis.
What is normal TLC?
7 L, usually goes up to 8 in obstructive lung diseases
Type 1 pneumocytes
97% of alveolar surfaces. Line the alveoli. Squamous; thing for optimal gas exchange
weight cutoff for inpatient stay
< 75% of expected body weight = Inpatient stay
What size makes a palpable lymph node concerning?
>1 cm
main requirement for diagnosis of acute leukemia
>20% of leukemic lymphoblasts (or myeloid blasts/blast equivalents) involving primarily in bone marrow and blood (leukemia) or occasionally in extramedullary sites (lymphoma) or a recurrent cytogenetic abnormal clone (may be <20% blasts in this case)
common mutation in hairy cell leukemia
>90% of cases are BRAF V600E mutations (immediately downstream of RAS in the MAPK cascade)
Wolf-Parkinson-White Syndrome
A *ventricular pre-excitation syndrome*; uses *Bundle of Kent* to bypass AV node and depolarize ventricles early -> delta wave, widened QRS complex, + shortened PR interval -Increased risk of forming *re-entry circuits -> SVT formation*
What is present in type A blood
A antigen, anti-B antibody
ventricular fibrillation
A completely erratic rhythm with no identifiable waves. Fatal arrhythmia without immediate CPR and defibrillation. Most important shockable cardiac arrest rhythm. The ventricles suddenly attempt to contract at rates of up to 500 bpm. This rapid and irregular electrical activity renders the ventricles unable to contract in a synchronized manner, resulting in immediate loss of cardiac output. The heart is no longer an effective pump and is reduced to a quivering mess. Unless advanced life support is rapidly instituted, this rhythm is invariably fatal. Prolonged ventricular fibrillation results in decreasing waveform amplitude, from initial coarse VF to fine VF and ultimately degenerating into asystole due to progressive depletion of myocardial energy stores.
leukoreduction
A filter is used to remove 99.99% of WBCs from cellular blood products, with a residual of < 5 x 106 All cellular blood products at UMHS are pre-storage leukoreduced, so you never need to order it! Benefits: Reduced febrile nonhemolytic transfusion reactions Reduced alloimmunization Reduced risk of CMV ("CMV safe")
granulomatous inflammation
A form of chronic inflammation characterized by collections of activated macrophages, often with T-lymphocytes & sometimes associated with central necrosis (caseating) Granuloma formation is the cellular attempt to contain an offending agent that is difficult to eradicate. Two types of granuloma: Foreign body granuloma>inert bodies; absence of T-cell mediated immune response Immune Granuloma>variety of agents that are capable of inducing a persistent T-cell mediated response.
myelodysplastic syndromes
A group of heterogeneous clonal hematopoietic stem cell diseases Ineffective hematopoiesis with peripheral pancytopenia Morphologic dysplasia Propensity for development of acute myeloid leukemia Splenomegaly and lymphadenopathy absent chromosomal deletions (especially 5 and 7) common
PKU
A human metabolic disease caused by a mutation in a gene coding for a phenylalanine processing enzyme (phenylalanine hydroxylase), which leads to accumulation of phenylalanine and mental retardation if not treated; inherited as an *autosomal recessive* phenotype. 1/10,000 live born white infants (less common AA and Jewish) -phenylalanine levels high can damage brain w/in few weeks of birth -> 6 months MR can occur (other sx cant walk, seizures, pigment decreased in skin/hair) -musty/mousy smell from phenylalanine metabolites (phe -dx: PKU >1200 uM (mass spect) -Tx: dietary restrictions (<360uM) -> much cheaper than tx mentally retarded PKU pt
Phospholamban
A molecule that, when phosphorylated, leads to increased Ca2+ ATPase activity and *increased cardiac contractility*
Hypersensitivity
A pathological immune response upon repeat exposure to an antigen (can be endogenous or exogenous antigens)
atrial flutter
A rapid succession of identical, back-to-back atrial depolarization waves. The identical appearance accounts for the "sawtooth" appearance of the flutter waves. Treat like atrial fibrillation. Definitive treatment is catheter ablation. Atrial flutter with predominantly 2:1 conduction. In contrast to atrial fibrillation, flutter waves are distinct waves, rate usually 250 - 300 bpm. Most atrial flutter arises from just above the tricuspid valve, so the flutter waves will be negative in II, III, and aVF, producing a "sawtooth" pattern to the baseline. Atrial flutter can be seen in similar conditions as atrial fibrillation.
acute inflammation timing
A- neutrophils shown B- lymphocytes shown
absence of wheezes in asthma indicates
Absence of wheezes is a detrimental finding in asthma- means airways have shut down wheezing means airways are constricted
sickle cell dz
AR mutation in B chain of hgb -> single AA change (*nl glutamic acid -> valine*) 10% AA carry (protective role with *falciparum malaria*) dz occurs when both B genes have mutation -> HbS >90% HbS polymerizes in RBC when under *deoxygenated* state -> polymers aggregate into needle-like structures -> sickle cells -> sickle and de sickling of RBC damage membrane when passing *microcirculation* -> intra and extravascular hemolysis -> massive erythroid hyperplasia (crewcut + chipmunk facies + HSM + risk of aplastic crisis) risk of sickling: *hypoxemia, dehydration, acidosis* HbF protects against sickling so protective in first few months - *hydroxyurea* increases these levels
Hemoglobin C
AR mutation of B chain of hgb (glutamic acid replaced with *lysine*) less common than Sickle cell dz presents: mild anemia and extravascular hemolysis HbC crystals in RBCs on smear
pyruvate kinase deficiency
AR pyruvate kinase defect -> low ATP -> rigid RBCs -> extravascular hemolysis increases levels of 2,3-BPG -> dec. hgb affinity for O2 findings: hemolytic anemia in newborn
ASD vs. Patent Foramen Ovale
ASD is distinct from patent foramen ovale in that septa are missing tissue rather than unfused
Left to Right Shunts
ASD, VSD, PDA -Most common= VSD 2o to fetal alcohol syndrome -Almost all ASDs are *osteum secundum* type; osteum primum is seen in Down syndrome
How does the release of ATII by the renin-angtiotensin system exacerbate CHF?
ATII constricts peripheral arterioles to increase peripheral resistance; also increases blood volume by causing release of aldosterone from the adrenal
Why is DIC risk inc in APL?
Abnormal promyelocytes contain numerous primary granules that increase the risk for DIC
How does myxoma appear on histology?
Abundant ground substance
most common cause of pleural effusion
Accumulation occurs when formation exceeds absorption LV failure (CHF)- inc interstitial fluid
Pneumothorax
Accumulation of air in pleural psace. Unilateral chest pain and dyspnea, unilateral chest expansion, decreased tactile fremitus, hyperresonance, diminished breath sounds, all on affected side. Primary spontaneous secondary spontaneous traumatic (blunt or penetrating) tension See pg 615 for more descriptions
How do you confirm TB vs. fungi after seeing caseating granulomas?
Acid Fast Stain
What is the functional unit of the lung?
Acinus (terminal bronchiole opens into alveolar air sac)
paroxysmal nocturnal hemoglobinuria
Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinsitol (GPI); renders cells susceptible to destruction by complement Blood cells coexist with complement; decay accelerating factor (DAF, CD55) on the surface of blood cells protects against complement = mediated damage by inhibiting C3 convertase. DAF is secured to the cell membrane by GPI (the anchoring glycolipid). Absence of GPI leads to absence of DAF, rendering cells susceptible to complement-mediated damage. CD59 inhibits MAC and is also anchored by GPI. Intravascular hemolysis occurs episodically, often at night during sleep Mild respiratory acidosis develops with shallow breathing during sleep and activates complement RBCs, WBCs, and platelets are lysed Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria (especially in the morning); hemosiderinuria is seen days after hemolysis. Findings: Associated with AML. Triad: Coombs ⊝ hemolytic anemia, pancytopenia, and venous thrombosis. Labs: CD55/59 ⊝ RBCs on ow cytometry. Treatment: Eculizumab (terminal complement inhibitor; Complement protein C5).
What cancer most commonly involves pleural involvement?
Adenocarcinoma (peripheral location)
What is a unique site of distant metastasis for lung cancer?
Adrenal gland
HTLV-1
Adult T-cell leukemia/lymphoma
hairy cell leukemia
Adult males. Mature B-cell tumor. Cells have filamentous, hair-like projections (fuzzy appearing on LM). Peripheral lymphadenopathy is uncommon (lymphocytes TRAPped in the bone marrow). • Causes marrow fibrosis dry tap on aspiration. Patients usually present with massive splenomegaly (hairy cells TRAPped in red pulp) and pancytopenia. • Stains TRAP (tartrate-resistant acid phosphatase) ⊕
When is adult coarctation of the aorta discovered?
Adulthood
What is the difference in laryngeal papillomas between adults and children?
Adults: single Children: multiple
When does acute rheumatic fever occur, and who does it affect?
Affects children 2-3 weeks after episode of strep pharyngitis
Who is sarcoidosis most commonly seen in?
African American women
Who does nasopharyngeal carcinoma classically appear in (2 demographics)
African children and Chinese adults
Risk factors for primary htn
Age, race (inc. in AA, dec. in Asians), obesity, stress, lack of physical activity, high salt diet (Na. inc. blood volume, and TPR)
3 types of respiratory events and their criteria
Apneas Complete pauses of no airflow ≥ 10 seconds without airflow NO oxygen desaturation criteria (but it often drops) Hypopneas Reduction of airflow by at least 30% Event must last at least 10 seconds Oxygen desaturation of 4% or greater Respiratory Effort-Related Arousal (RERA) Sequence of breaths lasting at least 10 seconds characterized by increasing respiratory effort or flattening of the nasal pressure waveform leading to an arousal from sleep when the sequence of breaths does not meet criteria for an apnea or hypopnea. Like hypopnea, but doesn't have O2 sat requirement
Why does dysplasia often occur?
Arises from: -longstanding pathologic hyperplasia (endometrial hyperplasia) -metaplasia (barretts)
Mucoepidermoid carcinoma
Arising from minor bronchial salivary glands Rare, <1% of lung neoplasms Very indolent Occasional metastatic spread - respond to TKIs (erlotinib) if EGFR mutant Hilar mass, can be symptomatic with very productive cough, hemoptysis Curative with resection in majority of cases, can recur locally
Why does mitral valve prolapse lead to mitral regurgitation at times?
As valve clicks backward, it can be stretched and become leaky
3o Syphilis is Linked to _____ (Cardiovascular)
Ascending (thoracic) aortic aneurysm
Truncus Arteriosus Give Rise to ______
Ascending aorta and pulmonary trunk
What characterizes myocarditis of acute rheumatic fever
Aschoff bodies with Anitschkow cells
Pneumonia commonly seen in alcoholics and comatose patients?
Aspiration pneumonia
delayed hemolytic transfusion rxn
Associated with PRBC transfusion Caused by pre-existing IgG alloantibodies in the recipient that bind to donor RBC antigens and cause EXTRAVASCULAR hemolysis within 7-10 days of transfusion Fever and anemia (or lack of appropriate increase with transfusion) days to weeks after transfusion; may also be asymptomatic NOTIFY BLOOD BANK Prevention: future reactions are prevented by transfusing antigen-negative blood, which will take extra time to find
delayed hemolytic transfusion rxn
Associated with PRBC transfusion; Caused by pre-existing IgG alloantibodies in the recipient that bind to donor RBC antigens and cause EXTRAVASCULAR hemolysis within 7-10 days of transfusion Fever and anemia (or lack of appropriate increase with transfusion) days to weeks after transfusion; may also be asymptomatic; NOTIFY BLOOD BANK Prevention: future reactions are prevented by transfusing antigen-negative blood
Notching of rib on x-ray
Associated with adult-form of coarctation of the aorta
Berylliosis
Associated with exposure to beryllium in aerospace and manufacturing industries. Granulomatous on histology and therefore occasionally responsive to steroids. Affects upper lobes
Association and location of small cell carcinoma
Associated with male smokers Central location
Asbestosis
Associated with shipbuilding, roofing, plumbing. "Ivory white," calcified, supradiaphragmatic and pleural plaques are pathognomonic of asbestosis. Associated with increased incidence of lung cancer (bronchogenic carcinoma > mesothelioma) Affects lower lobes. Asbestos (ferruginous bodies) are golden-brown fusiform rods resembling dumbbells, found in alveolar septum.
Association and location of squamous cell carcinoma
Association: male smokers Location: central
Association and location of adenocarcinoma
Association: non-smokers (most common lung cancer in non-smokers) and female smokers Location: peripheral lung
Association and location of bronchioloalveolar carcinoma
Association: not related to smoking Location: peripheral
Association and location of carcinoid tumor
Association: not to smoking Location: central or peripheral
Association and location of large cell carcinoma
Association: smoking Location: central or peripheral
What is the characteristic histologic feature seen in sarcoidosis?
Asteroid bodies seen within giant cells of the granulomas
4 examples of obstructive diseases
Asthma COPD Cystic Fibrosis Bronchiectasis
What is allergic rhinitis associated with (2)?
Asthma Eczema
Populations prone to get Allergic bronchopulmonary aspergillosis
Asthmatics CF patients
Is primary TB symptomatic or asymptomatic?
Astymptomatic, but leads to positive PPD
acute histoplasmosis presentation
Asymptomatic Infection>most cases. Acute Pulmonary Histoplasmosis: Self-limiting illness; several weeks after exposure. Fever, chills, fatigue, nonproducive cough, anterior chest discomfort, and myalgias. CXR: Patchy lobar or multilobar infiltrate Hilar or mediastinal adenopathy. Life threatening in immunosuppressed and those with heavy exposure to H. capsulatum. High spiking fevers, chills, prostration, dyspnea, and cough. CXRs show diffuse reticulonodular infiltrates and Acute Respiratory Distress Syndrome (ARDS) can occur. Granulomatous mediastinitis: Uncommon complication of acute pulmonary histoplasmosis Small proportion of patients have persistently enlarged lymph nodes that sometimes coalesce into a large encapsulated lesion>mass may impinge on other structures
What is the clinical picture of PiMZ heterozygotes in relation to A1AT deficiency emphysema?
Asymptomatic with decreased circulating levels of A1AT and increased risk for emphysema with smoking
Closure of the Foramen Ovale
At birth, respiration causes increased left atria pressure compared to right atrial pressure, causing rightward force on flap of foramen ovale to close it
Eisenmenger syndrome
At birth, shunts flow in a left to right direction; eventually, there will be increased blood in the pulmonary circulation, leading to pulmonary hypertension. this will reverse the shunt from right to let, causing cyanosis, RVH, polycythemia, clubbing
What do 90% of patients with sudden cardiac death have?
Atherosclerosis (severe)
What causes stable angina?
Atherosclerosis of coronary arteries with over 70% stenosis, so decreased blood flow can't meet metabolic demands of the myocardium on exertion
What usually causes IHD?
Atherosclerosis of coronary arteries, decreasing blood flow to myocardium
Asthma due to allergic stimuli
Atopic asthma
Defect in the septum that divides the right and left atria
Atrial septal defect
Endocardial Cushion Give Rise to ______
Atrial septum, membranous interventricular septum, AV and semilunar valves
Where does myxoma usually arise?
Atrium (left); can obstruct mitral valve and cause syncope
what is pernicious anemia?
Autoimmune destruction of parietal cells in the stomach, leading to loss of intrinsic factor and thus inability to take up vitamin B12 in ileum
Almost all inborn errors of metabolism are inherited this way. This also makes up the largest category of mendelian disorders
Autosomal recessive
How does trachea shift in tension pneumothorax?
Away from side of injury
dark zone
B cell proliferation
light zone
B cell recognition of Ag on follicular dendritic cells; selection of high-affinity B cells
3 types of APC's
B cells, dendritic cells, macrophages
B-thal minor
B/B+ which is mildest form ofdisease and is usually *asymptomatic* w/ increased RBC count *target cells* seen on blood smear (d/t dec. hgb so makes more membrane to bleb) electrophoresis shows: slightly lower HbA, increased HbA2 (5% vs 2.5%nl), HbF (2% vs 1%nl)
BMI formula
BMI = Weight (kg) / Height (m)2
What mutation is often associated with primary pulmonary hypertension
BMPR2 inactivating mutation, leading to proliferation of vascular smooth muscle; however etiology is unknown for primary pulmonary HTN
male breast cancer associated with?
BRCA2 mutation and Klinefelter Syndrome
Aortic regurgitation
Backward blood from from the aorta to LV during diastole
What causes fever in endocarditis?
Bacteremia
What usually causes endocarditis?
Bacterial infection
Secondary pneumonia definition
Bacterial pneumonia superimposed on a viral upper respiratory tract infection
Mitral valve prolapse
Ballooning of mitral valve into left atrium during systole
Where are granulomas located when secondary TB goes to the meninges?
Base of the brain
Where and how does radon often accumulate?
Basements as colorless, odorless gas
Wide Splitting
Basically an exaggerated inspiratory splitting; *due to increased RV emptying (e.g. pulmonic stenosis, RBBBs)*
What does Streptococcus viridans infect?
Because it is low virulence, it only infects previously damaged valves (i.e. chronic rheumatic heart disease and mitral valve prolapse)
How do the click and murmur of mitral valve prolapse change with squatting?
Become less due to increased systemic resistance decreasing left ventricular empyting
When does surfactant production begin, and when is it adequate?
Begins: 28 weeks Adequate: 34 weeks
What is a hamartoma?
Benign mass composed of disorganized tissue that is correct tissue for the location
Myxoma
Benign mesenchymal tumor of the heart with a gelatinous appearance and abundant ground substance on histology
Albuterol
Beta2 agonist Relaxes bronchial smooth muscle; used during acute exacerbation
Typical Location of Abdominal Aortic Aneurysm
Between renal arteries and the bifurcation of the aorta; can rupture if *>5cm*
What hastens disease onset of aortic stenosis?
Bicuspid aortic valve
immunohistochemistry markers for multiple myeloma
CD138+, CD20-
markers that tend to be positive in CLL
CD20+, CD23+, CD5+ B-cell neoplasm
what polymorphisms in regulatory T cells are associated with autoimmunity such as MS or DM?
CD25 polymorphisms
What CD marker is associated with HSC?
CD34+
Ag's eliminated by CD4 vs. CD8 cells
CD4 eliminate exogenous ags, such as those derived from extracellular microbes and soluble proteins that have been internalized into the cytoplasm of the APC CD8 eliminate endogenous antigens which are those derived from proteins that have been synthesized within a cell, such as viruses and tumor
what markers are associated with regulator T cells?
CD4+, CD25+ (IL2R), FOXP3+
melanoma assoc. oncogene
CDK4 (cyclin dependent kinase) amplification
Factors Causing Vasodilation in Muscles
CHALK CO2 H+ Adenosine Lactate K+
How does restrictive cardiomyopathy present?
CHF with low voltage EKG and diminished QRS CHF, due to filling problem the blood backs up behind the heart
Why does restrictive cardiomyopathy present as CHF?
CHF, due to filling problem the blood backs up behind the heart
What enzyme do you check in reinfarction in under 7-10 days?
CK-MB
CK-MB/CK ratio
CK-MB/CK > 2.5-3 makes it likely that the heart was damaged CK-MB/ CK < 2.5-3 makes it likely that skeletal muscle was damaged
most common leukemia overall
CLL
Richter transformation
CLL/SLL transformation into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) marked clinically by an enlarging lymph node or spleen
BCR-ABL mutation associated with
CML
Pancoast tumor (superior sulcus tumor)
Carcinoma that occurs int eh apex of the lung may cause Pancoast syndrome by invading cervical sympathetic chain causing Horner syndrome (ipsilateral ptosis, miosis, anhidrosis), SVC syndrome, sensorimotor deficits, or hoarseness.
What is heard during the asymptomatic stage of aortic stenosis?
Cardiac compensation leads to systolic ejection click with crescendo-decrescendo murmur
What can concentric left ventricular hypertrophy in aortic stenosis lead to?
Cardiac failure
complications of hypothermia
Cardiac function - Bradycardia may be physiologic in severe hypothermia and intervention is not needed unless bradycardia persists despite rewarming. Prolongation of all EKG intervals are a characteristic finding in hypothermic patients due to slowed impulse conduction through potassium channels. There may also be elevation of the J point. Hypothermic patients may exhibit arrhythmias (further precipitated by moving the patient) also rhabdo, excessive bleeding (but normal PT/PTT), lactic acidosis
What are three complications of MI within the first four hours?
Cardiogenic shock, congestive heart failure, arrhythmia
What does a biopsy of secondary pneumonia reveal?
Caseating granulomas
Restrictive/Infiltrative Cardiomyopathy
Caused by P LEASH: Post-radiation fibrosis Loffler syndrome Eendocardial fibroelastosis Amyloidosis Sarcoidosis Hemochromatosis
Febrile Nonhemolytic Transfusion Reaction (FNHTR)
Caused by antibodies in the recipient directed against white cells in the unit OR cytokines that accumulate in the plasma of the unit during storage (from WBCs in the unit) Defined by a rise in temp of ≥ 1°C during or within 4 hours after transfusion for which no other cause is identified (diagnosis of exclusion) May also cause tachycardia, palpitations, chills, cough, nausea/vomiting, headache, flushing Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, may administer antipyretics Prevention: Leukocyte reduction; no evidence for premedication (Benadryl) No contraindication to additional transfusion
allergic transfusion rxn
Caused by hypersensitivity to proteins or allergens in the plasma of the transfused unit>mast cell degranulation>histamine release Symptoms: variable severity; urticarial rash and itching, flushing, vomiting/diarrhea, wheezing; severe reactions (rare) may have respiratory distress requiring intubation and hypotension/shock Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, administer antihistamines; epinephrine/bronchodilators/steroids if severe, intubate and give pressors for BP support if needed Prevention: no evidence for pre-medication after mild allergic reactions, consider PAS platelets or washing if severe or recurrent reactions There is no contraindication to future transfusion
restrictive cardiomyopathy
Causes - Postradiation fibrosis, Loeffler syndrome, Endocardial fibroelastosis (thick fibroelastic tissue in endocardium of young children), Amyloidosis, Sarcoidosis, Hemochromatosis (although dilated cardiomyopathy is more common) (Puppy LEASH). Loeffler syndrome — associated with hypereosinophilic syndrome, histology shows eosinophilic infiltrates in myocardium. Diastolic dysfunction ensues. Can have low-voltage ECG despite thick myocardium (especially amyloid). Decreased compliance of the ventricular endomyocardium that restricts filling during diastole Presents as congestive heart failure; classic finding is low-voltage EKG with diminished QRS amplitude
PH due to left heart disease
Causes include systolic/diastolic dysfunction and valvular disease such as mitral stenosis
chronic histoplasmosis presentation
Cavitary disease (looks like TB) Progressive and often fatal form. Develops almost exclusively in older patients who have COPD. Symptoms: Fever, fatigue, anorexia, weight loss, productive cough (purulent sputum), & hemoptysis. CXR: unilateral or bilateral upper lobe infiltrates with multiple cavities and extensive fibrosis in lower lobes
Celiac vs. gluten sensitivity
Celiac disease is an allergy, gluten sensitivity is an intolerance (doesn't induce inflammatory cascade, misnomer- not HSR)
What is the hallmark of reversible cell injury?
Cellular swelling
What are the two major types of emphysema?
Centriacinar emphysema Panacinar emphysema
What type of emphysema do smokers get, and where is it most severe?
Centriacinar emphysema more severe in upper lobes
essential thrombocythemia
Characterized by massive proliferation of megakaryocytes and platelets. Symptoms include bleeding and thrombosis. Blood smear shows markedly increased number of platelets, which may be large or otherwise abnormally formed Associated with JAK2 kinase mutations; symptoms related to risk of bleeding and/or thrombosis
COPD
Characterized by persistent airflow limitation usually progressive associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases Persistent, while asthma is reversible- PFT's will never be normal in COPD even with treatments, they only go back to their baseline, not normal levels
chr translocations in APL
Characterized by t(15;17), which involves translocation of the retinoic acid receptor (RAR) on chromosome 17 to chromosome 15; RAR disruption blocks maturation and promyelocytes (blasts) accumulate t(15;17) PML/RARα, 95% sensitivity, 92% specificity t(11;17); t(5;17), don't respond to ATRA
Eosinophils major basic protein derived crystals in asthma
Charcot-Leyden crystals
How does stable angina present?
Chest pain lasting less than 20 minutes that ratiates to left arm/jaw, perhaps with diaphoresis and shortness of breath
Unstable angina definition
Chest pain that occurs at rest
When does asthma commonly present?
Childhood
Second most common cause of atypical pneumonia in young adults
Chlamydia pneumoniae
Group of diseases characterized by airway obstruction in which the lung does not empty and air is trapped
Chronic Obstructive pulmonary diseases
asthma
Chronic airways inflammation with various inflammatory cells and markers Airway hyperresponsiveness leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing mostly at night and/or early morning Variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment (bronchodilator) (must return to normal range to be considered pure asthma) Airway remodeling (inc smooth muscle cells and mucus glands) persists for the rest of one's life
Cough in chronic bronchitis vs. cough in emphysema
Chronic bronchitis- abundant sputum Emphysema- little sputum
What causes anemia of chronic disease in endocarditis?
Chronic inflammation
Bronchiectasis
Chronic necrotizing infection of bronchi leading to permanently dilated airways, purulent sputum, recurrent infections, and hemoptysis. Associated with bronchial obstruction, poor ciliary motility, CF, allergic bronchopulmonary aspergillosis
Definition of chronic bronchitis
Chronic productive cough lasting at least 3 months over a minimum of 2 years
What causes mitral stenosis?
Chronic rheumatic valve disease
Name three risk factors for lung cancer
Cigarette smoke, radon, asbestos
Where does bronchioloalveolar carcinoma arise from?
Clara cells
How is chronic bronchitis defined?
Clinically
IgM-mediated immune hemolytic anemia
Cold (IgM and complement)—acute anemia triggered by cold; seen in CLL, Mycoplasma pneumoniae infections, and infectious Mononucleosis ("cold weather is MMMiserable"). RBC agglutinates A may cause painful, blue fingers and toes with cold exposure IgM-mediated disease also usually involves extravascular hemolysis IgM binds RBCs and fixes complement in the relatively cold temperature of the extremities RBCs inactivate complement, but residual C3b serves as an opsonin for splenic macrophages resulting in spherocytes; extreme activation of complement can lead to intravascular hemolysis
What does lack of surfactant lead to?
Collapse of air sacs (making it hard to fill them back up) and formation of hyaline membrane disease
Surfactant & collapsing prssure
Collapsing pressure (P) = 2(surface tension)/radius Alveoli have an increased tendency to collapse on expiration as radius decreases pulmonary surfactant is a complex mis of lecithins, the most important of which is dipalmitoylphosphatidylcholine. Surfactant synthesis begins around week 26 of gestation, but mature levels are not achieved until around week 35.
