Exam 4 Flashcards
viral infection
lymphocytes > neutrophils
acute bacterial infection
leukocytosis (elevated WBC) and elevated neutrophils
parasitic infection
elevated eosinophils
Basophils
least common
allergic and helminth responses
release histamine and heparin (decreased clotting and increased blood flow from vasodilation)
Eosinophils
particularly found in GI and respiratory tracts
asthma and allergic reactions
release leukotrienes (airway smooth muscle contraction)
Neutrophils
most abundant "first responders" strongly phagocytic respond to and subsequently release cytokines to amplify immune response release anti-microbial proteins
Mast Cells
basophils that mature in the tissues
release histamine and heparin
massive release of histamine = anaphylaxis and body-wide vasodilation
Monocytes
differentiate into dendritic cells and macrophages when stimulated by pathogens
50% migrate to spleen
Dendritic cells
antigen-presenting cells (APC)
migrate to nearest lymph node once antigen is captured and presents to T and B cells
Langerhans cells = specialized dendritic cell in the skin
Macrophages
APC
large phagocytes
skin, lungs and GI tract
resting, primed and hyper-activated stages
Kupffer cells
specialized macrophages of the liver
destroy bacteria and old RBCs
*chronic activation via EtOH causes overproduction of inflammatory cytokines and chronic inflammation (cirrhosis and CA)
Natural Killer Cells (NK cells)
cytotoxic lymphocytes that do NOT need to recognize pathogen to kill it
killing activity enhanced by cytokines released from macrophages
kill via releasing perforins and proteases that cause cell membrane lysis or trigger apoptosis
opsonization
enhancing phagocytosis of antigens by “marking” them for destruction
membrane attack complex (MAC)
complement cascade resulting in cell lysis via puncturing cell membrane
humoral immunity
type of adaptive immunity
B cells and antibodies
defense against extracellular pathogens (ie. S. pneumonia, M. catarrhalis)
cell-mediated immunity
type of adaptive immunity
T cells and APCs (dendritic cells and macrophages)
defense against intracellular pathogens (ie. virus, fungi, protozoans)
secondary lymphatic organs
spleen
lymph nodes
tonsils
MALT (mucosal associated lymphoid tissue)
MHCII
B cells
dendritic cells
activated macrophages
thymic epithelial cells
T helper cells
T cell receptors and CD4 co-receptors
MHCII molecule presents antigen and has binding site for CD4
activated cells release cytokines to direct immune response
different subtypes activate different cells
T memory cells
recognize antigens from previous exposure
T regulatory (suppressor) cells
prevent immune reactions from getting out of hand
T killer cells (cytotoxic)
activated by T helper cells
CD8 co-receptor
MHCI molecules present antigens
secrete perforin and cytotoxins to cause cell death
primary response
IgM “iMmediate” produced first
IgG follows
B memory cells persist
secondary response
subsequent encounter with same antigen
previously generated B memory cells activated rapidly
IgM formed, but IgG most involved
IgG
75-85% of antibodies in the blood
major immunoglobin in the extravascular tissues and longest half life
*only one to cross placenta = fetal protection
secondary response
neutralize, opsonize, mediate complement and MAC
type II hypersensitivity reactions (ie. Rh factor, Graves’ disease)
IgM
acute infection - primary response
5-10% antibodies in the blood
neutralize, complement, agglutinate
good against carbs on bacterial cell walls
type II hypersensitivity reactions (ie. Rh factor, Graves’ disease)
IgA
10% antibodies in serum
monomer or dimer with J chain
mucosal areas and secreted in bodily fluids
found in breast milk = protects infant GI tract
blocks attachment and agglutinizes
IgD
required for B cell activation (found on mature B cell membranes)
IgE
binding on mast cell or basophil results in release of histamine
defense of parasites
type I hypersensitivity reactions (allergy/asthma, hives, food/drug)
