Pathology Flashcards
Acanthocyte
“Spiky” RBCs
Associated with liver disease, abetalipoproteinemia
Basophilic Stippling
See with lead poisoning, sideroblastic anemias (iron cannot be incorporated into Hb),
myelodysplastic syndrome
Dacrocyte
“Teardrop” cell
Bone marrow fibrosis
S&S: lower extremity bone pain and joint tenderness; unable to aspirate a sample from bone marrow
Degmacyte
“Bite cell”
Associated with splenic removal of ppt
Seen in G6PD deficiency
Echinocyte
“Burr cell”
Smaller and more uniform projections (looks kind of like an acathocyte though)
Associated with end-stage renal disease, liver disease, and pyruvate kinase deficiency
Elliptocytes
Hereditary elliptocytosis (usually asymptomatic)
Caused by mutations in genes encoding RBC membrane proteins (spectrin)
Macro-ovalocyte
Megaloblastic anemia (also hypersegmented neutrophils) Marrow failure
Ringed sideroblast
Sideroblastic anemia (excess iron in mitochondria)
Excess iron in mitochondria
Schistocyte
DIC, TTP/HUS, HELLP (HTN + hemolysis, elevated enzymes, low platelets) syndrome, mechanical hemolysis
Sickle cell (aka Drepanocyte)
Seen in sickle cell anemia
Sickling occurs with dehydration, deoxygenation, and high altitude
Spherocyte
Hereditary spherocytosis (spectrin/ ankyrin mutation) Drug and infection-induced hemolytic anemia
Target cell
“HALT said the hunter to his TARGET”
HbC disease (glutamic acid –> lysine)
Asplenia
Liver disease
Thalessemia (beta mainly- and alpha)
Heinz bodies
Inclusions in RBC (due to oxidation of -SH groups)
Subject to removal by spleen- causes bite cells
Seen also in G6PD (like bite cells)
Howell-Jolly bodies
Seen in sickle cell patients; patients with asplenia or hyposplenia
Inclusions are basophilic RNA remnants that are normally removed by the splenic macrophages (but impaired in people who have hypo or asplenia)
Microcytic (MCV < 80fL)
Iron deficiency Alpha-thalassemia Beta-thalassemia Lead poisoning Sideroblastic anemia
Macrocytic (MCV > 100fL)
Megaloblastic anemia (Folate deficiency, Vitamin B12 deficiency, Orotic aciduria, Diamond-Blackfan anemia)
Non-megaloblastic anemia
Normocytic, normochromic anemia
Intravascular and extravascular hemolysis
Nonhemolytic, normocytic anemia
Anemia of chronic disease
Aplastic anemia
Intrinsic hemolytic anemia
Hereditary spherocytosis G6PD deficiency Pyruvate kinase deficiency HbC disease Proxysmal nocturnal hemoglobinuria Sickle cell anemia
Extrinsic hemolytic anemia
Autoimmune hemolytic anemia
Microangiopathic anemia
Macroangiopathic anemia
Infections
Iron deficiency
Decreased iron due to chronic bleeding (GI loss, menorrhagia), malnutrition, absorption disorders, or increased demand (pregnancy)
Labs: decreased iron, increased TIBC, decreased ferritin
Symptoms: fatigue, conjunctival pallor, pica (consumption of nonfood substances), spooned nails (koilonychia)
Plummer-Vinson syndrome
Triad of:
- Iron deficiency anemia
- Esophageal webs
- Dysphagia
Alpha-thalassemia
Alpha-globin gene deletions –> Decreased alpha globin synthesis (cis (same chr) deletions- in Asia, trans (different chr) deletions- in Africa)
4 allele deletion: No alpha globin (hydrops fetalis- dx via presence of HbBarts- gamma4)
3 allele deletion: 1 alpha (HbH disease- presence of beta4)
2 allele deletion: 2 alpha (less severe)
1 allele deletion: 3 alpha (no anemia; clinically silent)
Beta-thalassemia
Point mutation in SPLICE SITES and PROMOTOR sequences (seen in Mediterranean populations)
Beta thal minor: B chain is underproduced; usually asymptomatic
Beta thal major: B chain is ABSENT; requires blood transfusions
S&S: severe microcytic, hypochromic anemia with target cells (anisopoikilocytosis- varying size and shape of cells)
Marrow expansion –> skeletal deformities; “Chipmunk facies”
Extramedullary hematopoiesis –> hepatosplenomegaly
