Exam #1 Flashcards
Auer rods
not very many
many
not very many : Acute myeloid leukemia (accumulation of MPO)
many: acute promyelocytic leukemia
t(15;17)
- retinoic acid receptor mutation leading to RAR disruption
- acute promyelocytic leukemia (subtype of AML)
myeloperoxidase stains
myeloblasts
CD33 and CD34 positive
CD33: immature myeloid cells
CD34: multipotent stem cells
means acute myeloid leukemia (AML)
CD15
CD64
CD15 and CD64: mature myeloid cells
t(9:22) Philadelphia chromosome
- outcome
- causes
- BCR-ABL protein fusion drives granulocytic and megakaryocytic progenitor proliferation
- Chronic Myeloid Leukemia and bad prognosis ALL
Smudge cells
Chronic lymphocytic leukemia and SLL
-fagile lymphocytes (usually B cells)
M-CSF
G-CSF
G/M-CSF
M-CSF: monocyte
G-CSF: granulocyte
G/M-CSF: monocyte/granulocyte
-given after chemotherapy
Tdt stains for
lymphoblasts
Neutropenia causes
Acute viral syndromes
Rickettsial diseases
Chemotherapy
granulocytes
eosinophil
neutrophil
basophil
Atypical lymphocytosis (Downey Cells)
- appearance
- causes
RBC indent lymphocyte
-seen in EBV/CMV
Dohle Body
- lighter than morulaes
- associated with left shifts and can be seen in conjunction with toxic granulation
Job’s Syndrome
- hyper IgE (diagnostic)
- retention of baby teeth
- skin issues
- facial abnormalities
Flower cells
Sezary syndrome
cutaneous CD4+ cell/T-cell lymphoma/leukemia
Hairy cells lineage and mutation
hairy cell leukemia
- B cell leukemia that is a subtype of CLL
- BRAF mutation
Morulae
dark spot in cytoplasm of cell that is darker than dohle body
-associated with Ehrlichiosis and Anaplasmosis
Rash associated with amoxicillin/ampicillin given
EBV
posterior cervical lymphadenopathy
EBV
Rubella
Epstein-Barr Virus type of autoimmune hemolytic anemia
IgM cold agglutinins
Plaque on the side of the tongue and cant scrape off unlike candida’s in which you can scrape
-associated with?
Hairy Cell Leukemia
-associated w EBV
Rapidly growing tumors around the mandible
Burkitt’s lymphoma (African form)
EBV can give rise to
Burkitt’s lymphoma (African form)
Hodgkin’s lymphoma
Nasopharyngeal carcinoma
Atypical lymphocytes (Downey cells0
Owl’s eyes
Hodgkin’s lymphoma (Reed-Sternberg cells)
CMV
Starry night pattern
Burkitt’s lymphoma
Reed-Sternberg cells of Hodgkins lymphoma disease
dormant hypnozoites in hepatocytes
P. vivax/ovale
banana shape on blood smear
P. falciporum
P. vivax
P. ovale
P. malariae
P. vivax - every 2 days
P. ovale - every 2 days
P. malariae -every 3 days
Severe symptoms of P. falciparum
Hemolytic anemia
Blackwater fever: hemolytic crisis with severe anemia, black urine, oliguria/acute renal failure from hemoglobinuria, jaundice
Malaria stain
Wright’s or Giemsa stain
ringforms in RBCs
Falciparum if high parasitemia (>60%) all others roughly 1-2%
artemisinins Atovaquone-proguanil Chloroquine Primaquine Quinine plus Clindamycin Quinidine
why to give
artemisinins - get from WHO Atovaquone-proguanil - go to drug in US mild-moderate severity Chloroquine - north of Panama Canal Primaquine - kill vivax and ovale Quinine plus Clindamycin - pregnant Quinidine - IV is severe
Chloroquine contraindications
psoriasis or porphyria
Primaquine contraindications
Pregnancy (fetus lack G6DPH)
G6PDH deficient patients
Atovaquone-proguanil
Chloroquine
Quinine & Quinidine
Artemisinin
MOA
Atovaquone-proguanil: inhibits ETC
Chloroquine: blocks heme polymerization
Quinine & Quinidine: blocks heme polymerization
Artemisinin: Inhibition of nucleic acid and protein synthesis
Neutrophilia causes
corticosteroids
epinephrine –> demargination
infection (C. diff)
inflammation
Eosinophilia causes
Parasitic infections
Allergies
Job’s syndrome
Hyper IgE
retention of baby teeth
plaque on tongue cannot be remove like candida
Basophilia causes
CML (BCR-ABL positive)
Neutropenia causes
Acute viral syndromes
Rickettsial diseases- Ehrlichiosis/Anaplasmosis
Chemotherapy and radiation therapy
2 lobed “dumb bell” neutrophil
Pelger-Huet anomaly
Long Island, Fire Island, Shelter Island, Nantucket Island and Martha’s Vineyard in the northeast US
Babesiosis
Babesios treatment
Atovaquone + axithromycin
Clindamycin + quinine
Powassan virus causes
neurological issues
Tick borne illnesses confections Ixodate bites
Babesios
Anaplasmosis
Powassan
Borrelia burgdorferi
difference between folate and B12 def
B12 present with neurological symptoms but after a long time
vitamin K dependent factors
II
VII (most sensitive)
IX
X
hemophilia A
hemophilia B
mutation and test
hemophilia A: mutated factor VIII (carried by mom and given to son)
-prolonged PT, normal PT
hemophilia B: mutated factor IX
-prolonged PT, normal PT
von Willebrand disease (type 1,2,3)
mutated (2) or def. (1,3) vWF type 1: mild-moderate (def. in vWF) type 2: defective multimer assembly type 3: severe (very low vWF) -lead to dec VIII bc stabilizes VIII -normal platelets -prolonged PTT
von Willebrand factor purpose
- Binds to exposed collagen and GPIb receptor on platelet surface
- Activated platelets release ADP & thromboxane A2 (TXA2)
- Carries/protects of Factor VIII
tissue plasminogen activator (t-PA)
enzyme that converts plasminogen to plasmin which breaks down fibrin and some clot factors
Heparan sulfate Thrombomodulin Protein C Plasmin Antithrombin
Heparan sulfate: Activates antithrombin
Thrombomodulin: binds to thrombin
Protein C: inactivates factors Va and VIIIa
Plasmin: degrades fibrin (D-dimers and FDP)neutralizes Antithrombin: inactivates thrombin and clotting factor Xa
what will vitamin K immediately effect when low
Factor VII (extrinsic but not intrinsic pathway) and protein C bc they have short half lives
Heparin inhibits
Warfarin inhibits
Heparin: 12, 11, 9, 10, 2
Warfarin: 10, 9, 7, 2
normal platelet count
150,000 - 450,000
ADAMTS13 (vWF metalloprotease) def.