symptoms of anemia
fatigue, weakness
lightheadedness/syncope
dyspnea
palpitations
often occur when Hb
signs of anemia
pallor tachycardia bounding pulses orthostatic bP heme in stool (GI blood loss) cardiac failure and shock (severe)
microcytic, hypochromic
Fe deficiency
thalassemia
sideroblastic
normocytic, normochromic
hypothyroidism
liver disease
chronic disease
macrocytic (megaloblastic)
folate deficiency
vitamin B12 deficiency
microcytic, hypochromic increased RDW (body tries to compensate) decreased ferritin decreased serum Fe increased TIBC
glossitis, chelitis, koilonychia
pica
dysphagia
restless leg syndrome
Tx: underlying cause
oral ferrous sulfate 325mg BID-TID x3-6mo
blood transfusions for select pts
Iron deficiency anemia (IDA)
most common cause of anemia worldwide
decreased ferritin because depletion of Fe stores occurs first
microcytic, hypochromic
normal RDW
normal to increased ferritin and serum Fe
poikilocytosis (abnormal shapes)
*Dx: Hb electrophoresis
Tx: tailored to severity of disease
folic acid supplement
AVOID iron supplement (overload)
regular transfusions and splenectomy if severe
Thalassemia
inherited disorder
Alpha Thalassemia
deletion of 1+ of the 4 alpha-globing chains
1 = silent carrier 2 = alpha trait, mild microcytic anemia (often asymptomatic) 3 = hemolytic anemia 4 = hydrops fetalis (incompatible with life)
Beta Thalassemia
reduced or absent beta-globing chains
minor (trait) = dysfunction of 1 chain (asymptomatic)
major = severe dysfunction of both chains –> most patients die before 30yo
normocytic, normochromic
normal to increased ferritin
variable serum Fe and TIBC
Tx: underlying disease
EPO may benefit
common: inflammation, organ failure, elderly
Anemia of Chronic Disease
MCV can be low, normal or slightly elevated
poikilocytosis and anisocytosis
anemia usually moderate
systemic iron overload
BM biopsy = ringed sideroblasts (nucleated RBC precursors)
Tx: underlying cause (ie. alcoholism, meds, lead poison)
refer if transfusion support needed
Sideroblastic Anemia
type of Myelodysplastic Syndrome (MDS)
hereditary or acquired
megaloblastic (elevated MCV)
peripheral smear = hypersegmented neutrophils
low serum B12
+ Schilling test or antibodies to IF (intrinsic factor)
*elevated serum methylmalonic acid and homocysteine levels
*neuro problems:
dec. vibratory and position sense
ataxia
paresthesia
confusion/dementia
Tx: parenteral B12 (can’t absorb oral)
daily IM 1000ug x1wk
then weekly x1mo, then monthly for life
Pernicious Anemia
1-2 ug/day B12 req
deficiency of IF causes B12 malabsorption
autoantibodies against gastric parietal cells impair IF secretion
megaloblastic
anemia sxs
low serum folate
*elevated homocysteine levels ONLY (not methylmalonic acid)
Tx: underlying cause (if known)
replacement therapy –> 1mg PO daily, 5mg PO if malabsorption
occurs in: alcoholism end of pregnancy malabsorption syndromes *hemolytic anemias (ie. sickle cell)
Folic Acid Deficiency Anemia
200 ug/day req.
4-5 mo. deprivation = anemia
anemia sxs
jaundice (increased unconjugated bilirubin)
gallstones
increased risk of infection from salmonella and pneumococcus
elevated retic count (polychromasia)
peripheral smear = nucleated RBCs and possible schistocytes (fragmented RBC)
destruction of RBCs
Hemolytic Anemias
Intravascular hemolysis
fragmented syndromes (ie. trauma from prosthetic heart valve) red cell enzyme defects (ie. G6PD deficiency = Heinz bodies)
serum haptoglobin is low
–> mucoprotein produced in liver which binds Hb released from lysed RBCs
Extravascular hemolysis
hereditary spherocytosis sickle cell anemia autoimmune hemolytic anemia incompatible blood transfusion drug-induced
normocytic but decreased SA (dense, globular w/o central pallor)
often asymptomatic
mild jaundice
splenomegaly
chronic hemolysis creates need for increased folate
+ osmotic fragility (RBC show increased hemolysis in hypotonic fluid due to membrane defect)
Tx: splenectomy - delay until adulthood if possible
