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Heme/Onc > Blood Disorders > Flashcards

Blood Disorders Flashcards

1
Q

Hemophilia A

A

Most common X linked disorder
F VIII deficiency
Genes located at tip of X chromosome
Hem A: large gene, intron 22 inversion (flip tip)

Complications: Musculoskeltal bleeds; hemarthrosis, ilipsoas, easy bruising
Life threatening hemorrhage of CNS, airway or GI
Bleeding with circumcision
Dental bleeding, hematuria, soft tissue bleeds

Severe hemophilia with hemoatoma following immunization (should put pressure for 15 mins)

Labs: prolonged PTT,
normal PT and bleeding time

Treatment: give VIII concentrate (evaluate for transmissible diseases)
Desmopressing increases release of VIII and vWF from endothelial cells

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2
Q

Hemophilia B

A

Most common X linked disorder
F IX deficiency
Genes located at tip of X chromosome
Hem B: smaller gene, missense, dysfunctional or absent protein

Complications: Musculoskeltal bleeds; hemarthrosis, ilipsoas, easy bruising
Life threatening hemorrhage of CNS, airway or GI
Bleeding with circumcision
Dental bleeding, hematuria, soft tissue bleeds

Neonatal hemophilia post circumcision bleed with hematoma dorsum

Labs: prolonged PTT,
normal PT and bleeding time

Treatment: give IX concentrate (evaluate for transmissible diseases)

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3
Q

Von Willebrand Disease

A

most common bleeding disorder-AD with inocmoplete penetrance
Characterized by mucocutaneous hemorrhages, easy bruising, heavy menses, nose and gingival bleeding
Defect of vW factor

VWF: large mutimeric glycoprotein
Produced and stored in endothelial cells and platelet alpha granules
Gene located on chormosome 12
Functions: tethering protein through platelet glycoprotein Ib
Carrier protein for VIII

Clinical: menorrhagia, epitaxis, easy bruising
Excessive bleeding with trauma-post op, tooth extraction
GI bleeding in severe deficiency

Lab values normal: platelet count, PT,and fibrinogen
Increased BT, Increased PTT due to decreased half life of VIII
Will not aggregate in ristocetin test

Specific tests: VWF Ag assay: ELISA
   Protein quantification
FVIII clotting activity or assay
Ristocetin cofactor assay: measures plasma levels of VWF
VWF multimers

Treatment: desmopressin stimulates vWF release from endothelium

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4
Q

Hereditary Hemorrhagic telangiectasia

A

Inherited:
Autosomal dominant
Arteriovenous malformation: nose bleeding, intracrania hemorrohage, GI, pulmonary

Acquired: 
Senile purpura
Vasculitis
     Henoch-shonlein purpura
     IgA meditaed, hematuria, joint swelling, abdominal pain, pupuric rash on buttock and extremities renal failure
Can be drug induced by steroids
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5
Q

Bernard Soulier

A

Platelet adhesion disorder
Autosomal Recessive
decreased GP Ib-IX the vWF receptor

Labs: large platelets
Increased BT, decreased platelet count

Mild thrombocytopenia
Decreased ristocetin aggregation
Markers: CD42b/42a

Symptoms: microhemorrhage, mucous membrane bleeding, epistaxis, petechiae, purpura,

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6
Q

Glanzmann’s thrombasthenia

A

Platelet aggregation disorder
Autosomal recessive
decreased GPIIb-IIIa fribrinogen receptor
Labs: platelet count normal, no response to collagen, epinephrine, thrombin, increased BT
Normal Ristoceitin aggregation, ADP test will not aggregate
Markers: CD41/61

Symptoms: microhemorrhage, mucous membrane bleeding, epistaxis, petechiae, purpura,

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7
Q

Immune thrombocytopenia

A

immunlogic destruction of platelets in response to unknown stimulus (may be triggered by viral illness)
NO hepatomegaly

Pathogenesis: IgG autoAbs interact with platelet specific Ags-GPIIb-IIIa or Ib/IX on platelets and megakaryocytes
Bind to FC receptor promoting phagocytosis in spleen
Decreased thrombopoietin production
T-cell mediated cytotoxicity