Thrombotic thrombocytopenic purpura (TTP)
Heparin-induced thrombocytopenia (Type I and II)
Type I: direct activation of platelets
Type II: antibodies (IgG) that recognize complexes of heparin and platelet factor 4, Fc region of antibody binds platelet causing activation –> severe thrombosis
immune thrombocytopenic purpura
Adult: autoantibody that destroys platelets (chronic in adults) usually secondary to SLE, HIV
Children: autoantibody that destroys platelets after viral infection (acute bc resolves after about 6 months)
Bernard-Soulier syndrome
deficiency of platelet membrane glycoprotein complex Ib-IX
Glanzmann thrombasthenia
defective platelet aggregation from deficiency or dysfunction of glycoprotein IIb-IIIa
Disorders of platelet secretion (storage pool disorders):
Defective release of mediators of platelet activation, unusual bleeding (after surgical procedure)
DiGeorge syndrome
Thymic hypoplasia
- 22q11.2 deletion syndrome (3/4 pharyngeal pouches)
- heart defect (ventricular septal defect)
- hypoparathyroidism (parathyroid disfunction
- cleft palate
Thymic hyperplasia (true vs. follicular)
True: inc size while maintaining normal architecture
Follicular: inc in B cell follicles
dermatitis herpetiformis
autoimmune blistering disorder that is associated with celiac disease (gluten sensitivity)
-immunofluorescence showing immunoglobulin A (IgA) in the papillary dermis
pernicious anemia
autoimmune destruction of parietal cells that release intrinsic factor resulting in malabsorption of B12
dactylitis
sickle cell anemia
CD 55 and CD 59
proximal nocturnal anemia
pseudohyphae
candida
narrow budding yeast
cryptococcus neoformis
pediculosis
lice
Cutaneous larva migrans
hook worm
Cutaneous Leishmaniasis
transmitted by sand fly
soldier returning from Middle East
Paronychia
Infection around a nail
Panniculitis
inflammation of subcutaneous fat
hyaluronidase
- Staphylococcus aureus and in Group A Streptococcus
- an extracellular enzyme that helps destroy some the polysaccharides that hold cells together, allowing these bacteria to spread through the tissues of the host
M proteins
on Streptococcus prevent opsonization by complement, making it more difficult to be phagocytized
Skin infections in unvaccinated children
Haemophilus influenza
dog and cat bites
Pasteurella
Wound infections after human bites
Eikenella corrodens
rat bite
Streptobacillus moniliformis and Spirillum minus
snakebites
Pseudomonas aeruginosa
Puncture/nail wounds through shoes that lead to infection
Pseudomonas aeruginosa
groin and axillary regions that fluoresce coral red with a Wood’s light (dark reddish/brown appearance)
Erythrasma
Corynebacterium minutissimum
Erythrasma vs Candida skin infection
Erythrasma: reddish brown with no satellite lesions
Candida: bright red with satellite lesions
-both interigo found in body folds
Panton-Valentine Leukocidin
Staph. aureus exotoxin
Nikolsky sign
when touched, and cleaves just below the stratum corneum
Fournier’s gangrene
necrotizing fasciitis that tends to occur in the perineum, groin and proximal thighs
Hidradenitis suppurativa
dysfunction of apocrine sweat glands and hair follicles causing recurrent inflammatory nodules develop in those areas, are painful and tend to break open leading to secondary, draining abscesses
raw oysters with liver failure or chucking oysters leading to necrosis fasciitis
Vibrio vulnificus
fish tank exposure
Mycobacterium marinum
45 degree hyphae on silver stain
Asperillosis
90 degree hypae on silver stain and association
Zygomycetes (Mucormycosis)
-associated with mucor lesion bc invades blood vessels which leads to ischemic/necrotic tissue
Tzanck smear with multinucleated giant cells
HSV 1/2
Varicella Zoster Virus can lay dormant in the…
dormant (latent) in the trigeminal and dorsal root ganglia
-trigeminal nerve can put the cornea at risk
how to distinguish between Varicella Zoster Virus and Variola Virus (small pox)
Varicella Zoster Virus:
- develops in crops over time
- doesnt include palms and soles
- sickness isn’t as severe
Variola Virus:
- crop develops at same time
- include palms/soles
- much more severe sickness
HVV6/7 (Roseola) vs Rubeola (measles)
Roseola
- rash: trunk -> extremities
- febrile seizures
- not as sick as rubeola
Rubeola
- Koplik’s spots
- cough, conjunctivitis and coryza (stuffy, runny nose)
- rash starts at back of ears and runs down body
- severely sick
HVV 8 is associated w
Kaposi’s sarcoma: angioproliferative tumor usually on the nose or inside the mouth
Herpes B virus(Herpes simiae) is commonly from
monkey bite
Hand, Foot and Mouth Disease cause and symptoms
Coxsackie virus A 16 and Enterovirus 71
-rash on the hands, feet, and inside the mouth
Herpangina cause and symptoms
Coxsackie virus A and B, Enterovirus 71
-grayish lumps form and develop into vesicles surrounded by erythema in the mouth and pharynx
Parvovirus B19
aka slap cheek or fifth disease
- children: red rash forms on cheeks and spares the nasolabial folds, forehead and mouth
- adults: palyarthrogias similar to RA