What causes nothing of ribs in adult coarctation of the aorta
Collateral circulation develops across the intercostal arteries in order to attempt to bypass the block; this causes engorged arteries and a notching of ribs on xray
Anthracosis definition
Collections of carbon-laden macropahges due to mild exposure to carbon (i.e. pollution); not clinically significant because it is common due to exposure to toxins in air
Langerhans cell histiocytosis
Collective group of proliferative disorders of dendritic (Langerhans) cells. Presents in a child as lytic bone lesions A and skin rash or as recurrent otitis media with a mass involving the mastoid bone. Cells are functionally immature and do not effectively stimulate primary T cells via antigen presentation. Cells express S-100 (mesodermal origin) and CD1a (and HLA-DR). Birbeck granules ("tennis rackets" or rod shaped on EM) are characteristic B. Langerhans cells are specialized dendritic cells found predominantly in skin. Derived from bone marrow monocytes; present antigen to naïve T cells
Common bifurcations
Common carotid bifurcates at C4 trachea bifurcates at T4 abdominal aorta bifurcates at L4
What layer of the heart do mets usually involve, and what does it cause?
Commonly involve pericardium; causes pericardial effusion
What is the next step upon finding a coin lesion on x-ray
Compare to prior x-ray to see if it is new (likely lung cancer) or not
plasma
Contains both pro- and anticoagulant factors Primarily used for replacing clotting factors Volume 250-300 mL From whole blood or apheresis collection Frozen at -18 °C for up to 1 year Thaw at 30-37 °C for 30 mins in water bath or validated microwave oven, expires 5 days from time of thawing Must be ABO compatible with pt's RBCs, Rh doesn't matter (recall that they don't have naturally-occurring Rh Ab's)
short bowel syndrome treatment
Continuous or small bolus feedings Reduces osmotic load in small bowel Higher fat diets Decreases osmotic load to the small bowel Stimulates gut adaptation Aggressive enteral nutrition Stimulates gut adaptation Vitamin & Mineral replacement Recognize & treat bacterial overgrowth (especially if IC valve resected)
Left Horn of Sinus Venosus Give Rise to ______
Coronary sinus
refeeding syndrome recommendations
Correct electrolyte deficiency prior to feeding Guidelines for 1st Week (pt's regimen must be individualized): Fluid Intake: 800 cc/day + insensible losses Fluid Accumulation: Weight gain > 0.25 kg/day or 1.5 kg/week Calories: ~ 15 kcal/kg (recall that 30 kcal/kg is recommendation for healthy person) Other Electrolytes: Liberal use of magnesium, phosphorus, potassium with normal Cr Monitor Daily: o Body weight Fluid intake Urine output o Blood glucose Electrolytes
What is the most common presenting symptom of sarcoidosis?
Cough
What usually causes myocarditis
Coxsackie A or B
Aortic Stenosis
Crescendo-decrescendo systolic ejection murmur (ejection click may be present); loudest at heart base, *radiates to carotids* -Can lead to Syncope, Angina, and Dyspnea on exertion (SAD) -Most commonly due to agerelated *calcification in older patients (> 60 years old) or in younger patients with early-onset calcification of bicuspid aortic valve*
critical closing pressure
Critical closing pressure (PCRIT) is the intraluminal pressure at which the UA collapses PCRIT becomes progressively less negative from non-snorers and snorers to OSA Activation of UA dilator muscles lowers PCRIT want it to be the most negative- most negative when awake
Clinical features of MI
Crushing chest pain for more than 20 minutes that radiates to left arm or jaw, diaphoresis, dyspnea, symptoms not relieved by nitroglycerin
cuffed vs. cuffless tracheostomy tubes
Cuffed Tubes - Patients who need ventilation require tracheostomy tubes that are blocked and sealed by a cuff (balloon) on the lower outer cannula. Cuff blocks any air from flowing around the tube and assures that the patient is well oxygenated. All the air must therefore flow in and out through the tube itself. Cuffless Tubes - Primarily used in non-ventilated patients that have no difficulty swallowing and have no danger of aspiration. Since there is no cuff, it allows air to pass into the upper trachea and larynx so the patient can cough and speak normally
How do defects with right to left shunting present at birth?
Cyanosis
What do you test a child with nasal polyps for?
Cystic fibrosis
DLCO
DLCO = diffusion capacity of the lung for carbon monoxide Single-breath DLCO measures the capacity of the lung to transfer gas Exhale to RV → inhale CO gas mixture → 10 sec breath-hold at TLC → exhale. Analyze exhaled gas for amount of CO transferred to capillary blood. DLCO components: 1) membrane conduction - gas transfer across alveolo-capillary membrane 2) blood conduction - COHb reaction rate & blood (Hb) volume
most common cause of PE?
DVT thromboembolus from femoral, iliac, or popliteal veins
Intrinsic mitochondrial pathway (apoptosis)
Damage (cell injury, DNA damage, decreased hormonal stimulation) -> inactivation of Bcl2 (normally stabilizes mito membrane) -> mito membrane damage -> leakage of cytC binds to form apoptosome -> caspase activated (caspase 9 is initiator) -> executioner caspases 3 and 6 activate DNases and other enzymes Major mechanism of apoptosis in mammal cells
Pathogenesis of ARDS
Damage to alveolar-capillary interface leads to leakage of protein-rich fluid, which causes edema and is reorganized with necrotic epithelial cells to form hyaline membranes in alveoli
Pathogenesis of Streptococcus viridans endocarditis (subacute endocarditis)
Damaged endocardial surface develops thrombotic vegetations with platelet and fibrin; transient bacteremia causes bacteria to be trapped in vegetations
What does ACE inhibitor do in MI treatment?
Decrease LV dilation
Pulmonary circulation perfusion limited vs diffusion limited
Decrease in PAo2 leads to pulmonary vasoconstriction. Perfusion limited: Oxygen (normal health), CO2, N2O. Gas equilibrates early along the length of the capillary. Diffusion can only be increased if blood flow increases. Diffusion limited: oxygen (emphysema, fibrosis), CO. Gas does not equilibrate by the time blood reaches the end of the capillary.
How is FRC altered in fibrosis?
Decreased
Spirometry findings in obstructive pulmonary diseases
Decreased FVC, decreased FEV1, decreased FEV1/FVC, increased TLC (due to air trapping)
TLC, FEV1, FVC, and FEV1:FVC in restrictive diseases
Decreased TLC, decreased FEV1, decreased FVC, and increased FEV1:FVC ratio
Ischemia
Decreased blood flow to an organ
Stenosis
Decreased caliber of the valve orifice
Restrictive cardiomyopathy definition
Decreased compliance of the ventricular endomyocardium that restricts filling during diastole
What activates renin-angiotensin system in CHF?
Decreased flow to kidney
What two things cause the clinical features of left sided CHF?
Decreased forward perfusion and pulmonary congestion
How does insulin affect surfactant production?
Decreases
What is the role of surfactant in the lungs?
Decreases surface tension in the lung to prevent the collapse of alveolar air sacs after respiration
thiamine (B1) deficiency
Deficiency in those with: s/p bariatric surgery EtOH abuse Chronic TPN Dry beriberi: Symmetrical peripheral neuropathy with sensory and motor (usually distal extremities) Wet beriberi: Neuropathy + Cardiac (cardiomegaly, cardiomyopathy, CHF, peripheral edema, tachycardia) Wernicke-Korsakoff Syndrome: Wernicke Triad: Nystagmus Ophthalmoplegia Ataxia Korsakoff Psychosis: Impaired short-term memory Confabulation Otherwise normal cognition
chronic bronchitis
Defined CLINICALLY productive cough for 3 months productive cough for 2 consecutive years Pathologic Findings Involvement of small (<2mm) and larger (2-4mm) airways Infiltration of surface epithelium Enlarged mucus secreting glands & goblet cells>mucus hypersecretion Other causes of productive cough must be excluded
emphysema
Defined PATHOLOGICALLY (but CT or xray can be used instead of biopsy) enlargement of air spaces distal to the terminal bronchioles destruction of air space walls dilatation & destruction of respiratory bronchioles Other findings Loss of elastic recoil & abnormal gas exchange Centrilobular emphysema Destruction of alveolo-capillary bed Pulmonary vascular changes: vessel wall thickening, intima thickening, increased smooth muscle, inflammatory infiltration of vessels
CML
Defined by the Philadelphia chromosome (t[9;22], BCR-ABL) and myeloid stem cell proliferation. Presents with dysregulated production of mature and maturing granulocytes (eg, neutrophils, metamyelocytes, myelocytes, basophils) and splenomegaly. May accelerate and transform to AML or ALL ("blast crisis") Splenomegaly is common. Enlarging spleen suggests progression to accelerated phase of disease; transformation to acute leukemia usually follows shortly thereafter Can transform to AML (2/3 of cases) or ALL (1/3) of cases since mutation is in pluripotent stem cell
Abscess formation
Definition: A localized collection of pus in any body part, resulting from invasion of a pyogenic bacterium or other pathogen. The abscess is surrounded by a membrane of variable strength created by macrophages, fibrin, and granulation tissue. Abscesses can disrupt function in adjacent tissues and can be life threatening in some circumstances.
What causes the gray hepatization that follows red hepatization in pneumonia?
Degradation of red cells within the exudate
acute respiratory distress syndrome
Diagnosis of exclusion characterized by respiratory failure within 1 week of alveolar insult, bilateral lung opacities, dec PaO2/FiO2 < 300 (hypoxemia due to inc intrapulmonary shunting and diffusion abnormalities), no evidence of HF/fluid overload. Many causes and associations, including sepsis, pancreatitis, pneumonia, aspiration, trauma, shock. Endothelial damage> inc alveolar capillary permeability>protein-rich leakage into alveoli>diffuse alveolar damage and noncardiogenic pulmonary edema (normal PCWP) Results in formation of intra- alveolar hyaline membranes Initial damage due to release of neutrophilic substances toxic to alveolar wall and pulmonary capillary endothelial cells, activation of coagulation cascade, and oxygen-derived free radicals. Diffuse damage to the alveolar-capillary interface (diffuse alveolar damage) Leakage of protein-rich fluid leads to edema that combines with necrotic epithelial cells to form hyaline membranes in alveoli Clinical Features: Hypoxemia and cyanosis with respiratory distress - due to thickened diffusion barrier and collapse of air sacs (increased surface tension); "white-out" on chest x-ray Secondary to a variety of disease processes including sepsis, infection, shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity reactions, and drugs. Activation of neutrophils induces protease-/free radical-mediated damage of type II/II pneumocytes Management: mechanical ventilation with low tidal volumes (+PEEP), address underlying cause. Recovery may be complicated by interstitial fibrosis; damage and loss of type II pneumocytes leads to scarring and fibrosis Renal Failure - Na+/H2O retention Mannitol - inc hydrostatic pressure from drawing water into ECF Treatment Nitrates; Opioids; Loop Diuretics
Jones Criteria
Diagnostic criteria for acute rheumatic fever
When does aortic regurgitation occur?
Diastole
Is diastole or systole affected by restrictive cardiomyopathy?
Diastole (can't fill)
What is the dysfunction (diastolic or systolic) in hypertrophic cardiomyopathy?
Diastolic due to left ventricular hypertrophy, ventricle can't fill
Mitral Stenosis
Diastolic murmur w/ *opening snap* (due to abrupt halt in leaflet motion in diastole, after rapid opening due to fusion at leaflet tips) -Often occurs 2° to *rheumatic fever*; chronic mitral stenosis can result in LA dilatation -*PCWP > LV end diastolic pressure*
obesity treatments for each BMI cutoff
Diet and physical activity recommended with BMI ≥ 30.0 or lower if risk factors present Pharmacotherapy recommended with BMI ≥ 30.0 or ≥ 27.0 if obesity-related disease present Bariatric surgery recommended with BMI ≥ 40.0 or ≥ 35.0 if obesity-related disease present (hypertension, diabetes, sleep apnea, incapacitating osteoarthritis)
How does x-ray of infant with neonatal respiratory distress syndrome appear?
Diffuse granularity of lung with ground glass appearance
Diffusion equation
Diffusion: Vgas= A/T x Dk(P1-P2) A = area T = alveolar wall thickness Dk(P1-P2) = difference in partial pressures: A decreases in emphysema T increases in pulmonary fibrosis
What is the most common cardiomyopathy?
Dilated cardiomyopathy
How does dilated cardiomyopathy cause left sided heart failure?
Dilation of the four chambers prevents them from pumping well
Coombs tests
Direct Coombs test—anti-Ig antibody (Coombs reagent) added to RBCs. RBCs agglutinate if coated with Ig. Indirect Coombs test—normal RBCs added to patient's serum. If serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent added
Where does coarctation in adult coarctation of the aorta lie?
Distal to aortic arch
Coronary Steal Syndrome
Distal to coronary stenosis, vessels are maximally dilated at baseline. Administration of vasodilators (e.g. dipyridamole, regadenoson) dilates normal vessels and shunts blood toward well-perfused areas -> decreased flow and ischemia in post-stenotic region -Principle behind *pharmacologic* stress tests!
Conducting Zone
Does not participate in gas exchange.
Why isn't reverse blood typing done with Rh D groups?
Don't do reverse type for Rh b/c Rh isn't naturally occurring- Rh negative person doesn't necessarily have Rh antibodies
When and how to give transfusion
Don't transfuse until someone gets down to 7 or 8, and give one unit at a time (evaluate after each unit is given)
transfusion-related acute lung injury (TRALI)
Donor anti-leukocyte antibodies against recipient neutrophils and pulmonary endothelial cells. Occurs within 6 hours. Clinical Presentation - Respiratory distress and noncardiogenic pulmonary edema. Number one cause of transfusion-related death Plasma containing blood products in the past, now probably RBCs new bilateral pulmonary infiltrates Does not improve with diuretics (as opposed to TACO) Majority of patients will recover, usually within 96 hours (as opposed to ARDS) Patient may receive additional transfusion, but donor may be permanently deferred
Secondary causes of interstitial fibrosis that need to be excluded when Idiopathic Pulmonary Fibrosis is on the Differential
Drugs (bleomycin and amiodarone) and radiation therapy
thrombotic thrombocytopenic purpura (TTP)
Due to decreased ADAMTS13, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation>large, uncleaved multimers lead to abnormal platelet adhesion>microthrombi Decreased ADAMTS13 is usually due to an acquired autoantibody; most commonly seen in adult females schistocytes, inc LDH, normal coag studies treatment- plasmapheresis, corticosteroids associated with history of viral illness and lymphoma/CLL/HIV/Connective tissue diseases
Mechanism of Hypertrophic Cardiomyopathy
Due to increased afterload and resulting increased wall tension, myocardium hypertrophies to decreased wall tension
Traumatic Aortic Rupture
Due to trauma and/or deceleration injury, most commonly at *aortic isthmus (proximal descending aorta just distal to origin of left subclavian artery)*
What is cancer risk from smoking directly related to?
Duration and amount of smoking (pack years)
What are the results of pulmonary edema in CHF?
Dyspnea, paroxysmal nocturnal dyspnea, orthopnea, crackles
What causes destruction of the air sacs in emphysema?
Either too many proteases released or deficiency of anti-proteases
Elastic recoil Resting chest capacity
Elastic recoil = tendency for lungs to collapse inward and chest wall to spring outward. At FRC, inward pull of lung is balanced by outward pull of chest wall, and system pressure is atmospheric. Elastic properties of both chest wall and lungs determine their combined volume. At FRC, airway and alveolar pressures are zero, and intrapleural pressure is negative (prevents pneumothorax). PVR is at minimum.
What are two tests to determine if there was a prior group A beta-hemolytic strep infection?
Elevated AS or anti-DNase B titers
lab findings in rhabdo
Elevated Creatine Kinase (CK) (5X upper limit) rises 2-12hrs, peaks 24-72hrs, declines 3-5d Elevations in aminotransferases and LDH may be seen Myoglobinuria - myoglobin released from damaged muscle is rapidly excreted in the urine. Proteinuria - this can be caused by the release of myoglobin and other proteins by damaged myocytes Fluid/electrolyte abnormalities - Hypovolemia; Hyperkalemia; Hyperphosphatemia; Hypocalcemia
What causes Janeway lesions, Osler nodes, Roth spots, and splinter hemorrhages in the nail bed in endocarditis?
Embolization of septic vegetations
2 types of lymphoid tissues
Encapsulated: connective tissue capsule Spleen, thymus, lymph nodes Unencapsulated (or partly encapsulated) Tonsils, Peyer's patches, lymphoid nodules in GI tract, respiratory tract, urinary & reproductive tracts
What is a cause of restrictive cardiomyopathy in children?
Endocardial fibroelastosis
What are HACEK organisms associated with?
Endocarditis with negative blood cultures because these organisms are hard to grow
Loffler Syndrome
Endomyocardial fibrosis w/ prominent *eosinophilic infiltrate* -> restrictive/infiltrative cardiomyopathy
Loeffler syndrome
Endomyocardial fibrosis with eosinophilic infiltrate and eosinophilia
Formation of Atherosclerotic Plaque
Endothelial cell dysfunction -> macrophage and LDL accumulation -> *foam cell* formation -> *fatty streaks* -> *smooth muscle cell migration* (involves *PDGF and FGF*), proliferation, and extracellular matrix deposition -> fibrous plaque complex -> calcium deposition and crystallization -> atheromas -https://www.youtube.com/watch?v=MjC1-odNY5k
chronic lymphadenitis
Enlarged and non-tender because enlargement occurs slowly over a longer period of time Groin and axillary nodes are common sites of involvement.
Emphysema (pink puffer)
Enlargement of air spaces, decreased recoil, increased compliance, decreased diffusing capacity for CO resulting form destruction of alveolar walls. Two types: Centroacinar (smoking) Panacinar (associated with alpha1-antitrypsin deficiency) Increased elastase activity leads to loss of elastic fibers and decreased lung compliance Exhalation through pursed lips to increase airway pressure and prevent airway collapse during respiration. Barrel chest.
oral appliances for OSA
Enlarging upper airway Decreasing upper airway collapsibility Mandibular repositioning appliances (MRA) Mandibular advancing device (MAD) Cover the upper and lower teeth Hold the mandible in an advanced position Only for snoring or mild to moderate OSA
Name the three layers of the heart; in which layer do the coronary arteries begin?
Epicardium; myocardium; endocardium; coronary arteries begin in the epicardium
Prinzmetal angina definition
Episodic chest pain unrelated to exertion but caused by coronary artery vasospasm (artery clamps down and cuts blood supply)
prinzmetal angina
Episodic chest pain unrelated to exertion. Occurs at rest 2° to coronary artery spasm; transient ST elevation on ECG. Smoking is a risk factor, but hypertension and hypercholesterolemia are not. Triggers may include cocaine, alcohol, and triptans. Due to coronary artery vasospasm; Represents reversible injury to myocytes (no necrosis) EKG shows ST-segment elevation due to transmural ischemia. Relieved by nitroglycerin or calcium channel blockers
enlarged epitrochlear node indicates
Epitrochlear nodes are not normally palpable, but are always pathologic:
HOCM Best Heard at _____ During _____
Erb's point during systole
Annular, nonpruritic rash with erythematous borders (more red at margins) that commonly involves trunk and limbs
Erythema marginatum in acute rheumatic fever
extrinsic receptor-ligand pathway (apoptosis)
FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases or TNF binds TNF receptor on target cell, activating caspases 8 and 10 -> activate DNases and proteolytic enzymes -> apoptotic bodies -eg. negative selection of thymocytes in thymus
What are the Jones criteria for diagnosing acute rheumatic fever
Evidence of prior group A beta-hemolytic strep infection with the presence of major and minor criteria
main treatment for hairy cell leukemia
Excellent response to 2-CDA (cladribine), an adenosine deaminase inhibitor; adenosine accumulates to toxic levels in neoplastic B cells
What causes vocal cord nodule?
Excessive use of vocal cords
How does pulmonary hypertension present?
Exertional dyspnea or right sided heart failure
result of transfusion of one unit of platelets
Expected response to 1 apheresis unit: 30-50K
result of transfusion of one unit of packed RBC's
Expected response to transfusion of one unit: Hemoglobin inc 1 g/dL, hematocrit inc of 3%
markers in hairy cell leukemia
Express B-cell markers CD19 and CD20, surface Ig (usually IgG), and CD11c, CD25, CD103, and annexin A1
hereditary spherocytosis
Extravascular hemolysis due to defect in proteins interacting with RBC membrane skeleton and plasma membrane (eg, ankyrin, band 3, protein 4.2, spectrin). Mostly autosomal dominant inheritance. Results in small, round RBCs with less surface area and no central pallor (inc MCHC)>premature removal by spleen. Findings: Splenomegaly, aplastic crisis (parvovirus B19 infection). Labs: osmotic fragility test ⊕. Normal to dec MCV with abundance of cells. Treatment: splenectomy. Membrane blebs are formed and lost over time - Loss of membrane renders cells round (spherocytes) instead of disc-shaped. Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in extravascular anemia.
What causes red hepatization phase in pneumonia?
Exudate, neutrophils, and hemorrhage filling the alveolar air spaces, giving the normally spongy lung a solid consistency
symptoms of TTP and HUS
FAT RN - Fever, MAH Anemia, Thrombocytopenia, Renal and Neurologic symptoms Renal insufficiency (more common in HUS) - Thrombi involve vessels of the kidney. CNS abnormalities (more common in TTP) - Thrombi involve vessels of the CNS
common causes of noncaseating granulomas
FB, sarcoidosis, beryllium exposure, Crohn dz, cat scratch dz (bartonella henselae)
cut-off value for obstructive disease
FEV1/FVC<.7 indicates obstruction Anything over .7 is considered to be normal but a healthy person should be able to expire at least 80% in first second
What markers indicates a poor prognosis in APL?
FLT3 (positive in 40% of cases)
IPEX syndrome is caused by what and what does it stand for?
FOXP3 mutations in regulatory T cells -immune dysregulation, polyendocrinopathy (thyroid and pancreas), enteropathy (diarrhea), X linked
Cause of Transposition of the Great Vessels
Failure of the aorticopulmonary septum to spiral
pathophys of OSA symptoms
Fall in SaO2 Snoring (alternating with periods of silence) Arrhythmias ↓ HR during UA obstruction ↑ HR during apnea termination Arousal at apnea termination ↑ BP in the immediate post‐apneic period
other OSA risk factors
Family history, obesity, age, male gender Smoking and alcohol use Medications (muscle relaxants) Primary disorders: Untreated hypothyroidism Acromegaly Androgen therapy (for low T) Neuromuscular disorders Stroke
types of psychotherapy for eating disorders
Family therapy Cognitive behavioral therapy (know your feelings) Psychodynamic psychotherapy (know how your day affects your behaviors) Non-specific supportive clinical management Interpersonal psychotherapy (know the connection between relationships and symptoms) Psychodynamic psychotherapy + Dialectical behavior therapy (develop skills to regulate behavior)
Trisomy 18 (Edwards Syndrome)
Features: PRINCE edward: prominent occiput, rocker-bottom feet, intellectual disability, nondisjunction, clenched fists, low set Ears, micrognathia 1/8000 births rarely live past 1 year
Trisomy 13 (Patau Syndrome)
Features: severe intellectual disability, rocker bottom feet, microphthalmia, microcephaly, cleft palate, holoprosenechephaly, polydactyly, polycystic kidney dz 1/15k births rarely live past 1 year
Clinical features of pneumonia
Fever and chills, productive cough with yellow-green (pus) or rusty (blood) sputum, tachypnea with pleuritic chest pain, decreased breath sounds, dullness to percussion, elevated WBC
Name two minor criteria in Jones criteria
Fever or elevated ESR
How does hypersensitivity pneumonitis present?
Fever, cough, dyspnea just hours after exposure
Clinical features of secondary TB
Fevers, night sweats, cough with hemoptysis, weight loss
What is the main complication during neutrophilic phase after MI (1-3 days)
Fibrinous pericarditis, which presents as chest pain and friction rub
Idiopathic pulmonary fibrosis defintion
Fibrosis of lung interstitium
Idiopathic pulmonary fibrosis findings on CT
Fibrosis, initially seen in subpleural patches but eventually results in diffuse fibrosis with end-stage "honeycombing" of the lung
crossmatching
Final safety step to screen for ABO incompatibility prior to prbc transfusion Take a sample of the prbcs you are planning to transfuse and mix with your patient's plasma Results: No agglutination=crossmatch compatible Agglutination (sticking)=crossmatch incompatible In patients with no prior history of any non-ABO antibodies, can perform an electronic crossmatch/computer crossmatch
intravascular hemolysis
Findings: dec haptoglobin, inc schistocytes on blood smear. Characteristic hemoglobinuria, hemosiderinuria, ad urobilinogen in urine. May also see inc unconjugated bilirubin. Notable causes are mechanical hemolysis (eg, prosthetic valve), paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemia
extravascular hemolysis
Findings: macrophages in spleen clear RBCs. Spherocytes in peripheral smear (most commonly hereditary spherocytosis and autoimmune hemolytic anemia), no hemoglobinuria/ hemosiderinuria. Can present with urobilinogen in urine
CPAP
First line treatment of OSA Provides continuous (fixed) pressure above ambient pressure Pressure remains relatively constant through each phase of the respiratory cycle, varying only slightly as the patient breathes Pressure stents airway open Moderate to Severe OSAS (AHI ≥ 15) [Indicated] Mild OSAS (AHI ≥ 5 - 14.9) [Recommended] Must have symptoms of Excessive Daytime Sleepiness HTN, Ischemic Heart Disease, or History of Stroke Impaired Cognition, Mood disorder, or Insomnia
cardinal signs of inflammation?
First signs: redness (vasodilation-histamine), warmth (relaxation of arteriolar SM 2/2 histamine, bradyk, PGs) Followed by: swelling (exudate from vas. perm and proteins leak out-histamine, LT, brady), pain (PGE2 and bradyk), then: fever (IL-1 from macrophages or TNF ->COX stimulation ofperivascular cells of hypothalamus -> PGE2 produced -> raised temp set point of body)
Primary TB
Focal, caseating necrosis in lower lobe of the lung and hilar lymph nodes that undergo fibrosis and calcification, forming a Ghon complex
Aschoff bodies
Foci of chronic inflammation with Anitschkow cells, giant cells, and fibrinoid material
JONES Criteria
For rheumatic heart disease Joints (migratory polyarthritis) <3 (carditis) Nodules (subq nodules) Erythema marginatum Sydenham chorea
How does carcinoid tumor appear if it is centrally located?
Forms polyp-like mass in bronchus
maxillomandibular advancement
Fracture mandible and maxilla and move them forward Radical, but very effective in severe cases, especially in those with retrognathia
What does pericarditis of acute rheumatic fever cause?