give pneumococcal vaccine early
Hereditary Spherocytosis
autosomal dominant
normocytic, normochromic
usually develop in childhood as HbF –> HbA
delayed growth and development
increased susceptibility to infections
*vaso-occlusive ischemic tissue injury ==> pain crises
Sickle Cell Anemia (SSA)
autosomal recessive
RBCs become “sickle shaped” when deoxygenated causing painful sxs
Sickle Cell Anemia Labs and Tx
elevated relic (10-20%) *Hb electrophoresis reveals HbS peripheral smear = sickled, nucleated RBCs, Howell Jolly bodies, thrombocytosis
Tx: avoid precipitating factors
RBC transfusions PRN
analgesics, fluids and O2 during pain crises
hydroxyurea to decrease incidence of pain crises
bone marrow transplant may help
clinical features variable
caused by antibodies that adhere to surface of RBCs and induce hemolysis by fixing complement and damaging cell membrane
elevated retic and spherocytes formed
ex: incompatible blood transfusion, hemolytic disease of newborn
+ Coombs test can detect antibodies of the patient
Tx: identify and treat underlying cause
corticosteroids helpful (inflammatory process)
splenectomy
folic acid supplementation
Autoimmune Hemolytic Anemia
pancytopenia (anemia, leukopenia, thrombocytopenia)
bone marrow shows absence of precursors of these cells
Tx: bone marrow transplant
hematology referral
50% idiopathic
drug/chem exposure, viral illnesss, ionizing radiation
Aplastic Anemia
acquired abnormality of bone marrow stem cells (total or selective)
bruits are predictive of CAD/future MI and CV death
– area where carotid vessel bifurcate = disturbance
low sensitivity but high specificity
symptomatic pt:
contralateral weakness
contralateral sensory deficits
amaurosis fugax - shade coming down over eye (retinal branch is first off internal carotid)
hollenhorst plaque - cholesterol deposits get stuck in vessels
*generally >75% occlusion of a vessel needed for sxs
Carotid endarterectomy (CEA) - open surgery preferred
Carotid Artery Disease (CAD)
Ascending
compression, pain, hoarseness (RLN), valve regurgitation
Arch and descending
wheezing/coughing/SOB, hemoptysis, hoarseness,
dysphagia, chest/back pain
Tx:
beta blockers - decrease force of ejection
angiotensin II receptor blockers
statins (decrease cholesterol b/c atherosclerotic)
smoking cessation
control HTN
5-6cm SURGERY
4.5-5cm or rapid growth for Marfans = SURGERY
Thoracic Aortic Aneurysm
acute onset “tearing” pain in chest/abdomen/back
HTN - check both arms and legs
*spiral CT scan with contrast is GOLD STD
Tx:
beta blockers, pain control and HTN control initially
Arch/Ascending = emergency surgery
Descending = med therapy if no rupture, surgery if rupture (use a stent)
Aortic Dissections
abdominal pain
pulsatile abdominal mass
tenderness
hypotension
U/S for Dx and follow size
>5.5cm, symptomatic, or rapid expansion (>0.5cm 6-12mo)
–> endovascular stent graft, often bifurcated
Abdominal Aortic Aneurysm (AAA)
Chronic
younger, typically female
work up with angiogram or MRI
Tx: angioplasty +/- stenting
Acute *neuro deficit including paralysis *ABSENT femoral pulses saddle embolism at bifurcation vascular emergency Tx: quick imaging --> OPERATE
Aorta-Iliac Occlusive Disease
rare –> >2cm is risk factor
thrombosis or embolization with limb ischemia
DDx: Baker’s cyst or varicose veins
Tx: surgery or endovascular therapy
Popliteal Aneurysm
Signs of Peripheral Vascular Disease (PVD)
- Claudication - mild (more than 2 blocks walking)
moderate (1 block)
severe (less than 1 block) - rest pain (toes and dorsum of foot)
- Leriche syndrome (decreased femoral pulse, impotence and butt/thigh claudication)
hair loss on leg/foot (poor perfusion)
atrophic skin and nail changes
pallor with raised extremity
delayed capillary refill
Ankle-Brachial index (ABI) ankle systolic P/brachial systolic P --> normal 1.0-1.1 >0.8 = no claudication 0.5-0.8 = claudication 0.2-0.5 = rest pain less than 0.2 = limb threat
Arterial Insufficiency
Pain Pallor Paresthesia Paralysis Pulselessness