- bone marrow suppression and pancytopenia in immune compromised patients (AIDS), even leading to aplastic crisis
subacute sclerosing panencephalitis
- progressive brain inflammation caused by persistent infection with measles virus, which can be a result of a mutation of the virus itself
- occurs in rubeola (measles)
- give vitamin A
F protein
- rubeola
- mediates cell-to-cell fusion of infected to uninfected cells, forming giant cells
Mumps symptoms
- parotitis
- orchitis (red swollen testicles)
Rubella (German Measles) symptoms
- lymphadenopathy involves posterior cervical, posterior auricular and suboccipital nodes
- petechia on soft palate (*Forshheimer spots)
Acute HIV
- Days-weeks after exposure 50-90% experience symptoms of acute (i.e. primary infection) HIV, which is a mononucleosis-like symptoms
- RETRO-ORBITAL headache
- macular or maculopapular rash is non-pruritic, mostly on the upper body
Human Papillomavirus associated with
cervical and oropharyngeal cancers
Orf virus
handling infected sheep or goats
Molluscum Contagiosum
water warts
Dengue Fever vs. Chikungunya Fever symptoms
Dengue Fever (South/Central America, Australia, Africa)
- retro-orbital headache
- biphasic/saddleback fever
- “Islands of white in a sea of red” rash
- Faget’s sign
Chikungunya Fever
-same as Dengue fever but severe arthralgias
Heterophile antibody test
aka monospot test used to test for EBV
Give amoxicillin/ampicillin to EBV
hypersensitivity reaction rash all over body involving palms
anemia associated with EBV
autoimmune hemolytic anemia with IgM cold agglutinins
X-linked lymphoproliferative syndrome/Duncan’s syndrome
- associated in males develop during primary exposure
- a large proliferative response of polyclonal B/T cells, along with macrophages, in response to primary EBV infection
how to tell the difference between oral hairy cell leukemia and candida?
Oral Hairy Leukemia: can’t scrape of oral plaque
Candida: can scrape off oral plaque
cancers associated with EBV
Oral hairy cell leukemia
Hodgkin’s lymphoma
Burkitt’s lymphoma (afrcan epidemic)
NASOPHARYNGEAL CARCINOMA
B symptoms
- fever of more than 38°C for at least three days
- drenching night sweats
- unintentional weight loss >10% over a six-month period
- associated with Hodgkin’s and Non Hodgkin’s lymphoma and sometimes Tb
- these cancers can be associated w EBV
CMV illness association
CMV is the most common cause of fatal myocarditis in immunocompetent people
most common pathogen in liver transplant patients?
CMV
Involucrum
Layer of new bone growth, outside of existing bone (heterotopic ossification) that is infected, often surrounding a sequestrum
-associated with chronic osteomyelitis
Brodie’s abscess
an abscess walled off by fibrous and granulation tissue, usually associated with chronic osteomyelitis where frank bone and marrow tissue has been absorbed
Pott’s Puffy Tumor
a subperiosteal abscess due to osteomyelitis of the frontal bone of the skull as a result of acute or chronic sinusitis, intranasal cocaine or methamphetamine abuse or frontal sinus surgery
Osteomylitis in adults and children (location)
Adults: epiphysis
Children: metaphysis
Pott’s disease
osteomyelitis in the spine often caused by Tb
Batson’s plexus of veins
how infections (osteomyelitis) can spread from GI/GU (gram neg. rods) to the spinal cord
Osteomyelitis/Septic arthritis Kids: Nail through shoe: Unvaccinated kids: Sickle Cell: Animal Bite: Human Bite:
Kids: Kingella or Streptococcus agalactiae
Nail through shoe: Pseudomonas aeruginosa
Unvaccinated kids: Haemophilus influenzae
Sickle Cell: Salmonella
Animal Bite: Pasteurella or Bartonella
Human Bite:Eikenella and Strep. viridans
Sinus tracts to skin are often seen with chronic osteomyelitis cancer
squamous cell carcinoma
Nuclear medicine 3 phase bone scan
shows hot spots in bone (osteomyelitis)
-MRI is the diagnosis tool of choice
In sexually active young adults under 40, the most common cause of spontaneous, hematogenous, septic arthritis…
disseminated gonococcal infection
- tends to develop either around a recent menstrual period (within 7 days of start of menses) or post-partum
- lesion on hands
Viscosity drop test results meaning
-if the drop does not string –> infection/inflammation
Reactive arthritis symptoms
Triad: arthritis, conjunctivitis, and urethritis
- cant see, cant pee, cant climb a tree
- autoimmune reaction by prior infection of genitourinary system usually chlamydia
- Reiter’s Syndrome
G-CSF (Filgrastim/tradename-Neupogen) vs. G-CSF/polyethylene glycol
G-CSF (Filgrastim/tradename-Neupogen): short half-life
G-CSF/polyethylene glycol: longer half-life
-used in individuals with chemotherapy
Neutrophilia causes
corticosteroids/epinephrine: demmargination
Increased production: infection
Neutrophilia lab amount
25,000-50,000
Philadelphia chromosome and/or BCR-ABL gene mutation seen in
CML
Lymphocytosis causes
Increased bone marrow release: infection
CLL/ALL
Eosinophilia causes
Allergic disorders (asthma)
Parasitic infections
SLE
Hodgkin’s disease
Hyper IgE syndrome (Job’s syndrome)….
