Anemias Flashcards
Hb
Men- 14-18 g/dL Women 12-16 g/dL 90-95% of the cytoplasm of RBC
Hct
Men- 42-52% Women- 37-47%
MCV
Mean red blood cell volume/size estimate Hct/Rbc 80-100 fL (10^-15 L) 100 macrocytic 80-100- normocytic
Mean cell Hb concentration
Hb/ Hct Differentiate bt hypo and normo chromatic 32-36 g/dL
RDW
Red cell distribution width Std of MCV Tells how much cells differ in size, low = uniform / minimal anisocytosis 12-13.5 %
WBC
4.5-11*10^9/L
4,500 to 11,000/mm3
PMNs
45-70% 2-8 *10^9
Lymphocytes
25-33%
1-4 *10^9
Monocytes
1-8% 0.1-0.8
Eosinophils
0-6% 0-0.5
Basophils
0-1% 0-0.3
Platelet count
150-450*10^9/L
Mean platelet volume
Depends on count Low count body tries to compensate by making platelets bigger
Common causes of iron deficiency anemia
- Infants/Children: diet, breastfeeding
- Adults: GI bleed, peptic ulcer, menorhhagia, pregnancy, colon polyps, carcinoma
- Tropical: hookworm (nicator and anstilastima)
- Celiac/ Malabsorption
- Gastrectomy ( acidity of stomach maintains iron as fe2+ which binds to heme better so loss of some of stomach means less fe2+)
Megloblastic anemia
Impaired DNA synthesis
B12 or folate deficiency (methotrexate, folate anagonist)
Other rapidly dividing cells effected too - enlarged epithelial cells in gut; macrocytic RBCs and hyper segmented PMNs (greater than 5 lobes) giant red cells and neutrophil precursors (band cells) also seen in bone marrow ; increased lactic acid dehydrogenase (LDH-2); glossitis
Pathophysiology of hereditary spherocytosis
Autosomal Dominant; Extravascular normocytic anemia
RBC cytoskeleton membrane tethering protein defect in spectrin or ankyrin, band 3.1, which causes instability and breakage of RBCs
Change in shape makes cells less able to navigate splenic sinusoids and consumed by macrophages in spleenic sinusoids
G6PD deficiency
X linked recessive disorder that reduces half life of RBC that renders cell vulnerable to O2 stress; common in black males
RBCs use glutathione to protect against oxidative stress (H2O2 +GSH (reduced glutathione)–> GS-SG; needs to be reduced back to GSH via NADPH which is produced by G6PD)
In red cells African variant: mildly reduced half life G6PD; older cells destroyed
Mediterranean variant: marked reduced G6PD half life; when ox stress more cells die
Protective against falciparum malaria
Infections, drugs (antimalarials, sulfadrugs, aspirin, vit K), fava beans
The increased free radicals denature the bonds between heme and glob in making globin form a glob –> Heinz bodies–> bite cells by spleen –> intravascular hemolysis, Hemoglobinuria, and back pain (nephrotoxic)
Enzymatic studies after disease has resolved (during crisis all the cells without the enzyme are dead)
Sickle cell anemia mutation
Autosomal recessive point mutation at residue 6 in beta globin gene where glutamic acid gets replaced with valine
Protective against Plasmodium falciparum malaria
Thalassemia
Decreased production of a globin chain, leading to decreased hemoglobin production and also tetramers due to unpaired chains
Common in Mediteranian/Greek, Asian, and African populations
Warm antibody Immunohemolytic Anemia
IgG anti red blood cells antibodies that bind well at 37 Celsius (central body) and are consumed by macrophages in the spleen; slow loss of membrane from cell results in spherocytosis
- Idiopathic
- Secondary immune system disease: SLE, RA, or Drugs (PCN- haptens, methyldopa- production of antibodies and binds existent antigens)
Chronic mild anemia with moderate splenomegaly
Diagnosis: Coomb +
Treat: IVIG (splenic marcophages will eat IVIG instead of red cells); Steroids, removal of drug; splenectomy (removes antibodies and destruction)
Microangiopathic Hemolytic Anemia
Pathology in small blood vessels that results in a hemolytic anemia (some sort of thrombus that blocks the vessel partially)