Labs: decreased PC, increased BT
incrased megakaryocytes on BM biopsy

Treatment: steroids

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8
Q

DIC

A

Triggers: release of Tissue Factor, endothelial damage and cytokine release: TNF, IL-1, 6 and 10

Characteristics: increased thrombin generation
Supressed anticoagulant pathway
Activation of subsequent fibrinolysis (plasmin) releases D dimers
Activation of inflammatory pathway

Causes: Sepsis (gram negative), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Burns

Secondary disease
Death due to organ failure
Pathogenesis: widespread activation of clotting leads to a defieciency in clotting factors creating a bleeding state

Clinical: Bleeding from puncture sites, generalized bleeding, organ failure, gangrene, shock, acidosis
Pathology: fragmented red cells, thrombocytopenia, fibrin deposition in kidneys

Labs: decreased platelet count , PT and PTT prolonged, increased bleeding time, D-dimers increased, Fibrinogen decreased, antithrombin, decreased, protein C decreased

Treatment: treat underlying cause, blood component therapy, Anticoagulants and Antithrombin concentrates

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9
Q

TTP

A

ADAMTS13 deficiency or inhibition (vWF metalloproteinase)
Unusually large multimers of vWF produced in endothelium, megakaryocyte and stored in Weibel Palade bodies
Binds efficiently to glycoprotein 1b-IX

Pathogenesis: large vWF increased platelet adhesion leading to increased platelet aggregation and thrombosis

Labs: decreased PC, Increased BT
Schistocytes, Increased LDH

Clinical: Thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, renal failure, fever

Treatment: Plasmaperesis/plasma exchange, Anti CD20, Supportive care, Solirus-eculizumab, steroids

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10
Q

HUS

A

Normal levels of ADAMTS13
E-coli O157:H7 and Shigella produce Shiga toxin (verotoxin) stimulating cells to produce ULM
Follows acute diarrhea
Non-epidemic is a complement factor H defect
Clinical: Microangiopathic hemolytic anemia, Thrombocytopenia, renal failure, fever
Occurs in children
Treatment: antibiotics

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11
Q

Vitamin K deficiency

A

Vit. K dependent factors=II, VII, IX and X, proteins C and S

Causes: hemorrhagic disease of the newborn, warfarin, malbsorption, biliary obstruction, congenital deficiency

Lab: increased PT and PTT
Normal bleeding time

Treatment: oral Vita K or IV/IM
All babies are born with low vitamin K-prophylactically treat

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12
Q

Venous Thrombosis

A

Venous blood flow is propelled by muscle activity and affected by gravity
Tissue Factor Pathway Inhibitor, Protein C and S, Antithrombin II and III provide a balance to rapidly formed clots required for hemostasis without promoting systemic activation
Factors reduce opportunity for thrombus formation and obstrucction of venous flow
Risks: immobility, mechanical obstruction, hyperviscocity (dehydraion, polycythemia, diuretics, Tissue damage, surgeries
Contributing factors: pothrombin 20210A, Factor V Leiden, Dysfribrnoenemia, Antithrombin III deficiency, Protein C deficiency, Protein S deficiency
Diagnosis: edema, cyanosis of extremities
Imaging: doppler ultrasound venogram
Complication: propagation of clot release of fragments into the venous flow to be deposited in the filtering vasculature of the lung -pulmonary emboli can be a lethal complication
treatment: Anticoagulants, fibronolytic agents, circulation enhancement

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13
Q

Arterial Thrombosis

A

less subject to statsis and activation of plasma clotting proteases
Damage to endothelium plays major role in arterial thrombosis
Disruption of endothelium associated with diabetes, smoking, plaque formation, narrowing of arterial lumen and finally obstruction of flow
Destruction of endothelium allows for platelets to bind vWF and eliminates protective effects of attached glycosaminoglycan molecules (heparan) which complex with Antithrombin to circulating Thrombin
Symptoms: Extremities cold, painful, weak or absent pulse
Diagnosis: Doppler Ultrasound, arteriogram, CT scan
Risk factors: smoking, diabetes, hypertension, dyslipidemia, cardiac arrhythmia, obesity, Age, family history
Embolism obstruct vessels with small lumens
Atrial fibrillation associated with arterial thromboembolism