Increased HbF (alpha2gamma2)- therefore kid only becomes symptomatic after 6mo
HbS/ beta-thalassemia heterozygote
Mild to moderate sickle cell disease
Lead poisoning
Lead inhibits ferrochetalase and ALA dehydratase
Leads to decreased heme synthesis and increased RBC protoporphyrin
rRNA degradation inhibited by lead –> RBCs retain aggregates of rRNA (basophilic stippling)
Consider risk in people who live in old houses
LEAD poisoning- symptoms
Lead Lines on gingivae (Burton lines) and on metaphases of long bones
Encephalopathy and Erythrocyte basophilic stippling
Abodomial colic and sideroblastic Anemia
Drops (wrist drop and foot drop); Dimercaprol and EDTA are 1st line of treatment
Lead poisoning- tx
Dimercaprol
EDTA
Succimer- used for chelation for kids
Sideroblastic anemia
Defect in heme synthesis- due to X-linked defect in delta-ALA synthase gene (NOT to be confused with ALA dehydratase that is affected in lead poisoning)
Sideroblastic anemia- causes
Can be genetic, acquired (myelodysplastic syndrome), and reversible (alcohol, lead, vitamin B6 deficiency, copper deficiency, isoniazid)
Sideroblastic anemia- lab findings
increased iron, normal/ decreased TIBC, increase ferritin
Stain: Prussian-blue
Peripheral blood smear: basophilic stippling of RBCs
Sideroblastic anemia- treatment
pyridoxine (B6- cofactor for delta-ALA synthase)
Megaloblastic anemia
Impaired DNA synthesis (maturation of nucleus is delayed relative to maturation of cytoplasm)
RBC macrocytosis, hypersegmented neutrophils, glossitis
Caused by: folate def, vitamin B12 def, orotic aciduria, Diamond-Blackfan anemia
Folate deficiency
Caused by malnutrition (alcoholics), malabsorption, drugs (methotrexate, trimethoprim, phenytoin), increased requirement (hemolytic anemia, pregnancy)
Increased homocysteine, NORMAL methylmalonic acid; NO NEUROLOGIC symptoms (vs. B12 deficiency)
Vitamin B12 (cobalamin) deficiency
Caused by insufficient intake, pernicious anemia, ileal resection/ gastrectomy, malabsorption (Crohn), Diphyllobothrium datum
Increased homocysteine and methylmalonic acid Neurological symptoms (subacute combined degeneration- degeneration of posterior column, lateral CS tract, and spinocerebellar tract)- this is due to B12's involvement in fatty acid pathways and myelin synthesis
Schilling test
Method of diagnosing cause of B12 deficiency:
Stage I: Low levels of urinary B12 Stage II (+oral IF): If levels of urinary B12 become normal --> indicates pernicious anemia Stage III (+antibiotics): If levels of urinary B12 become normal --> indicates small intestinal bacterial overgrowth Stage IV (+pancreatic enzymes): If B12 levels become normal --> indicates pancreatic enzyme insufficiency
Orotic aciduria (AR)
Can’t convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of a defect in UMP synthase
IDed via orotic acid in the urine
Tx: uridine monophosphate (UMP) to bypass mutated enzyme
Orotic aciduria- S&S
S&S: children demonstrate failure to thrive, developmental delay, and megaloblastic anemia refractory to folate and B12
(NO HYPERAMMONEMIA –> vs. ornithine transcarbamylase deficiency where there is increased orotic acid WITH hyperammonemia)
Diamond-Blackfan anemia
Rapid onset anemia within 1st year of life due to defect in erythroid progenitor cells
Patients here present with anemia (vs. Fanconi anemia- where they present with pancytopenia)
Diamond-Blackfan anemia
Increase %HbF (but decrease in total Hb)
Short stature, craniofacial abnormalities and upper extremity malformations (triphalageal thumbs)
Non-megaloblastic anemia
Macrocytic anemia in which DNA synthesis is unimpaired
Causes: alcoholism, liver disease
RBC macrocytosis WITHOUT hypersegmented neutrophils
Normocytic, normochromic anemia
Can be classified in hemolytic vs. non-hemolytic