Tear up blood cells –> Schitocytes ( pointy red cell fragments)
Causes: TTP ; HUS; DIC; Maligant hypertension, SLE, disseminated cancer
Pathophysiology of anemia of chronic disease
Associated with chronic disease or cancer (inflammation, infection, malignancy)
Inflammation (IL6) produce acute phase reactant Hepcidin (made in liver) that sequesters iron by blocking ferroportin and also suppresses EPO; protective mechanism because bacteria need iron to proliferate (body thinks any inflammation is bacterial)
Aplastic anemia
Multipotent myeloid stem cells are supressed resulting in pancytopenia
- Idiopathic
- Myelotoxic agent (choramphenicol, benzene, alkalating agents, antimetabolites, or idiosyncratic hypersentitivity rxn)
- Viral agents (parvovirus b19, EBV, HIV, HCV)
- Congenital: Fanconi anemia
Empty marrow on marrow biopsy (>90% fat)
Cessation of causative drugs, transfusion, marrow stimulating factors (EPO, GM-CSF, G-CSF); immunosuppression (if etiology is autoimmune); bone marrow transplant
Anemia
Decrease in the oxygen -transporting capacity of the blood usually steming from a decrease in the red blood cell mass to subnormal levels
Measure of mass of rbcs Less than 13.5 g/dl males and 12.5 g/dl females
Iron metabolism
In meat( heme derived, better absorb) and veg Absorbed in duodenum by enterocytes, reduce to Fe2+ in lumen, dimethyltransferase brings it into enterocyte and then transported into blood via ferroportin on the basolateral side ; and oxidized to Fe3+ (hephestin) no way for body to get rid of iron so regulates fe through enterocytes Bound to transferrin in blood ( bc can make free radicles via Fenton rxn) and then transported to liver or bone marrow macrophages for storage and stored bound to ferritin
Fe lab measures
For every three transferrin molecules one will carry an iron and then bound to ferritin in macrophage Serum iron- iron in blood Transferrin in blood- tibc. Total iron binding capacity %sat- how much transferrin is bound to fe Serum ferritin- how much iron is present in bone marrow macrophages and liver
Stages of iron deficiency
1.) bone marrow uses up stored fe making new rbcs ( serum ferritin decreases; tibc increases - liver recognizes fe is down and pump out transferrin) 2.) serum iron consumed ( serum iron goes down, percent saturation of iron decreases) 3.) normocytic anemia- bone marrow continues to make rbcs, but has less fe, so make less of them 4.) microcytic, hypochromic anemia- so severe that can’t produce normal rbcs so has to send out cells smaller than normal with less color , expanded central area of pallor
Clinical features of iron deficiency
Anemia
Koilonychia- spoon shaped nails
Pica
Plummer Vincent syndrome
Iron deficiency anemia with esophageal web ( outfold of mucosa obstructs lumen of the esophagus that can cause dysphasia), and atrophic glottis
Presents with anemia, dysphasia, and beefy red tongue
Sideroblastic anemia
Defective protoporphyrin synthesis
Pp synthesized by a series of rxns that occur within cytoplasm and mitochondria in the erythroblasts
Gives you ringed sideroblast cells with ring of blue in a Prussian blue stain representing iron in the mitochondria
Steps in protoporphyrin synthesis
- ) succinyl coa —> aminolevelunic acid catalyst ala synthase ( rate limiting step) and vit b6 is a cofactor
- ) ala –> porphobelinagin catalyst ala dehydrogenase
N) protoporphyrin binds to iron to make heme via ferrokelatase and rxn occurs in mitochondria ( iron from bone marrow macrophages is transferred to erythroblasts and into mitochondria so with low pp iron enters in mitochondria and gets trapped and piles up and creates a ring of iron loaded nucleus around the cell : ring sideroblast)
Where is the iron located in sideroblastic anemia?