Friction rub and chest pain
Vitamin B12 (cobalamin)
Function: FUNCTION DEFICIENCY Cofactor for methionine synthase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase. Important for DNA synthesis. Deficiency: Macrocytic, megaloblastic anemia; hypersegmented PMNs; paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin. Associated with increased serum homocysteine and methylmalonic acid levels, along with 2° folate deficiency. Prolonged deficiency irreversible nerve damage. Found in animal products. Synthesized only by microorganisms. Very large reserve pool (several years) stored primarily in the liver. Deficiency caused by malabsorption (eg, sprue, enteritis, Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), absence of terminal ileum (surgical resection, eg, for Crohn disease), or insufficient intake (eg, veganism). Anti-intrinsic factor antibodies diagnostic for pernicious anemia.
Vitamin K (phytomenadione, phylloquinone, phytonadione) function
Function: Activated by epoxide reductase to the reduced form, which is a cofactor for the γ-carboxylation of glutamic acid residues on various proteins required for blood clotting. Synthesized by intestinal flora. -K is for Koagulation. Necessary for the maturation of clotting factors II, VII, IX, X, and proteins C and S. Warfarin inhibits vitamin K-dependent synthesis of these factors and proteins. Deficiency: Neonatal hemorrhage with PT and aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitamin K). Can also occur after prolonged use of broad-spectrum antibiotics. Not in breast milk; neonates are given vitamin K injection at birth to prevent hemorrhagic disease of the newborn.
Vitamin A (retinol)
Function: Antioxidant constituent of visual pigments (retinal); essential for normal differentiation of epithelial cells into specialized tissue (pancreatic, mucus secreting); prevents squamous metaplasia. Used to treat measles and APL Retinol is Vitamin A --> retin-A (used to treat wrinkles and Acne) -oral isotretinoin for sever cystic acne Found in liver and leafy vegetables Deficiency: Night blindness (nyctalopia), dry, scaly skin (xerosis cutis), corneal deregulation (keratomalcia); Bitot spots of conjunctiva; immunosuppresion Excess: Acute- nausea, vomiting, vertigo, and blurred vision Chornic- alopecia, dry skin (scaliness), hepatic toxicity, and enlargement arthraligas, psedotumor cerebra Teratogenic (cleft palate, cardiac) -negative pregnancy test and two forms of contraception are required before isotretinoin
Vitamin C (ascorbic acid)
Function: Antioxidant; also facilities iron absorption by reducing it to Fe2+ state. Necessary for hydroxylation of proline and lysine in collagen synthesis. Necessary for dopamine beta-hydrolase, which converts dopamine to NE -Ancillary treatment for methemoglobinemia Deficiency: Scurvy—swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, "corkscrew" hair. Weakened immune respons Excess: Nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis. Can risk of iron toxicity in predisposed individuals (eg, those with transfusions, hereditary hemochromatosis).
Vitamin B3 (niacin)
Function: Constituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan. Synthesis requires B2 and B6. Used to treat dyslipidemia; lowers levels of VLDL and raises HDL Deficiency: Glossitis. Severe leads to pellagra, which can be caused by Hartnup disease, malignant carcinoid syndrome (increase tryptophan metabolism), and isoniazid (decrease B6). Pellagra- Diarrhea, Dementia (and hallucinations), Dermatitis (C3/C4 dermatome circumferential "broad collar" rash [Casal necklace], hyper pigmentation of unexposed limbs Hartnup- autosomal recessive. Deficiency of neutral amino acid (tryptophan) transporter in proximal renal tubular cells and or erythrocytes --> neutral aminoaciduria and decrease absorption from gut --> decrease tryptophan conversion to niacin --> pellagra-like symptoms. Treat with high protein diet Excess: facial flushing (induced by prostaglandins, not histamine, can avoid by taking aspirin with niacin), hyperglycemia, hyperuricemia
Vitamin B6 (pyridoxine)
Function: Converted to pyridoxal phosphate (PLP), a cofactor used in transamination (ALT/AST), decarboxylation reactions, glycogen phosphorylates. Synthesis of cystathione, heme, niacin, histamine, neurotransmitters. Deficiency: Convulsions, hyper irritability, peripheral neuropathy (deficiency inducible by isonaizd and OCT), sideroblastic anemia due to impaired hemoglobin synthesis and excess iron
Vitamin B9 (folate)
Function: Converted to tetrahydrofolic acid (THF), a coenzyme for 1-carbon transfer/methylation reactions. Important for the synthesis of nitrogenous bases in DNA and RNA; Found in leafy green vegetables. Absorbed in jejunum. Folate from foliage. Small reserve pool stored primarily in the liver. Deficiency: Macrocytic, megaloblastic anemia; hypersegmented polymorphonuclear cells (PMNs); glossitis; no neurologic symptoms (as opposed to vitamin B12 deficiency). Labs: homocysteine, normal methylmalonic acid levels. Most common vitamin deficiency in the United States. Seen in alcoholism and pregnancy. Deficiency can be caused by several drugs (eg, phenytoin, sulfonamides, methotrexate). Supplemental maternal folic acid at least 1 month prior to conception and during early pregnancy to risk of neural tube defects.
Zinc
Function: Mineral essential for the activity of 100+ enzymes. Important in the formation of zinc fingers (transcription factor motif). Deficiency: Delayed wound healing, hypogonadism, decreased adult hair (axillary, facial, pubic), dysgeusia, anosmia, acrodermatitis enteropathica A . May predispose to alcoholic cirrhosis.
Vitamin B1 (thiamine)
Function: Thiamine pyrophosphate (TPP), a cofactor for several dehydrogenase enzyme reactions -pyruvate dehydrogenase (glycolysis link to TCA) -alpha-ketoglutarate dehydrogenase (TCA cycle) -Transketolase (HMP shunt) -Branched-chain ketoacid dehydrogenase Deficiency: impaired glucose breakdown --> ATP deletion worsened by glucose infusion; Highly aerobic tissues (brain, heart) affected first. In alcoholic/malnourished, give thiamine before dextrose to decrease risk of Wernicke encephalopathy Diagnosis --> increase RBC transketolase activity following B1 adminstration
Vitamin B5 (pantothenic acid)
Function: essential component of CoA (cofactor for acyl transfers) and fatty acid synthase Deficiency: Dermatitis, enteritis, alopecia, adrenal insufficiency
Why do those with hypertrophic cardiomyopathy get syncope with exercise?
Functional aortic stenosis due to subaortic hypertrophy of ventricular septum
What does chronic rheumatic heart disease cause in aoritc valve when it is involved?
Fusion of the commissures
acute hemolytic transfusion rxn
Generally occurs with PRBCs Caused by preformed IgM ABO alloantibodies in recipient that bind to antigens on the transfused red blood cells and cause acute INTRAVASCULAR hemolysis Most common initial symptom is fever, also may have flank pain, "sense of impending doom", hemoglobinuria, renal failure, nausea/vomiting, hypotension/shock Severity of the reaction is directly proportional to the volume of rbcs infused Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, supportive care No additional transfusions until the etiology is determined, unless it is a bleeding emergency Usually occurs due to ABO mismatch (mistake)
What is the most common cause of aspiration pneumonia, generally and then 3 organisms specifically?
Generally: most often due to anaerobic bacteria in the oropharynx Specifically: Bacteroides, Fusobacterium, peptococcus
Genes Involved in HOCM
Genes encoding for sacromeric proteins such as: -*Myosin binding protein C* -*Beta-myosin heavy chain* -Is associated w/ *Friedreich ataxia*
Homocystinuria
Genetic defect: *Cystathionine* synthase deficiency, *low affinity* of cystathionine synthase for B6, or *methionine synthase* deficiency Inheritance: AR *All forms result in excess homocysteine* Features: *HOMOCY*stinuria -> high Homocysteine in urine, Osteoporosis, Marfanoid habitus, Ocular changes (downward and inward lens sublux), CV effects (thromobsis and atherosclerosis -> stroke and MI), kYphosis, intellectual disability Treatment: depends on enzyme affected - increase downstream product and add B6 and folate
Digeorge syndrome
Genetic defect: 22q11.2 deletion - TBX1 gene is in this region -> responsible for development of palate, parathyroids, thymus Features: Cleft palate, Abnormal facies, Thymic aplasia -> T-cell deficiency, Cardiac defects, and Hypocalcemia 2° to parathyroid aplasia. (*CATCH-22*) 1/4000 live births Dx: with FISH
Maple Syrup Urine Disease
Genetic defect: Blocked degradation of *branched* amino acids (Isoleucine, Leucine, Valine) d/t decreased *branched chain alpha-ketoacid dehydrogenase* (B1) -> HIGH alpha-ketoacids in blood, esp of leucine Inheritance: AR Features: vomiting, FTT, urine smells like burnt sugar -> severe CNS effects, intellectual disability, death Treatment: restriction of branched chain AA, B1 supplementation
Huntington disease
Genetic defect: CAG repeat -> polyglutamine repeats in huntingtin gene on Chr 4 Inheritance: AD patho: neuronal death via NMDA-R binding and glutamate excitotoxicity Features: caudate and putamen atrophy -> has decreased ACh and GABA, increased dopamine, and ex vacuo ventriculomegaly; sx start 20-50 YO with chorea, athetosis, aggression, depression, dementia Anticipation occurs
Alkaptonuria
Genetic defect: Congenital deficiency of *homogentisate oxidase* -> cannot degradate tyrosine to fumarate -> pigment-forming homogentisic acid accumulates in tissue Inheritance: AR *BENIGN* Features: bluish-black CT, ear cartilage, sclerae; urine turns black on prolonged exposure to air can have debilitating arthralgias
Cri du chat syndrome - *cry* of the *cat*
Genetic defect: Congenital deletion of short arm of chr 5 Inheritance: Features: microcephaly, moderate to severe intellectual disability, high-pitched *cry*ing/*meow*ing, epicanthal folds, VSD
Williams Syndrome
Genetic defect: Congenital microdeletion of long arm of Chr 7 (includes elastin gene) Inheritance: Congenital Features: distinctive *elfin facies*, intellectual disability, hypercalcemia (increased sensitivity to vitamin D), cocktail personality, CV problems (supravalvular aortic stenosis, renal artery stenosis) Think *Will* Ferrell in *ELF*
Friedreich ataxia
Genetic defect: GAA triplet expansion in the *Frataxin gene (FXN) on chr 9* -> cannot make mitochondrial protein for iron hemostasis -> Frataxin usually binds iron -> iron accumulates in mitochondria -> cell death Inheritance: AR Features: damage to cerebullum, LCST, dorsal columns -> ataxia in school aged pt with sensory loss, weakness, and wheelchair bound by young adulthood; hypertrophic cardiomyopathy, DM, pes cavus, hammer toes presents in childhood with kyphoscoliosis
Tuberous sclerosis
Genetic defect: TSC1 mutation (hamartin-GTPase) on Chr 9 or TSC2 (tuberin) on chr 16 = Tumor suppressor genes -> *normally form complex that inhibits mTOR and other proteins in AKT pathway* Inheritance: AD, variable expressivity Features: *HAMARTOMAS*: Hamartomas in CNS (tubers) and skin; Angiofibromas; Mitral regurg; Ash leaf spots; cardiac Rhabdomyoma; Tuberous sclerosis; autosomal dOminant; Mental retardation; renal Angiomyolipoma; Seizures; Shagreen patches behavior and self injury problems Classic triad: Hypopigmented macules + seizures + MR Tx: anticonvulsants, possible mTOR inhibitors
Beckwith-Wiedemann syndrome
Genetic defect: WT2 mutation, overactivity of IGF2, no activity of CDKN1C ( Inheritance: most are sporadic, but some have *paternal* UPD on chr 11 Features: Wilms tumor, macroglossia, organomegaly, hemihyperplasia
Klinefelter syndrome
Genetic defect: XXY 90%, others are mosaic or have >2 Xs -> extra dosage of X can lead to less masculine features Features: male hypogonadism, wide hip bones, long body, lack of deep voice, beard, male hair distribution, lower mean IQ (not MR), Mitral valve prolapse, reduced spermatogenesis DX: after puberty mainly 1/660 live male births
Tay Sachs dz
Genetic defect: cannot catabolize Gm2 gangliosides in lysosome d/t deficient *Hexosaminidase a-subunit deficiency* on Chr 15 Inheritance: AR Features: Mostly neurons and retina involved d/t degradation of these gangliosides often -> *6 months age motor and mental deterioration, blindness, dementia* - cherry red spots on macular are pathognomonic -> death by 3yo prevalent in ashkenazic jews Tay-SaX lacks heXosaminidase
Turner syndrome
Genetic defect: complete or partial monosomy of X chromosome -> 75% of time abnormality in *paternal* gametogenesis Features: hypogonadism in females -> single most important cause of primary amenorrhea (1/3 cases), hypothyroid (1/2), infantile genitalia and breast, little pubic hair, *short stature* (SHOX gene) cause of still birth in first trimester -> see hydrops fetalis and cystic hygroma 1/2500 live female births
aflatoxin
HCC from aspergillus which can contaminate stored rice and grains
predictive factors: Her2-neu expressivity? rec located where?
HER2/neu amplification of receptor makes cells susceptible to excess growth/tumor formation -responds to herceptin/trastuzumab (Anti-Her2 Abs) -receptor located on cell surface
Phenylketonuria
Genetic defect: d/t decreased *phenylalanine hydroxylase* or decreased *tetrahydrobiopterin* (BH4) cofactor -> increased phenylalanine -> phenyl ketones in urine Inheritance: AR (1/10k) Features: intellectual disability, growth retardation, seizures, fair complexion, eczema, musty body odor (Aromatics) Treatment: lower phenylalanine and increase tyrosine in diet, BH4 supplementation Screen 2-3 days after birth maternal pku: infantile microcephaly, retardation, congenital heart defects
Marfan Syndrome
Genetic defect: defect in FBN1 gene -> defect in fibrillin-1 -> loss of structural support and excessive TGFB signaling Inheritance: AD Features: tall, long tapering fingers, hypermobile, chest deformity, lens dislocation, dilated aorta, mitral valve prolapse 70-85% familial, rest sporadic tx: Beta blockers (aorta protection) mainstay
Cowden Syndrome (Multiple Hamartoma Syndrome)
Genetic defect: germline mutation in PTEN (tumor suppressor) Inheritance: AD Features: *trichilemmomas* on face, papules in mouth, thyroid adenomas/goiter, macrocephaly, intellectual disability, GI hamartomas, Lhermitte Dulcos dz (benign cerebellar tumor) increased risk for endometrial cancer, thyroid cancer DX: macrocephaly, GI hamartomas, Lhermitte Dulcos Treatment: prophylactic mastectomy and thyroidectomy
a1-antitrypsin deficiency
Genetic defect: mutation in SERPINA1 gene -> not enough gene product patho: deficiency results in unopposed elastase activity -> emphysema; older age has low dermal collagen and elastin misfolded gene product protein aggregates in hepatocellular ER -> cirrhosis with PAS+ globules in liver Inheritance: Codominant trait
Familial Hypercholesterolemia
Genetic defect: mutation in gene encoding *LDL receptor* involved in transport and metabolism of cholesterol - 5 groups of mutations with main one causing protein improper folding, can't make it to cell membrane Inheritance: AD - homozygotes worse prognosis Features: 2-6 fold increase in plasma cholesterol levels -> builds up in macrophages and vessel walls -> skin xanthomas, coronary, cerebral, and peripheral vascular atherosclerosis - MI can occur before age 20
Down Syndrome
Genetic defect: trisomy 21, 4% are robertsonian translocation, 1% somatic mosaicism Features: congenital heart dz 40% (VSD, ASD, AV malformed), 10-20x risk Acute leukemia, almost all develop Alzheimer >40yo, immune deficiency Most common trisomy - 1/700 newborns maternal age factor: 1/25 newborns in women 45yo
What usually causes hypertrophic cardiomyopathy?
Genetic mutations in sarcomere proteins, most commonly AD
hemoglobin C
Glutamic acid-to-lyCine (lysine) mutation in β-globin. Causes extravascular hemolysis. Patients with HbSC (1 of each mutant gene) have milder disease than HbSS patients. Blood smear in homozygotes: hemoglobin Crystals inside RBCs, target cells.
where to tap for thoracentesis
Go above rib b/c neurovascular bundle is below rib
chronic sarcoidosis
Gradual, insidious onset Lupus pernio Multiorgan involvement at time of presentation: Chronic eye involvement (chronic uveitis, cataracts, glaucoma, or keratoconjuctivits sicca). Bone involvement Pulmonary infiltrates Nephrocalcinosis Cor pulmonale Persistence of the disease and recurrence.
Name examples of lesions that can produce coin lesions in patients and mimic lung cancer on x-ray
Granuloma (due to TB or fungus like Histoplasma in the midwest) Bronchial hamartoma
What is seen histologically in hypersensitivity pneumonitis?
Granulomas with eosinophils
Hypersensitivity pneumonitis definition
Granulomatous reaction to inhaled organic agents (i.e. pigeon breeder's lung)
What is the gross change and complications during fibrosis in the months after MI?
Gross: white scar Complications: aneurysm, mural thrombus, Dressler Syndrome
Ehlers-Danlos Syndrome (EDS)
Group of 6 types resulting in defect in synthesis or structure of fibrillar collagen Genetic defect: either collagen genes or enzymes responsible for assembly (eg lysyl hydroxylase) - classic is defect in type 5 collage Inheritance: AD except type 4 and 6 which are AR Features: skin/joint hypermobility, bruising, and others d/t lack of tensile strength -> large artery rupture (type 4) or ocular fragility are serious complications
Cardiomyopathy definition
Group of myocardial diseases that result in cardiac dysfunction
Ischemic Heart Disease Definition
Group of syndromes related to myocardial ischemia
TP53 role
Guardian of the genome regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis, is the most frequently mutated gene in human cancers *activated by phosphorylation via ATM/ATR family 2/2 anoxia, DNA damage, signals from mutated oncoproteins* becomes liberated from MDM2 after phosphorylated *most of work is done via p21*
What is the most common cause of acute epiglottitis?
H influenzae type B (in both immunized and non-immunized children)
HAP vs. HCAP
HAP- hospital acquired pneumonia HCAP- health care associated pneumonia (nursing, home IV abx, etc) HAP- hospitalized > 48h before onset of sxs HCAP- inpt in 90d, LTCF?, home IV antibiotics, HD etc
HBV and HCV
HCC
sickle cell anemia
HbS point mutation causes a single amino acid replacement in β chain (substitution of glutamic acid with valine at 6th residue [E6V]). Causes extravascular and intravascular hemolysis. Pathogenesis: low O2, high altitude, or acidosis precipitates sickling (deoxygenated HbS polymerizes) anemia, vaso-occlusive disease. Newborns are initially asymptomatic because of inc HbF and dec HbS. Heterozygotes (sickle cell trait) also have resistance to malaria. 8% of African Americans carry an HbS allele. Sickle cells are crescent-shaped RBCs A. "Crew cut" on skull x-ray due to marrow expansion from erythropoiesis (also seen in thalassemias). Complications in sickle cell disease: Aplastic crisis (due to parvovirus B19); Autosplenectomy (Howell-Jolly bodies)> inc risk of infection by encapsulated organisms (eg, S pneumoniae); Splenic infarct/sequestration crisis; Salmonella osteomyelitis; Painful crises (vaso-occlusive): dactylitis (painful swelling of hands/feet), priapism, acute chest syndrome, avascular necrosis, stroke; Renal papillary necrosis (dec Po2 in papilla) and microhematuria (medullary infarcts). Diagnosis: hemoglobin electrophoresis. Treatment: hydroxyurea (inc HbF), hydration.
Fixed Splitting
Heard in *ASDs*; ASD -> left to right shunt -> increased RA and RV volumes -> increased flow thru pulmonic valves such that respiratory phases don't affect splitting
Paradoxical Splitting
Heard in conditions delaying *aortic valve closure* (e.g. stenosis, LBBB); Normal order of valve closure is reversed so that P2 sound occurs before delayed A2 sound. Therefore on inspiration, P2 closes later and moves closer to A2, thereby "paradoxically" eliminating the split
What is treatment for dilated cardiomyopathy
Heart transplant
How does hypertension cause congestive heart failure?
Heart undergoes hypertrophy, making it harder to perfuse oxygen through the hypertrophied wall, causing ischemic damage and left sided CHF
Hemoglobin
Hemoglobin (Hb) is composed of 4 polypeptide subunits (2alpha and 2beta) and exists in 2 forms: - T (taut; deoxygenated) form has low affinity for O2 - R (relaxed; oxygenated) form has high affinity for O2 (300x). Hb exhibits positive cooperativity and negative allostery. "Taut in tissues; relaxed in respiratory tract" Increases in Cl, H, CO2, 2,3-BPG, and temperature favor taut form over relaxed form (shifts dissociation curve right --> increases oxygen unloading) Fetal hemoglobin (2alpha and 2gamma) has lower affinity for 2,3-BPG than adult Hb and thus higher affinity for O2.
What are heart failure cells?
Hemosiderin laden macrophages that eat up blood when there is intraalveolar hemorrhage due to congested capillaries in the lungs
right heart failure
Hepatosplenomegaly (nutmeg liver) - inc central venous pressure>inc resistance to portal flow. Rarely, leads to "cardiac cirrhosis." Jugular Venous Distention - inc venous pressure. Peripheral Edema - inc venous pressure>fluid transudation. Most commonly due to left-sided heart failure; other important causes include left-to-right shunt and chronic lung disease (cor pumonale) Cor pulmonale causes - COPD (Chronic Bronchitis, Emphysema, Bronchiectasis), Pulmonary Hypertension (1° BMPR2 mutation in young adult females or 2° to hypoxemia (e.g., COPD and interstitial lung disease) or increased volume in the pulmonary circuit (CHF); may also arise with recurrent pulmonary embolism
What does the liver secrete in anemia of chronic disease to trap iron in storage form and increase ferritin?
Hepcidin
Is Staphylococcus aureus a high or low virulence organism?
High (unlike Streptococcus viridans), so it infects normal valves
How does acute epiglottitis present?
High fever, sore throat, drooling with dysphagia, muffled voice, inspiratory stridor
Pulmonary hypertension definition
High pressure in the pulmonary circuit (mean arterial pressure over 25 mmHg)
Aortic Regurgiation
High-pitched "blowing" early diastolic decrescendo murmur -Shows long diastolic murmur, hyperdynamic pulse, and *head bobbing* if severe and chronic -Often due to aortic root dilation, bicuspid aortic valve, endocarditis, rheumatic fever. *Progresses to left HF*
What nodes does lung cancer spread to first?
Hilar and mediastinal
histoplasmosis
Histoplasma capsulatum var capsulatum The most common endemic mycosis in the US. Most infections are self-limited, but the organism has the ability to cause acute and chronic pulmonary infections and disseminated infection Pathophysiology: Inhalation of microconidia Localized pulmonary infection Neutrophils and Macrophages phagocytize the organism (survives intracellularly)>L.N. & RES After weeks, sensitized T-cells activates macrophages killing intracellular fungi (highlighting the importance of cell-mediated immunity)
How does Laryngotracheobronchitis (croup) present?
Hoarse, "barking" cough and inspiratory stridor
How does laryngeal papilloma present?
Hoarseness
How does vocal cord nodule present?
Hoarseness
How does laryngeal carcinoma present?
Hoarseness, cough, stridor
Mitral/Tricuspid Regurgitation
Holosystolic, high-pitched *"blowing murmur"* -Mitral= loudest at apex and *radiates toward axilla*; MR is often due to ischemic heart disease (post-MI), MVP, LV dilatation -Tricuspid= loudest at tricuspid area and *radiates to right sternal border*; often due to RV dilatation -*Rheumatic fever and infective endocarditis* can cause either MR or TR
Murmur in mitral regurgitation
Holosytolic blowing murmur
VSD Auscultory Pattern
Holosytolic, *harsh-sounding* murmur; best heard at tricuspid listening post
Types of Arteriolosclerosis
Hyaline: thickening of vessel walls in *essential hypertension or diabetes mellitus* due to protein leakage inducing hyalinization Hyperplastic: "*onion skinning*" in *severe HTN* with *proliferation of smooth muscle cells* -Hyaline= chronic; hyperplastic= acute
what is the most damaging free radical?
Hydroxyl free radical formed by ionizing radiation turning water into it metals unbound to carrier do too (Fe and copper examples)
Chronic bronchitis (blue bloater)
Hyperplasia of mucus-secreting glands in bronchi --> Reid index (thickness of gland layer/total thickness of bronchial wall), >50% Productive cough for >3 months per year (not necessarily consecutive) for >2 years Findings: wheezing, crackles, cyanosis (early onset hypoxemia due to shunting), late onset dyspnea, CO2 retention (hypercapneia), secondary polycythemia
What is Allergic bronchopulmonary aspergillosis?
Hypersensitivity reaction to aspergillus leading to chronic inflammatory damage
Type 1 HSR
Hypersensitivity reaction where IgE antibody is produced -> release of vasoactive amines and other mediators from *mast cells* -> recruitment of other inflam. cells manifests: itchy skin, eyes, nasal d/c or bronchial asthma/anaphylaxis ex: anaphylaxis, allergies, bronchial asthma
type 4 HSR
Hypersensitivity resulting from T cell mediated immune response initiated by activated or memory T cells (CD4 or CD8) -It is a delayed response (allow T cells proliferation and migration to site of antigen where they recruit and activate macrophages) ex: contact dermatitis (poison ivy), DM1, MS, RA, TB, IBD
Type 3 HSR
Hypersensitivity resulting from formation of antigen-antibody complex -> deposit in joints, skin, kidneys, lungs ex: SLE, RA, Polyarteritis nodosa, hypersensitivity pneumonitis, glomerulonephritis, reactive arthritis, SERUM SICKNESS (drugs most common cause)
type 2 HSR
Hypersensitivity that results when antibodies bind to cell surfaces or ECM ex: destruction of blood cells from blood transfusion, Hemolytic dz of newborn, Acute rheumatic fever, MG Drugs also can cause: ITP, hemolytic anemia
How does adult coarctation of the aorta present?
Hypertension in upper extremites and hypotension with weak pulses in lower extremities
dumping syndrome
Hypertonic gastric contents emptied rapidly into duodenum 25% of plasma volume may be transferred suddenly to small intestine Nausea Cramping Diaphoresis Palpitations Treatment: Frequent ingestion of small meals containing fat, protein, complex CHO Fluid intake restricted and separated from solid food intake High pectin-containing foods slow gastric output (bananas, oranges)
Common cause of sudden death in young athletes
Hypertrophic cardiomyopathy
Histologic Patterns of Hypertrophic vs. Dilated Cardiomyopathy
Hypertrophic= marked *concentric* hypertrophy (sarcomeres are in *parallel*) Dilated= *eccentric* hypertrophy (sarcomeres are in *series*
What does transposition of great vessels cause?
Hypertrophy of RV and atrophy of LV
Hypertrophic cardiomyopathy
Hypertrophy of the left ventricle
What does increased volume in the pulmonary circuit (as in congenital heart disease) cause in the smooth muscle?