Can be classified by cause into intrinsic vs. extrinsic
Can be classified further by location into intravascular vs. extravascular
Intravascular hemolysis
Findings: decreased haptoglobin, increased LDH (lactate dehydrogenase), schistocytes, and increased reticulocytes on blood smear
Hemoglobinuria, hemosiderinuria, and urobilinogen in urine; may also see an increase in uncojugated bilirubin
Causes: mechanical- artificial heart valve, paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemia
Extravascular hemolysis
Findings: macrophages in spleen clear RBCs
Spherocytes seen in peripheral smear, increased LDH, no hemoglobinuria/ hemosiderinuria, increased unconjugated bilirubin (can cause jaundice)
May have urobilinogen in urine
Anemia of chronic disease
Inflammation –> increases hepcidin (inhibits iron txport) –> decreased release of iron from Mphages and decreased iron absorption from gut
Associated with RA, SLE, neoplastic disorders, and chronic kidney disease
Anemia of chronic disease- findings and tx
Decreased iron, decreased TIBC, increased ferritin (NOT TO BE CONFUSED WITH iron deficiency- where ferritin levels decrease and TIBC increases
Generally normocytic- can become microcytic
Tx: erythropoietin
Aplastic anemia
Failure or destruction of myeloid stem cells
Lots of causes: radiation and chemo, viral agents (parvo B19, EBV, HIV, hepatitis), Fanconi anemia, idiopathic
Characterized by decreased reticulocyte count, increased EPO
Pancytopenia: characterized by severe anemia, leukopenia, and thrombocytopenia (normal cell morphology, but hypo cellular bone marrow with fatty infiltration –> dry bone marrow tap (like myelodysplastic syndrome- associated with dacrocytes))
Aplastic anemia- symptoms
fatigue, malais, pallor, purpura, mucosal bleeding, petechiae, infection
Fanconi anemia- cause and symptoms
DNA repair defect (like XP, HNPCC, etc) causing bone marrow failure
S&S: short stature, increased risk of tumors/leukemia, cafe-au-lait spots, thumb/radial defects (e.g. polydactyly and radial hypoplasia), small testicles, and kidney malformations
Tx: Bone marrow transplant
Aplastic anemia- tx
remove offending agent, give GM-CSF, bone marrow allograft, RBC/platelet transfusion
Hereditary spherocytosis
Extravascular hemolysis- due to defect in proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, spectrin)
Results in small, round RBCs with less SA and no central pallor (increased MCHC) –> premature removal by spleen
Hereditary spherocytosis- findings & tx
Splenomegaly, aplastic crisis (when infected with parvovirus B19)
Labs: osmotic fragility test +, normal to decreased MCV with abundance of cells
Tx: splenectomy
G6PD deficiency (XR)
Defect in G6PD –> decreased glutathione –> increased RBC susceptibility to oxidant stress (sulfa drugs, antimalarials, infections, fava beans)
Drugs that induce allergy: sulfa drugs (sulfonamide– e.g. furosemide (switch pts to ethacrynic acid), dapsone, primaquine, aspirin, ibuprofen, and nitrofurantoin)
Causes intra and extravascular hemolysis
G6PD- S&S
Male (generally African, Asian, or Mediterranean) with hemolysis, scleral icterus, mild splenomegaly, progressive fatigue, and exertional dyspnea
Pyruvate kinase deficiency (AR)
Defect in pyruvate kinase –> decreased ATP –> rigid RBCs –> EXTRAVASCULAR hemolysis
Causes hemolytic anemia in a newborn
HbC disease
Glutamic acid (-) –> lysine (+) mutation in beta globin
Causes EXTRAVASCULAR hemolysis
Labs: blood smear shows hemoglobin crystals inside RBCs and target cells
Paroxysmal nocturnal hemoglobinuria
Increased complement-mediated INTRAVASCULAR RBC lysis
impaired GPI anchor that normally protects RBC membrane from complement (acquired mutation in stem cells)
Increased risk of acute leukemias
Paroxysmal nocturnal hemoglobinuria- S&S and tx