In the mitochondria in erythroblasts
Normal types of hemoglobin
Fetal Hb- HbF which is alpha 2 gamma 2
HbA which is alpha2beta2
Hba2 which is alpha2delta2
Folate and b 12 in DNA biochem
Folate enters body as tetrahydrofolate and is methylated; to make DNA precursors needs to loose methyl group which is taken by b12; B12 then wants to get rid of methyl group so gives it to homocysteine Homocysteine takes methyl group and becomes methionine Methionine then acts as a methyl donor in other rxns
B12 is also used to succinyl coA into methylmalonic acid
Other causes of macrocytic anemia non megaloblastic
- Alcoholism
- Liver disease
- Drugs 5-fu
macrocytic rbcs but no hyperseg PMNs or megaloblastic change in other rapidly dividing cells
Folate Digestion
Leafy green vegetables
Absorbed in jejunum ; conjugated to glumatic acid, but can only have one glutamate residue to be absorbed, polygutimated again in cell (cannot diffuse back out)
Used to make pyrines and pyrimadines, converts U–> T
Develop deficiency in months bc body stores are minimal
Vit b12 digestion and absorption
B12 animal derived protein via meat or egg, bound to meat products
Cleaved in stomach by acid and bound to r-binder produced by salivary glands
Cleaved in small bowel by proteases made by pancreas
Vb12 binds intrinsic factor made by parietal cells in body of stomach
Absorbed in ileum via cubilin transporter, dissociates from IF in enterocytes and binds to transcobalimin to be transported in the blood
Takes yrs to develop bc large hepatic stores
Reticulocyte count
Young rbcs released from bone marrow Larger with blueish cytoplasm due to residual RNA in cytoplasm Normal 1-2% Anemia generally increases reticulocytes to greater than 3% Measured as percentage of total rbcs so will be more elevated in anemia than actually increase in production so need to correct for anemia by multiplying by Hct/45 ( normal Hct) Low (less than 3%) corrected reticulocyte count suggests production problem in bone marrow
Shared features of Hemolysis
- decreased lifespan of RBCs
- retention of breakdown products
- increase EPO and reticulocytosis
RBC count
Men: 4.5-6 * 10^12 /L Women: 3.8 - 5.2 10^12 /L
RBC lifespan
120 days
Corrected Reticulocyte count
CRC = Reticulocyte count * (Hct/Normal Hct) Usually normal Hct of 45 is used >3% CRC indicates loss of RBCs with compensatory production of recticulocytes
How does the body respond to anemia?
Decrease in the mass of RBCs results in hypoxia, this signals the JGA of the kidney to release EPO which acts on RBC precursors in the bone marrow to produce reticulocytes (can see increased reticulocytes in blood- usually around 1% which represents the turnover per day, but in anemic patients should be corrected to 3% or above)
Thrombocytosis
increased platelets in the blood
Primary: myeloproliferative disease (essential thrombocytothemia)
Secondary: often seen in inflammation because TPO is an acute phase reactant; iron deficiency anemia, decrease fn of spleen or loss of spleen, over mediation with drugs to treat thrombocytopenia can also occur in patients with polycythemia vera
Apotransferrin
Transferrin when it is not bound to iron Transferrin itself has a high affinity for Fe3+ which is why it is oxidized to Fe3+ after exiting the enterocyte
Apple core lesion
Can cause anemia before other symptoms (think about in adult men, elderly post menopausal women)
Ddx:
1.) colonic adenocarcinoma
- ) Lymphoma
- ) Chron’s disease
- ) Chonic ulcerative collitis
- ) Chlaymidia infection
- ) Intestinal TB
What is the risk associated with IV iron?