Hypertrophy, which can lead to pulmonary hypertension
when NOT to transfuse plasma
Hypovolemia Most Plasma exchange procedures (exceptions: TTP or coagulopathy) Wound healing/Burns Immunodeficiency states Non-bleeding patients with liver disease and prolonged INR (treat bleeding, not the number in these patients) Minimally elevated PT/INR (INR of a bag of plasma is ~1.3)
Compensatory Response to Hypovolemia
Hypovolemia -> decreased arterial pressure -> decreased stretch -> decreased afferent baroreceptor firing -> increased efferent sympathetic stimulation + decreased efferent parasympathetic firing -> vasoconstriction, increased BP/HR/contractility
Clinical features of ARDS
Hypoxemia and cyanosis with respiratory distress due to thickened diffusion barrier and collapse of air sacs due to increased surface tension
Complications of bronchiectasis
Hypoxemia with cor pulmonale and secondary AA amyloidosis
How does lung disease cause right sided heart failure?
Hypoxia causes blood vessels of the lung to constrict, increasing the pressure that the right heart must pump against, leading to RHF
5 classes of pulmonary hypertension
I- pulmonary arterial hypertension (primary, the only group with treatments that directly target the PAH) II- pulmonary hypertension due to L-sided heart disease III- pulmonary hypertension related to lung disease or hypoxia IV- chronic embolic pulmonary hypertension V- pulmonary hypertension related to multifactorial mechanisms (everything else, but especially fistulas in dialysis/renal failure)
lung cancer staging and how it affects treatment
IA-IB, IIA-IIB, IIIA-IIIB, IV Most cancers stage IIIA and earlier are surgically amenable
IC valve vs. colon resection
IC Valve Resection: Small bowel bacterial overgrowth Colon Resection: Absorbs water, electrolytes, short chain fatty acids
Lung volumes total lung capacity
IRV + TV + ERV + RV volume of gas present in lungs after maximal inspiration
How does p53 cause apoptosis?
If DNA damage too great, p53 recruits Bax (Bcl-2 family member). Bax causes release of cytochrome-c and activation of the caspase cascade, leading to apoptosis.
How do you distinguish aortic stenosis due to rheumatic fever from aortic stenosis due to wear and tear?
If aortic stenosis alone, then it is not due to rheumatic fever (mitral would be involved) If the commissures are not fused, then it is not due to rheumatic fever (commissures are fused in aortic stenosis due to rheumatic fever)
hemolytic transfusion rxns (IgG vs. IgM)
IgG alloantibodies generally cause extravascular hemolysis (delayed) IgM alloantibodies generally cause intravascular hemolysis (acute), although many non-ABO IgM antibodies react best at cold temps are not clinically significant at 37°C Increased time to find antigen-negative blood, in some cases may need to request searches of rare donor registry
What is the imbalance and cause of emphysema?
Imbalance of proteases and antiproteases
PV vs. reactive polycythemia
In PV, erythropoietin (EPO) levels are decreased, and SaO2 is normal. In reactive polycythemia, due to high altitude or lung disease, SaO2 is low, and EPO is increased In reactive polycythemia due to ectopic EPO production from RCC, EPO is high and SaO2 is normal
body's response to cold
In response to cold, the hypothalamus stimulates heat production through shivering and increasing thyroid, catecholamine and adrenal activity. The initial response results in: Reduced heat loss: Catecholamine vasoconstriction dec blood flow to the skin where heat loss occurs. Increased heat production: Shivering inc CO, cellular metabolism, and ventilation (heat generation)
What is the problem in restrictive lung diseases?
Inability to fill due to interstitial diseases of the lung or other chest wall abnormalities
bronchodilator response
Increase FEV1 or FVC from baseline By at least 12% By at least 200 mL Both values must be met
Myocardial O2 Demand Increases w/ ______
Increased "myo*CARD*ial" demand due to increased: Contractility Afterload Rate (heart rate) Diameter of ventricle (2o to increased wall tension)
Modifications to the Pressure-Volume Loop
Increased afterload Increased preload Increased contractility
ANP Signaled due to Increased ____ Whereas BNP is due to ____
Increased blood volume vs. wall tension
How is FRC altered in emphysema?
Increased in emphysema, resulting in "barrel-chest"
essential thrombocythemia
Increased megakaryocytic proliferation and platelet production
Physiology of Carotid Massage
Increased pressure on carotid sinus -> increased stretch -> increased afferent baroreceptor firing -> increased AV node refractory period -> decreased HR
What causes paroxysmal nocturnal dyspnea?
Increased venous return when lying flat
How does murmur in mitral regurgitation change with squatting and expiration?
Increases (due to increased resistance and increased blood, respectively)
Adenosine in Cardiac Arrhythmias
Increases *K+ efflux* from cells -> hyperpolarizes cell and decreases Ca2+ conduction (hence why it's drug of choice for SVT!) -Effects blunted by *theophylline and caffeine* as both are adenosine receptor antagonists
Mechanism of Increasing or Decreasing Heart Rate
Increasing (e.g. catecholamines): the slope of Phase 4 becomes shorter, increases HR Decreasing (e.g. adenosine, ACh): the slope of Phase 4 becomes longer, decreases HR
upper airway soft tissue abnormalities that inc risk of OSA
Increasing neck circumference Nasal congestion Macroglossia Low-lying soft palate Tonsillar & adenoid hypertrophy Retrognathia- overbite
How do you treat PDA?
Indomethacin
MOA of indomethacin in treating PDA
Indomethacin decreases PGE, which is what keeps ductus arteriosus open
Hemoglobin modifications: methemoglobin
Induced methemoglobinemia (using nitrites followed by thiosulfate) may be used to treat cyanide poisoning. Nitrites AND benzocaine cause poisoning by oxidizing iron.
Two actions of histamine
Induces vasodilation at arterioles and leaking of fluid at post-capillary venules
What are the two forms of coarctation of the aorta?
Infantile and adult
malaria
Infection of RBCs and liver with Plasmodium; transmitted by the female Anopheles mosquito RBCs rupture as part of the Plasmodium life cycle, resulting in intravascular hemolysis and cyclical fever Spleen also consumes some infected RBCs; results in mild extravascular hemolysis Malaria—fever, headache, anemia, splenomegaly treatment: Chloroquine (for sensitive species), which blocks Plasmodium heme polymerase; if resistant, use mefloquine or atovaquone/ proguanil; If life-threatening, use intravenous quinidine or artesunate (test for G6PD deficiency); For P vivax/ovale, add primaquine for hypnozoite (test for G6PD deficiency)
Complication of chronic rheumatic heart disease
Infectious endocarditis
4 categories of granulomatous diseases and examples
Infectious: Histoplasmosis TB Allergic: Hypersensitivity Pneumonitis Autoimmune: Granulomatosis with Polyangiitis (formerly Wegener's Granulomatosis) Unknown Etiology: Sarcoidosis neoplasms can also result in granuloma formation
time period for localized cervical nodes
Inflamed cervical nodes that develop over a few days, especially in children, are typically caused by staphylococcal and streptococcal infection. Those that develop over weeks to months without significant inflammation or tenderness suggest infection with Mycobacteria or Bartonella henselae, the agent of cat scratch disease.
Endocarditis definition
Inflammation of endocardium that lines the surface of cardiac valves
Acute epiglottitis definition
Inflammation of the epiglottis
What causes the late phase reaction in asthma?
Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction
What causes TB?
Inhalation of aerosolized mycobacterium tuberculosis
What is the defect in Kartagener syndrome?
Inherited defect in dynein arm of cilia, preventing ciliary movement
Hereditary Hemorrhagic Telangiectasia
Inherited disorder to blood vessels causing *blanching skin lesions, recurrent nose bleeds, AVMs, GI bleeds, hematuria*
Ranolazine
Inhibits the late phase of sodium current thereby reducing diastolic wall tension and oxygen consumption -Used for *angina that is non-responsive* to other therapies -Does not affect heart rate or contractility
Where is endocardium located?
Inner layer of the heart; lines the valves
Inspiratory Splitting
Inspiration causes drop in intrathoracic pressure -> increased venous return -> increased RV filling -> increased RV stroke volume -> increased ejection time -> delayed closure of pulmonic valve -> split heart sound
Lung volumes inspiratory capacity
Inspiratory reserve volume + tidal volume
How does maternal diabetes increase risk for neonatal respiratory distress syndrome
Insulin is increased in the fetus due to high blood sugar in the mom; insulin decreases surfactant production
Increased lung markings on CXR. What type of pneumonia are you considering?
Interstitial (atypical) pneumonia
Pneumonia characterized by diffuse interstitial infiltrates
Interstitial (atypical) pneumonia
What does chronic exposure of organic agents that cause hypersensitivity pneumonitis result in?
Interstitial fibrosis
Pneumoconioses definition
Interstitial fibrosis due to occupational exposure, which results in chronic exposure to small, fibrogenic particles
What can complicate recovery of ARDS?
Interstitial fibrosis- loss of type II pneumocytes prevents regeneration
Differential diagnosis of an enlarged Virchow's node (left supraclavicular)
Intra-abdominal malignancy (gastric, pancreas, GB, etc) Prostatic, testicular, ovarian malignancies Infection (e.g. of the arm)
Ommaya reservoir
Intraventricular catheter system that can be used for the aspiration of cerebrospinal fluid or for the delivery of drugs (e.g. chemotherapy) into the cerebrospinal fluid Indications - Treatment of brain tumors, leukemia/lymphoma or leptomeningeal disease by intrathecal drug administration. In the palliative care of terminal cancer, an Ommaya reservoir can be inserted for intracerebroventricular injection (ICV) of morphine Complications - Infection; Malfunction; Mechanical Damage to Brain...
What causes Left-Sided Heart Failure
Ischemia, hypertension, dilated cardiomyopathy, myocardial infarction, restrictive cardiomyopathy
What is the leading cause of death in US?
Ischemic heart disease
What causes aortic regurgitation most commonly?
Isolated aortic root dilatation
Why is the sputum in bronchiectasis foul smelling?
It has been rotting while sitting in the lung, unable to escape the airways
what is MPO deficiency?
It means MPO-hydrogen peroxide system defect, ergo decreased microbial killing (genetic) - defect in leukocyte function - increased risk of candida infxn but most pt a-sx NBT test nl, o2-> h2o2 intact
histoplasmosis treatment
Itraconazole - for mild to moderate histoplasmosis Serum concentration should be > 1µg/mL after 2 weeks (steady state). Lipid-formulation of Amphotericin B - initial therapy for severe, life-threatening infections.
Erythematous non-tender lesions on the palms and soles associated with endocarditis
Janeway lesions
Net Fluid Flow=
Jv = net fluid flow = Kf [(Pc − Pi) − ς(πc − πi)] where: Kf = permeability of capillary to fluid ς = permeability of capillary to protein
best diets for weight loss
Low-fat diets typically result in more weight loss at 6 months than low-carb diets No fad diets result in sustained weight loss for >1 year except Weight Watchers (b/c it incorporates behavior modification, nutrition, and pharm)
What extremities suffer from cyanosis in Eisenmenger syndrome due to PDA?
Lower extremity
How does coarctation of the aorta infantile form present?
Lower extremity cyanosis (often at birth)
Name the layers of the bronchus
Lumen- lined by pseudostratified columnar ciliated epithelium Lamina propria- contains the venules that warm air before it goes to the bottom of the lung for exchange Submucosa- contains serous and mucinous glands Cartilage
most common cancers to met to brain
Lung > breast > melanoma, colon, kidney 1/2 brain cancer is mets (multiple well circumscribed tumors at gray/white junction)
What does Berylliosis increase the risk for?
Lung cancer
What is the most common cancer mortality in the US?
Lung cancer
What are uranium miners at increased risk for, and why?
Lung cancer, because uranium degrades into radon, which increaseas lung cancer risk
Treatment for idiopathic pulmonary fibrosis
Lung transplantation (no way to remove the fibrosis)
purpose of lymph nodes
Lymph nodes are organized to optimize contact between antigen and cells of the adaptive immune system.
cystic lung diseases
Lymphangioleiomyomatosis Langerhans cell histiocytosis (PLCH) Birt Hogg Dube syndrome- associated with skin lesions Desquamative Interstitial Pneumonia (DIP) Lymphocytic Interstitial Pneumonia (LIP)- more common in patients with HIV, Sjogren syndrome, multiple myeloma
Calculation of Resistance of a Vessel
Majority of resistance comes from arterioles
Mesothelioma
Malignancy of the pleura associated with asbestosis. May result in hemorrhagic pleural effusion (exudative), pleural thickening. Psammoma bodies seen on histology Smoking NOT a risk factor
What is transposition of great vessels associated with?
Maternal diabetes
Prader Willi syndrome
Maternally derived genes are silenced (imprinted) -dz occurs when Paternal allele is deleted or mutated on chr 15 q11.2q13 (think SNORP genes play role) sx: hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia, short stature, small hands and feet 25% of cases d/t maternal uniparental disomy
Transfusion associated graft vs host disease (TAGVHD)
May occur in severely immunocompromised patients Stem cell transplant, certain chemotherapy drugs, premature neonates Not in HIV, solid organ transplants, other immunosuppressed states May also occur in healthy recipients who share similar HLA types with their donor (related donors) Transfused donor T lymphocytes attack recipient cells Generally starts with fever, skin rash, vomiting/diarrhea, abnormal LFTs and progresses to pancytopenia within 4-30 days after transfusion Nearly universally fatal; fortunately very rare! Supportive treatment; prevention through irradiation of cellular blood products
Transfusion Associated Graft Vs Host Disease
May occur in severely immunocompromised patients: Stem cell transplant, certain chemotherapy drugs, premature neonates Not in HIV, solid organ transplants, other immunosuppressed states May also occur in healthy recipients who share similar HLA types with their donor (related donors) Transfused donor T lymphocytes attack recipient cells Generally starts with fever, skin rash, vomiting/diarrhea, abnormal LFTs and progresses to pancytopenia within 4-30 days after transfusion; Nearly universally fatal; fortunately very rare! Supportive treatment; prevention through irradiation of cellular blood products
Post-Natal Remnant of the Allantois
Median umbilical ligament
How do you treat tension pneumothorax?
Medical emergency treated with chest tube
Polyarteritis Nodosa
Medium vessel vasculitis; related to *hepatitis B* (HBsAg); typically involves renal (shows *innumerable renal artery microaneurysms) and visceral vessels, spares lungs*; shows *transmural inflammation w/ fibrinoid necrosis* in *varying stages* -Tx w/ steroids, *cyclophosphamide*
Beurger Disease
Medium vessel vasculitis; seen in *heavy smokers*; intermittent claudication may lead to gangrene, autoamputation of digits, superficial nodular phlebitis; *Raynaud phenomenon* common
Name common sites of systemic spread of secondary TB
Meninges Cervical lymph nodes Kidneys (sterile pyuria) Lumbar Vertebrae (Pott's Disease)
What cells line the pleura, and what do they make?
Mesothelial cells line the pleura, and they make fluid to lubricate the pleural space
Malignant neoplasm of mesothelial cells that is associated with occupational asbestos exposure
Mesothelioma
typical ABG pattern in sepsis
Metabolic acidosis with superimposed resp alkalosis suggests sepsis.
What types of tumors are most prominent in heart: primary or metastatic?
Metastatic
bronchoprovocation challenge test
Methacholine (Mch) challenge test: Increasing doses of Mch given (0.031-16 mg/dl) Stopped upon response or 16mg/dl Positive test if 20% FEV1 decrease with <16mg/dl Negative predictive value for asthma >95% Positive predictive value 50% False positives in allergic rhinitis, CF, COPD, CHF, bronchitis
PE finding in mitral valve prolapse
Mid-systolic click followed by regurgitation murmur
CML is distinguished from a leukemoid reaction (reactive neutrophilic leukocytosis) by:
Negative leukocyte alkaline phosphatase (LAP) statin (granulocytes in a leukemoid reaction are positive Increased basophils (absent with leukemoid reaction) t(9;22) (q34;q11) (absent in leukemoid reaction)
Adult T Cell Leukemia/Lymphoma
Neoplastic proliferation of mature CD4+ T cells Associated with HTLV-1 (associated with IV drug abuse); most commonly seen in Japan and the Caribbean Clinical features include rash (skin infiltration), generalized lymphadenopathy with hepatosplenomegaly, and lytic (punched-out) bone lesions with hypercalcemia Cells are multilobated nuclei ("cloverleaf" or "flower" cells). HTLV-1 encodes Tax protein (activator of NF-κB)>inc growth/survival Rapidly progressive disease; fatal in months to 1 year
polycythemia vera
Neoplastic proliferation of mature myeloid cells, especially RBCs (granulocytes also inc) Associated with JAK2 kinase mutation Clinical symptoms are mostly due to hyperviscosity of blood: Blurry vision and headache Incrased risk of venous thrombosis (e.g., hepatic vein, portal vein [Budd-Chiari], and dural sinus) Flushed face due to congestion (plethora) and itching especially after bathing (due to histamine release from increased mast cells) Without treatment, death usually occurs within one year (from bleeding or thrombosis)
myelofibrosis
Neoplastic proliferation of mature myeloid cells, especially megakaryocytes Associated with JAK2 kinase mutation in 50% of cases Megakaryocytes produce excess platelet derived growth factor PDGF causing marrow fibrosis Clinical features are: Massive splenomegaly due to extramedullary hematopoiesis Leukoerythroblastic smear (tear-drop RBCs, nucleated RBCs, and immature granulocytes) Increased risk of infection, thrombosis, and bleeding Details: Chief pathologic feature is extensive collagen deposition in marrow by non-neoplastic fibroblasts. Hyperuricemia and secondary gout due to a high rate of cell turnover can complicate the picture
Recombinant BNP
Nesiritide; used to tx HF
Outflow Tract Formation
Neural crest and endocardial cell migrations -> truncal and bulbar ridges that spiral and fuse to form aorticopulmonary septum -> ascending aorta and pulmonary trunk -*Truncal abnormalities occur if poor neural crest cells migration*
heart remodeling in heart failure
Neurohormonal activation — Progressive HF is associated with neurohormonal activation>progression of structural abnormalities. Net effect is inc release of the 3 "hypovolemic" hormones (renin, norepinephrine, and antidiuretic hormone) proportional to severity of the ventricular dysfunction. Initially adaptive, neurohormonal activation is bad long term - contributes to remodeling. Plasma BNP concentrations are also inc in HF but protects against pathologic remodeling. Role of Angiotensin II — Mechanical stretch directly increases angiotensin II release from cardiac myocytes. AT1 receptors have been identified on fibroblasts that respond to angiotensin II with AT1 receptor-mediated collagen synthesis, an effect that can be reduced by ACE inhibition. Also acting on the AT1 receptor, angiotensin II increases protein synthesis and induces hypertrophy in cardiac myocytes
Is nicotine carcinogenic?
Nicotine isn't super toxic (doesn't cause cancer)- why we can give nicotine replacement therapy
How do you relieve unstable angina
Nitroglycerin
What relieves unstable angina
Nitroglycerin or Ca channel blockers (to relieve vasospasm)
Does Streptococcus viridans destroy the valve?
No
Does nitroglycerin relieve MI symptoms?
No
diverticulosis
No evidence for avoidance of: Seeds Hard small particles give Fiber: Reduces occurrence of symptomatic diverticular disease
acute respiratory failure definition
No rigid criteria. PaO2 < 50mmHg on room air and/or PCO2 > 50mmHg associated with a decrease in pH to 7.3 or lower
Is adult coarctation of the aorta associated with PDA?
No, only infantiles
Non-Dihydropryidines vs. Dihydropryridines
Non-D: works on *vasculature smooth muscle*; includes the "-dipine's" (amlodipine, nicardipine etc.) D: works on *heart*; includes verapamil, diltiazem
Janeway lesions
Non-painful, associated with endocarditis
What are presenting symptoms of lung cancer
Non-specific (cough, weight loss, hemoptysis, postobstructive pneumonia)
histology of pulmonary sarcoidosis
Noncaseating Granuloma: Well formed, noncaseating epitheliod cell granuloma, surrounded by a rim of lymphocytes and fibroblasts, with varying degrees of collagen deposition. Asteroid bodies (not specific to sarcoidosis) Schaumann's bodies (not specific to sarcoidosis) Disease of exclusion
Berylliosis definition
Noncaseating granulomas in the lung, hilar lymph nodes, and systemic organs
Normal AaDO2 (oxygen delivery from alveoli to arteries)
Normal AaDO2: (Age/4) + 4 gradient inc with age
lymph node fixation
Normal lymph nodes are freely movable in the subcutaneous space. Abnormal nodes can become fixed to adjacent tissues by invading cancers or inflammation in tissue surrounding the nodes. Neurologic deficits
Pulmonary hypertension
Normal: 10-14 mmHg Htn: ≥25 mmHg at rest Results in arteriosclerosis, medial hypertrophy, intimal fibrosis of pulmonary arteries. Course: severe respiratory distress leads to cyanosis and RVH leads to death form decompensated cor pulmonale Five classification groups based on cause and treatment - Pulmonary arterial hypertension - PH due to left heart disease - PH due to lung disease or hypoxia - chronic thromboembolic PH - multifactorial PH
acute hypoxemic respiratory failure
Normocapnic Respiratory Failure Physiologic causes of hypoxemia: Shunt V/Q mismatch Diffusion impairment (pulmonary fibrosis) Hypoventilation (AaDO2 is normal) Low mixed venous O2 (SvO2): DO2/VO2 imbalance (anemia, hypoxemia, inadequate CO, increased oxygen consumption, shock) Symptoms: dyspnea, tachypnea, cyanosis, ANXIETY, AGITATION, tachycardia Prognosis: CAN BE FATAL
Epistaxis
Nose bleed. Most commonly occurs in anterior segment of nostril (kiesselbach plexus). Life threatening hemorrhages occur in the posterior segment (sphenopalatine artery, a branch of the maxillary artery)
universal donor vs. universal acceptor
O- is the universal donor (no antigens), AB+ is the universal acceptor (no antibodies)
X-linked disorders
Oblivious Female Will Often Give Her Boys Her x-Linked Disorders -Ornithine transcarbamylase def. -Fabry dz -Wiskott-Aldrich -Ocular albinism -G6PD def -Hunter syndrome -Bruton agammaglobulinemia -Hemophilia A and B -Lesch-Nyhan syndrome -Duchenne (and becker) muscular dystrophy Female w/ Turner more likely to have X-linked recessive dz
Obstructive lung disease
Obstruction of air flow result sin air trapping in lungs. Airways close prematurely at high lung volumes leading to increased RV and decreased FVC. V/Q mismatch. Chronic hypoxic pulmonary vasoconstriction can lead to cor pulmonale. Note: obstructive lung volumes > normal (increased TLC, FRC, RV) PFTs: - large decrease in FEV1 - decrease in FVC - decrease in FEV1/FVC ratio is the hallmark (<70%) Chronic bronchitis, emphysema, asthma, and bronchiectasis.
Rhinosinusitis
Obstruction of sinus drainage into nasal cavity leading to inflammation and pain over the affected area (typically maxillary sinuses in adults). Most common, acute cause is viral URI; may cause superimposed bacterial infection. S. pneumoniae, H. influenzae, m. catarrhalis
Superior vena cava syndrome
Obstruction of the SVC that impairs blood drainage from the head (facial plethora; note blanching after fingertip pressure), neck (JVD, and upper extremities. Medical emergency. Can raise intracranial pressure leading to headaches and dizziness and increased risk of aneurysm/rupture of intracranial arteries
mixed ventilatory pattern
Obstructive pattern: FEV1/FVC < 0.7 AND Restrictive pattern: TLC < 80% predicted Examples Lung fibrosis with emphysema (or asthma) Obesity with emphysema (or asthma) Obstructive lung disease with thoracic surgery Obstructive lung disease with diaphragm paralysis Sarcoidosis
disseminated histoplasmosis presentation
Occurs mostly in immunosuppressed patients: Increased risk: AIDS with CD4+ counts <150/µL, infants, hematologic malignancy, organ transplant recipient, systemic steroids, or TNF antagonists Symptoms & Signs: chills, fever, anorexia, weight loss, hypotension, dyspnea, hepatosplenomegaly, and skin & mucous membrane lesions. Pancytopenia, diffuse pulmonary infiltrates on chest imaging, DIC, and acute respiratory failure. Similar symptoms to sepsis
smoking-dependent genes in lung cancer
Oncogenes: c-myc, K-ras, and c-erbB-2 Tumor suppressor genes: p53, Rb1, and p16
irradiation
Only indication is to prevent Transfusion Associated GVHD in high risk patients Prevents lymphocytes from replicating/engrafting Indications: Hematologic malignancy or certain solid tumors (neuroblastoma, sarcoma, Hodgkin disease) Certain chemotherapy medications (fludarabine, ATG) Stem cell transplant patients Premature neonates Related donors NOT indicated for solid organ transplants, HIV
open biopsy of nodes
Open biopsy generally is the best diagnostic test because histologic examination of intact tissue provides information about both the presence of abnormal cells (carcinoma, microorganisms) and abnormal node architecture, which is necessary for the diagnosis of lymphomas. False negative results occur when an uninvolved node is sampled. Biopsy is usually performed under local anesthesia.
What does fibrinolysis/angioplasty do in MI treatment?
Open blocked vessel
True Ventricular Aneurysm
Outward bulge w/ heart contraction; seen 2w-months after MI
What is the L:S ratio that indicates adequate surfactant production?
Over 2
Central and Peripheral Chemoreceptors
Peripheral: carotid and aortic bodies are stimulated by decreased PO2 (< 60 mm Hg), increased Pco2, and decreased pH of blood Central: stimulated by changes in pH and Pco2 of brain interstitial fluid, which in turn are influenced by arterial CO2 -> Do not directly respond to Po2
bronchiectasis
Permanent dilatation of airways due to the destruction of tissue caused by chronic necrotizing inflammation and obstruction
Bronchiectasis definition
Permanent dilation of bronchioles and bronchi causing a loss of airway tone and resultant air trapping (large airway presents airway from being accelerated out the other end)
how do free radicals cause cellular injury?
Peroxidation of lipids Oxidation of DNA and proteins (DNA damage is implicated in aging and oncogenesis)
Adenocarcinoma
Pg 619
Pacemaker Potentials
Phase 0 (upstroke): Na+ funny channels inactivated and Ca2+ channels open -Phases 1 and 2 are absent, unlike myocardial contraction! Phase 3: inactivation of Ca2+ channels and activation of K+ channels -> K+ efflux Phase 4: restoration of funny channels
What is the major component of surfactant?
Phosphatidylcholine (lecithin)
Pericardium is Innervated by the ______
Phrenic nerve
What is the normal allele associated with A1AT?
PiM (two copies PIMM)
What is the most common clinically relevant mutation leading to A1AT deficiency, and what does it cause?