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14
Q

Iron Deficiency Anemia

A

Four causes: Chronic blood loss, Increased requirements, Malabsorption, Poor diet
Produces hypochromic microcytic anemia
No stain on Prussian blue stains
Chronically causes koilonychia, alopecia, atrophic changes of tongue, and gastric mucosa, Pica, Fissures and ulcerations on corners of mouth
Labs: Hg decreased, hematocrit decreased, serum iron low, ferritin low, total plasma iron capaciy high, transferrin saturation low

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15
Q

Plummer Vinson Syndrome

A

Associated with iron deficiency
Microcytic hypochromic anemia
Esophageal webs (can’t swallow)
Atrophic glossitis

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16
Q

Sideroblastic Anemia

A

Causes microcytic, hypochromic anemia
Iron fails to combine with prootoporphyrin
Iron remains in mitochondria-stain using Prussian blue stain-ringed sideroblast
Can be due to X linked defect in ALA synthase

Can be due to alcohol, lead, isoniazid (Vit B6 deficiency, B6 a cofactor for protopophyrin synthesis), copper deficiency, or myelodysplasia

Labs: increased ferritin, decreased transferrin binding capacity, increased serum iron, and increased % saturation of transferrin

Treatment is pyridoxine

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17
Q

Anemia of Chronic Disease

A

Most common form of anemia in hospitals
Impaired RBC production due to systemic inflammation

Lab findings: MCV normal, Serum iron low, total iron binding capacity low, abundant iron in macrophages, increased ferritin

IL-6 increases hepatic production of hepcidin
Hepcidin released from liver binds ferroportin on intestinal mucosal cells and macrophages inhibiting iron transport leading to decreasd release of iron from macrophages
Low erythropoietin levels
Treat underlying disease

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18
Q

B12 deficiency anemia

A

Megaloblastic anemia
Impairment of DNA synthesis leads to ineffective hematopoiesis
Nucleated RBCs in BM wait for nucleus to develop and die (LDH and unconjugated bilirubin elevated)

Histology: Neutorphils show nuclear hypersegmentation
Megaloblastic changes in all stages of erythroid development-giant metamyelocytes and bands form

Pathogenesis: Generally Ab prevent binding of intrinsic factor to Vitamin B12 complex to ileal receptor
insufficient intake (vegans), malabsorption (Crohns), Diphyllobothrium latum (fish tapeworm), proton pump inhibitors

Symptoms: Fundic gland atrophy, glandular epithelium replaced by goblet cells (metaplasia increases risk of gastric carcinoma), atrophic glossitis (tongue shiny and beefy), Demyelination of dorsal and lateral spinal tracts (hyperreflexia and + babinski sign), peripheral neuroapthy with sensorimotor dysfunction, dementia

Diagnosis:Elevated homocysteine levels (thrombosis and atherosclerosis) and methlymalonic acid (myelin synthesis abnormalities)

Treatment: high dose vit B12 cures anemia (dramatic increase in reticulocytes right away then slow increase in hemoglobin and erythrocytes) not neurological symptoms
Treating with folate worsens symptoms by decreasing unmethylated cobalamin available for methylamalony-CoA processing

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19
Q

Folate deficiency anemia

A

Megaloblastic anemia
Impairment of DNA synthesis leads to ineffective hematopoiesis-pancytopenia
Nucleated RBCs in BM wait for nucleus to develop and die (LDH and unconjugated bilirubin elevated)
THF necessary for synthesis of amino acids, thymidine and pruines
Folic acid is a carrion donor for purine and pyridine synthesis

histology: Neutorphils show nuclear hypersegmentation
Megaloblastic changes in all stages of erythroid development-giant metamyelocytes and bands form

Mostly due to decreased uptake in diet-alcoholics, methotrexate, trimethoprim, phenytoin, increased requirement-hemolytic anemia, pregnancy

Deficiencies much quicker than Vit. B12

Diagnosis: decreased folate levels in serum or red cells, increased homocysteine and methylmalonate concentrations normal
Glossitis