anaphylaxis
Pernicious anemia
Autoimmune disorder that results in destruction of parietal cells (pink, protons, pepsin, pernicious anemia)
Autoantibodies to mucosal parietal cells; antibodies that block B12 and intrinsic factor binding; antibodies that prevent B12-intrinsic factor from binding to cubulin
Increased risk: Northern Europeans and African Americans, autoimmune thyroid disease, Addisons, vitilligo, and DM
Complications: gastric carcinoma and carcinoid tumors
Recommended amt of folate
400 ug per day normal 800 ug per day pregnant
Sickle Trait
Only one mutated beta allele
Production of B is more efficient than S so more like 55% HbA (less than 50% HbS)
No sickling EXCEPT in the renal medulla (extreme hypoxia and hypertonicity)
Asymptomatic except for renal effects (microinfarctions in medulla, microscopic hematuria and decreased ability to concentrate urine)
Don’t see sickle cells or target cells on smear, metabisulfite can induce cells to sickle (screen can sickle cell trait) Hb electrophoreisis confirms amt and presence of HbS–> sickle cell anemia no HbA; sickle trait has HbA, HbS, and HbA2
Hemoglobin C
AR mutation in the beta chain of Hb
Glutamic is replaced by lysine; less common than sickle cell disease
Mild anemia mostly due to extravascular hemolysis
Characteristic HbC crystals are seen in RBCs
Paroxysmal Nocturnal Hemoglobinuria (PNH) mutation
Only acquired somatic mutation in myeloid stem cells x-linked PIGA gene mutation in early myeloid progenitor with self renewal capacity, protective against aplastic anemia
Malaria
Infection of RBC and liver with plasmodium Transmitted by female anopheles mosquito
RBC rupture as part of the plasmodium live cycle; results in fever P falciparum (daily fever)
P vivax and ovale (fever every other day)
Primarily intravascular hemolysis but spleen consumes some so you get some extravascular hemolysis with spleenomegaly
Underproduction anemia
Low reticulocyte count: microcytic, macrocytic, renal failure (low EPO), damage to precursor bone marrow
Parvo virus B19
Infects progenitor red cells Stops erythropoesis Symptomatic with pre-existing marrow stress Treatment is supportive (virus is self limited)
Myelophthisic anemia
Pathologic process that replaces bone marrow (e.g. metastatic cancer)
Hematopoeisis is impaired, resulting in pancytopenia
Teardrop shaped cells on peripheral blood smear
Treat underlying condition
Hemolytic test
Ldh, billrubin, haptoglobin
DDx for reticulocytosis
Hemolysis or Acute blood loss
Leukocytosis
Primary- bone marrow problem
Secondary- exogenous to bone marrow, ie infection
Other causes of fatigue in pregnancy
Hypothyroidism
Blood smear signs of fe def
Anisopoikilocytosis High rdw Pencil cells
Pathophysiology for thrombocytosis in fe def
See an increase in EPO as well as TPO which increases platelet numbers
DDx for a macrocytic anemia
Megloblastic anemias: - B12 and/or folate deficiency, orotic aciduria
Macrocytic only- alcoholism, liver disease, hypothyroidism, myleoproliferative disease, reticulocytosis ( bigger) , monoclonal hemopathies
Normal LDH
140-250 U/L
Fanconi Anemia
- most common form of inherited aplastic anemia.
Inherited defects in non-homologous end joining (a mechanism of double-stranded DNA repair)
Clinical: Hypopigmented skin; Café au lait spots; Microcephaly; Thumb abnormalities; Evidence of bone marrow failure by age 10.
Lab: may show increased HbF on electrophoresis and elevated serum α-fetoprotein (>50% of cases)
Diagnose: by culturing lymphocytes and observing extensive chromosomal breakage in the presence of DNA cross-linking agents (i.e. mitomycin).
Complications: Acute myelogenous leukemia Myelodysplastic syndrome Squamous cell carcinoma of the head, neck, or vulva
What endproduct substrate are B12 and folate responsible for synthesizing?
deoxythymidine monophosphate (dTMP)
PNH mechanism
PIGA gene makes PIG protein which anchors DAF( decay accelerating factor, CD55) and MIRL in myeloid membranes which are protective against complement
All leukocytes are vulnerable but RBCs are more sensitive
Complement activated by decrease in pH that occurs during shallow breathing in sleep
PNH clinical picture, diagnosis, and treatment
Intravascular hemolysis
Coombs -, Pancytopenia, increased risk of venous thrombosis
Look for lack of CD55/59;
Can develop AML (mutation in myeloid stem cell can result in AML)