PiZ, causes significantly low levels of circulating A1AT
Beta-Blockers to Avoid in Tx Angina
Pindolol and acebutolol
Closure of the Ductus Arteriosis
Placental separation causes decreases in prostaglandins -> closure of ductus arteriosis -Indomethacin can be used to help close a PDA via lowering *prostaglandins E1/E2*
Xanthomas
Plaques or nodules composed of *lipid-laden histiocytes* in skin, esp. on eyelids (aka xanthelasma)
transfusion-related acute lung injury (TRALI)
Plasma containing blood products in the past, now probably RBCs uncommon, but is number one cause of transfusion-related death Caused by anti-HLA or anti-neutrophil antibodies in the donor which cause cytokine release, pulmonary capillary endothelial damage, and non-cardiogenic pulmonary edema HLA Ab's common in females who have been pregnant, so these women can usually only donate RBC's Strict definition: Symptoms start within 6 hours of transfusion Sudden onset Hypoxemia (<90% O2 saturation on room air OR PaOs/FiO2 < 300) New bilateral pulmonary infiltrates No underlying cardiac or pulmonary disease to explain symptoms Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, chest xray, BNP, supportive therapy including mechanical ventilation if necessary Does not improve with diuretics (as opposed to TACO) Majority of patients will recover, usually within 96 hours (as opposed to ARDS) Patient may receive additional transfusion, but donor may be permanently deferred
What Ag's do platelets express? Is cross-matching required?
Platelet antigen expression: HLA class I antigens Platelet specific antigens ABO antigens (minimal amount, so they don't need to be ABO-matched) No Rh antigen expression Platelets do not require crossmatching- Any patient of any blood type can receive any platelets
Light's criteria
Pleural fluid protein divided by serum protein > 0.5 Pleural fluid ldh divided by serum ldh > 0.6 Pleural fluid ldh > than 2/3 of the upper limit of normal for serum ldh Meeting any of the criteria results in the diagnosis of an exudate Light's Criteria is very sensitive but sacrifices specificity Some Transudates appear to be exudates
What lesions are seen in severe, long standing pulmonary hypertension?
Plexiform lesions
What are the hallmarks of granulation tissue 1-3 weeks post MI?
Plump fibroblasts, collagen, and blood vessels
Infection of the lung parenchyma
Pneumonia
How does bronchioloalveolar carcinoma appear on imaging?
Pneumonia-like consolidation
The Queen Proclaims Diso's Pyramid!
Pneumonic for Class 1A Na+ channel blockers: the Quinidine Procainamide Disopyramides pyramid(es)
I'd Buy LIDdy's MEXIcan Tacos
Pneumonic for Class 1B Na+ channel blockers: I (one) B LIDocaine MEXIleTine
Can I have Fries Please
Pneumonic for Classic 1C Na+ channel blockers: Class IC Flecainide Propafenone
Accumulation of air in the pleural space
Pneumothorax
What is Functional Residual Capacity (FRC)?
Point at which the tendency of the chest to push outwards meets the tendency of the lungs to collapse
Name the two most mutagenic carcinogens in cigarette smoke
Polycyclic aromatic hydrocarbons and arsenic
Chronic ischemic heart disease definition
Poor myocardial function due to chronic ishemic damage (with or without infarction)
what to do if Ab screen is positive
Positive Ab screen (b/c there was rxn to any Ab)- must determine the Ab before finding blood for the patient, so must do an Ab panel Same as screen, but it's run with 10 cells instead of 2 cells
Name for TB in lumbar vertebrae
Pott's Disease
monoclonal light chain in multiple myeloma
Predominantly kappa or lambda (monoclonal) Serum free light chain (FLC) measures the level of free kappa and lambda light chains Useful in nonsecretory MM and in patients with low serum and urine M levels FLC k/L ratio <.26 are monoclonal L FLC k/L ratio >1.65 are monoclonal k Ratio will be very high or very low in MM (b/c it's monoclonal)
ileal resection
Primary water absorber of fluid from jejunum Increased fluid loss with simple CHO B12 & bile acid absorption > 60cm Resection = Impairment of B12 absorption > 100cm Resection = Bile salt deficiency & fat malabsorption >100 MAD (malabsorptive diarrhea)- treat with medium chain fatty acid diet (doesn't need bile acid to be absorbed) < 100cm Resection = Bile-acid induced diarrhea (secretory diarrhea with hyperabsorption of oxalate>kidney stones) <100 BAD (bile acid diarrhea)- treat with bile acid binder (cholestyramine)
metastasis and prognosis of squamous cell carcinoma
Prognosis: poor; 5 year overall survival for stage IV 0% More locally advanced disease: metastases to bone and adrenals
What is the risk of unstable angina
Progression to MI
acute megakaryoblastic leukemia
Proliferation of megakaryoblasts; lack MPO Associated with Down syndrome (usually arises before the age of 5) 10% of AML; >50% megakaryoblasts; Trisomy 21, inversions or translocations of chromosome 3, t(9;22); t(1;22) in infants; CD61, CD41, CD42b
acute monocytic leukemia
Proliferation of monoblasts; usually lack MPO Blasts characteristically infiltrate gums. Contains granulocytic and monocytic cells; 7-10% of AML. CD13, CD14, ANBE positive Large cells; Moderate amount of cytoplasm; Very prominent nucleoli; Faint or no granules; Monoblastic or monocytic (>80%); CNS involvement
What does BMPR2 inactivating mutation associated with?
Proliferation of vascular smooth muscle, leading to primary pulmonary hypertension
Coal workers' pneumonoconiosis the black lung
Prolonged coal dust exposure leads to macrophages laden with carbon leads to inflammation and fibrosis. Affects upper lobes.
Beta-Blocker to Avoid in Prinzmetal Angina
Propanolol
What decreases risk for Streptococcus viridans subacute endocarditis?
Prophylactic abx (for those with damaged valves getting dental procedures)
Prostaglandins that Keep the Ductus Arteriosus Open
Prostaglandins E1 and E2 (these k*EE*p the ductus arteriosus open); *can be used to keep baby perfused in right to left shunts until surgery*
Where does Staphylococcus epidermidis cause endocarditis?
Prosthetic heart valves
macroangiopathic hemolytic anemia
Prosthetic heart valves and aortic stenosis may also cause hemolytic anemia 2° to mechanical destruction of RBCs. Schistocytes on peripheral blood smear. RBCs are destroyed as they pass through circulation; Iron deficiency anemia occurs with chronic hemolysis
Kwashiorkor
Protein malnutrition resulting in skin lesions, edema due to decreased plasma oncotic pressure, liver malfunction (fatty change due to decrease apoliportein synthesis). Clinical picture: small child with swollen abdomen MEALS -Malnutrition -Edema -Anemia -Liver (fatty) -Skin lesions (hyperkeratosis/hyperpigmentation)
Pneumonia in cystic fibrosis patients
Pseudomonas aeruginosa
What kind of cells are found in the conducting zone but not in the respiratory zone?
Pseudostratified ciliated columnar cells airway smooth muscle cells
What does pulmonary congestion cause?
Pulmonary edema
Quincke Pulse
Pulsating nail beds commonly seen in aortic regurgitation
anorexia nervosa behaviors
Purging Behaviors: Self-induced vomiting Laxatives and/or enemas Diuretics Stimulants (caffeine, ephedra, cocaine, Ritalin) Non-purging Behaviors: Excessive physical activity Fasting, skipping meals, restrictive pattern eating Inappropriate withholding of insulin (in DM)
A1AT accumulation in hepatocytes on histology
Purple or pink colored globules are alpha-1 anti trypsin that are PAS positive
antibody screen
Purpose is to screen for non-ABO antibodies (usually IgG) in the patient's plasma (over 300 different blood group antigens besides ABO!) Patient plasma is added to reagent red blood cells with known phenotypes Requires incubation to 37 degrees, so it takes longer (about an hour) All are indirect Coombs test (indirect anti-globulin test) uses 2 or 3 of patient's RBC's
gold standard for diagnosis of pulmonary hypertension
R heart catheterization
Occurrence of Cyanosis in Cardiac Shunting Patterns
R to L: eaRLy L to R: LateR
what other autoimmune dz is Sjogren assoc. with?
RA - RF often present even if RA is absent though also SLE and Scleroderma associated
follicular hyperplasia
RA, Toxo, and early stages of HIV
carcinomas, melanoma, and lymphoma assoc. oncogene
RAS gene family (GTP binding protein) point mutation -> GTPase activating protein (GAP) can't tell RAS to turn down RAS is most common type of abnormal oncogene in human tumors (HRAS, KRAS, NRAS)
extravascular hemolysis
RBC destruction via RES (macrophages in spleen, liver, lymph nodes) globin -> AAs heme -> iron and protopophyrin (iron recycled, protophoryin -> unconjugated bilirubin) clincal and labfindings: -anemia w/ HSM (hypertophy), jaundice w/ unconjugated bili, increased risk of bili gallstones corrected RC >3%
What causes microangiopathic hemolytic anemia in aortic stenosis
RBCs damaged as they cross the calcified valve, producing schistocytes
What coronary artery supplies the mitral valve?
RCA
when to give ventilatory support/intubation
Respiratory rate > 35/minute VC < 15 ml/kg and/or max inspiratory pressure < 25 cm H2O PaO2 < 55mmHg on a non-rebreather mask (FiO2 1.0) Respiratory acidosis with pH< 7.2 Altered mental status
How long does respiratory vs. metabolic compensation take?
Respiratory system compensates quickly Renal compensation takes 24-72 hrs
Most common cause of atypical pneumonia in infants?
Respriatory syncytial virus (RSV)
How do you relieve stable angina
Rest or nitroglycerin
Treatment of vocal cord nodule?
Resting of voice
Low voltage EKG with diminished QRS classic for...
Restrictive cardiomyopathy
neuromuscular pattern
Restrictive pattern with normal DLCO Greater loss of VC with chronic muscle weakness ↓Lung compliance (microatelectasis) ↓Chest wall compliance (stiff ligaments or joints) Decrease in maximal inspiratory pressure (MIP) & MEP Decrease in maximal voluntary ventilation (MVV) Change in FVC between upright and supine >20%
Problem in restrictive lung diseases versus problem in obstructive lung diseases
Restrictive: can't fill Obstructive: can't empty
chronic myelogenous leukemia
Results from the Philadelphia (Ph) chromosome By t(9;22)(q34;q11.2) reciprocal translocation, results in der(22q) (or Ph chromosome) With the fusion gene BCR/ABL1 and fusion mRNA Produces BCR/ABL1 fusion oncoprotein (p210) with increased tyrosine kinase activity of ABL1 in intracellular signaling Increased cell proliferation and decreased apoptosis Manifest initially as an indolent granulocytic proliferation, but transformed to an accelerated phase and then a blast phase Process of multiple hematopoietic lineages, including neutrophils, basophils, eosinophils, and even lymphoid cells
Does stable angina represent reversible or irreversible injury to myocytes?
Reversible
Is prinzmetal angina reversible or irreversible injury in myocytes?
Reversible
H1 blockers second generation
Reversible loratadine, fexofenadine, desloratadine, cetirizine Clinical use: allergy Toxicity: far less sedating than first generation because of decreased entry into CNS
Is unstable angina reversible or irreversible injury to myocytes?
Reversible (no necrosis)
Asthma definition
Reversible airway bronchoconstriction, most often due to allergic stimuli
H1 blockers first generation
Reversible inhibitors of H1 histamine receptors Diphenhydramine, dimenhydrinate, chlorpheniramine Clinical use: allergy, motion sickness, sleep aid Toxicity: sedation, antimuscarinic, anti-alpha-adrenergic
Benign hamartoma of cardiac muscle
Rhabdomyoma
What is the most common primary cardiac tumor in children?
Rhabdomyoma
Anti-streptolysin O Markers Suggest ______
Rheumatic fever
What is black lung associated with?
Rheumatoid arthritis, called Caplan Syndrome [seen in coal workers' pneumoconiosis]
Inflammation of the nasal mucosa
Rhinitis
What is the most common cause of rhinitis?
Rhinovirus (adenovirus??)
What are the two types of CHF?
Right and left sided
Cor pulmonale
Right heart failure secondary to increased lung pressures
Classic presentation of aspiration pneumonia, and why?
Right lower lobe abscess; right mainstem bronchus branches at a less acute angle than the left mainstem bronchus
Lung relations
Right lung has 3 lobes; left has less lobes (2) and lingula (homolog of the right middle lobe). Right lung is more common site for inhaled foreign body because the right main stem bronchus is wider and more vertical than the left If you aspirate a peanut: - while upright - enters lower portion of right inferior lobe - while supine - enters superior portion of right inferior lobe
Shunt direction in Tetralogy of Fallot
Right to left
What can pulmonary hypertension eventually lead to?
Right ventricular hypertrophy with eventual cor pulmonale
infectious mono complications?
Risk for splenic rupture -rash if given *ampicillin* -Recurrence and risk for B-cell lymphoma development (*esp. in immunodeficient pt, HIV*)
types of bariatric surgery
Roux-en-Y gastric bypass- restrictive (small gastric pouch>limits caloric intake) and has malabsorptive component (results in a little diarrhea); most common currently Gastric bands- only restrictive, not malabsorptive Biliopancreatic diversion with duodenal switch- only restrictive, but patients have massive diarrhea (severe malabsorption); Resulted in a lot of weight loss, but many patients died, so not used any more
What causes a spontaneous pneumothorax?
Rupture of an emphysematous bleb
What usually causes MI? Name three lesser causes
Rupture of atherosclerotic plaque with thrombosis and complete occlusion of a coronary artery Other causes: prinzmetal angina, vasculitis, emboli
What usually causes unstable angina
Rupture of atherosclerotic plaque with thrombosis and incomplete occlusion of a coronary artery
What characterizes endocarditis in acute rheumatic fever
Small vegetations along lines of closure in the mitral valve (sometimes aortic) that lead to regurgitation
What are three complications that occur during the macrophage phase 4-7 days post MI?
Rupture of ventricular free wall leading to cardiac tamponade, interventricular septal rupture leading to shunt, or papillary muscle rupture leading to mitral valve insufficiency
Acute Endocarditis is due to ______
S. aureus
Colon Cancer Induced Endocarditis is due to ______
S. bovis (aka S. gallolyticus)
Prosthetic Valve Endocarditis is due to ______
S. epidermidis
Lobar pneumonia
S. pneumoniae most frequently Also legionella & klebsiella Intra-alveolar exudate leading to consolidation; may involve entire lobe or lung
Bronchopneumonia
S. pneumoniae, S. aureus, H influenzae, klebsiella Acute inflammatory infiltrates from bronchioles into adjacent alveoli; patchy distribution involving ≥1 lobe
S3/S4 Heart Sounds
S3: due to rapid ventricular filling; can be *normal* in healthy, young people or *can be pathologic in mitral regurg or HF* S4: due to "splash back" of *stiff ventricle* during ventricular filling; *always pathologic*; best heard w/ patient in *left lateral decubitus position*
conduction pathway
SA node>atria>AV node>bundle of His>right and left bundle branches>Purkinje fibers>ventricles; left bundle branch divides into left anterior and posterior fascicles.
platypnea
SOB relieved when lying down, worse standing/sitting
typical presentation and labs for PE?
SOB, hemoptysis, pleuritic chest pain, pleural effusion V/Q, CT spiral, and D dimer abnormal -grossly, wedge shaped hemorrhagic infarct (2/2 duel blood supply spilling in)
NSTEMI Will Show ____ on EKG
ST *depression* (due to it being subendocardial)
What does an EKG in stable angina show?
ST segment depression due to subendocardial ischemia
What does continued or severe ischemia in MI cause on EKG, and why?
ST segment elevations due to transmural infarction
EKG in unstable angina
ST-segment depression due to subendocardial ischemia
What does EKG show in unstable angina and why?
ST-segment elevations due to transmural ischemia
CO=
SV x HR
Tx for Beta Blocker Overose
Saline + atropine + glucagon
Who is silicosis seen in?
Sandblasters and silica miners
What do you not want to confuse berylliosis with?
Sarcoidosis
radiologic staging system for pulmonary sarcoidosis
Scadding Staging System: Stage 0- Normal chest radiograph Stage 1 - Bilateral hilar and mediastinal lymphadenopathy Stage 2 - Bilateral hilar or mediastinal lymphadenopathy and pulmonary opacities. Stage 3 - Parenchymal abnormalities & absence of hilar or mediastinal lymphadenopathy. Stage 4 - Fibrosis.
ascorbic acid (vitamin C) deficiency
Scurvy: Due to impaired collagen synthesis with disordered connective tissue As early as 3 months post-deficiency Clinical Manifestations: Ecchymosis Bleeding gums Petechiae Coiled hair Hyperkeratosis Arthralgias Impaired wound healing bleeding gums are key
What does atypical pneumonia caused by influenza virus increase the risk for
Secondary bacterial pneumonia by S aureus or H influenza
Type II pneumocytes
Secrete pulmonary surfactant --> decrease alveolar surface tension and prevents alveolar collapse (atelectasis). Cuboidal and clustered. Also serve as precursors to type I cells and other type II cells. They proliferate during lung damage.
Restrictive lung disease
See page 611 FEV1/FVC ratio ≥80% Types: - poor breathing mechanics - interstitial lung diseases
Small cell (oat cell) carcinoma
See pg 619
Fusion of aortic valve commisures
Seen in chronic rheumatic heart disease
Mitral valve vegetations
Seen in endocarditis during acute rheumatic fever
Ivabradine
Selectively inhibits Na+ funny channels which prolongs depolarization (Phase 4) -> decreased SA node firing -> reduced cardiac O2 demand -Used to tx *stable angina in patients who can't take beta-blockers* -ADE: *luminous phenomena/visual brightness*
Name some causes of ARDS (lots!)
Sepsis, infection, shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity reactions, drugs
What are the two types of glands in the submucosa of the bronchus of the lungs, and what do they each do?
Serous- produces watery fluid that humidifies air Mucinous- produces mucus to line epithelium and prevent bad things from entering the lungs
How can asthma result in death?
Severe, unrelenting attack can cause status asthmaticus and death
Biopsy of nasopharyngeal carcinoma
Shows pleomorphic keratin-positive epithelial cells in a background of lymphocytes
shunt
Shunt- perfusing an area that isn't ventilated Giving O2 to patient with a shunt won't help
What does the ductus arteriosus do in development?
Shunts blood from the pulmonary artery to the aorta (below branching of great vessels), bypassing the lungs
Fibrotic nodules in upper lobes of the lung is caused by exposure to what?
Silicosis (pneumoconioses) Upper lobes is a hint- this can increase TB risk, and TB is in the upper lobes also
What are risk factors for IHD?
Similar to those for atherosclerosis; incidence increases with age
Risk of Papillary Muscle Rupture S/p MI is due to ______
Single blood supply from posterior descending artery
Granulomatosis w/ Polyangiitis
Small vessel vasculitis; aka Wegners gramulomatosis; shows: 1. Upper respiratory tract: *perforation of nasal septum*, chronic sinusitis, otitis media, mastoiditis 2. Lower respiratory tract: hemoptysis, cough, SOB 3. Renal: hematuria, red cell casts -*c-ANCA +* (aka PR3-ANCA)
Henoch-Shonlein Purpura
Small vessel vasculitis; most common childhood vasculitis, *often 2o to a URI*; Classic triad: palpable purpura on buttocks/legs, arthralgias, and abdominal pain -Shows *increased IgA* (which deposits in vessels to cause the problem) -Associated w/ *IgA nephropathy*
Churg-Strauss
Small vessel vasculitis; shows *granulomatous, necrotizing vasculitis with eosinophilia*; *asthma*, sinusitis, skin nodules or purpura, peripheral neuropathy, *wrist and/or foot drop* -*p-ANCA +* (aka MPO-ANCA) w/ increase IgE level (hence the eosinophilia)
Microscopic Polyangiits
Small vessel vasculitis; similar presentation to granulomatosis w/ polyangiitis but *without nasopharyngeal involvement or granuloma formation* -*p-ANCA +* (aka MPO-ANCA)
What is chronic bronchitis associated with?
Smoking
What is the most common cause of emphysema?
Smoking
Name two causes of emphysema
Smoking Alpha-1 Anti Trypsin Deficiency
Primitive Pulmonary Vein Give Rise to ______
Smooth part of *left* atrium
Right Horn of Sinus Venosus Give Rise to ______
Smooth part of *right* atrium
Bulbus Cordis Give Rise to ______
Smooth parts (outflow tracts) of left and right ventricles
How does rhinitis present?
Sneezing, congestion, runny nose (common cold)
Curschmann spirals
Spiral shaped mucus plugs seen in asthmatics
Physical exam finding in ASD
Split S2; as pressure builds up in the lungs, the pulmonic valve will begin to close later than the aortic valve
Lung cancer defined histologically by keratin pearls or intercellular bridges
Squamous cell carcinoma
What lines the vocal cords?
Squamous epithelium
stable vs. unstable angina
Stable Angina - Chest pain that arises with exertion or emotional stress. Unstable angina - Chest pain that occurs at rest.
FVC
Stands for forced vital capacity; amount of air you can breath out after maximum inhalation
Types of Aortic Dissections
Stanford Type A: proximal; involves ascending aorta w/ possible extension into aortic arch and descending aorta; can cause cardiac tamponade; tx w/ surgery Stanford Type B: distal; involves descending aorta *below ligamentum areriosum*; tx w/ beta blockers then vasodilators
2nd most common cause of secondary pneumonia; often complicated by abscess or empyema
Staph Aureus
What is the most common cause of endocarditis in IV drug abusers?
Staphylococcus aureus
Name five causes of bronchopneumonia
Staphylococcus aureus Haemophilus influenzae Pseudomonas aeruginosa Moraxella catarrhalis Legionella pneumophilia
What is the main cause of endocarditis in prosthetic valves?
Staphylococcus epidermidis
What causes Libman-Sacks endocarditis?
Sterile vegetations that arise in association with SLE
What causes nonbacterial thrombotic endocarditis?
Sterile vegetations that arise in association with hypercoagulable state or underlying adenocarcinoma
Name two bacterial causes of lobar pneumonia
Streptococcus pneumoniae Klebsiella pneumoniae
What are the most common causes of lobar pneumonia?
Streptococcus pneumoniae (95%) and Klebsiella pneumoniae
What is the most common cause of endocarditis
Streptococcus viridans
Why is C-section associated with increased risk for neonatal respiratory distress syndrome?
Stress induced steroids are not released, and steroids do two things: (1) increase the synthesis of surfactant (2) cause the surfactant present in Type II pneumocytes to be released out
Diaphragm structures
Structures perforating diaphragm: - T8: IVC - T10: esophagus, vagus (CN10; 2 trunks) - T12: aorta, thoracic duct, azygos vein Diaphragm is innervated by C3, 4, and 5 (phrenic nerve). Pain from diaphragm irritation (air or blood in peritoneal cavity) can be referred to shoulder (C5) and tapezius ridge (C3, 4)
Name for endocarditis from Streptococcus viridans
Subacute endocarditis (does not destroy the valve)
What causes functional aortic stenosis in hypertrophic cardiomyopathy
Subaortic hypertrophy of ventricular septum
What part of the myocardial wall does the initial phase of infarction involve?
Subendocardial necrosis involving less than 50% of the myocardial thickness (ST depressions)
What area of the heart is most susceptible to damage with coronary atherosclerosis?
Subendocardium
sign of leser-trelat
Sudden appearance of multiple seborrheic keratoses that may be associated with internal malignancy assoc. w/ GI adenocarcinomas
lymph node tenderness
Suggests recent, rapid enlargement that has put pain receptors in the capsule under tension. This typically occurs with inflammatory processes, but can also result from hemorrhage into a node, immunologic stimulation, and malignancy.
Right Common Cardinal and Right Anterior Cardinal Veins Give Rise to ______
Superior vena cava
Nutmeg liver
Surface of a normal liver should have equal color; congested central veins here causing nutmeg appearance
Neonatal respiratory distress syndrome
Surfactant deficiency ground glass appearance of lung fields lecithin:sphingomyelin ratio <1.5 in amniotic fluid is predictive of NRDS. Persistently low oxygen tension leads to risk of PDA. Therapeutic supplemental O2 can result in retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia Risk factors: prematurity, maternal diabetes (due to increased fetal insulin), c-section delivery (decreased release of fetal glucocorticoids) Complications: metabolic acidosis, PDA, necrotizing enterocolitis Tx: maternal steroids before birth; artificial surfactant for infant
Treatment of VSD
Surgical closure, although small VSDs may close spontaneously
Migratory polyarthritis in acute rheumatic fever
Swelling and pain in a large joint that resulves within days and migrates to involve another large joint
Causes of aortic root dilation causing aortic regurgitation
Syphilitic aneurysm, aortic disection
Acute Rheumatic Fever
Systemic complication of pharyngitis due to group A beta-hemolytic streptococci; affects children 2-3 weeks after an episode of streptococcal pharyngitis
Sarcoidosis definition
Systemic disease characterized by noncaseating granulomas in multiple organs
metastasis of small cell carcinoma
Systemic: high propensity for brain/bone mets and visceral disease
What dysfunction does dilated cardiomyopathy cause, and why?
Systolic dysfunction; heart is so dilated that it can't pump, leading to biventricular CHF
Systolic vs. Diastolic Heart Failure
Systolic dysfunction= reduced EF, increased EDV; decreased contractility often 2° to ischemia/MI or dilated cardiomyopathy Diastolic dysfunction= preserved EF, normal EDV; decreased compliance often 2° to myocardial hypertrophy
What is the PE finding in aortic stenosis
Systolic ejection click with crescendo-decrescendo murmur
Pulse Pressure=
Systolic pressure - diastolic pressure -PP is inversely related to arterial compliance and directly related to SV -Increased pulse pressure seen in *aortic regurge*
locations of T vs. B lymphocytes
T cells in paracortex, B cells in germinal centers
characteristic causes of caseating granulomas
TB and fungal infxn (stain via AFB or GMS)
What does silicosis increase the risk for, and why?
TB, because it impairs phagolysosome formation by macrophages when it enters the macrophages
What is released from injured pneumocytes in idiopathic pulmonary fibrosis that induce fibrosis?
TGF-Beta
small cell carcinoma is often positive for which immunohistochemical markers?
TTF1+, napsin+, synaptophysin+ Napsin and synaptophysin are neuroendocrine markers and this is the only neuroendocrine primary lung tumor
intercept platelets and plasma
Takes out anything with nucleic acid, but platelets don't have nucleic acid Inactivates most bacteria, viruses, and WBCs May prevent transfusion transmission of emerging diseases with no tests available Usually given to heme-onc patients or patients who need irradiated blood products
markers that tend to be positive in ALL
TdT+ (DNA polymerase, marker of pre-T and pre-B lymphoblasts), CD10+ (marker of pre-B cells)
Classic age/sex of angiofibroma
Teenage male
How does angiofibroma present?