Folate can exacerbate Vit B12 deficiency so rule out VIt. B12 before administering folate
I

20
Q

Aplastic Anemia

A

Primary hematopoietic failure and pancyotpenia (anemia, thromocytopenia, and neutorpenia)

Drugs and chemical exposure (benzene, chloramphenicol, alkylating agents, antimetabolites, carbamazepine, sulfonamides),
viral infections (parvovirus B19, EBV, HIV, HCV)
Fanconi anemia (DNA repair defect
Indipathic-immune mediated may follow acute hepatitis

Morphology: bone marrow devoid of hematopoietic cells, often only fat cells, fibrous stroma and scattered lymphoctyes and plasma cells
NO splenomegaly, low reticulocytes

Symptoms: anemia, petechiae, persistent and recurrent infections, macrocytic and noromochromic red cells, fatigue, malaise, mucosal bleeding, purpura

Diagnosis: bone marrow biopsy-extremely hypocellular

Treatment: bone marrow transpaantion or immunosuppressive therapy (antithymocyte globulin, cyclosporine), G-CSF, GM-CSF, tranfusions

21
Q

Pure Red Cell aplasia

A

Only red cell precursors are absent in marrow
Transient: parvovirus B19 resolves in 5-10 days
Chronic: congenital: diamond blackfan syndrome
Recessive affects chromosome 19
Autoimmune: idiopathic or associated with thymoma

22
Q

B Thalassemia

A

Caused by mutations of B globin chains encoded on single B globin gene chromosome 11
B0=absent B globin synthesis B+=reduced B synthesis
Due to splicing mutations (B+), Promoter region mutations (reduced transcription B+), Chain terminator mutations (B0) also can be due to guanine to cytosine mutation in Kozak consensus leading to abnormal mRNA ribosome binding

Causes subnormal oxygen transport capacity and diminished survival of red cells and precursors
Unpaired a chains precipitate causing membrane damage leading to ineffective eryhtropoiesis and extravascular hemolysis (precipitation of a chains leads to premature lysis of RBCs)

Clinical:
Major: (no beta) severe requires blood transfusions
6-9 months after birth
treatment: HSC transplantation
Intermedia: severe requiring blood transfusions
Minor or trait: (half normal B) Asymptomatic with mild or absent anemia
Electrophoresis shows elevated HbA2 level

Morphology: Variation in size and shape of RBCs and hypochromia
Target cells present, basophilic stippling
Nucleated RBCs present
Crewcut appearance on Xrays-skeletal deformities
Extramedullary hematopoiesis-hepatosplenomegaly
Increased risk of parvovirus B19 aplastic crisis

23
Q

Alpha Thalassemia

A

Deletions leading to reduced or absent synthesis of alpha globin chains

Silent carrier: deletion of 1 singe a globin chain- asymptomatic
A-thalassemia trait: 2 deletions from a single (cis) chromosome or 2 deletion from different chromosomes (trans)
Minimal anema and no abnormal physical findings
Hemoglobin H disease: deletion of 3 globin genes
High affinity for oxygen leading to tissue hypoxia
Sequestration in spleen
Hydrops Fetalis: severe deletion of all four alpha globins
excess of hemoglobin barts
really high affinity for oxygenn
Lifelong dependence on blood transfusions, or HSC replacement

24
Q

Hereditary Spherocytosis

A

Autosomal dominant
Intrinsic hemolytic nomorcytic anemia-extravascular destruction

Intrinsic disorder caused by intrinsic defects in red cell membrane skeleton causing a spheroid less deformable cell
Caused by mutations in anykyrin, spectrin and band proteins leading to insufficiency of membrane skeletal components

Spherocytes destroyed by spleen
Pigment stone and splenomegaly often seen

Clinical: Anemia, splenomegaly, and jaundice
Aplastic crisis-B19 parvovirus infection

Tests: sensitive to osmotic lysis when incubated in hypotonic salt solutions causing influx of water into spherocytes with little room for expansion
Eosin-5-maleimide binding test useful for screening
Increased Mean hemoglobin concentration, increased red cell distribution width, normal to decreased MCV
NO central pallor in RBCs