Treatment : eculizumab, antibody therapy against MAC, increases risk of Neisseria infections
Cerebral malaria
P. Falciparum ; normally red cells negative charge keeps them from interacting with endothelial membrane P. Falciparum produces proteins that create positively charged “knobs” on red cells and they can bind to ICAM -1 on endothelial cells and trap in cerebral vessels and occlude them
Convulsion, coma, death
Associated with massive intravascular hemolysis
Lab picture of iron deficiency anemia
- Cells are microcytic ( less than 80) and hypochromatic ( just a ring of Hb around cell edge) ; with increased rdw ( red blood cell distribution width, large spectrum of size it is large, iron def starts normocytic so there is a spectrum)
- Decreased reticulocytes ( decreased rbc production) and increase platelet count
- Decreased serum iron, decreased sat, and ferritin, increased total iron binding capacity; FEP( protoporphyrin normal so some of pp in rbcs not bound to fe so free erythrocytes pp high) high
Treatment iron deficiency anemia
Treat with oral iron supplements ( ferrous sulfate) after determining cause- don’t want to miss GI bleed
Clinical picture hereditary spherocytosis
Spleenomegaly (work hypertrophic) jaundice, increased risk br gallstones, increased risk of aplastic crisis w parovirus b19 infection
Lab picture hereditary spherocytosis
Spherocytes , large rdw( oldest cells smaller bc lost more membrane)
Increase mchc- mean corpuscular hemoglobin concentration, size decreases, get more Hb for cytoplasm
Positive Osmotic fragility test- hypotonic solution , water into cell, normal biconcave cell can expand a bit, spherocyte cannot
Treatment for Hereditary spherocytosis
Treat- splenectomy ( no issue w spherocytes, just destruction) Howell-jolly bodies on blood smear; fragments of nuclear material in rbcs normally removed by spleen persists in patients w/splenectomy
Lab values for anemia of chronic disease
Inability to use stored iron so ferritin is high and tibc is low
Serum iron low and percent sat also low
Increase in FEP
Starts as normocytic and then becomes microcytic
Treatment for Anemia of Chronic Disease
Treat - address underlying cause, decrease inflam decreases hepcidin, can give EPO esp those with cancer
L to uL conversion
1 L = 1.0 * 10^6 uL
Compensation for chronic or slow onset anemia
- increase plasma, increase CO, increase RR, increase the 2,3 diphosphoglycerate / 2,3, BPG (enhances the release of O2 from hemoglobin by stabilizing the low oxygen affinity T state)
Anemia of acute blood loss
Blood loss of more that 20%; if patient survives hemodilution begins and acheives full effect in 2-3 days; see a normochromatic, normocytic anemia; anemia leads to an tissue hypoxia and an compensatory increase in EPO which stimulates reticulocytes and RBC production in 5-7 days
Extravascular hemolysis
Reticuloendothelial system destruction (macrophages in spleen, liver, and lymph nodes consume rbcs and break down Hb into amino acids (globin), fe, and unconjugated billrubin( protoporphyrin ) )
RBCs have to navigate splenic sinusioids so any decrease in their deforming ability leads to extravascular hemolysis
Anemia with spleenomegaly (reactive hyperplasia of mononuclear phagocytes), jaundice( excess uncongugated bilirubin overwhelms conjugation system in liver) ; increased risk of bilirubin gallstones
Haptoglobin is usally increased because some hemoglobin invariably escapes into plasma; increased LDH
Intravascular hemolysis
Mechanical forces (thrombi, mechanical valves) or biochemical or physical agents that damage RBCs (complement, toxins, heat)
Haptoglobin (protein that binds and clears free Hb depleated), high levels LDH (released from RBCs)
Hemoglobinemia, Hemoglobinuria, Hemosideronuria ( Hb piles up and binds as hemosiderin in renal tubule cells and then when the cells slough off you get hemosiderin in urine)
Overview of splenic structure
Celiac trunk –> Splenic arteries –> central arteries –> white pulp (follicular noduls (B cells), periarteriolar lymphoid sheath PALS (T cells) and marginal zone(APCs) –> follicular arteries –> red pulp (cords of billroth, sinuoids, macrophages, destroy old or deformed RBCs or encapsulated bacteria) –> venus sinusoids –> splenic veins –> portal vein
Pathophysiology of sickle cell anemia
HbS form long polymers that distort the shape of the red blood cells when deoxygenated.