Teenage male with diffuse epistaxis
Boot Shaped CXR in Neonate =
Tetralogy of Fallot
Boot shaped heart
Tetralogy of Fallot
Third Degree (Complete) AV Block
The atria and ventricles beat independently of each other. P waves and QRS complexes not rhythmically associated. Atrial rate > ventricular rate. Usually treated with pacemaker. Can be caused by Lyme disease. Complete heart block: hallmark is AV dissociation. Complete heart block with ventricular escape usually reflects disease of the conduction system below AV node. Can be seen in acute MI or as natural progression of LBBB with age.
CMV negative
The donor center performs testing for the presence of CMV IgG/IgM on a subset of units, and labels the negative units as "CMV negative" Still a small residual risk of CMV transmission from CMV negative units, due to window period (acute infection where no Ab's have been formed yet) No further benefit over leukoreduction Doing both leukoreduction and CMV-negative doesn't further reduce risk During acute phase, CMV is also present outside of WBC's Usually just use leukoreduction, but may use CMV negative in intrauterine transfusion (CMV is a TORCH infection)
J Point on EKGs
The junction between the end of the QRS complex and the start of the ST segment
What is the mucociliary escalatory, and how can it become damaged?
The lungs are lined by ciliated epithelium, and the cilia help push mucus up out of the airway to be swallowed. It can become damaged in a viral pneumonia, which will then increase the risk of a superimposed bacterial pneumonia
most common cause of cardiac arrest in hospital
The most common cause of cardiac arrest in house is failure to recognize impending respiratory failure/arrest !!
Class IV Antiarrhythmics
The non-dihydropyridine CCBs (verapamil, diltiazam)
How do patients with Tetralogy of Fallot respond to cyanotic spell?
The squat (increases arterial resistance allowing less blood to go from RV to aorta, and more to go to the lungs)
Why are the particles that cause pneumoconioses small?
They must be small enough to escape the defenses of the lung and reach the bottom to activate macrophages, which induce the fibrosis that results in problems
What does chronic rheumatic heart disease cause in mitral valve?
Thickening of chordae tendinae and cusps
cryosupernatant
This is fresh frozen plasma that has had the cryoprecipitate removed and is thus depleted of high-molecular-weight von Willebrand multimers, which have a pathogenic role in TTP. Lower content of vWF multimers in Cryo-Poor Plasma might reduce the formation of platelet-rich thrombi, especially in the CNS
indications for platelet transfusion
Thrombocytopenia or dysfunctional platelets (drugs, cardiopulmonary bypass pump, etc.)
tingible body macrophages
Tingible body macrophages have abundant clear cytoplasm + debris (eating up clones that weren't specific enough) Follicular lymphomas don't have tingible body macrophages
Name the two risk factors for laryngeal carcinoma
Tobacco and alcohol
Class III ANtiarrythmics Can Cause ______ (Arrhythmia)
Torsades de pointes
TLC (what is it and how does it change in COPD?)
Total lung capacity (increased in chronic obstructive pulmonary diseases)
Minute ventilation (VE)
Total volume of gas entering lungs per minute VE = VT x respiratory rate (RR)
How is trachea shifted in spontaneous pneumothorax?
Toward side of collapse
Primitive Atrium Give Rise to ______
Trabeculated part of left and right atria
Primitive Ventricle Give Rise to ______
Trabeculated part of left and right ventricles
hypertensive emergency treatment
Treat with clevidipine, fenodapam, labetalol, nicardipine, or nitroprusside. Nitroprusside - Short acting; inc cGMP via direct release of NO. Can cause cyanide toxicity (releases cyanide). Fenoldopam - Dopamine D1 receptor agonist - coronary, peripheral, renal, and splanchnic vasodilation. dec BP, inc natriuresis. Also used postoperatively as an antihypertensive. Can cause hypotension and tachycardia.
pulmonary hypertension treatment
Treatment of group 2, group 3 and group 5 PH is the treatment of the causal disease and PAH therapeutics are not recommended. Below is for group 1. Primary goal: target the underlying pulmonary disease decrease in pulmonary vascular resistance and relieve the pressure overload on the RV General principles: decreasing the work of breathing using noninvasive mechanical ventilation, bronchodilation, and steroids treating any underlying infection vaccination Adequate oxygenation (oxygen saturation 90-92%) will also decrease pulmonary vascular resistance and reduce the demands on the RV Pulmonary rehab Diuretics, low sodium diet Digoxin (helps RV, but can worsen arrhythmias)
Physiology of the Cushing Reflex
Triad of HTN, bradycardia, and bradypnea is due to: increased ICP constricts cerebral arterioles -> cerebral ischemia -> increase pCO2 and decreased pH -> central sympathetic reflex -> increase in BP -> increased stretch -> reflex peripheral baroreceptor induced bradycardia and bradypnea
What are the two laboratory tests to detect MI?
Troponin I (peaks 2-4 hours after infarction and returns to normal 7-10 days later) CK-MB (reinfarction, returns to normal by 72 hours)
TNM stands for...
Tumor size and local extension Nodes Mets
What is associated with infantile coarctation of the aorta
Turner's Syndrome (45 X)
allergic/anaphylactic rxn to transfusion
Type I hypersensitivity reaction against plasma proteins in transfused blood. IgA-deficient individuals must receive blood products without IgA. Within minutes to 2-3 hours Clinical Presentation - Urticaria, pruritus, fever, wheezing, hypotension, respiratory arrest, shock; variable severity; urticarial rash and itching, flushing, vomiting/diarrhea, wheezing; severe reactions (rare) Caused by hypersensitivity to proteins or allergens in the plasma of the transfused unit>mast cell degranulation>histamine release Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, administer antihistamines; epinephrine/bronchodilators/steroids if severe, intubate and give pressors for BP support if needed Prevention: No evidence for pre-medication after mild allergic reactions, consider PAS platelets or washing if severe or recurrent reactions; There is no contraindication to future transfusion
Febrile Nonhemolytic Transfusion Reaction
Type II hypersensitivity reaction. Host antibodies against donor HLA antigens and WBCs. Within 1-6 hours Clinical Presentation - Fever, headaches, chills, flushing. Tachyardia, palpitations, cough, nausea/vomiting, Caused by antibodies in the recipient directed against white cells in the unit OR cytokines that accumulate in the plasma of the unit during storage (from WBCs in the unit) Defined by a rise in temp of ≥ 1°C during or within 4 hours after transfusion for which no other cause is identified (diagnosis of exclusion) Treatment: STOP THE TRANSFUSION, NOTIFY BLOOD BANK, may administer antipyretics Prevention: Leukocyte reduction; no evidence for premedication; No contraindication to additional transfusion
acute hemolytic transfusion rxn
Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs). Within 1 hour Clinical Presentation - Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinuria (intravascular hemolysis), jaundice (extravascular). "sense of impending doom", renal failure, shock Generally caused by PRBCs; Caused by preformed IgM ABO alloantibodies in recipient that bind to antigens on the transfused red blood cells and cause acute INTRAVASCULAR hemolysis Severity of the reaction is directly proportional to the volume of RBCs infused
What is the stem cell of the lung?
Type II pneumocytes
What makes surfactant?
Type II pneumocytes
Chinese adult male with large cervical lymph nodes
Typical presentation of nasopharyngeal carcinoma
methods by which whole blood vs. platelets are collected
US blood supply comes from altruistic volunteer donors majority of RBC's come from whole blood donation majority of platelets come from apheresis (collection of individual components)
Post-Natal Remnant of the Umbilical Arteries and Vein
Umbi*l*ical Arteries: media*l* umbilical ligaments Veins: ligamentum teres hepatis (aka round ligament), which is held in the falciform ligament
What is endocarditis from Streptococcus bovis associated with?
Underlying colorectal carcinoma
Sudden cardiac death definition
Unexpected death due to cardiac disease that occurs without symptoms or less than 1 hour after symptoms
Etiology of idiopathic pulmonary fibrosis
Unknown, but likely related to cyclical lung injury and TGF-Beta from injured pneumocytes, which induces fibrosis
What is etiology of sarcoidosis?
Unknown; likely due to CD4+ helper T cell response to unknown antigen
Etiology of mitral valve prolapse, and two conditions where it is seen
Unknown; may be seen in Marfan or Ehlers Danlos syndrome
Hypertensive Emergency vs. Hypertensive Urgency
Urgency is BP >180/120 *without* end organ damage, where as emergency is *with* end organ damage
bronchoscopy
Useful for diagnosis and staging of lung cancer Less invasive and risk of pneumothorax (<3%) than CT guided biopsy >90% yield for endobronchial lesions Better for central or hilar lesions
mediastinoscopy and VATS
Useful for diagnosis and staging of lung cancer More invasive, for accurate nodal staging and excisional bx Mediastinoscopy for nodal staging (esp if PET +) Video-assisted thoracoscopic surgery (VATS) for wedge resection, excisional biopsy
Use for CKMB Measurement
Useful for dx of *re-infarction* following acute MI because levels return to normal after 48h (vs. 7-10 days for troponin)
markers that tend to be positive in B-ALL
Usually characterized by lymphoblasts (TdT+) that express CD10, CD19, and CD20.
acute lymphadenitis
Usually in response to infection but also will react to foreign matter introduced into the blood, cell debris, etc. Common in the cervical and axillary regions due to infections in the oral cavity or in the extremities Often painful Almost always resolve on their own- don't require biopsy
when and how T-ALL usually presents
Usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)
Pulmonary emboli
V/Q mismatch leads to hypoxemia leads to respiratory alkalosis. Sudden onset dyspnea, chest pain, tachypnea, tachycardia. May present as sudden death. Lines of Zahn are interdigitating areas of pink (platelets and fibrin) and red (RBCs) found only in thrombi formed before death; help distinguish pre and postmortem thrombi Types: Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor CT pulmonary angiography is imaging test of choice for PE
Chronic rheumatic heart disease
Valve scarring that arises as a result of rheumatic fever
Lung Vasculature is Unique in that it ______ During Hypoxia
Vasoconstricts (i.e. only well-ventilated areas are perfused); all other tissues -> vasodilation in response to hypoxia
What do Nitrates do in MI treatment?
Vasodilate veins and coronary arteries
What is nitroglycerin's mechanism of action?
Vasodilation of arteries and veins
Where are vegetations in Libman-Sacks endocarditis located and what do they cause?
Vegetations are located on both sides of the mitral valve; cause mitral regurgitation
What causes heart murmur in endocarditis?
Vegetations on the valves that disrupt flow
ventilation vs. perfusion in 3 lung zones
Ventilation>perfusion in upper zones Equal in middle zones Ventilation<perfusion in lower zones
Where does Rhabdomyoma usually arise?
Ventricle
Ventricular Hypertrophy is Protective Against ______
Ventricular free wall rupture (5-14 days post-MI)
Defect in septum that divides the right and left ventricles
Ventricular septal defect
Prognosis of large cell carcinoma?
Very poor
Subacute Endocarditis is due to ______
Viridans strep; think *post-dental procedures*; most common cause of endocarditis
Interstitial pneumonia (atypical)
Viruses (influenza, CMV, RSV, adenoviruses) Mycoplasma, legionella, chlamydia Diffuse patchy inflammation localized to interstitial areas at alveolar walls; diffuse distribution involving ≥1 lobe. Generally follows a more indolent course ("walking" pneumonia)
What are the two layers of pleura?
Visceral (on lungs) and parietal (on chest wall)
packed RBC's
Volume: 250 - 350 mL RBCs: 200-250 mL Plasma: < 50 mL Few WBCs & platelets Anticoagulant (citrate- binds calcium and prevents coagulation cascade) 63-70 mL Iron: 200-250 mg Shelf life: 42 days at 1-6°C Expected response to transfusion of one unit: Hemoglobin increase of 1 g/dL, hematocrit increase of 3%
leukopenia
WBC <5k decrease in WBC typically d/t one particular cell lineage
leukocytosis
WBC >10k increase in WBC typically d/t one particular cell lineage
IgG-mediated immune hemolytic anemia
Warm (IgG)—chronic anemia seen in SLE and CLL and with certain drugs (eg, α-methyldopa) ("warm weather is Great") IgG-mediated disease usually involves extravascular hemolysis IgG binds RBCs in the relatively warm temperature of the central body (warm agglutinin); membrane of antibody-coated RBC is consumed by splenic macrophages, resulting in spherocytes Associated with SLE (most common cause), CLL, and certain drugs (penicillin and cephalosporins) Drugs may attach to RBC membrane (penicillin) with subsequent binding of antibody to drug-membrane complex Drugs may induce production of autoantibodies (alpha-methyldopa) that bind self-antigens on RBCs (alpha-methyldopa alters Rhesus factor and creates a new autoantibody) Treatment involves cessation of the offending drug, steroids, IVIG, and splenectomy if necessary
washing
Washing removes most of the plasma (so you can't wash plasma) but you can wash RBC's and platelets Used for severe recurrent allergic (anaphylactic) transfusion reactions, patients with severe IgA deficiency, for large volume transfusions of irradiated older blood for neonates, or for neonates with HDFN from a high-incidence antibody that require maternal red cell transfusion Disadvantage: Some of the red cells or platelets are lost during washing, and platelets may all be activated by the washing process Recall that platelets are high-maintenance So only done when there is no other choice
What causes aortic stenosis
Wear and tear causing fibrosis and calcification
When do congenital defects usually arise?
Weeks 3-8
What can cause missing nasal septum?
Wegener's granulomatosis or cocaine snorting
what ANA is highly assoc. w/ diffuse scleroderma?
anti Scl70 (DNA topoisomerase I ab)
How does chronic bronchitis cause cor pulmonale?
When the entire lung is infected, arterioles everywhere try to clamp down and send blood elsewhere for oxygenation; this leads to increased pressures, causing the right heart to hypertrophy and then eventually fail
Chest x-ray finding in ARDS
White out
What causes hyperdynamic pulses in aortic regurgitation
With regurgitation, diastolic pressure decreases; with increased stroke volume due to regurgitation, systolic pressure increases; increases pulse pressure
Becker muscular dystrophy
X linked disorder d/t *non-frameshift deletion* in dystrophin gene (partially truncated and functional) onset: early adulthood
hemophilia A
X linked factor 8 deficiency deep tissue, joint, and postsurgical bleeding high PTT, normal PT; low factor 8 amount tx: recombinant factor 8
Hypophosphatemic rickets
X-linked Dominant formerly known as vitamin D-resistant rickets inherited disorder results in increased phophate wasting at proximal tubule -> rickets presentation
Fragile X Syndrome
X-linked dominant Trinucleotide repeat CGG in 5' UTR (>230) of FMR1 gene with expansion occurring during oogenesis -> hypermethylated into promoter -> decreased expression of FMR1 protein most common *inherited* intellectual disability sx: post-pubertal macroorchidism (90% cases), long face with large jaw, large everted ears, autism, mitral valve prolapse 5-6x more common to affect male vs female 30-50% carrier females are affected (MR)
Duchenne muscular dystrophy
X-linked dz d/t *frameshift* or nonsense mutation -> *DMD gene* affected -> *truncated or absent dystrophin* -> malfunctioned anchoring b/t actin and membrane proteins -> progressive myofiber damage sx: weakness beginning in pelvic girdle and moves upward - pseudohypertrophy of calves d/t fatty replacement - waddling gait labs: increased CK and aldolase; genetic test to confirm onset <5yo cause of death? dilated cardiomyopathy usually Gower sign - use UEs to help stand
G6PD deficiency
X-linked recessive disorder -> reduced half-life of G6PD -> RBCs susceptible to oxidative stress -> intravascular hemolysis (typical stress from infection, drugs, fava beans) need enzyme to regenerate NADPH so it can regenerate glutathione (*glutathione needed to take care of H2O2 in RBCs) 2 variants: *african* (*mildly* reduced half life) and *mediterranean* (*markedly* reduced half life) protective role in F. malaria oxidative stress precipitates Hb -> *heinz bodies* -> spleen removes making *bite cells* presents: hemoglobinuria and back pain hours after oxidative stress exposure check for heinz bodies to screen; enzyme study confirms *Stress* makes me eat *bites* of *fava beans* with *Heinz* ketchup
What is the gross change during the inflammatory phase up to 1 week after MI?
Yellow pallor
Does acute endocarditis (Staphylococcus aureus endoacarditis) destroy the valve?
Yes, it results in large vegetations that destroy the valve
Who is classically affected with primary pulmonary hypertension?
Young adult females
In who is a spontaneous pneumothorax seen?
Young adults
sarcoidosis
a multisystem, inflammatory disorder characterized by noncaseating granulomas that can infiltrate almost any organ but, most commonly, involves the lungs (but variable lung symptoms, PFT's, etc)
paroxysmal nocturnal hemoglobinuria
acquired mutation in PIGA gene -> impaired synthesis of *GPI* anchor for decay-accelerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59) which *protect RBC from complement* DAF inhibits C3 convertase mutation acquired in hematopoietic stem cell *intravascular hemolysis episodically especially at night* - shallow breathing->resp. acidosis-> activated complement->RBCs, WBCs, and platelets lysed sucrose test (activates complement) and *acidfied serum test or flow cytometry to detect lack of DAF confirm* main cause of death = *thrombosis of hepatic, portal, or cerebral veins from destroyed platelets activating thrombosis* complications: iron def. anemia (peeing out hgb) and AML (10% pt)
CD8 t cell role
activated via MHC1 presentation + IL2 from Th1 cell kill via perforin and granzyme -> activate caspases -> apoptosis also express FasL to bind Fas receptor on host cell
what is the role of MYC?
activates many genes involved in cell growth -cyclin D, ribosomes, Warburg effect -can upregulate telomerase it can be translocated, amplified, and mutations can lead to oncogene activation
what three things are needed to activate coagulation aka secondary hemostasis?
activating substance (SEC or TF) phospholipid surface of platelets calcium (from dense granules of platelets)
what is the end goal of the apoptotic pathways?
activation of caspases
what role does C3b play?
acts as an opsonin for phagocytosis or adds to C3 convertase to make C5 convertase
Löfgren's Syndrome
acute form of sarcoidosis Acute erythema nodosum; Bilateral hilar lymphadenopathy; Fever; & Polyarthritis. Abrupt onset; Transient course Higher probability of spontaneous resolution Good prognosis
What disease is common in Down syndrome arising before 5 years of age?
acute megakaryoblastic anemia (type of AML)
Acute respiratory distress syndrome
acute onset resp failure, bilateral lung opacities. Causes: trauma, sepsis, shock, gastric aspiration, uremia, acute pancreatitis, amniotic fluid embolism. Diffuse alveolar damage leads to increased alveolar capillary permeability and protein leakage into alveoli and noncardiogenic pulmonary edema. Results in formation of intra-alveolar hyaline membranes. Initial damage due to release of neutrophilic substances toxic to alveolar wall, activation of coagulation cascade, and oxygen-derived free radicals. Tx: mechanical ventilation with low tidal volumes, address underlying cause
List the non-small cell carcinomas
adenocarcinoma squamous cell carcinoma large cell carcinoma bronchial carcinoid tumor
dimpling of skin + nipple retraction
advanced invasive ductal carcinoma
refeeding syndrome
adverse clinical events secondary to refeeding a severely malnourished pt Fluid Overload: Decrease in cardiac mass & contractile function Increase in Na & water retention (insulin-mediated) Electrolyte Abnormalities: Mechanism: Insulin-stimulated cellular uptake & intracellular utilization during anabolism Hypophosphatemia (MOST IMPORTANT): Muscle weakness, paresthesias, seizures, coma, CP decompensation, death Hypokalemia Hypomagnesemia Cardiac Arrhythmias: Bradycardia + Refeeding = Ventricular tachyarrhythmias (1st wk) and prolonged QT Glucose Intolerance: Insulin Resistance + Refeeding = Blood glucose GI Dysfunction: Functional Deterioration + Refeeding = Diarrhea (1st wk) decreased mucosa, pancreas mass & synthesis
reason for the warburg effect?
aerobic glycolysis provides rapidly dividing tumor cells with metabolic intermediates that are needed for the synthesis of cellular components, whereas mitochondrial oxidative phosphorylation does not glutamine and glucose used heavily to make intermediates -> then proteins, nucleotides, and lipids for a new cell
2 components of germinal center rxn
affinity maturation and isotype switching
Lung volumes residual volume
air in the lung after maximal expiration; cannot be measured on spirometry
Lung volumes Inspiratory reserve volume (IRV)
air that can still be breathed in after normal inspiration
Lung volumes expiratory reserve volume (ERV)
air that can still be breathed out after normal inspiration
Monckeberg Sclerosis
aka *medial calcific sclerosis*; a form of arteriosclerosis; affects *medium-sized arteries* causing *calcification* of internal elastic lamina and media -> vascular stiffening -Shows *pipestem* appearance of X-ray -DOES NOT obstruct blood flow
what is P-glycoprotein?
aka multidrug resistant protein 1 (MDR1) - classically seen in adrenocortical carcinoma but also in other cancers (colon, liver) MOA: pumps out toxins from cell including chemotherapeutics
most common transfusion complication
alloimmunization
Amniotic fluid embolus
amniotic fluid leaks out during delivery -shortness of breath, neurologic symptoms, and DIC bc amniotic fluid has tissue thromboplastin -have keratin and squamous debris
what is amyloidosis?
amyloid is a misfolded protein that deposits in extracellular space damaging tissues -multiple proteins can deposit this way -this can be systemic or localized
growth adaptation
an increase, decrease, or change in stress on an organ can result in this
macrocytic anemia
anemia >100 most common causes *B12 or folate deficiency* other causes are alcoholism, liver disease, and drugs (5-FU), Fanconi anemia, Orotc aciduria, Diamond-Blackfan anemia
vinyl chloride
angiosarcoma of liver (occupational exposure)
SLE pathogenesis
antigen-antiboy complex damage multiple tissues (type 3 HSR) poorly cleared apoptotic debris (eg UV damage) activates self reactive lymphocytes -> produce ab to host nuclear antigens complexes taken up by dendritic cells -> activate cytoplasmic TLRs -> increased IFN-a complexes subsequently generated more and deposit in multiple tissues
how are free radicals eliminated?
antioxidants (glutathionine, vit A, C, E) enzymes (SOD, glutathione peroxidase, catalase) metal carrier proteins (transferrin and ceruloplasmin) carry keeping metals from reacting
pathologic hyperplasia
any stress on an organ that can lead to dysplasia and eventually cancer eg. endometrial hyperplasia from too much estrogen vs progesterone exception is BPH (pathologic but not assoc. w/ cancer)
Large vessel vasculitis affects what vessels? what are 2 high yield dz?
aorta and major branches -Temporal (giant cell) arteritis + Takayasu arteritis
S2
aortic and pulmonic valve closure
Cheyne-Stokes Respirations
apnea --> hypercapnea --> hyperventilation --> hypocapnia
how many divisions occur in cancer cells before clinical symptoms arise?
approximately 30
What confirms exposure to asbestos?
asbestos bodies/ferruginous bodies
alkaline phosphatase serum tumor marker
asosciated with mets to bone or liver, paget dz of bone, and seminoma (placental ALP) exclude hepatic origin by checking LFTs and GGT
mixed cellularity HL
associated with *abundant eosinophils* (IL-5)
Hypertrophic osteoarthropathy
associated with *adenocarcinoma of lung* abnormal proliferation of skin and bone at distal extremities -> clubbing, arthralgia, joint effusions, periostosis of tubular bones
acanthosis nigricans paraneoplastic syndrome
associated with *gastric adenocarcinoma* and other visceral mallignancies hyperpigmented velvety plaques in axilla and neck
Silicosis
associated with foundries, sandblasting, mines. Macrophages respond to silica and release fibrogenic factors leading to fibrosis. It is thought that silica may disrupt phagolysosomes and impair macrophages, increasing susceptibility to TB. Also increased risk of bronchogenic carcinoma. Affects upper lobes "Eggshell" calcification of hilar lymph nodes
Fat emboli
associated with long bone fractures and liposuction; classic triad of hypoxemia, neurologic abnormalities, petechial rash
dermatomyositis paraneoplastic syndrome
associated with ovarian adenocarcinoma progressive proximal muscle weakness, Gottron papule, heliotrope rash
Anthracosis
asymptomatic condition found in many urban dwellers exposed to sooty air
What is antiphospholipid antibody?
autoantibody directed against proteins bound to phospholipids -anticardiolipin (False+ VDRL/RPR), anti B2 glycoprotein I, and Lupus anticoagulant (falsely elevate PTT) all examples 1/3 SLE pt have these present
scleroderma pathophys
autoimmune damage to mesenchyme possible initiator endothelial dysfunction leads to inflammation (inc. endothelin, dec. NO), vasoconstriciton, secretion of GFs (TGFB and PDGF) fibroblasts activated and fibrosis initially perivascular -> progresses causing organ damage
Sjogren syndrome pathophys and presentation
autoimmune destruction of lacrimal and salivary glands (type 4 HSR - lymphocyte damage with fibrosis) dry eyes and dry mouth and reccurent dental caries in older women (50-60yo) can progress to ulceration of corneal epithelium or oral mucosa
systemic sclerosis (scleroderma)
autoimmune dz with sclerosis of skin and visceral organs - Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis (middle age females 30-50yo) 75% female
Immune Thrombocytopenic Purpura (ITP)
autoimmune production of IgG against platelet antigens (eg GP2b/3a) -> splenic macrophages consume platelets most common cause of thrombocytopenia in adults and children *acute* (common in children 2/2 viral illness or immunization; self limited) and *chronic* forms (women child bearing age; 1' or 2', SLE) tx: corticosteroids -> IVIG or splenectomy
How do you treat SLE?
avoid sun exposure + glucocorticoids for flares severe or refractory, use other immunosuppressive drugs
most common transfusion-transmitted infection
bacterial contamination 1:4000 units contain detectable bacteria, although severe reactions are uncommon Platelets most likely to get contaminated b/c they're stored at room temp
nonionizing (UVB from sunlight most common source)
basal cell carcinoma, squamous cell carcinoma, melanoma of skin from formation of pyrimidine dimers in DNA excess exposure overruns DNA repair mechs
hemangioma
benign tumor comprised of blood vessels commonly present at birth -> regresses during childhood -Most often involves *skin and liver*
what are the features of amyloid proteins?
beta pleeted sheet, congo red staining and apple-green birefringence seen under polarized light
Deep venous thrombosis
blood clot within a deep vein leading to swelling, redness, warmth, and pain. Predisposed by virchow triad of stasis, hypercoagulability (defect in coagulation cascade proteins, such as factor V leiden), and endothelial damage (exposed collagen triggers the clotting cascade. 95% of pulmonary emboli arise form proximal deep veins of lower extremity. Use unfractionated heparin or LMWH for prophylaxis or acute management> Use oral anticoagulants such as warfarin or rivaroxaban for treatment (long term prevention)
gross exam shows what for fibrocystic change?
blue-dome appearance of cysts
BRCA1 mutation associated with?