Triad: Coombs negative hemolytic anemia, pancytopenia, and venous thrombosis
Morning urine is darker in color
Tx: eculizumab (terminal complement inhibitor)
Sickle cell anemia
HbS point mutation: causes single AA replacement in beta chain (substitution of glutamic acid with valine)
Causes extra and intravascular hemolysis
Pathogenesis: low O2, high altitude, or acidosis –> precipitates sickling (deoxygenated HbS polymerizes) –> anemia and vaso-occlusive disease
Complications of sickle cell disease
Aplastic crisis (parvovirus)
Autosplenectomy (Howell-Jolly bodies) –> increased risk of infection by encapsulated organisms (S. pneuma)
Splenic infarct/ sequestration crisis
Salmonella osteomyelitis
Painful crises: dactylitis, priapism, acute chest syndrome, avascular necrosis, stroke
Renal papillary necrosis (decreased PO2 in papilla) and microhematuria (medullary infarcts)
Sickle cell disease- dx and tx
Dx: via Hb electrophoresis (will be closer to the cathode (-) than normal HbA, because of substitution of glutamic acid (-) for valine (neutral))
Tx: hydroxyurea (increases HbF), and hydration
Autoimmune hemolytic anemia (AIHA)
Divided into warm and cool
Caused by antibodies against RBCs
S&S: Increased unconjugated (indirect) bilirubin and elevated LDH and low haptoglobin levels
Generally Coombs +
Warm AIHA
IgG mediated; triggered by heat
Causes: SLE, CLL, alpha-methyldopa (alpha 2 agonist)
Cool AIHA
IgM mediated; triggered by cold
Causes: Mycoplasma pneumo infection, infectious Mononucleosis, CLL)
Direct Coombs test
Test blood + antibodies with anti-Ig (Coombs reagent) (to see if antibodies are present on the blood –> will agglutinate with the addition of Coombs reagent)
Indirect Coombs test
Test serum for antibodies with RBCs (to see if RBCs agglutinate once Coombs reagent is added- if antibodies are present in the serum)
Microangiopathic anemia
RBCs are damaged when passing through obstructed/ narrow vessel lumen
Seen in DIC, TTP/HUS, SLE, and malignant HTN
Schistocytes seen on blood smear due to mechanical destruction
Macroangiopathic anemia
RBCs damaged when passing through mechanical valves
Schistocytes also seen
Iron deficiency
Serum iron: decrease
Ferritin (iron stores): decrease
Transferrin (transports): increase (because body needs more iron)
TIBC (saturation of transferrin): decrease (because less iron)
Anemia of chronic disease
Serum iron: decreases
Ferritin (iron stores): increases
Transferrin (transports iron): decreases (less is circulating so pathogens do not get access to iron)
TIBC (sat of transferrin): normal (because both iron levels and transferrin levels are decreasing)
Hemochromatosis
Serum iron: increases
Ferritin (stores): increases
Transferrin (transport): decreases (tissue has too much iron)
TIBC (total iron/ transferrin): increases (too much iron relative to what is needed)
Pregnancy/ OCP use
Serum iron: (same)
Ferritin: (same)
Transferrin: increases
TIBC (stored/ transported): decreases (because iron is the same while the amount that is being transported is increasing)
Conditions that deplete eosinophils
Cushing syndrome, corticosteroids
Left shift
More neutrophil precursors/ bands (immature cells)
Leukoerythroblastic response
When left shift occurs with RBCs
Occurs when there is fibrosis/ bone marrow failure/ tumor
Lead poisoning
Due to deficiency in ALA dehydratase and ferrochetalase; causes accumulation of protoporphyrin
Symptoms:
Lead Lines
Encephalopathy
Anemia (sideroblastic) and abdominal pain
Drop (wrist and foot); tx with dimercaprol and EDTA
Acute intermittent porphyria
Due to deficiency in prophobilinogen deaminase; causes accumulation of porphobilinogen
Port-wine colored urine (urine darkens when exposed to light)
Painful abdomen
Polyneuropathy
Psychological disturbances
Precipitated by drugs (CYP-450 induces, alcohol, etc.)