Tx: emergency surgical consultation to remove thrombus/embolus
anticoagulation via heparin keeps clot from getting worse
Acute Arterial Obstruction
Pain out of proportion to findings Passive stretch pain Paresthesias Paralysis Pulselessness Poikliothermia (inability to regulate core body temp)
commonly seen after repercussion of ischemic limb
Tx: fasciotomy with delayed closure often with skin grafts
Compartment Syndrome
may be asymptomatic
aching/burning sensation
“tired” or “heavy” feeling in the extremities
worse with standing or sitting with legs bent
relieved by elevation
dilated, tortuous superficial veins
start distally and move upward
can rupture, bleed and erode
ulcerations near ankle
Tx: compression stockings and short frequent walks
sclerotherapy, laser therapy, vein stripping
Varicose Veins
due to valvular incompetence or as a result of DVT with residual damage to the vein
veins rigid and thick-walled
high pressure develop and distend the walls creating further valve incompetence
Tx: limb elevation compression stockings wound care (dry/wet non-adherent) diuretics for edema or abs for secondary infection surgery
Chronic Venous Insufficiency
often asymptomatic swelling of LE pain warmth and redness palpable cord (thrombosed vein)
Deep Vein Thrombosis (DVT)
Virchow’s Triad
stasis - alterations in blood flow
hyper-coagulability - alterations in constituents of blood
–> acquired or hereditary
vessel wall injury (vascular endothelium)
DVT diagnostics
Homan’s sign (sensitive but not specific)
*Wells criteria
*compression US test of choice
D-Dimer - detectable at >500ng/mL in ALL pts with VTE (venous thromboembolism) = sensitive but not specific
impedance plethysmography
contrast venography (invasive)
DVT treatment
prevent PE
decrease risk of recurrent VTE
*anticoagulation therapy (admit to hospital)
–> initial administration 5-10 days during high risk period SQ LMWH
–> long term administration for minimum 3 months (extended to 6-12mo in some pts) WARFARIN
early ambulation
compression stockings
dyspnea (and tachypnea) tachycardia pleuritic pain DVT sxs may vary from no sxs to shock and sudden death
Pulmonary Embolism (PE)
PE classification criteria
hemodynamic stability --> instability means systolic BP under 90mmHg temporal pattern anatomic location presence/absence of sxs
PE diagnostics
if hemodynamically unstable - imaging unsafe, so bedside US works better
if hemodynamically stable - Wells criteria, CTPA of chest and d-dimer
pulmonary angiography was once gold std
*now CT pulmonary angiography (CTPA) test of choice
–> less accurate for detection of smaller PE
–> exclude use if IV contract allergy or renal dysfunction
V/Q scan (sensitive but not specific)
EFG (nonspecific) - S1Q3T3 pattern
CXR - not specific or sensitive
–> Hampton’s hump (opacity = infarct of tissue)
–>Westermark sign (oligemia = decreased Bf)
PE treatment
- anticoagulation therapy (admit to hospital)
- -> initial administration 5-10 days during high risk period SQ LMWH most often
- -> long term administration for minimum 3 months (extended to 6-12mo in some pts) WARFARIN most often
IVC filter if anticoagulation is contraindicated, high risk of bleeding or recurrent PE (use acutely)
thrombolytics = good for unstable patients with PE
thrombectomy/embolectomy
prophylactic measures = sequential compression devices, TED hoes and low dose SG UFH/LMWH for hospitalized pts
anemia --> angina --> dyspnea on exertion --> fatigue and pallor neutropenia - increased risk of infection thrombocytopenia = problems clotting
AUER RODS on peripheral smear
bone marrow biopsy - blasts more than 20% of sample
*most common acute leukemia in adults
accumulation of leukemic blasts (immature cells)
65yo at dx
Acute Myelogenous Leukemia (AML)
cytopenias
ineffective hematopoiesis
may progress to AML (unfavorable)
typically asymptomatic
Tx: immunosuppressive, hematopoietic growth factors
Myelodysplastic Syndrome (MDS)