breast and ovarian carcinoma -breast: medullary carcinoma of breast -ovary/fallopian tube - serous carcinoma
BRCA1/BRCA2 (DNA repair protein) tumor suppressor gene associated with waht cancers
breast, ovarian, pancreatic these function in homologous end joining DNA repair aggressive and ugly high grade cancers 2 hit hypothesis (loss of heterozygosity) Triple negative Cancers
Cartilage and goblet cells extend until what part of the respiratory tree?
bronchi
yellow nails may indicate
bronchiectasis, chronic sinusitis, lymphedema, nicotine stains
mainstay of therapy in COPD
bronchodilators < 10% increase in FEV1 reduce hyperinflation improve dyspnea improve exercise capacity Combination with anticholinergics may be more effective in reducing exacerbations Long acting formulations are preferred over short acting
radon carcinogen
by-product of uranium decay, accumulates in basements associated with lung cancer (2nd leading cause after smoking)
Vitamin K deficiency
cannot carboxylate factors 10, 9, 7, 2 and proteins C and S -occurs in: *newborns* (lack of GI bacteria to synthesize it) - give injection at birth; *long-term abx tx* (destroys bacteria in GI who produce); *malabsorption* (deficiency in ADEK)
Which type of cancer usually metastasizes to lymph nodes?
carcinoma
cigarrette smoke
carcinoma of oropharynx, esophagus, lung, kidney, bladder, and pancreas *polycyclic hydrocarbons* particularly carcinogenic
lymphatic spread of cancer characteristic in what?
carcinomas (epithelium drained by lymphatics)
what are the 3 permanent tissues that have little to no stem cells?
cardiac and skeletal muscle and nerves can only do hypertrophy
TTP
cause of MAHA 2/2 *ADAMTS13* enzyme decreased -> usually chops up vWF multimers into monomers multimers lead to abnormal platelet adhesion -> microthrombi decreased enzyme d/t acquired antibody to ADAMTS13 (adult females) -uncommon to be genetic
Methemoglobinemia
cause of hypoxia d/t iron in Fe+3 form (PaO2 nl, SaO2 dec.) seen in oxidant stress (nitrate and sulfa drugs) and newborns (immature ability to reduce Fe+3) findings: cyanosis and chocolate-colored blood tx: IV methylene blue - reduces Fe+3 back to Fe+2 (binds O2)
Glanzmann thrombasthenia
caused by genetic GP2b/3a deficiency -> platelet aggregation impaired
carbon tetrachloride
causes free radical formation via liver converting to CCL3 by P450 system -> cells swell and RER does too -> decreased protein synthesis of apolipoproteins -> fatty changes in liver, can't deliver to body
multifactorial PH
causes include hematologic, systemic, and metabolic disorders
exudate
causes include infection, PE, malignancy requires further diagnostic evaluation: Appearance Red blood cell count White blood cell count Differential Glucose Amylase LDH pH Cytology
how do cells grow in invasive lobular carcinoma and why?
cells grow in single-file pattern (signet-ring morphology) -due to lack of E-cadherin adhesion protein -no duct formation
exudate characteristics
cellular (cloudy) high protein (>2.9 g/dL) d/t: lymphatic obstruction (chylous), inflammation/infxn, malignancy
metaplasia
change in stress on an organ leading to change in cell type that is better able to handle the stress
markers that tend to be positive in T-ALL
characterized by lymphoblasts (TdT+) that express markers ranging from CD2 to CD8 (e.g., CD3, CD4, CD7). The blasts do not express CD10.
free radicals
chemical species with an unpaired electron in outer orbit physiologic gen from oxidative phosphorylation pathologic: ionizing radiation, inflammation, metals, drugs and chemicals
Stable angina definition
chest pain that arises with exertion or emotional stress
what dz states is SAA increased in?
chronic inflammatory states (lupus, RA, crohns, UC) malignancy familial mediterranean fever (FMF)
JAK2 (tyrosine kinase) oncogene associated with what cancers
chronic myeloproliferative disorders
Barrett esophagus
classic example of metaplasia nonkeratinizing squamous epithelium -> nonciliated, mucin producing columnar cells (d/t acid reflux) can progress to adenocarcinoma of esophagus
How does complement get activated? how do you regulate?
classical pathway (C1 binding IgG or IgM which is bound to antigen) Alternative (microbial products directly activate) Mannose-binding lectin (MBL) -> MBL binds mannose on microorganisms Regulate with: C1 inhibitor, Decay accelerating factor (C3 blocked)
what 3 things does plasmin do?
cleaves fibrin and serum fibrinogen destroys coag factors blocks platelet aggregation
clumped vs. fine chromatin
clumped chromatin- more mature cells fine chromatin- more immature cells
CDKN2A tumor suppressor
codes for p16/INK3a -> blocks CDK4/cyclin D from phosphorylating RB codes for p14/Arf -> blocks MDM2 so lets p53 become activated mutations in this gene assoc. with *melanomas along with others*
zinc in wound healing
cofactor for collagenase, replacing type 3 with type 1 collagen
copper in wound healing
cofactor for lysyl oxidase -> cross links lysine and hydroxylysine forming stable collagen
hypertrophic scar
collagen organization: parallel edge borders confined to orginal wound
most common cancers to met to liver
colon >> stomach > pancreas
KRAS (GTPase) oncogene associated with what cancers
colon cancer, lung cancer, pancreatic cancer
APC (negative regulator of B-catenin/WNT pathway) tumor suppressor gene associated with what cancer
colorectal cancer (associated with Familial adenomatous polyposis) role of B catenin is to activate TF to make MYC, cyclin D, and other genes
why are granulomatous dz associated with hypercalcemia?
common to see high calcitriol production via activated macrophages in granulomas
anaplasia
complete lack of differentiation of cells in a malignant neoplasm
stable tissues
comprised of cells that are quiescent (Go) but can reenter cell cycle to regenerate tissue if necessary liver (compensatory hyperplasia), PCT in nephron
how does iron enter the body?
consumption of heme (meat derived) and non-heme (vegetable derived) forms occurs in *duodenum* via enterocytes with *DMT1 transporters* (heme form more readily absorbed) -enters enterocytes and passes into blood via *ferroportin* *transferrin* carries it in blood to liver and marrow macrophages for storage *ferritin* holds iron intracellularly preventing the *Fenton rxn*
Fluticasone, budesonide
corticosteroids inhibit the synthesis of virtually all cytokines. Inactivate nf-kb, the transcription factor that induces production of TNF-alpha and other inflammatory agents. First line therapy for chronic asthma
sarcoidosis treatment
corticosteroids are first-line Methotrexate Cyclosporin A Azathioprine Antimalarial Cyclophosphamide Anti-TNF-α
Atypical pneumonia with high fever (Q fever)
coxiella burnetii (seen in farmers and vets)
What kind of cells are present in the respiratory zone?
cuboidal cells in respiratory bronchioles. simple squamous up to alveoli. Cilia terminate in respiratory bronchioles. Alveolar macrophages are present.
Lymphangioleiomyomatosis
cystic lung disease associated with tuberous sclerosis Almost exclusively in females Treat with mTOR inhibitor (sirolimus)- doesn't cure condition, but prolongs life by a few months Only cure is lung transplant
How do myelodysplastic syndromes usually present?
cytopenias, hypercellular bone marrow, abnormal maturation of cells, increased blasts *(<20%)* -most pt die from infection or bleeding, however some can progress to *acute leukemia*
atherosclerotic embolus
d/t atherosclerotic plaque which dislodges -> characteristic of *cholesterol clefts* in embolus
microcytic anemia
d/t decreasaed production of hemoglobin (ie Fe, protoporphyrin, globin) -> MCV <80 2/2 extra division of RBC progenitors to maintain *proper concentration of hgb* *HY causes*: iron def., anemia of chronic dz, sideroblastic, thalassemia
sideroblastic anemia
d/t defective protoporphyrin synthesis -> cannot produce heme -> cannot produce hemoglobin -> microcytic anemia causes are congenital or acquired (*ALAS enzyme defect or alcoholism, lead poisoning, vit. B6 def.*) *alcoholism most common cause* *iron laden mitochondria*(iron sent to RBCs too much and can't be used) in *erythroid precursors* = ringed sideroblasts in bone marrow labs = high ferritin, low TIBC, high serum iron, high %sat (iron-overloaded state)
FMF (Familial Mediterranean Fever)
d/t dysfunction of neutrophils (AR) in persons of mediterranean decent presents: episodic fever and serositis (mimicing appy, arthritis, MI) Very high SAA released during attacks deposits as AA amyloid in tissues
normocytic anemia basics
d/t increased peripheral destruction or underproduction -use retic count to distinguish between the two
disorders of fibrinolysis
d/t plasmin overactivity -> excessive cleavage of serum fibrinogen -> presents like DIC seen in: *radical prostatectomy* (urokinase released); *cirrhosis of liver* (dec. production of a2-antiplasmin) D dimers *NOT* present b/c fibrin thrombi are absent; also nl platelet count
thromboembolus
d/t thrombus that dislodges - most common type (>95% of emboli)
key PFT finding in pulmonary vascular disease
dec DLCO
B-thalassemia basics
decreased production of globin chains for hgb d/t *gene mutations* (point mutation in promoter or splice site) -seen in African or mediterranean decent 2 B genes on *chromosome 11* (one on each) Bo = absent B+ = diminished production forms include minor-> major with ones between
Transudate pleural effusion
decreased protein content. Due to increased hydrostatic pressure or decreased oncotic pressure
atrophy
decreased stress (dec. hormone stimulation, disuse, or decreased nutrients/blood) lead to decrease in organ size
liver disease
deficiencies are common Increased aromatic amino acids: Normally removed by liver Acts as false neurotransmitters Postulated to precipitate hepatic encephalopathy Treatment: Do NOT limit protein (cirrhotic pts have an increased protein demand) Hypoglycemia: May result with rapid taper of EN or PN due to low glycogen stores Nutritional support before liver transplant improves outcomes
localized amyloidosis
deposition of amyloid to a single organ ex include: -senile cardiac amyloidosis, -familial aymloid cardiomyopathy -type II DM (amylin, from insulin, deposits in islet of pancreas) -AD -dialysis-associated amyloidosis (B2-microglobulin from MHCI deposits in joints) -medullary carcinoma of thyroid (calcitonin deposits w/in tumor)
intravascular hemolysis
destruction of RBCs w/in vessels labs: -*hemoglobinemia, hemoglobinuria, hemosiderinuria* (renal tubular cells pick up hgb and breakdown accumulating as hemosiderin - cells sloath into urine couple days later) -low *haptoglobin* (grabs and takes to sleen to recycle iron)
defibrillator
device that delivers a dose of electric current (called a countershock) to heart, depolarizing a large amount of the heart muscle, and ultimately ending the dysrhythmia
drug used to prevent dilated cardiomyopathy from anthracycline use (doxo and daunorubicin)
dexrazoxane
pulsus paradoxus
difference between 1st systolic beat during expiration and 2nd systolic beat during inspiration 8-12 mmHg drop in SBP during inspiration may be normal >20 mmHg drop in SBP during inspiration is ABNORMAL Mechanism = increase in RVEDV and decrease in LV stroke volume during inspiration
allelic heterogeneity
different mutations in the same locus produce same phenotype B-thal
Chagas disease
dilated cardiomyopathy with apical atrophy, megacolon, megaesophagus; predominantly in South America; Unilateral periorbital swelling (Romaña sign) characteristic of acute stage; Transmission: Reduviid bug ("kissing bug") feces, deposited in a painless bite (much like a kiss) Diagnosis - Trypanosoma cruzi; Trypomastigote in blood smear Treatment - Benznidazole or nifurtimox; Cruzing in my Benz, with a fur coat on
malignant tumor histologic characteristics
disorganized growth (loss of polarity), nuclear pleomorphism and hyperchromasia, high nuclear:cytoplasm ratio, high mitotic activity w/ atypical mitosis, invasion (through BM and local tissues)
endothelial cell damage
disrupts protective function of endothelial cells -*block exposure of SEC* -*produce PGI2 and NO* (vasodilate and inhibit aggregation) -*secrete heparin-like molecules* (augment antithrombin3 -> inactivates thrombin) -*secrete tPA* -*secrete thrombomodulin* (works to cause thrombin to activate protein C)
treatment for food allergy/intolerance
don't eat that food
ductal carcinoma biopsy shows?
duct-like structures in desmoplastic stroma
MC type of invasive carcinoma?
ductal carcinoma
carcinoma in dermal lymphatics -inflamed, swollen breast (tumor blocks lymph drainage) -no discrete mass -often mistaken for mastitis (but antibiotics don't help) -poor prognosis (already in lymphatics)
ductal carcinoma: inflammatory carcinoma (peau de orange)
large, high grade cells growing in sheets -assoc'd with LYMPHOCYTES and plasma cells -well-circumscribed mass -good prognosis -seen in BRCA1 carriers
ductal carcinoma: medullary carcinoma
carcinoma with abundant extracellular mucin (tumor cells floating in mucous pool) -older women (70 years old) -good prognosis
ductal carcinoma: mucinous carcinoma
hemolytic uremic syndrome
due to endothelial damage by drugs or infection Classically seen in children with E coli O156:H7 dysentery, which results from exposure to undercooked beef. E coli verotoxin also dec ADAMTS13 similar labs as TTP
McCune-Albright syndrome
due to mutation affecting G-protein signaling sx: unilateral cafe-au-lait spots w/ ragged edges, polyostotic fibrous dysplasia (bone replaced by collagen and fibroblasts), and one endocrinopathy (precocious puberty) lethal if mutation occurs before fertilization, but survivable in pt with *mosaicism*
breast during pregnancy and after menopause?
during preg undergoes hyperplasia driven by est/prog made by CL (1st tri), fetus, placenta (late). undergoes atrophy in menopause
What deficiency is assoc. with SLE?
early complement protein (C1q, C4, C2) deficiencies
what causes pain in acute inflammation?
edema compresses mechanonociceptors PGE2 and bradykinin both decrease pain threshold of nerve endings
secondary intention
edges not well approximated -> granulation tissue fills the defect -> myofibroblasts then contract wound, scar forms
hyper IgM syndrome
elevated IgM *d/t mutated CD40L (helper T cell) or CD40r (B cell)* 2nd signal not there -> no B cell activation or class switching low IgA, G, and E -> recurrent pyogenic infection (poor opsonization) especially at mucosal sites
Apoptosis
energy (ATP) dependent, genetically programmed cell death involving single cells or small groups of cells ex. endometrial shedding (menstruation), removing cells during embryogenesis, CD8 T cell killing viral infected cells pathologic examples: DNA damage, accumulation of misfolded proteins, infections esp. viral (HIV or adenovirus)
pulmonary hypertension drugs prostacyclin analogs
epoprostenol, iloprost PGI2 with direct vasodilatory effects on pulmonary and systemic arterial vascular beds. Inhibit platelet aggregation. Side effects: flushing, jaw pain
physical exam signs in anorexia
everything in body slowing Bradycardia Hypotension Hypothermia Breast tissue atrophy Muscle wasting Peripheral neuropathy Russell's sign: Excoriation on the dorsum of the hand from chronic scraping against incisors Hypo/hyperactive bowel sounds Dental erosion Parotid hypertrophy
saponification
example of dystrophic calcification where calcium deposits on dead tissues
dominant negative mutation
exerts a dominant effect - a heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning -ex. mutation of a TF in its allosteric site. nonfunctioning mutant can still bind DNA, preventing wild type TF from binding or example of collagen subunit mutant so can't form full collage molecule
Which part of respiration is passive (requires no muscle effort)?
expiration
chloroma
extra-myeloid neoplasm Some patients will present with them initially, but some will develop them after AML diagnosis These patients must be treated for acute leukemia b/c 90% will develop it within 1 year
What does Prothrombin time measure?
extrinsic pathway (factor 7) and common pathway (2,5,10)
accessory nipple due to?
failure of involution of mammary ridge -can occur anywhere along the milkline -MC congenital anomaly -usu asx but can be hormone responsive
mass on physical exam or abnormal calcification on mammography (but not breast cancer)
fat necrosis of breast -due to trauma
biopsy that shows necrotic fat with associated calcifications and giant cells
fat necrosis of breast -secondary to trauma
What is associated with VSD?
fetal alcohol syndrome
babesiosis
fever and hemolytic anemia; predominantly in northeastern United States; asplenia inc risk of severe disease; Ixodes tick (same as Borrelia burgdorferi of Lyme disease; may often coinfect humans) Diagnosis: Blood smear: ring form C1, "Maltese cross" C2; PCR Treatment: Atovaquone + azithromycin
what are classic findings of SLE?
fever, wt loss, lymphadenopathy, raynaud malar rash, discoid rash (esp. exposure to sun) oral/nasal ulcers, arthritis, serositis, psychosis renal damage (diffuse proliferative glomerulonephritis *MOST common* and most sever injury of kidney -> nephritic or nephrotic syndrome) type 2 HSR to blood cells (anemia, thrombocytopenia, leukopenia) Libman sack endocarditis (small vegetations on both sides of mitral valve) ANA + (sensitive), DsDNA and Sm (highly specific)
B symptoms
fevers, night sweats, weight loss, pleuritis
5 things cryoprecipitate contains
fibrinogen, factor VIII, factor XIII, vWF, and fibronectin Generally used to treat fibrinogen deficiency; Cold insoluble portion of fresh frozen plasma One bag of cryo raises fibrinogen level by 7 mg/dL in 70 kg adult One bag of cryo contains the equivalent fibrinogen of ½ bag of FFP
Acute phase reactants
fibrinogen, ferritin, C-reactive protein, SAA, mannose binding lectin, complement, hepcidin notably induced via IL-6, IL1, TNF negative APRs (albumin to save AA for +APR; transferrin by macrophages to sequester iron)
MC benign neoplasm of breast
fibroadenoma
well-circumscribed, mobile, marble-like mass in pre-menopausal female? cancer risk?
fibroadenoma -estrogen sensitive -benign -no increased risk for carcinoma
MC change in pre-menopausal breast? presents as?
fibrocystic change -hormone-mediated presence of fibrosis and cysts -presents as lumpy breast, esp upper outer quadrant
2 functions of lymph nodes
filtration and immune system activation
Light criteria
fluid is exudative if 1 or more is met: -pleural effusion protein/serum protein ratio >0.5 -pleural effusion LDH/serum LDH >0.6 -pleural effusion LDH >2/3 of upper limit of normal for serum LDH
Hardy-weinberg population genetics
if population is in this equilibrium and if p and q are in frequencies of separate alleles, then: p2 + 2pq + q2 = 1; and p + q = 1 p2 = frequency of homozygosity for allele A q2 = frequency of homozygosity for allele a 2pq = frequency of heterozygosity X linked recessive dz frequencey: males = q, females = q2
loss of heterozygosity
if pt inherits or develops a mutation in a tumor suppressor gene, complementary allele must be deleted/mutated before cancer develops not true for oncogenes Rb, lynch syndrome, Li Fraumeni syndrome
examples of disruption of nl blood flow
immobilization cardiac wall dysfunction (afib, MI) aneurysm (stasis)
what is used to characterize tumors that are difficult to classify on histology?
immunohistochemistry
what does lack of folate or b12 result in?
impaired division of RBC precursors -> megaloblastic anemia impaired division of granulocytic precursors-> hypersegmented neuts also seen in rapidly dividing epithelial cells (intestinal)
vitamin C in wound healing
important cofact in hydroxylation of proline and lysine in procollagen syn.
S3
in early diastole during rapid ventricular filling phase. Associated with inc filling pressures (mitral regurgitation, HF) and more common in dilated ventricles (can be normal in children/young adults)
S4
in late diastole ("atrial kick"). Best heard at apex with patient in left lateral decubitus position. High atrial pressure. Associated with ventricular noncompliance (eg, hypertrophy). Left atrium must push against stiff LV wall. Consider abnormal, regardless of patient age
polycythemia vera
inc RBC production Symptoms and signs related elevated red cell mass and hyperviscosity Associated with thrombocytosis The most frequent cause of death is thrombosis and hemorrhage, median survival 10 y The major differential Dx is 2o erythrocytosis ↑Epo: renal tumor, lung disease, smoker, high altitude... Treatment: Phlebotomy Chemotherapy: hydroxyurea Low-dose aspirin
left heart failure
inc pulmonary venous pressure>pulmonary venous distention and transudation of fluid. Presence of hemosiderin-laden macrophages ("HF" cells) in lungs. (PCWP >18) Causes - ischemia, myocardial infarction, dilated cardiomyopathy, restrictive cardiomyopathy, and HTN. Clinical features are due to decreased forward perfusion and pulmonary congestion Pulmonary Edema - Results in dyspnea, paroxysmal nocturnal dyspnea (due to increased venous return when lying flat), orthopnea, and crackles (pulmonary edema) Small, congested capillaries may burst, leading to intraalveolar hemorrhage marked by hemosiderin-laded macrophages ('heart-failure" cells) Decreased flow to kidneys leads to activation of renin-angiotensin system (fluid retention exacerbates CHF; mainstay of treatment is ACE inhibitor
how does LCIS present?
incidentally (no mass or calcifications) -usu discovered incidentally on biopsy -often multifocal and bilateral
what does von willebrand dz labs show and how do we tx?
increased bleed time, high PTT (vWF normally stabilizes factor 8), normal PT abnormal ristocetin test tx: desmopressin - ADH analog (increases vWF release from WP bodies of endothelial cells)
Exudate pleural effusion
increased protein content, cloudy. Due to malignancy, pneumonia, collagen vascular disease, trauma. Must be drained due to risk of infection
C5-C9 deficiencies
increased risk for Neisseria infection (gonorrheae and meningitidis)
anticipation
increased severity or earlier onset of dz in succeeding generations ex. trinucleotide repeat dz (huntington, fragile x)
hyperplasia
increased stress on an organ causes increased amount of cells via stem cell
hypertrophy
increased stress on an organ causes increased size of cells via gene activation -> protein synthesis -> production of organelles + cytoskeleton
Theophylline
inhibits phosphodiesterase leading to increased cAMP levels due to decreased cAMP hydrolysis narrow therapeutic index (cardiotoxicity, neurotoxicity)
vital capacity
inspiratory and expiratory reserves + tidal volume
aortic dissection
intimal tear w/ dissection of blood through media of the aortic wall -happens in proximal 10cm of aorta (high stress zone) w/ preexisting weakness of media presents as sharp, tearing CP radiating to back complications: pericardial tamponade (*most common cause of death*), rupture w/ fatal hemorrhage, or obstruction of branching arteries (*coronary or renal*) w/ resulting end organ ischemia
bloody nipple discharge in pre-menopausal female
intraductal papilloma -papillary growth in a large duct -lined by normal epithelial (luminal) and myoepithelial cells
benign tumor histologic characteristics
organized growth, uniform nuclei, low nuclear:cytoplasm ratio, minimal mitotic activity, lack of invasion, no metastatic potential
intraductal papilloma vs papillary carcinoma
intraductal papilloma -pre-menopausal female -papillary growth lined by luminar and myoepithelial cells papillary carcinoma -post-menopausal female -no myoepithelial cells lining papillary growth
Microangiopathic hemolytic anemia
intravascular hemolysis results from vascular pathology -> RBC destroyed when passing through ciruclation -iron def. occurs with *chronic hemolysis* causes: microthrombi (TTP-HUS, DIC, HELLP) -> *schistocytes* form
what does partial thromboplastin time measure?
intrinsic pathway (12,11,9,8) and common pathway
firm rock hard mass with sharp margins and small, glandular cells + stellate infiltration
invasive ductal carcinoma
MC histo type of male breast cancer
invasive ductal carcinoma (males have very few lobules)
common chromosomal abnormalities in AML
inversion of chr 16, (15, 17), (8,21) All have good prognoses
Imprinting
involves transcriptional silencing of the paternal or maternal copies of certain genes during gametogenesis only one functional copy exists in the individual -> loss of this functional allele by deletion gives rise to dz
what is most common cause of anemia?
iron deficient anemia - most common nutritional def. in world, estimated to affect 1/3 of world pop.
pathophys of pulmonary hypertension
is usually reversible with supplemental oxygen but sustained or repeated exposure to hypoxia results in increased muscularization of the pulmonary vascular bed and remodeling of the distal pulmonary circulation that is only partially reversed on correction of hypoxia. Abnormal expression of a variety of vascular and inflammatory mediators Mechanical stress Destruction of the pulmonary capillaries due to lung remodeling PH/increased afterload will lead to RV dilation, with or without the development of concomitant RV hypertrophy Increased afterload causes RV to fail and septal displacement (bulges into left side) RV decreased output Decreased LV filling and CO
basics of cancer formation
it is initiated by damage to *DNA of stem cells* damage is not lethal to cell but overcomes DNA repair mechanisms
how does the inflammasome mediate acute inflammation?
it recognizes products of dead cells, microbial products and crystals (ie uric acid) -> activation of IL-1 and inflammatory response
permanent tissues
lack significant regenerative potential myocaridium, skeletal muscle, neurons
why do you see discohesive cells in LCIS (lobular carcinoma in situ)
lacks E-cadherin adhesion protein
what are psammoma bodies and what are they seen in?
laminated, concentric spherule with dystrophic calcification seen in: *P*apillary carcinoma of thyroid, *S*erous papillary cystadenocarcinoma of ovary, *M*eningioma, malignant *M*esothelioma
Lung cancer general
leading cause of cancer death Presentation: cough, hemoptysis, bronchial obstruction, wheezing, "coin" lesion on CXR or noncalcified nodule on CT Sites of mets from lung cancer: adrenals, brain, bone, liver Mets go to lung from breast, colon, prostate, and bladder
what does a systemic embolism typically arise from?
left heart -> most commonly affects lower extremities
alkylating agents
leukemia/lymphoma - side effect of cancer
pursed lip breathing
like breathing through a straw on exhalation, inc pressure inside airway stents airway open so they have more time to exhale out
Hyaline Arteriolosclerosis caused by...
longstanding benign htn or diabetes -it is caused by proteins leaking into vessel wall, producing vascular thickening; seen as pink hyaline -reduced vessel caliber with end-organ ischemia -classically producing *glomerular scarring* -> progresses to Chronic renal failure
how does renal artery stenosis cause secondary htn?
low BF to affected kidney -> JGA releases renin -> makes ATI -> ACE turns it to ATII -> ATII stimulates contraction of arteriolar SM, and promote aldosterone release will see high plasma renin, unilateral atrophy to affect kidney
what are lab findings in DIC?
low platelets high PT and PTT low fibrinogen MAHA elevated D dimer (best screening test)
what lab findings found in ITP?
low platelets often <50k normal PT/PTT high megakaryocytes on bone marrow biopsy
nickel, chromium, beryllium, or silica
lung carcinoma occupational exposure
asbestos
lung carcinoma and mesothelioma more common for lung cancer to occur old roofing material, shipyard workers
steps involved in granuloma formation
macrophages process and present antigen on MHCII to CD4 cell -> macrophage stimulated to release IL-12 -> CD4 turns into Th1 cell -> IFN-y is produced by Th1 and activates macrophages to epitheliod histocytes -> TNFa produced by them which induces and maintains granuloma -must test for TB prior to anti-TNF therapy
mechanism of tissues regen/repair
macrophages secrete GF to target fibroblasts TGF-a - it is an epithelial and fibroblast GF TGF-b - fibroblast GF as well as antiinflammatory PDGF - endothelium, smooth muscle, and fibrolast GF VEGF - for angiogenesis
BRCA2 mutation associated with?