Tx with glucose and heme
Porphyria Cutanea Tarda
Due to deficiency in uroporphyrinogen decarboxylase; causes buildup of uroporphyrinogen
Causes cutaneous lesions/ blistering photosensitivity
“Ur skin is affected by uroporphyrinogen deficiency”
Iron poisoning
Tx with deferoxamine, deferasirox (oral), dialysis
S&S: metabolic acidosis, nausea, vomiting, gastric bleeding, lethargy, etc
Coagulation disorders- hemophilia
Hemophilia A- VIII and B- IX (XR) and C- XI (AR)
Treat with cryoprecipitate (contains factors VIII, IX, XIII, etc.)
Pts with demonstrate elevated PTT, normal PT
S&S: bleeding into joints, easy bruising, trauma after dental procedure
Coagulation disorder- vit K deficiency
Depletion of Factors II, VII, IX, X, C and S (C first to go- hyper coagulable state); of factors: VII first to go, II last to go
S&S: elevated PT and PTT; easy bleeding
Normal bleeding time
Platelet disorders- Bernard-Soulier
Deficiency in GpIb (normally binds to vWF –> helps platelet adhere to endothelium); increased bleeding time
Ristocetin assay identifies (vWD and BS; if BS- with the aden of plasma- problem will still not be corrected)
Platelet disorders- Glanzmann
Deficiency in GpIIb/IIIa (fibrinogen binds to this to stabilize clot)
Causes increased bleeding time
HUS (hemolytic uremic syndrome)
Classified by triad of: thrombocytopenia, hemolysis (microangiopathic), and renal failure
Seen in children– often after exposure to Shiga-like toxin (in EHEC/ Shigella)
Immune thrombocytopenia
Antibodies against GpIIb/IIIa
Causes splenic macrophage consumption of splenic-macrophage complex
Tx with steroids, IVIG, splenectomy
Thrombotic Thrombocytopenic Purpura
Inhibition or deficiency of ADAMTS –> causes decreased degradation of vWF
Increased vWF causes increase platelet clumping; therefore causing triad of: thrombocytopenia, microangiopathic hemolysis, and renal failure –> also see neurological disturbances and fever
Will see increased LDH and low haptoglobin
Tx: steroids, plasmapheresis
von Willebrand disease
Does not generally bleed into joints
Will see increased bleeding time and PTT (because of its effect on increasing VIII half life)
Ristocetin assay (platelets will not clump until plasma is added)
Desmopressin- used to release vWF from the endothelial cells
DIC
Caused by sepsis, trauma, pregnancy, pancreatitis, nephrotic syndrome, AML
All coag factors and platelets randomly clump in some places, causing hemorrhage in other places
Causes increase in PT, PTT, and bleeding time
Hypercoagulable states
Antithrombin III def (normally inhibits factors IIa and Xa- vs. Protein C- which inhibits V and VIII)
Factor V Leiden- too active, not able to be inactivated by protein C
Protein C or S def- normally inactivates V and VIII
Prothrombin gene mutation: mutation in 3’ untranslated region –> causes increased prod of factor II
Blood transfusion therapy- RBCs
Used for acute blood loss, anemia
Platelets
Used for low platelet ct/ platelet defects, bleeding caused by thrombocytopenia
Fresh frozen plasma
Contains coagulation factors
Used for warfarin excess, Vit K def, DIC, cirrhosis
Cryoprecipitate
Contains factors I, VIII, XIII, vWF, fibronectin
Used for hemophilia A, coag defects involving factors II and VIII
Non-Hodgkin vs. Hodgkin lymphoma
Hodgkin: characterized by mass, Reed-Sternberg cells, localized (generally single group of nodes with contiguous spread), strong association with EBV, bimodal distribution, demonstrates constitutional “B” symptoms
Non-hodgkin: more common, can present as lymphoma/mass or in blood (extra nodal), not contiguous; most involve B cell lineages, occurs in children and adults
Reed Sternberg cells
CD 15 and CD 30 positive
B cell origin
Secrete cytokines that attract lymphocytes
Non-Hodgkin lymphoma- B cell origin
B-cell origin
Burkitt: 8:14 (c-myc); kid from Africa presents with enlarging jaw mass