increased K+ (arrhythmia risk) increased phosphate nucleic acids hypocalcemia (tetany) hyperuricemia
EMERGENCY –> high mortality
associated with ALL and CML
Tumor Lysis Syndrome (TLS)
Tumor Lysis Syndrome (TLS) treatment
prevention, fluids frequent monitoring allopurinol seizure precautions dialysis treat hyperkalemia and hyperphosphatemia
fatigue, malaise
splenomegaly
B sxs: fever, weight loss, night sweats
*more than 90% due to Ph chromosome translocation
Chronic Myelogenous Leukemia (CML)
Chronic Myelogenous Leukemia (CML) phases and complications
Chronic = 80% pts, asymptomatic, WBC >100,000 (high chance of remission)
Accelerated = 10-19% blasts, symptomatic
Blast (crisis) = more than 20% blasts, more serious sxs including splenomegaly
TLS hyperleukocytosis (tx with leukapheresis or else hyperviscosity syndrome) --> spontaneous bleeding --> visual disturbances (retinopathy) --> neuro = HA/vertigo, seizures, coma
Chronic Myelogenous Leukemia (CML) diagnostics and treatment
bone marrow biopsy = Ph chromosome
depends on stage:
tyrosine kinase inhibitor (Imatinib/Gleevec)
monoclonal antibodies
stem cell transplant in later phases (cure but not many can tolerate)
*testicular mass
cytopenias
*most common CA in children and teens
associated with Down Syndrome and NF-1
more favorable if: B cell rather than T cell (hyperleukocytosis and older age) under 35yo @ dx favorable cytogenetics absence of CNS disease
Acute Lymphocytic Leukemia (ALL)
Acute Lymphocytic Leukemia (ALL) diagnostics and treatment
lymphoblasts on peripheral smear
chemotherapy - induction, consolidation, maintenance
monoclonal antibodies
oral tyrosine kinase inhibitors
cytopenias --> can be asymptomatic/indolent advanced disease: organomegaly B sxs atypical infections death due to infection/bleeding
accumulation of incompetent lymphocytes
*highest inheritability of any malignancy
*most prevalent chronic leukemia in adults in Western countries
72yo at dx
Chronic Lymphocytic Leukemia (CLL)
Chronic Lymphocytic Leukemia (CLL) diagnostic and treatment
bone marrow biopsy
lymph node biopsy
chemotherapy/radiation
immunotherapy with Rituximab (CD20) and other monoclonal antibodies
splenectomy
painless LAD (often cervical, but also supraclavicular and mediastinal)
pruritic
EtOH-induced pain of affected lymph nodes
enlargement of:
lymph nodes
spleen
liver
REED-STERNBERG cells = multinucleated B cells (arrested development)
etiology: Epstein-Barr virus in 40-50% cases
most common 15-34yo
Hodgkin Lymphoma
Hodgkin Lymphoma diagnostics and treatment
Reed-Sternberg cells in biopsy of lymph node tissue
combo chemo often with radiation
stem cell transplant
worse prognosis: B sxs (fever, weight loss, night sweats) bulky distant spread affects lymph nodes on both sides of diaphragm
*painless, persistent LAD B sxs (more common) = fever, night sweats, weight loss
associated with HIV, EBV, Hep B/C, H. pylori, etc.
66yo at dx
aggressive = rapidly growing, B sxs, elevated LDH and uric acid
*someone with CLL can develop this
Non-Hodgkin Lymphoma (NHL)
Non-Hodgkin Lymphoma (NHL) diagnostics and treatment
biopsy enlarged lymph nodes
CT- staging
bone marrow biopsy (cytopenias)
lumbar puncture
based on stage and clinical status
indolent = radiation alone
aggressive = chemo, immunotherapy, autologous HCT (hematopoietic cell transplant)
back pain
bone pain - low back and ribs - osteoporosis
bleeding (from thrombocytopenia)
hypercalcemia (all malignancies)
pathologic fractures
hyperviscosity syndrome = spontaneous bleeding, visual disturbances and neuro sxs)
65yo at dx
instead of making Ig, plasma cells secrete paraproteins
–> replace bone marrow
–> destroy bone
–> forms tumors (spinal cord compression)
Multiple Myeloma
Multiple Myeloma diagnostics and treatment
protein electrophoresis on blood and urine (SPEP & UPEP)
*M spike (monoclonal)
*Bence-Jones proteins in urine
CRAB: calcium >10.5, renal insufficiency (Cre >2), anemia (Hb less than 10), bone lesions
refer to oncology
*bone marrow transplant
combo chemo
IV bisphosphate