High IgE
rendition of baby teeth
skin issues
weird fascial features
Monocytosis causes
TB infection
acute monocytic leukemia, chronic myelomonocytic leukemia, Hodgkin’s disease
Basophilia causes
CML
Neutropenia causes
Acute viral syndromes Chronic viral syndromes (HIV) Rickettsial diseases Autoimmune diseases (SLE, RA) B12 and folate deficiency Ethanol direct toxicity in the bone marrow Chemotherapy and radiation therapy Methotrexate
Neutropenic Fever
A common complication seen during the neutropenic period, that tends to occur 7-14 days after a typical round of chemotherapy. The neutropenia lasts several days and can be profound with <100 total neutrophil count. Shortened, and often less severe, if G-CSF is given prophylactically by the Oncologist.
Pelger-Huet anomaly
dumbbell-shaped basophils
Sezary syndrome
advanced stage mycosis fungoides (cutaneous CD4+ cell)
-Sezary cells: convoluted (“cerebriform”) or flower cells
thymus embryonic origin
3/4 pharyngeal arch
myasthenia gravis association
thyoma
Digeorge Syndrome
thymic hypoplasia
- 22q11 partial deletion (envolves 3 /4 pharyngeal arches)
- heart defect (ventral septal), hypoparathyroidism (low Ca2+), cleft palate
Thymus sections and residents
Cortex: developing T cells and macrophages
Medulla: Hassalls corpuscles, immunocompetent T-cells, macrophages, dendritic cells
thyoma types
Noninvasive thymomas: composed of medullary type epithelial cells
Mixed thymomas: medullary, and polygonal cortical type epithelial cells
Invasive thymoma: epithelial cells most commonly cortical (more likely to metastasize)
thymic carcinoma association
EBV
White pulp
Marginal Zone
Follicle
Periarteriolar Lymphatic Sheath
-Marginal Zone: macrophages that remove debris and dendritic cells processing antigens
Follicle: B cells
Periarteriolar Lymphatic Sheath (PALS): surrounds arteries (T cells)
KNOW ANATOMY
Red pulp
where macrophages remove old RBCs and where platelets are stored
-sinusoids: allow RBC to pass through to get to the cords of Billroth where macrophages are located
Sinusoids
cause cells extreme deformation so RBCs get trapped in the cords and are readily phagocytosed
Congestive splenomegaly
Caused by chronic venous outflow obstruction with portal or splenic vein hypertension
- Liver cirrhosis
- spontaneous portal vein thrombosis
- R sided heart failure
Spleen function
- phagocytize RBCs
- antibody production (dendritic cells -> T cells -> B cells)
- hematopoiesis (fetus, chronic anemia)
- sequestration of blood elements (platelets, RBCs)
elevated ASO
recent strep infection
Heinz bodies are found in
G6P def. anemia
-use Heinz prep to test for G6P def anemia
Desmopressin
increases release of vWF from Weibel-Palade bodies
RANK
RANKL
RANK: osteoclast
RANKL: osteoblast
-binding leads to survival of osteoclasts by osteoblasts releasing M-CSF
-PTH increases RANKL on osteoblasts
WNT
binds to osteoblasts and produces OPG which competitively binds to RANK inhibiting the production of osteoclasts
Osteopetrosis
Adult autosomal dominant, chloride channel dysfunction
Osteitis fibrosa cystica
loss of bone mass, weak bones as calcified structures replaced with fibrous tissue (peritrabecular fibrosis), and formation of cyst-like brown tumors
-High PTH results in high osteoclastic activity
Osteonecrosis (avascular necrosis) cause
fractures
corticosteroids
predisposed alcohol abuse
bisphosphonate therapy
Rheumatoid factor
serum IgM or IgA autoantibodies that bind Fc parts of IgG
Mononeuropathies
Mononeuritis
Polyneuropathies
Polyradiculoneuropathies
- Mononeuropathies affect single nerve, deficits in restricted distribution dictated by normal anatomy; causes are trauma, entrapment, infections
- Mononeuritis multiplex damages several random nerves; commonly vasculitis
- Polyneuropathies affect multiple usually symmetrical nerves and axons effects are length dependent, so deficits start in feet and ascend; “stocking and glove”; example is diabetic neuropathy
- Polyradiculoneuropathies affect nerve roots and peripheral nerves (polyneuropathy and polyradiculopathy occur together), diffuse symmetric symptoms proximally and distally; example is Guillain–Barré syndrome
Guillain-Barré Syndrome
immune-mediated demyelinating neuropathy
-beginning in distal limbs, rapidly advancing proximally, “ascending paralysis” (distal –> proximal)
Dermatomyositis antibodies
Anti-Mi2: gottron papules and heliotrope rash
Anti-Jo1: interstitial lung disease, nonerosive arthritis, mechanic hands
-elevated CK
Dystrophin
- forms interface between cytoskeletal proteins and group of transmembrane proteins
- mutations in dystrophin are associated with X-linked muscular dystrophies
X-Linked Muscular Dystrophy with Dystrophin Mutation/Duchenne and Becker Muscular Dystrophy
- Pseudohypertrophy of leg
- Positive Gowers’ sign
- Serum creatine kinase elevated
- Absence of dystrophin
- Fat replaces muscle
Lucent lesion
punched out (osteolytic) bright on X-ray
osteoma association
Gardner’s Syndrome (colin polyps)
OSTEOID OSTEOMA on xray
round lucent nidus surrounded by extensive sclerosis
-can look targetoid
what makes someone at risk for osteosarcoma
RB, Paget’s
Maffuci’s syndrome vs Ollier’s syndrome
Maffuci’s syndrome: multiple chondromas and soft tissue hemangiomas
Ollier’s syndrome: multiple enchondromas
Chondroma associated rearrangement
11q13-15
Chondroblastoma histology resembles
chicken wire
Chondrosarcoma xray description
rings and arcs
Ewing’s sarcoma arises from
neural ectoderm
osteoblastic tumors
Prostate
SCLC
Hodgkin lymphoma
Medulloblastoma
What infectious diseases have rashes that typically involve the palms and soles?