Follicular: 14:18 (bcl-2–> anti-apoptosis); waxing and waning presentation, slower growing
Mantle: 11:14 (cyclin D1); occurs in adult males, aggressive
Diffuse large B cell: aggressive, (can progress into this from mantle cell and SLL/CLL)
Adult lymphoma: associated with HIV, round and enhancing lesions on CT –> distinguished from Toxo via CSF analysis
Non-Hodgkin lymphoma- T cell origin
Adult T cell lymphoma: preceded by infection with HTLV-1 (also causes myelin degradation in brain and spinal cord/ myelopathy); adult Asian presents with cutaneous lesions (resembling seborrhic keratoses); Bone lytic lesions and hypercalcemia are unique to this
Mycosis fungoides: Presents with skin plaques (cutaneous T cell lymphoma and may progress to T cell leukemia)
Multiple myeloma
Plasma cell proliferation (generally causes M spike in IgG or IgA); rouleaux formation; Bence-Jones proteins (Ig in urine); plasma cells with “clock-face” chromatin
CRAB findings: hyperCalcemia, Renal failure, Amyloidosis and Anemia, Bone/lytic lesions
Waldenstrom Macroglobulinemia
Increase in IgM
Causes hyper viscosity and blurred vision
No observed CRAB findings
Myelodysplastic syndrome
Ineffective hematopoiesis –> causes defects in ALL myeloid lineages
Can progress to AML
Leukemias- lymphoid
ALL: Seen in kids, better if you have the 12:21 translocation; precursor mc stain + for TdT+, CD10 (if pre-B)
CLL/SLL: seen in adults (CD20+, CD5+, B-cell origin), can progress into DLBL (Richter); crushed little lymphocytes seen on smear
Hairy cell: mature B cell tumor, dry tap on aspiration, +TRAP, tx with cladribine and pentostatin
Leukemias- myeloid
CML- generally assoc. with Philadelphia chromosome (9:22); causes over activation of BCR-ABL (tyrosine kinase); responds well to imatinib; pts present with chronic weakness and increased myeloid cells (generally mature) on blood smear; can progress to AML/ALL in a process known as “blast crisis” –> wherein pts often present with DIC as well
LAP (leukocyte alkaline phosphatase) is low in these patients as opposed to those who are undergoing a normal leukemoid reaction
AML: dysregulated proliferation of myeloblasts; one subtype (APML- 15:17) –> presents with Auer rods; treat with all trans retinoic acid (forces T cells to differentiate); DIC is a common presentation
Langerhan cell histiocytosis
Presents with proliferation of dendritic/ Langerhan cells (which are predominantly in the skin)
Cell are immature, do not effectively stimulate T cells, and express S-100 (like Schwannoma) and CD1a
Kids present with lytic bone lesions (as opposed to adults in MM)
Pathoma’s helpful tips:
if two names in title: happens in kids <2
if three names in title: happens in kids>3
if named after someone –> presentation involves cutaneous lesions/ skin rash and is malignant
Chronic myeloproliferative disorders
General: associated with mutations in JAK2 receptor (causing chronic activation of cytoplasmic tyrosine kinases)
Polycythemia vera- increased RBCs, WBCs, and platelets; presents with erythromelalgia (itching, pain, and red-blue coloration) –> due to blood clots in vessels of extremities (responds to ASPIRIN)
Essential thrombocythemia- increased proliferation platelets and megakarycytes; may also present with erythromelalgia, and increased thrombosis and bleeding
Myelofibrosis- fibrosis of marrow (due to increased fibroblast activity) –> causes dacrocytes and dry bone marrow tap
Polycythemia- normal and abnormal causes/ classifications
Relative: decreased plasma volume –> due to dehydration/ burns
Appropriate absolute: increased RBCs, increased EPO; due to decreased O2 sat –> caused by high altitude, congenital heart disease etc.
Inappropriate absolute: increased RBCs, increased EPO; due to malignancy
Polycythemia vera: increased RBCs, decreased EPO (because of negative feedback)