Treatment: splenectomy

25
Q

Ehlers Danlos Syndrome

A

Autsomal Dominant
Six types-Type IV is vascular type
Mutation in COL3A1 gene (heterogenous)
Leads to think skin, arterial or uterine rupture, small joint hyperextensiblity

Gene Abnormalities affect overall synthesis, secretion and synthesizing abnormal collagen III

Rupture of large arteries and colon common

26
Q

Sickle Cell disease

A

Point mutation in B-globin that promotes the polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia and microvascular obstruction

B-glboin point mutation from glutamic acid to valine (hydrophobic interaction among Hg molecules)

Protects agains falciparum malaria-infected cells increase sickling and get phagocytosed

Pathogenesis
HbS molecules stack into polymers when deoxygenated creating a viscous gel
HbF inhibits polymerization of HbS (infants not symptomatic)
Intracellular pH decrease reduces the oxygen affinity increasing the number of deoxygenated HbS and sickling occurs
transit time in spleen, bone marrow and inflamed vascular beds is slow making them more prone to sickling and occlusion
HbS polymers project from cell cuasing influx of Ca2+ which induces cross linking of membrane porotiesn and activates ion channels causing efflux of K+ and H2O leading to sickling and extravascular hemolysis

Morphology: peripheral blood has sickled cells, reticulocytosis and target cells
Howell Jolly bodies (small nuclear remnants) present in red cells due to asplenia
Bone Marrow hyperplastic for compensation leading to bone resorption and secondary formation resulting in prominent cheekbones and changes in skull (crewcut appearance)
Extramedullary hematopoiesis can appear
Increased breakdown of RBCs leads to gallstones and hyperbilirubinemia
Splenomegaly in early child progresses to autosplenectomy
Spleen will appear brown, shrunken and fibrotic after vasocclusive crises
Vascular stagnation causes leg ulcers

Clinical: hemolyic anemia punctuated by crises
vaso-occlusive or pain crises of hypoxic injury commonly in bones, lungs, liver, brain, spleen and penis (erectile dysfunction)
Dactylitis of hands and feet
Acute chest syndrome (most common form of death-vasocclussive crisis in pulmonary vasculature), avascular necrosis, stroke and blindness can occur
Aplastic crises due to parvovirus B19
Impairment of growth, increased susceptibility to infections with encapsulated organisms
Renal papillary necrosis-microhematuria
Salmonella osteomyelitis (Vi Ag prevents phagocytosis)

Diagnosis: clinical, sickled cells, mixing blood sample with oxygen consuming agent (metabisulfite) induces sickling, electrophoresis demonstrates presence of HbS
Increased indirect bilirubin, increased LDH, decreased haptoglobin

Treatment: inhibitor of DNA synthesis
increases red cell HbF levels (hydroxyurea), anti-inflammatory effects-inhibition of leukocyte production
Gardos channel blockers

27
Q

Paroxysmal Nocturnal Hemoglobinuria

A

Acquired mutations in the phosphatidyliniositol glycan complementation group A (PIGA) gene an enzyme essential for synthesis of membrane associated complement regulatory proteins

PIGA is X linked and susceptible to acquired mutations and inactivation leading to less proteins bound to phospholipid bilayer by glycosylphosphatidylinisoitol (GPI)
Causative mutations in Hematopoietic stem cells so RBCs, WBCs, and platelets all affected
CD59 most important proteins affected (inhibitor of C3 convertase)
RBCs lacking GPI linking factors (for decay accelerating factor) susceptible to lysis or injury by complement leading to intravascular hemolysis by MAC
Can lead to iron deficiency

Triad of -Coombs test hemolysis, pancytopenia and Thrombosis (hypercoagulability) is leading cause of death mostly venous thrombosis
Dark urine in morning

Diagnosed by flow cytometry detecting Red cells deficient in GPI linked proteins such as CD59 and CD55

Treatment: eculizumab prevents conversion of C5 to C5a and lowers risk of thrombosis (high cost and increase risk of fatal meningococcal infections)
HSC transplantation