Coxsackievirus
Rocky Mountain Spotted Fever
Where is vWF located
Weibel-Palade bodies of endothelium
Alpha granules of platelets
markers for Chronic Lymphocytic Leukemia (CLL)
CD5 CD20
severe anemia, black urine, oliguria/acute renal failure from hemoglobinuria, jaundice (from indirect hyperbilirubinemia)
P. falciparum
Chloroquine MOA and contraindication
blocks heme polymerization into hemozoin causing a buildup of heme
contraindication: psoriasis/porphyria, vision issues
Primaquine indication and contraindication
Indication: infection of vivax and oval or render falciparum gametes noninfective to mosquitoes
Contraindication: G6P def. and pregnancy (bc G6P def.)
-Primaquine effects parasites mitochondria causing build up of ROS, this can exacerbate a G6P def.
Atovaquone + Aguanil MOA
Atovaquone: disrupting mitochondrial electron transport
Aguanil : inhibitor of the parasites dihydrofolate reductase-thymidylate synthetase (enhances atovaquone effect)
indication: falciparum infection
Mefloquine indication and contraindication
indication: drug of choice for chemoprophylaxis against chloroquine-resistant strains of malaria
contraindication: epilepsy and cant give with Quinidine and quinine
Quinine & Quinidine indication and contraindication
indication: sever falciparum infection
contraindication: mefloquine, can raise warfarin/digoxin levels
Artemether MOA, indication
MOA: prodrugs that causes inhibition of nucleic acid and protein synthesis
indication: severe falciparum infection
Pyrimethamine + sulfdoxine MOA
MOA: Synergist effects which acts slowly against erythrocytic forms of susceptible strains of all four human malaria species (blocks folate production in parasite)
Contraindication: if given to pregnant women must supplement with folate (blocks folate production in parasite)
Pernicious Anemia
autoimmune destruction of parietal cells leading to dec intrinsic factor
B12, Fe2+ are absorbed where
B12: ileum
Fe2+: distal duodenum
Hepcidin
decrease Fe2+ release from enterocyte (dec ferroportin) and macrophages as well as decreasing EPO
- low when iron stores decrease or when erythropoiesis is stimulated
- high whenstorage sites full of iron and erythropoiesis normal
alpha/beta thalassemia chromosomes
alpha: 16
beta: 11
Silent carrier state
α-Thalassemia trait
HbH disease
Hydrops fetalis
Silent carrier state: 1 deletion
α-Thalassemia trait: 2 deletions (mild anemia)
HbH disease: 3 deletions tetramers of β-globin form HbH (high affinity for oxygen with tissue hypoxia)
Hydrops fetalis: 4 deletions γ-globin chains form tetramers (hemoglobin Barts) with a high affinity for oxygen that deliver little oxygen to tissues
β-thalassemia major
β 0 / β 0
- ineffective erythropoiesis causes massive erythroid hyperplasia in marrow and extensive extramedullary hematopoiesis -> “crewcut”
- target cells
IL-6 stimulates an increased
hepatic hepcidin seen in chronic inflammatory states
spherocytosis
Howell-Jolly bodies
autosomal dominant
splenectomy
paroxysmal nocturnal hemoglobinuria doesnt have
glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59 (DAF)
-inhibit C3 convertase
IgM vs. IgG
IgM: fixes compliment (cold)
IgG: macrophage destruction (warm)
Holly-Jowell bodies
emerges on blood smear following splenectomy in a patient with hereditary spherocytosis
pentad of symptoms seen in thrombotic thrombocytopenic purpura (TTP)
FAT RN:
F: Fever
A: Anemia (MAHA)
T: Thrombocytopenia
R: Renal symptoms
N: Neurologic symptoms
Marker difference between ALL and CLL
ALL: CD10, 19, 20, 22
CLL: CD5, 19, 20, 23
-CD5 differentiates the two plus involvement of lymph nodes in CLL (specifically SLL)
HTVL-1 causes
Adult T cell leukemia/lymphoma
t(14;18)
BCL-2 translocations
follicular lymphoma
Diffuse large B-cell lymphoma (DLBCL) immunophenotype had mutation
Positive CD10, CD19 and CD20, and BCL6
CD19, CD20, usually CD5 positive and CD23 negative
-what can this be confused with
Mantle cell lymphoma
-CLL will have CD23 and CD5
t(11;14)
overexpression of cyclin D1
Mantle cell lymphoma
HHV-8 causes
Kaposi sarcoma
Lymphoplasmacytic Lymphoma causes
secrete usually monoclonal IgM, but can also be IgG or IgA that causes hyperviscosity syndrome called Waldenström macroglobulinemia
CD15/30
Hodgkin’s lymphoma (Nodular sclerosis type)
CD 138/56
multiple myeloma
mutations in transcription factor STAT3
Large granular lymphocytic (LGL) leukemia
- T-cell variants are CD3+
- NK-cell CD3−, CD56+
Erythema multiforme and associated diseases
immune related symmetrical targetoid lesions following a HSV1/2 infection
- Steven Johnson Syndrome: 10-30% children
- Toxic Epidermal Necrolysis: >30% elderly
psoriasis histology
elongation of dermal papillae (test tubes in a rack)
Pemphigus vulgaris
Dsg 1 and Dsg 3
antibodies throughout epidermis
bullae rupture easily
Pemphigus faliaceus
Dsg 1
Bullous pemphigus
BAPG (hemidesmosomes)
antibodies along dermal/epidermal junction
-tense bullae that won’t rupture
Seborrheic Keratosis
liver spot associated with GI carcinoma
linear melanocyte hyperplasia
Nevi main mutation
BRAF
Acatinic Keratosis
leads to squamous cell carcinoma
Squamous cell carcinoma histology give away
keratin pearl
Dermitis Herpetiforms
IgA antibody against reticulin (helps anchor BM)
- antibodies at tips of dermal papillae
- associated with gluten allergy
RMSF
Rickettsia rickettsia
- rash starting on wrist/ankles -> palms, soles, trunk
- edema and intra-vascular volume depletion due to vascular leak
American Tick Bite Fever vs. African Tick Bite Fever vs. Boutonneuse/Mediterranean Fever
American Tick Bite Fever: single eschar at bite site
-south US
African Tick Bite Fever: multiple eschars
Boutonneuse/Mediterranean Fever: single, large eschar
-around Mediterranean seas
-all caused by rickettsia virus
Human Monocytic Ehrlichiosis
- morulae in monocyte/macrophage
- south US
- Amblyomma americanum
- Leukopenia, Thrombocytopenia, Elevated transaminases,
Anaplasmosis
Anaplasma phagocytophilum