male breast carcinoma
Letterer-Siwe disease
malignant langerhan cells -skin rash w/ cystic skeletal defects in infant (<2yo) -multiple organs involved - rapidly fatal
plasma cells with chronic inflammation seen on breast biopsy
mammary duct ectasia "green-brown nipple discharge"
periareolar mass with green-brown nipple discharge (seen in multiparous post-menopausal female)
mammary duct ectasia -inflammation with dilation of subareolar ducts -histo shows plasma cells
numbers of afferent vs. efferent lymph vessels
many afferent vs. few efferent
MALToma
marginal zone lymphoma of mucosal sites -Gastric MALToma could regress w/ tx for H pylori
sinus histiocytosis
marked expansion of the sinuses by macrophages. Seen in hilar/mediastinal nodes in smokers, tattoo reaction, and in nodes draining cancers as in breast carcinoma.
how does invasive ductal carcinoma present?
mass detected usu by PE or mamography -clinically detected at 2 cm or more -mammographically detected at 1 cm or greater -advanced tumors: can cause dimpling of skin and nipple retraction
ateriosclerosis basics
means 'hard ateries' - d/t thickening of blood vessel wall 3 pathologic patterns = *atherosclerosis (large/medium vessels intimal thickening), arteriolosclerosis (small BV hyaline thickening or hyperplastic) or Monckeberg medial calcific sclerosis*
BRAF oncogene associated with what cancers?
melanoma, non-hodgkin lymphoma, papillary thyroid carcinoma
S-100 is marker for what type of tissue
melanoma, schwannoma, langerhans cell histiocytosis
vimentin marker for what type of tissue
mesenchyme
Are primary tumors or metastasis in the lung more common?
metastasis
what is most important factor in breast cancer prognosis? most useful factor?
metastasis axillary LN spread
what is hallmark of malignancy?
metastic potential
What causes neuro and renal symptoms in TTP?
microthrombi in brain and kidney
opening snap followed by diastolic rumble
mitral stenosis
atherosclerosis risk factors
modifiable: htn, hypercholesterolemia, smoking, diabetes nonmodifiable: age, gender, genetics
NF1
most common NF (aka von Recklinausen dz) AD, 100% penetrant highly variable manifestations 1/2 familial, remainder de novo (worse with increasing paternal age) Chromosome 17q11.2 -> gene that encodes *neurofibromin* which functions as tumor suppressor gene -> functions to activate RAS GTPase cafe-au-lait macules, axillary/inguinal freckling, lisch nodules (iris hamartomas), neurofibromas, optic pathway gliomas pilocytic astrocytoma benign and malignant tumors
Von willebrand dz
most common inherited coag disorder -> vWF deficiency many subtypes, causing quantitative and qualitative defects - *most common is AD decreased vWF* presents: mild mucosal and skin bleeding
PAX5
most sensitive and specific marker for B-cell lineage
what are clinical features of primary hemostasis disorders?
mucosal and skin bleeding -epistaxis, hemoptysis, GI bleeding, hematuria, menorrhagia (intracranial bleeding if severe) petechiae, purpura, or ecchymoses
where does LCIS usu occur
multifocal and bilateral
Ipratroprium
muscarinic antagonist competitively blocks muscarinic receptors preventing bronchoconstriction. Also used for COPD. Tiotropium is long acting
Methacholine
muscarinic receptor (M3) agonist. Used in bronchial challenge test ot help diagnose asthma
desmin marker for what type of tissue
muscle
Medium vessel vasculitis affects what vessels? what are 3 high yield dz?
muscular arteries which supply organs -Polyarteritis Nodosa, Kawasaki dz, Buerger dz
tumor suppressor gene
must have two copies knocked out before tumor formation p53 loss is seen in >50% of cancers
oncogenes
mutated genes that lead to cell growth GFs, GF receptors, signal transducers, nuclear regulators, and cell cycle regulators all categories MAPK and PI3K/AKT esp. important
Prothrombin gene mutation (G20210A)
mutation in 3' untranslated region --> increased production of prothrombin --> increased plasma levels and venous clots
Autoimmune Lymphoproliferative Syndrome (ALPS)
mutation in either Fas ligand or Fas receptor -> anergy or apoptosis of self reactive lymphocytes not possible -> IgG made by self reactive lymphocytes opsonizing blood cells -lymphadenopathy, HSM, hemolytic anemia, thrombocytopenia, neutropenia possibly increased risk for lymphomas
gonadal mosaicism
mutation only in egg or sperm cells if parents and relatives do not ahve the disease, supsect gonadal mosaicism
somatic mosaicism
mutations arise from mitotic errors after fertilization and propogates through multiple tissues or organs
lcous heterogeneity
mutations at different loci can produce a similar phenotype albinism
Why are most Y-linked genes not inherited?
mutations lead to infertility
Auer rods
myeloperoxidase ⊕ cytoplasmic inclusions (crystal aggregates) seen mostly in APL
myeloproliferative vs. myelodysplastic syndromes
myeloproliferative neoplasms- overproliferation with maturation myelodysplastic syndromes- inc apoptosis with abnormal maturation
Aortic stenosis
narrowing of aortic valve orifice
EBV as oncogenic virus
nasopharyngeal carcioma, Burkitt lymphoma, CNS lymphoma in AIDS
how do you dx amyloidosis? tx?
need a tissue biopsy usually taken from abdominal fat or rectum must transplant damaged organs - cannot remove amyloid
Rb protein role
negative regulator at G1/S transition governor of cell cycle Ways cancer can occur: ▪ Loss-of-function mutations affecting RB ▪ Gene amplifications of CDK4 and cyclin D genes ▪ Loss of cyclin-dependent kinase inhibitors (p16/INK4a) ▪ Viral oncoproteins that bind and inhibit RB (E7 protein of HPV)
what is a neonate at risk for if the mother has +Anti-SSA and sjogren syndrome?
neonatal lupus and congenital heart block
CML
neoplastic prolif of mature myeloid cells, esp. *granulocytes and precursors* *Basophils are characteristically increased!* t(9;22) (Ph chr) *defining genetics* -> BCR-ABL fusion -> *increased tyrosine kinase activity* -imatinib tx features: *splenomegaly* which suggests accelerated phase which could *transform to acute leukemia* (either AML or ALL since mutation in pluripotent cell)
What is acute leukemia?
neoplastic proliferation of *BLASTS w/ >20% blasts in bone marrow* (nl 1-2%) *acute presentation* - d/t BLASTS crowding out hematopoiesis -> *anemia* (fatigue), *thrombocytopenia* (bleeding), or *neutropenia* (infection) -BLASTS can enter blood -> *high WBC* - *large, immature, often punched out nucleoli* -subdivided into ALL or AML based on type of blast
main characteristics/symptoms of CLL
neoplastic proliferation of naive B cells Often asymptomatic, progresses slowly; smudge cells in peripheral blood smear Hypogammaglobulinemia (mature B cells not made)-Infection is the most common cause of death in CLL autoimmune hemolytic anemia (mature B cells not made well) CLL = Crushed Little Lymphocytes (smudge cells). Involvement of lymph nodes leads to generalized lymphadenopathy called small lymphocytic lymphoma
Opsoclonus-myoclonus ataxia syndrome as paraneoplastic syndrome happens in
neuroblastoma (children), small cell lung cancer (adults) "dancing eyes, dancing feet"
GFAP is marker for what type of tissue
neuroglia (astrocytoma)
neurofilament is marker for what type of tissue
neurons
neoplasia
new tissue growth that is unregulated, irreversible, and MONOCLONAL (vs hyperplasia or repair)
Air emboli
nitrogen bubbles precipitate in ascending divers; treat with hyperbaric oxygen
how does uremia affect platelets?
nitrogenous wast products disrupt platelet function -> adhesion and aggregation become impaired
Are any drugs effective for gaining weight in anorexia or bulimia?
no
What does hardy-weinberg law assume?
no mutation occurring at the locus completely random mating no net migration natural selection is not occurring
Should you give platelet transfusion in TTP?
no, platelet transfusion makes TTP worse>would lead to more microthrombi
does bilateral mastectomy make your cancer risk zero?
no, still small risk for carcinoma due to breast tissue that can extend into axilla or chest wall
incomplete penetrance
not all individuals with mutant genotype show mutant phenotype % penetrance x prob. of inheriting genotype = risk of expressing phenotype BRCA1 gene mutations dont always result in breast or ovarian cancer
metastatic calcification (a pathologic calcification)
occurs when high serum calcium or phosphate (ABNORMAL) levels lead to calcium deposition in NORMAL tissues (ex hyperparathyroidism)
scar formation
occurs when repair cannot be accomplished by cell regeneration alone -> replaced by CT two types: hypertrophic, keloid in event of repair of wound, type 3 collagen is replaced with type 1 collagen via *collagenase* (Requires zinc) this increases tensile strength
uniparental disomy
offspring receives 2 copies of a chromosome from 1 parent and no copies from other *HeterodIsomy:* (heterozygous) indicates meiosis 1 error *IsodIsomy*: (homozygous) indicates a meiosis II error or postzygotic chromosomal duplication of one of a pair, and loss of the other pair
pleiotropy
one gene contributes to multiple phenotypic effects untreated PKU -> light skin, intellectual disability, musty body odor
Lymphadenopathy (LAD) basics
painful = usually d/t draining of acute infection painless = chronic inflammation, metastatic carcinoma, lymphoma inflammation LAD d/t *hyperplasia of particular regions of LN* -*Follicular hyperplasia* B cell region - RA and early HIV infection (CD4+ cells) -*Paracortex hyperplasia* T cell region - viral infxns (mono) -*sinus histiocyte hyperplasia* - draining tissue with cancer
AngelMan syndrome
paternally derived UBE3A gene (ubiquitin ligase) is silenced (imprinted) in brain tissue but not other tissues dz occurs when the Maternal allele is deleted or mutated on Chr 15 sx: inappropriate laughter (happy puppet), seizures, ataxia, and severe intellectual disability 5% cases from paternal uniparental disomy
DIC
pathologic activation of coag cascade -> widespread microthrombi resulting in ischemia/infarction consumption of platelets and factors -> bleeding, esp. from IV sites and mucosal surfaces 2/2 another dz process!
Microangiopathic Hemolytic Anemia
pathologic fomration of platelet microthrombi in small vessels -> platelets used up -> RBCs shear going past them -> hemolytic anemia seen in TTP, HUS, DIC, SLE, HELLP syndrome, htn emergency tx: plasmapheresis and corticosteroids, particularly in TTP
reverse type
patient plasma mixed with reagent group A and group B RBC's agglutination will occur if patient has Ab's against that type if agglutination occurs in A vial, the patient is type B and vice versa
forward type
patient's RBC's are mixed with anti-A, anti-B, and anti-D antibodies Each vial contains antibodies against that blood type- if agglutination occurs, the patient is positive for that type
variable expressivity
patients with same genotype have varying phenotype (NF1)
paracortical
pattern typically seen with processes that trigger T-cell responses, such as viral infections.
Cytotoxic CD8 T cell mediated pathway
perforins secreted by CD8 make pores in membrane of target cell granzyme enters target cell and activates caspases
subareolar mass with nipple retraction
periductal mastitis (inflammation of subareolar ducts) usu seen in smokers
what stimulates chronic inflammation
persistent infection (most common cause) TB, T pallidum -> lead to type 4 HSR -> granuloma infxn w virus, mycobacteria, parasites, fungi autoimmune dz FB - silica, atherosclerosis some cancers
what symptom in quantitative platelet disorders is common?
petechiae (not usually seen in qualitative disorders)
Bronchial carcinoid tumor
pg 619
Large cell carcinoma
pg 619
Squamous cell carcinoma
pg 619
treatment for PV
phlebotomy, hydroxyurea, ruxolitinib (JAK1/2 inhibitor)
what are useful labs to assess platelet disorder?
platelet count, (<50k leads to sx), bleed time (2-7 min nl), blood smear (assess # and size), bone marrow biopsy (assess megakaryocytes)
Heparin-induced thrombocytopenia (HIT)
platelet destruction that arises secondary to heparin tx happens when *heparin bind platelet factor 4* and Ig are formed against -> spleen consumes frags of destroyed platelets can lead to activate other platelets -> thrombosis -typically give another anticoag w/ to avoid, *Not warfarin (higher incidence of skin necrosis)*
the 4 myeloproliferative disorders
polycythemia vera, essential thrombocythemia, myelofibrosis, and CML
malignant tumors
poor differentiation, erratic growth, local invasion, mets, and decreased apoptosis (upregulated telomerase)
labile tissues
possess stem cells that continously cycle to regenerate the tissue small and large bowel, skin, bone marrow(CD34+ HSC), lung (type2 pneumocyte)
heteroplasmy
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited dz mtDNA passed from mother to all children
mosaicism
presence of genetically distinct cell lines in the same individual
Wall Tension=
pressure x radius (aka Laplace's law) OR (pressure x r) / (2 x wall thickness) -Explains why Starling's laws apply and why one has hypertrophic cardiomyopathy to lower wall tension in chronic heart disease
autoimmune basics
prevalence 1-2% more common in women; classically of child bearing age (estrogen may reduce apoptosis of self-reactive B cells) enviromental trigger (bystander activation or molecular mimicry) in genetically susceptible pt common causes: LAck of tolerance, molecular mimicry, HLA MHC1 and 2 subtypes clinically progressive: relapse, remit, and show overlapping features (epitope spreading)
regulators of apoptosis
prevent apoptosis in normal cells, but promote in mutated cells where DNA cant be repaired (eg Bcl2)
what drugs are associated with causing oxidative stress in G6PD deficiency?
primaquine, sulfa drugs, dapsone
DiGeorge Syndrome
primary immunodeficiency from developmental failure of 3rd and 4th pharyngeal pouches (d/t 22q11 microdeletion) T-cell deficiency, hypocalcemia (lack parathyroids), abnormalities of heart, great vessels, and face TBX gene associated with -> part of 3rd and 4th pharyngeal development
inflammation
process allowing inflammatory cells, plasma proteins (complement), and fluid to exit BV entering ECM -acute and chronic types triggers include: infection, tissue necrosis (MI), FB (splinters), immune rxns started by cell receptors for microbes, intracellular sensors of damage (uric acid, ATP, low K in cells,) -> inflammosome created
reperfusion injury
produces free radicals leading to continued rise in cardiac enzymes after reperfusion of infarcted myocardial tissue d/t arrival of inflammatory cells that produce superoxide ions as well as high levels of O2; also increased calcium w/in blood to injured cells promotes mitochondrial permeability
what do all three pathways of complement activation lead to?
production of C3 convertase (C3-> C3a and C3b) this makes C5 convertase (C5-> C5a and C5b) C5b works with C6-9 to make MAC
what is erythrocyte sedimentation rate?
products of inflammation (such as fibrinogen APR) coat RBCs and cause aggregation denser RBC aggregates fall faster rate in pipette tube -> increased ESR
PGI2, PGD2, PGE2
prostaglandins which mediate vasodilation (at arteriole) and increased vascular permeability (at post cap. venule)
most common cancers to met to bone
prostate, breast > kidney, thyroid, lung Lead (PB) KeTtLe axial skeleton predilection
What are 3 paraneoplastic syndrome associated with thymoma?
pure red cell aplasia (anemia w/ low retics) Good syndrome (hypogammaglobulinemia) MG
malignant tumor characteristics
rapid growth, poorly circumscribed, infiltrative, fixed to surrounding tissues and local structures
mitochondrial myopathies
rare disorders; often present with myopathy, lactic acidosis, and CNS eg. *MELAS syndrome* (mitiochondrial encephalomyopathy, lactic acidosis, and stroke like episodes) *2/2 failure in oxidative phosphorylation* -> muscle biopsy often shows "ragged red fibers" (accum. of dz mitochondria) mtDNA encodes for 13 subunits in respiratory chain enzymes
What is CD16/Fc receptor?
receptor found on cells including neuts used to recognize Ig that opsonize microbes etc
how does phagocytosis and oxidative burst in phagolysome occur?
recognition, engulfment, killing/degrading o2 -> o2- via NADPH oxidase o2- -> H2O2 via SOD H2O2 -> HOCL (bleach) via MPO Also iNOS enzyme -> NO
anemia
reduction in circulating RBC mass (concentration dependent - can have physiologic like in pregnancy)
how does p53 work?
regulates progression of cell cycle from G1 to S phase (most regulated part of cell cycle) -if p53 detect DNA damage, slow cell cycle and upregulates repair enzymes if not possible, then send cell to apoptosis
most common cause of death in SLE?
renal dz other notables = infections, CVD (accelerated CAD) 5 yr survival >90% (used to be 15%)
repair
replacing damaged tissue with fibrous scar (occurs if regenerative stem cells lost or damage to permanent tissue) initial phase is *granulation tissue* formation (*fibroblasts deposit type 3 collagen, capillary which bring nutrients, and myofibroblasts contract wound*) M2 macrophages play critical role in clearing dead tissue, GF production, and cytokines to stimulate fibroblasts
rengeneration
replacing damaged tissue with native tissue -> depends on regenerative capacity of tissue tissues are either: labile, stable, or permanent
functional residual capacity
residual volume + expiratory reserve volume Volume of air in the lungs at end-expiratory tidal position Where chest wall pushing out and lungs pulling in are equal (all muscles at rest)
malignant tumor nomenclature
sarcoma (mesenchymal origin) carcinoma (epithelial)
hematogenous spread is characteristic of what?
sarcomas (mesenchymal->more close to blood) and some carcinomas (renal cell carcinoma, HCC, follicular carcinoma of thyroid, choriocarcinoma)
keloid
scar with disorganized collagen and heavy type 3 collagen deposition frequent recurrence and higher incidence in those wiht darker skin
what are outcomes of chronic inflammation?
scarring and amyloidosis and neoplastic transformation (HCV infxn -> chronic inflam -> HCC; H pylori -> gastritis -> gastric adenocarcinoma)
STOP-BANG
screening for OSA Snoring Tired Observed apnea blood Pressure BMI >35 Age >50 Neck >40cm (~16inch) Gender - male 5-8 high risk for OSA
Pulmonary vascular resistance
see page 606 Essentially ∆P = Q x R
leukemoid reaction
severe elevation in WBC (>40k) caused by some stressors or infxn (eg C diff) -can see immature neut precursors but rarely myeloblasts higher LAP vs in CML which is low b/c neuts aren't mature enough
what is malignant htn?
severe htn >180/120 - this is also cutoff for hypertensive urgency becomes emergency when you have end organ damage (ARF, HA, papilledema)
causes of low ESR?
sickle cell (altered shape, slower rate of fall) polycythemia (inc. RBCs dilute aggregation factors) HF, microcytosis, hypofibrinogenemia
pulmonary hypertension drugs PDE-5 inhibitors
sildenafil; tadalafil inhibit cGMP PDE5 and prolong vasodilatory effect of NO. Also used to treat erectile dysfunction.
what are clinical findings in MAHA (TTP or HUS)
skin and mucosal bleeding, fever, renal insufficiency (more common in HUS - thrombi in vesseles), CNS problems (more common in TTP - thrombi in vessels)
Diffuse scleroderma
skin involvement is diffuse with rapid and *early* visceral involvement -Any organ (Most common: vessels, GI tract (esophagus), Lungs-> interstitial fibrosis and pulm. htn, kidneys->scleroderma renal crisis) most common cuase of death: lung dz; 2nd is kidney dz (Tx w/ ACEi)
mycosis fungoides
skin patches/plaques (cutaneous T-cell lymphoma), characterized by atypical CD4+ cells with "cerebriform" nuclei and intraepidermal neoplastic cell aggregates (Pautrier microabscess). May progress to Sézary syndrome (T-cell leukemia) Late disease progression is characterized by extracutaneous spread, most commonly to lymph nodes and bone marrow. may progress to Sézary syndrome (T cell leukemia)
Benign tumor characteristics
slow growing, well circumscribed, distinct, mobile
paraneoplastic encephalomyelitis
small cell lung cancer antibodies against Hu antigens in neurons
Lambert eaton associated cancer
small cell lung cancer antibodies against presynaptic calcium channels at NMJ
short bowel syndrome
small intestine: < 2 m (normal 3-8 m, but typically closer to 8 m) Etiologies- congenital, surgical removal (ischemic bowel, Crohn's, tumors, trauma) Physiology depends on location of resection
Rett syndrome
sporadic De novo mutation of *MECP2 gene* on X chromosome that almost exclusively affects girls (males die in utero) sx: start 1-4yo w/ regression in motor, verbal, and cognitive abilities; ataxia; seizures, growth failure, stereotyped hand-wringing
alcohol associated cancer
squamous cell carcinoma of oropharynx, upper esophagus, HCC
arsenic
squamous cell carcinoma of skin, lung cancer, angiosarcoma of liver found in cigarette smoke, herbicides, metal smelting
Bcl2
stabilizes mitochondrial membrane, blocking release of cytochrome c -if overexpressed, apoptosis wont happen and can lead to cancer (follicular lymphoma - t14;18)
international staging system (ISS) for multiple myeloma
stage I- beta-2 microglobulin <3.5 and serum albumin >=3.5 stage II- neither stage I nor stage III stage III- beta-2 microglobulin >5.5
MC organism of acute mastitis? tx?
staph aureus tx with dicloxacillin and continued drainage (breastfeeding)
atherosclerosis morphologic stages
starts as *fatty streak* (flat yellow lesions of intima consisting of lipid-laden macrophages) *early in life, in most teenagers* progresses to atherosclerotic plaque
nitrosamines
stomach cancer (found in smoked foods) cause of high stomach carcinoma in japan
how does male breast cancer present?
subareolar mass -males have highest density of breast tissue underneath nipple -can produce nipple discharge
hypertrophic obstructive cardiomyopathy
subset of hypertrophic cardiomyopathy asymmetric septal hypertrophy and systolic anterior motion of mitral valve>outflow obstruction>dyspnea, possible syncope
metaplasia most commonly involves change of what type of cell?
surface epithelium (eg squamous, columnar, urothelial) to another
secondary systemic amyloidosis
systemic deposition of AA amyloid, derived from serum amyloid-associated protein (SAA) SAA is an acute phase reactant
primary systemic amyloidosis
systemic deposition of AL amyloid which is derived from Ig light chain -this is associated with plasma cell dyscrasias (eg multiple myeloma) where they make too much light chain for Ig vs heavy chain
2 chr abnormalities with good prognosis in B-ALL
t(12;21)(p13;q22); has a good prognosis; more commonly seen in children
3 chr abnormalities with poor prognosis in B-ALL
t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+ALL) t(11q23) is unfavorable; There's also TEL-AML1 (ETV6-RUNX1)
food allergy
take-away: know allergic vs. intolerant untoward rxn occurring after the ingestion of a food Toxic Reaction: Any exposed individual Non-toxic Reaction: Depends on individual susceptibilities Immune-mediated (food allergy or food hypersensitivity) IgE non-IgE: Peyer's patches>macrophages>T helper cells Nonimmune-mediated (food intolerance) Enzymatic (Lactase deficiency) Pharmacologic (Vasoactive amines) Idiopathic
TRAP stain identifies what type of cancer?
targets tartrate-resistant acid phosphatase in *hairy cell leukemia*
linkage disequilibrium
tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance measured in a population, not a family, and often varies in different populations
Differential diagnosis of an enlarged right supraclavicular node
tends to drain thoracic malignancies: Mediasastinal malignancies Lung malignancies Esophageal malignancies
compliance
the amt of pressure it takes to move volume of the lung up
FEF 25-75%
the mean expiratory flow during the middle half of the FVC maneuver; reflects flow through smaller airways (<2 mm diameter) - possible early sign of obstruction (small airways>bronchiolitis) use to evaluate small airway obstruction
what are clinical finds of systemic amyloidosis?
they are diverse since almost any tissue can be affected classically: -nephrotic syndrome (kidney most common organ involved!) -restrictive cardiomyopathy or arrhythmia -tongue enlargement, malabsorption, HSM
how do you screen for mono? diagnose?
use *monospot test* - detects IgM antibodies that react with horse or sheep RBCs *negative result suggests CMV!* or test too early (positive after 1 week infxn) -definitive dx - serologic EBV viral capsid antigen
what is ristocetin test?
used to assess von willebrand dz it induces platelet agglutination by causing vWF to bind to GP1b; lack vWF -> impaired agglutination -> abnormal test
delta/delta in ABG analysis
used to check for underlying non gap problems Change in AG over change in HCO₃ If HCO₃ did not drop as far as AG, then there is a secondary metabolic alkalosis If HCO₃ dropped farther than AG, then there is a secondary metabolic acidosis
secondary hemostasis disorders
usually due to factor abnormalities clinical features: deep tissue bleeding into muscles and joints, and rebleeding after surgery
Why is there mitral tricuspid valve regurgitation in dilated cardiomyopathy
valves stretch
LTC4, LTD4, LTE4
vasoconstricion, increased venular permeability (via pericyte contraction), bronchoconstriction
How does metaplasia occur?
via reprogramming of stem cells, which then produce new cell type -reversible if driving stress is removed -can progress to dyplasia if stressor is persistent -> then cancer
residual volume and how to calculate
volume of air in lungs after maximum exhalation Residual volume is calculated; it is not measured Measured indirectly; RV = FRC - ERV
TNM staging system
way to look at tumor size, node involvement, and metastases each of these has independent prognostic value, but *N and M are often most important* you determine this after final surgical resection of tumor
what is cachexia?
weight loss, muscle atrophy, and fatigue that occur in chronic dz (eg cancer, AIDS, heart failure, COPD) mediated by TNF, IFN-y, IL-1, IL-6 low CO, insulin resistance, muscle breakdown, thrombus formation
benign tumor characteristics
well differentiated, well demarcated, low mitotic activity, no mets, no necrosis
primary intention
wound edges are brought together (suture) leading to minimal scar
how do you grade a cancer?
you look at the degree of cellular differentiation and mitotic activity on histo low (well differentiated) to high grade (poor differentiation or anaplastic) staging better prognostic value than grading
how do you stage a cancer?
you look at the degree of localization/spread based on site and size of primary lesion, spread to regional LNs, and presence of mets use the TNM staging system
causes of rhabdo
•Traumatic or muscle compression - Direct injury to muscle cell>sarcolemma disruption>leakage Crush injury; Significant blunt trauma; Prolonged immobilization; compartment syndrome Non-traumatic Exertional - Supply insufficient to meet demand (Sickle cell trait; Hypokalemia; Cross Fit) Non-traumatic Non-exertional - e.g. Drugs (Daptomycin, statins)