28
Q

Sickle Cell Trait

A

Asymptomatic condition in which individuals are heterozygous for HbS

29
Q

HbSC disease

A

symptomatic sickling disorder caused by HbC increasing HbS tendency to polymerize (lose salt and water and become dehydrated)

30
Q

Immunohemolytic Anemia-warm agglutinin

A

Hemolytic anemia caused by Abs that bind to red cells leading to their premature destruction

Diagnosis: by direct Coombs antiglobulin test or indirect Coombs antiglobulin test

Most common form of immunohemolytic anemia
Most commonly IgG
Mostly extravascular
IgG coated red cells bind to Fc receptors on phagocytes which remove red cell membrane during partial phagocytosis leads to spherocytes which are destroyed by spleen

Moderate splenomegaly is seen
Antigenic drug induced immunohemolytic anemia follows large IV drug doses occurring 1-2 weeks after therapy is initiated
tolerance breaking drugs induced immunohemolytic anemia (methyldopa) induce Abs against Red cell Ags in Rh blood group

Also called autoimmune hemolytic anemia due to being assoiciated with SLE, CLL or drugs-a methyldopa

treatment: remove drug, immunosuppressive therapy and splenectomy

31
Q

Immunohemolytic anemias-cold agglutinin

A

Hemolytic anemia caused by Abs that bind to red cells leading to their premature destruction

Diagnosis: by direct Coombs antiglobulin test or indirect Coombs antiglobulin test

Caused by IgM Abs that bind red cells at low temps
Occur after infections with mycoplasma pneumonia, EBV, cytomegalovirus, influenza, and HIV-self limited though

Chronic cold agglutinin associated with B cell neoplasms,CLL

Clinically in cold areas of body:fingers toes and ears
Red cells agglutinate and fix complement rapidly leading to opsonization within spleen, liver and bone marrow

Vascular obstruction causes pallor, cyanosis and raynaud phenomenom in cold body parts

treatment: remove drug, immunosuppressive therapy and splenectomy

32
Q

Factor V Leiden mutation

A

Single nucleotide mutation-glutamine to arginine substitution
Factor V becomes resistant to cleavage and inactivation by protein C (hypercoagluability)
Recurrent DVT prominent association, cerebral vein thrombosis, and recurrent pregnancy loss

33
Q

Glucose-6-Phosphate Dehydrogenase Deficiency

A

intrinsic hemolytic normocytic anemia
Abnormalities in hexose monophosphate shunt or glutathione metabolism resulting from deficient enzyme function reducing the ability of red cells to protect themselves against oxidative injuries leading to hemolysis

G6PD reduces NADP to NADPH while oxidizing glucose-6-phosphate
NADPH converts oxidized glutathione to reduced glutathione protecting against oxidant injury

X linked recessive trait (africans, asisans, mediterranean)

Associated with hemolysis due to misfolding of a protein-older cells more susceptible

Protective against malaria falciparum

Episodic (intravascular and extravascular) hemolysis caused by exposures that generate oxidant stress ( sulfa drugs, antimalarials infections, and fava beans)
Back pain and hemoglobinuria (purple urine) after stress

Oxidant stress causes sulfhydryl groups on globin chains to denature becoming Heinz bodies (cause intravascular hemolysis and bite cells)

Recovering phase characterized by reticulocytosis

34
Q

Polycythemia (Erythrocytosis)

A

Abnormally high red cell coutn usually corresponding to increases in hemoglobin level

Relative polycythemia: dehydration or stress characterized by hypertension, obesity, and anxiousness

Absolute polycythemia: primary due to intrinsic abnormality in hematopoietic precursors
Secondary: when RBCs responding to increased erythropoietin

Most common cause is polycythemia vera a myeloproliferative disorder associated with mutations leading to erythropoietin-independent growth of red cell progenitors

Congenital Causes: inherited Erythropoietin receptor mutations, defects that stabilize HIF-1a affinity (chuvash polycythemia, prolyl hydroxylase mutations)
Acquired-
Primary: Polycythemia Vera
Secondary: Lung Disease, high altitude living, cyanotic heart disease, paraneoplastic