- north and northeast, CA, Europe
- Ixodes scapularis and pacificus
- morulae occur in granulocytes
Tularemia
Francisella tularensis
- passed by ticks and flies
- ULCEROGLANDULAR
- Faget’s sign (high temp, low/normal pulse)
Tularemia treatment
Quinolones or Doxycycline or Gentamicin
Q fever
- undergoes biphasic antigenic variation without morphologic changes
- Phase II antibodies in ACUTE
- Phase I antibodies CHRONIC
STARI
Amblyomma americanum
targetoid erythema chronicum migrans lesion usually smaller than Lyme disease
Powassan Virus
meningoencephalitis
Lyme Disease
Borrelia burgdorferi sensu lato
- sphirocytes seen on histo
- erythema chronicum migrans that increases in size
- BELL’S PALSY
- conjunctivitis
Erythema multiforme vs. Lyme disease vs. STARI
Erythema Multiforma: targetoid lesions on palms and soles
Lyme disease: large targetoid lesion that grows over time
STARI: small targetoid lesions
Co-infection with Ixodes ticks
Lymes Disease, Anaplasma, Babesia and Powassan virus
Colorado Tick Fever
-biphasic illness starting around 1 week after a bite
Bartonella
localized lymphadenopathy
Amblyomma tick infections
ATBF
HME
Q fever
STARI
schistocytes
thrombotic thrombocytopenia purpura
hemolytic uremia syndrome
thrombotic thrombocytopenia purpura vs hemolytic uremia syndrome
thrombotic thrombocytopenia purpura: ADAM13 def. resulting in large vWF multimers leading to abnormal platelet adhesion -> microthrombi
-neurological symptoms
hemolytic uremia syndrome: damage to endothelium (usually E. coli) resulting in platelet thrombi
-renal failure, diarrhea
Both:
- skin/mucosal bleeding
- MAHA
- fever
- normal PT/PTT
- schistocytes
immune thrombocytopenic purpura
adults: secondarily to SLE, HIV, B-cell neoplasms like CLL/SLL
children: acute ITP by unknown mechanism that trigger autoantibodies
- autoantibodies mostly against platelet membrane glycoproteins IIb-IIIa or Ib -IX
will vWF have a prolonged PT or PTT and why
prolonged PTT bc vWF stabilize clot factor VIII so there will be a def in VIII as well leading to a decreased VIII
Warfarin Test
PT
Heparin test
PTT
vWF disease vs Hemophilia A bleeding
vWF disease: cuts and nose bleeds that bleed excessively
Hemophilia A: severe deep tissue bleeding
Chromoblastomyces
look like copper pennies aka sclerotic boides/muriform cells
erysipelas and cause
bright red rash w distinct borders caused by GAS
Hot tub
pseudomonas
MRSA/MSSA gene
mecA codes for penicillin binding site
how is Staph a. shock diff
includes diarrhea and rash
bullous impetigo
staph a. exclusively
Streptolysin O and S
digest RBCs
-antibodies against show ASO titer
Strep erythrogenic/pyrogenic toxin
causes rash of scarlet fever
streptokinase
activates plasminogen and digest fibrin
most common cause of lobar pneumonia in adults and otitis media in children
Strep pneumoniae
What is associated with Strep gallolyticus/bovis
colon cancer so if seen order colonoscopy
brain control of temperature
preoptic region of ant. hypothalamus
treatment for malignant hyperthermia (fever caused by anesthetics)
dantrolene
seretonin syndrome
fever caused by the administration of two or more serotonin drugs
relapsing fever and association
fever spike followed by days of no symptoms followed by return of fever
-associated with malaria, babesiosis, or HODGKIN’S LYMPHOMA
Diencephalic fits/seizures
fever from traumatic brain injury or hemorrhagic strokes around the hypothalamus/thalamus
Malignant neuroleptic syndrome
fever caused byreaction to neuroleptic antipsychotic drugs and phenothiazine-anti-nausea meds
Lipopolysaccharide
part of Gram-negative bacteria wall can cause fever, most likely mediated through other cytokines such as TNF-a and Il-1
Pulse-temperature dissociation is associated with
Salmonella sp and typhoid fever
PAMPs include
- LPS on Gram-negative rods
- lipoteichoic acid and peptidoglycan on Gram-positive organisms
- flagellin on bacterial flagella
- lipoarabinomannan in AFB/mycobacterial cell walls
- mannan in the wall of fungi
- unique bacterial and viral nucleic acids
Pro-inflammatory mediators vs. Anti-inflammatory mediators
Pro-inflammatory mediators: Il-2, Il-6, Il-8, Il-10, platelet activating factor
Anti-inflammatory mediators: Il-4, Il-6, Il-10, Il-11, cortisol
Sepsis criteria
- temp >38 (100) or <36 (96.8)
- HR >90 bpm
- Resp rate > 20 rpm or PaCO2 < 32
- WBC >12,000 or <4,000 or >10% band cells
Septic shock
Refractory Septic Shock
Septic shock: sepsis w persisting hypotension after volume resuscitation requiring vasopressors
Refractory Septic Shock: requires more vasopressors after initial volume resuscitations and vasopressors
qSOFA score
- BP <100 mmhg
- Resp rate >22
- altered mentation
- 2 or more = bad outcome
what to do w sepsis
- obtain blood cultures
- administer broad spectrum antibiotics
- measure lactate level
- administer 30ml/kg of ns or rl for hypotension of if lactate is >4
- apply vasopressors if hypotension persists after fluid resuscitation
- repeat lactate levels if initial was elevated
- use central line to measure CVP or venous O2 sat
warm vs cold hypo dynamic shock
warm: high bp and low PVR
cold: low bp and high PVR
is aspirin good w gout
no
Aspirin indication
prophylactic against MI and recurrent transient ischemic attacks/stroke of the brain
Aspirin pharmacology
acetylation of COX1 inhibiting the production of TXA2
Aspirin effect on stomach
low pH in stomach 3.5 makes aspirin non polar allowing it to enter gastric mucosal cells
pH in mucosal cells is higher 7.0 trapping aspirin in cell
aspirin inhibits the production of PGE2 which is needed for the healing
which drugs does aspirin effect
- displaces warfarin inc its toxicity
- blunts the diuretic action of furosemide and thiazides
- reduces the K+ conserving action of spironolactone (used to dec blood pressure)
Contraindications of aspirin
- children with flu/chicken pox –> Reye’s syndrome
- pregnancy
- peptic ulcers
- high doses –> G6PD def.