35
Q

ABO disease of newborn

A

Exposure to A or B like Ags in food, bacteria, viruses or just naturally occurring
IgG (normally IgM Ab) to A or B Ag crosses placenta

Leading to hemolysis in newborn with Ag to IgG Ab

Jaundice in first day of life

Can occur in first pregnancy

36
Q

Erythroblastosis fetalis (Rh group)

A

Rh- mother exposed to RH+ blood of fetus during delivery
Develops Anti-Rh IgG
Subsequent pregnancies anti Rh IgG crosses placenta leading to hemolytic disease of the newborn

Erythroblastosis fetalis: anemia, jaundice, edema (hypoxic liver and cardiac injury)
Nucleated erythrocytes and persistent extramedullary hematopoiesis

37
Q

Lead Poisoning

A

Lead inhibits ferrochelatase and ALA dehydratase leading to decreased heme synthesis and increased RBC protoporphyrin
(lead has strong affinity for sulfydryl groups leading to inhibition)
However D-aminolevulinic acid can be formed via succinyl CoA and glycine using pyridoxal phosphate (D ALA increased in urine and blood during poisoning)

Lead inhibits rRNA degradation (basophlilic stippling)

High risk in old houses with chipped pain, soil, pottery, moonshine

Symptoms: weakness, abdominal pain, constipation, lead lines on gingiviae and metaphyses of long bones on X-Ray
Encephalopathy and Erythrocyte basophilic sippling, wrist and foot drops

Sideroblastic anemia

Treat with Dimercaprol and EDTA 1st
Succimer chelation for kids

38
Q

Orotic aciduria

A

Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) defect in UMP synthase (orotate phosphoribosyl transferase and OMP decarboxylase which catalyze oratate to UMP)
AR

Children present with megaoblastic anemia that cannot be cured with folate or B12 with failure to thrive

No hyperammonemia (vs ornithine transcarbamylase deficiency)

Hypersegmented neutrophils, glossitis, orotic acid in urine

Treatment: uridine monophosphate (inhibits carbomoyl phosphate synthetase II leading to attenuated orotic acid production) to bypass mutated enzyme

39
Q

Intravascular hemolysis

A

decreased hpatoglobin, increased LDH, schistocytes and Increased reticulocytes on peripheral blood smear
Urobilonogen in urine

Causes: paroxysmal nocturnal hemoglobinuria, mechanical destruction, microangiopathic hemolytic anemias

40
Q

Extravascular hemolysis

A

Macrophage in spleen clears RBC

Spheocytes in peripheral smear

Increasd LDH plus increased unconjugated bilirubin which leads to jaundice

41
Q

Pyruvate Kinase Deficiency

A

AR
Intrinsic hemolytic normcytic anemia
Extravascular

Defect in pyruvate kinase leads to decreased ATP which leads to rigid RBCs

Hemolytic anemia in a newborn

42
Q

Heterozygote Sickle Cell

A

May still have renal papillary necrosis and microhematuria
Limited ability to concentrate urine

Normal peripheral smears (no sickle cells, normal reticulotytes and MCHC)

Will still sickle when exposed to sodium metabisulfite

43
Q

Deficiency of protein C and S

A

Decreased ability to inactivate factors V and VIII

Increased risk of thromobotic skin necrosis with hemorrhage following warfarin administration (hypercoagulable state)

44
Q

Leukomoid Reaction

A

Acute inflammatory response to infection
Increase WBC count and Increase neutrophils and neutrophil precursors-band cells
increased leukocyte ALP (not in CML)

45
Q

Relative Polycythemia

A

Decreased plasma volume
Normal RBC Mass
Normal O2 saturation
Normal EPO levels

Decreased plasma volume (dehydration, burns, diuertics)

46
Q

Appropriate/Physiologic absolute Polycythemia

A

Normal Plasma volume
increased RBC mass
Decreased O2 saturation
Increased EPO levels

Lung disease, congenital heart disease, high altitude

47
Q

Inappropriate absolute polycythemia

A

Normal plasma volume
Increased RBC mass
Normal O2 saturation
Increased EPO levels

RCC, Wilms tumor, cyst, HCC, hydronephrosis

Ectopic EPO

Heme/Onc (3 decks)

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