Reye’s Syndrome
causes by giving aspirin to children that have had chicken pox and the flu
Dipyridamole action
phosphodiesterase inhibitor which breaks down cAMP
- increase cAMP
- ↓RBC uptake of adenosine
P2Y12 inhibitors includes
-“grel” or “clop”
-“or” = reversible inhibitor
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
Ticlopidine
Clopidogrel action
irreversibly binds to P2Y12
PRODRUG:
1st CYP2C19
2nd CYP2C9, CYP2C19, CYP3A
Prasugrel action
irreversibly binds to P2Y12
PRODRUG
1st hydrolysis
2nd CYP3A4 CYP2C19
quick acting
Ticagrelor action and how broken down
Reversible inhibition of P2Y12
-broken down by CYP3A4 so avoid other drugs that use this
Ticagrelor drug interaction
blocks the pump that removes digoxin from cell so increases it toxicity
Cangrelor
Reversible inhibition of P2Y12
-quick acting
Ticlopidine action, side effects, and drug interaction
Irreversible inhibition of P2Y12
- side effects: neutropenia, thrombocytopenia, leukopenia
- drug interaction: monitoring theophylline (decreased metabolism) and phentynoin (displacement of plasma proteins) plasma conc. is recommended
Abciximab action and often use
antibody that binds directly to GPIIb/IIIa
- 15 days or more in a platelet-bound state
- bridge therapy given with other drugs so hypercoagobility will not occur
Eptifibatide and Tirofiban action and clearance
- small fibrinogen sequences that reversibly inhibit GPIIb/IIIa
- cleared by kidneys
Vorapaxar action and us
oral selective, reversible, competitive antagonist of PAR-1 which is the activation site of thrombin
-given to patents with liver failure for the reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease (PAD)
Unfractionated heparin action
used as a cofactor for antithrombin to increase break down of thrombin > Xa, IXa, XIa, XIIIa, V, VIII
Heparin indications
- venous thromboembolism in surgical and high-risk medical patients.
- prevent blood clotting during surgery of the heart or blood vessels, during blood transfusion, in individuals with (DIC)
- acute arterial occlusion
- given before warfarin
how is heparin given
what would you expect initially
clearance
Subcutaneous and infusion line (not IM bc cause hematoma)
-initial it will dec in blood bc it binds to endothelium and macrophage –> cleared by liver
heparin side effects
- Heparin-induced thrombocytopenia (HIT)
- hyperkalemia: ↓ aldosterone synthesis resulting in the sequestion of K+
- osteoporosis with long term use
what is given to reverse heparins effects
protamine sulfate
Heparin resistance
Excessive heparin-binding proteins in plasma
Deficient antithrombin III
heparin contraindications (5)
- asthma/history of allergy
- pregnancy
- liver impairment
- hypertension
- combined with NSAIDs
Low molecular weight (LMW) heparins names
Dalteparin, enoxaparin and danaparoid
Low molecular weight (LMW) heparins action and difference from heparin
stronger inhibition of Xa > thrombin
- lower affinity to endothelial cells, macrophages and plasma proteins
- Less frequent HIT
- Lesser effect on aPTT
Low molecular weight (LMW) heparins clearance
renal clearance
Fondaparinux clearance
renal clearance
Fondaparinux action and difference from LMWH
Xa»_space; more than LMWH
-least likely for HIT
Xa Inhibitors names
“xaban”
Oral direct Xa Inhibitors given for
Prophylaxis and treatment (prevents extension) of DVT and preventing stroke in patients with AFib
-does not require monitoring
Oral direct Xa Inhibitors indication
drugs that inhibit CYP3A4 and P-gp
Direct thrombin (IIa) inhibitors names
-intRUDIN and gator Bivalirudin Argatroban Lepirudin Dabigatran (oral)
Lepirudin use and clearance
for pateints with HIT and liver failure
Bivalirudin given for
percutaneous coronary angioplasty
Argatroban use
for pattens with HIT with renal failure
Dabigatran use and clearance
Oral direct Xa Inhibitor
-renally excreted
Disseminated intravascular coagulation may occur secondary to malignant such as
acute promyelocytic leukemia
what do you give patients when they cant take heparin or is having HIT
Direct Thrombin Inhibitors
- Bivalirudin
- Argatroban
- Dabigatran (given orally)
what to give patient with HIT and Liver failure.. Kidney failure
Liver failure: Dabigatran
Kidney failure: Argatroban
Where do hairy cells collect and what does this cause
red pulp causing splenomegaly
What vasssopressors to use
- 1st
- if MAP is still <65
- someone w severe tachycardia
- norepinephrine
- norepinephrine + vasopressin
- phenylephrine
DGI triad and timing
- tenosynovitis
- polyarthritis
- rash of small papules that turn into tender pustules on broad erythematous bases and with necrotic centers
- most common seen in sexual active females
- timing: within 7 days of start of menses
CD11c and CD25
hairy cell leukemia
Warfarin action
Inhibits vitamin K epoxide reductase complex 1 (VKORC1) interferes with hepatic synthesis (carboxylation) of vit K-dependent clotting factors II (prothrombin), VII, IX and X, also proteins C and S
why is it important to bridge warfarin with heparin
warfarin inhibits the production of protein C which is a anticoagulant and has the shortest half life of all products warfarin inhibits via epoxide reductase
-initially hyper coagulation can occur bc of dec in protein C
warfarin clearance and what is warfarin most potent form
- liver via P450 CYP2C9
- S-warfarin is four times more potent
warfarin indications
- Prophylaxis and treatment of DVT and pulmonary thromboembolism.
- Prophylaxis of thromboembolism associated with chronic atrial fibrillation, myocardial infarction or in individuals with prosthetic heart valves.
warfarin contraindications
- pregnancy
- cyp mutations
- uncontrolled HTN
warfarin drug interactions
- increase toxicity
- decrease toxicity
- GI drugs that inhibit excretion
- impair vit K and warfarin absorption
- erythromycin
- rifampicin
- cimetidine and omeprazole
- colestyramine
Thrombolytic drugs and highest affinity for fibrin bound plasminogen
Tenecteplase > Alteplase > Streptokinase
Steptokinase action and problem
plasminogen (both clot-bound, and circulating forms)
-after initial does antibodies build up against it since it is derived from streptococci
why is Tenecteplase the best thrombolytic drug to give
- Higher fibrin-selective activation
- Higher resistance to inhibition by PAI-1
- Give immediately for STEMI
Fibrinolytic inhibitors and why given
Aminocaproic acid (EACA) Tranexamic Acid (7x more potent) -given to prevents plasmin binding to fibrin, specifically antidote for fibrinolytic agents
Tranexamic acid
Binds to lysine-binding site on plasminogen and is 7x more potent than EACA
Desmopressin
Causes release of vWF from platelets and endothelial lining -> increases VIII t½
-can give for mild forms of hemophilia A
oral contraceptives effect on coagulation and who not to give to
- Increased levels of factors II, VII, VIII, and X and fibrinogen
- Do not give to patient with hemophilia A
spondylitis vs spondylosis vs Spondylolisthesis
spondylitis: is inflammation of one or more vertebrae
spondylosis: degeneration of intervertebral disks
Spondylolisthesis: forward or backward displacement of the body of one vertebrae in relation to an adjacent vertebra
greenstick fracture
bone bends and cracks
Fractures I II III IV V
SALTER I: Straight across II: Above III: beLow IV: Through V: cRush growth plate
koilonychia and what it means
flat nails seen in iron def anemia
Fever of Unknown Origin main causes
-Infections: Tb, abscess, diverticulitis, cholecystitis/cholangitis
Neoplasms: lymphoma
Rheumatologic diseases: Temporal arteritis
Familial Mediterranean Fever symptoms
Recurrent fever
Abdominal pain
Chest pain
Joint pain
Cyclic Neutropenia Related Fever
fever due to low neutrophil count
-will subside when neutrophil count >500
Periodic Fever with Aphthous Stomatitis, Pharyngitis and Adenitis population
most common fever in children
TNF receptor-1 associated periodic syndrome (TRAPS)
TRAPS is in the gene that encodes the receptor for TNF (TNFR1)……leading to an excess in TNFR1 (caused by decreased shedding of the receptor, increasing receptor numbers on cells, making cells more susceptible to TNF)
Borrelia hermsii appearance
small squiggly line in blood smear
normal WBC
left shift
Neutropenia
- 4,500 to 11,000
- 25,000 to 50,000
- 500-1000 or lower
Toxic Granulations association
Associated with inflammatory conditions such as sepsis
-
Bollus with dark red/purple exudate with bruising around
necrotizing fasciitis
-Bullous Cellulitis will have a more clear exudate
Pseudo-Pleger Huet Cells association
myelodystplastic syndrome
-cell with two separate lobes (not connected like Pleger Huet Cells “dumbbell cells’)
particular to rubeola
- rash starting at ear and moving down
- koplik spot
- cough, conjunctivitis, coryza (3 C’s)
- SSP
- F protein
cervical lymphenadopathy illnesses
EBV -> monospot/heterophile test
CMV
Rubella -> forshherimer’s spot
Acute HIV -> retro-orbital headache/history
microcytic anemis
T halassemia A nemia of chronic disease I ron deficiency anemia L ead poisoning (basophilic stippling) S iderblastic anemia
rashes of the palms and soles
Variola Virus
Hand, Foot, and Mouth
Rocky Mountain Spotted Fever
Erythema multiforme
parasites carried by dermacentor ticks
RMSF
Tularemia
normal MCV
80-100
aspirin messes up what drugs
- furosemide, thiazide, and spironolactone
- displaces warfarin at low doses
what patients should you not give aspirin to
- children with history of flu/chicken pox = Reye’s Syndrome
- patients with gout
ticagrelor increases what drugs toxicity
increases digoxin toxicity
Ty Cobb or ticlopidine use and you must monitor what drugs
irreversible PY212 that takes a 3-7 days to kick in
-theophylline and phentyrion
Vorapaxars 1 contraindication
Liver failure
22q11.2 deletion syndrome
digeorge syndrome
chronic venous outflow obstruction causes
Liver cirrhosis
impinge on portal or splenic veins
butcher or fisherman
erysipelothrix rhusiopahtiae
chronic vs acute DIC
Acute DIC, associated with obstetric complications or major trauma, is dominated by a bleeding diathesis
Chronic DIC, as occurs in cancer patients, tends to present with thrombotic complications