Reoxygenation initially reverses the sickling but over time, influxes of Ca and effluxes of K and water damage the membrane and lead to hemolysis
Sickle stresses: hypoxemia, high altitude, acidosis, increased transit time through microcirculation (e.g. inflammation), dehydration
Clinical picture of sickle cell disease
Asymptomatic until 6 months
- Chronic hemolytic anemia (20 day mean lifespan, moderate to severe ); risk of aplastic crisis with parovirus B19
- Microvascular obstruction (tissue damage and pain crisis, commonly in bone marrow, acute chest syndrome, dactylitis in infants)
- Autosplenectomy ( increase risk of infection with encapsulated bacteria) or sequestration crisis (trapping of blood in the spleen causing shock)
- Hyperplasia of bone marrow (crew cut and chipmunk faecies)
- Salmonella osteomyelitis
- Renal papillary necrosis and microhematuria
Acute chest syndrome
complication of sickle cell anemia
Pulmonary infections or fat emboli from infarcted bone marrow makes blood flow sluggish in lungs (like spleen) and leading to sickling in hypoemic pulmonary beds; this makes the initial pulmonary issues worse, leading to a downward spiral of worsening pulmonary and systemic hypoexmia, sickling, and vaso-occulsion
acute chest syndrome and stroke are major causes of death in sickle cell patients
Sickle cell patients are esp suceptible to infection because have no spleen (even spleenomegalic children are more susceptible)
Sickle Cell lab and treatment
Sickle cells, target cells, and Howel Jolly bodies on smear
Diagnosis confirmed by electrophoresis to confirm HbS percentage
Treat with hydroxyurea to increase HbF
Prophylatic PCN treatment for pneumococcal infections (also at risk for osteomyeolitis from Salmonella infection)
Alpha Thalasemia
Gene deletion
1 gene gone asymptomatic
2 genes mild anemia with increased Rbc: Cis or trans deletion, cis deletion is worse bc associated with increased risk of thalassemia in offspring seen in Asians, trans more common in Africa
3 genes- severe anemia, ok in utereo bc fetal Hb but born increases risk of forming beta chain tetramers HbH that damages rbcs and HBH is seen of electrophoresis
4- will express in fetus as gamma tetramers; die in utero( hydropsfetalis) with Hb Barts on electrophoresis which is gamma tetramers
Beta Thalassemia
Two beta genes, chromosome 11, mutations; point mutations at promotor regions or splice sites
Beta thalassemia minor: relatively asymptomatic with target cells on blood smear, isolated increase in HbA2 (>3.5%)
Beta thalassemia major- anemia 6 months after birth( HbF protective temporarily) ; alpha tetramers damage rbc, massive erythroid hyperplasia- chipmunk facies, crew cut, spleenomegaly and heptaomegaly, risk of aplastic crisis with parvovirus b19
Need transfusions which can lead to risk of secondary hemachromatosis
Hypochromic microcytic anemia with target cells and some nucleated rbcs because made in liver and spleen and can escape into blood, no HbA on electrophoresis
Cold Antibody Immunohemolytic Anemia
IgM antibodies bind clumps of RBCs in periphery where it is less than 30 Celsius , complement also binds
When cells reach warmer parts of the body, IgM dissociates leaving C3b which leads to splenic phagocytosis by macrophages
Pentavalent IgM binding can also cause agglutination in the periphery leading to Raynaud’s phenomenon
Associated with myoplasma pneumoniae and infectious mononucleosis; B cell neoplasms, or idiopathic
Causes of sideroblastic anemia
- ) Congenital- most commonly x linked defect in ala synthase,
- ) Acquired- alcoholism ( mitochondrial poison which hurts production of pp), lead poisoning ( can denature ala dehydrogenase or ferrokelatase ), b6 deficiency, isoniazid treatment, copper deficiency
Lab values associated with sideroblastic anemia
Lab- increased ferritin, decrease tibc, high serum iron, increased sat ( iron builds up in mito and makes free radicles and cell dies, iron leaks out, bone marrow macrophages eat, high ferritin, high serum iron) / similar lab findings to hemachromatosis
Causes of folate deficiency
- Poor diet ( alcoholics and elderly)
- Increased demand- preg cancer hemolytic anemia;
- Folate antagonist- methotrexate inhibits dihydrofolate reductase which can result in a folate deficiency
Presentation of follate deficiency and labs
Macrocytic anemia w/ hyperseg PMNs
Glossitis- lack of cell turnover in tongue, irritation
Decreased serum folate, increased serum homocysteine (b12 can’t methylate homocysteine to become methionine) Normal methylmalonic acid ( becomes succinyl coa via b12) which indicates no vit b12 def
Common causes of B12 deficiency anemia
- Pernicious anemia m
- Lack of acid in the stomach also makes it hard to cleave B12 from animal protein (age (older less acid), atrophic gastritis, proton pump antagonists)
- Pancreatic insuff ( proteases to cleave away from r-binder)
- Damage to terminal ileum via crohns or diphyllobothrium latum/ fish tapeworm;
- Diet- vegans Lab- macrocytic anemia, hyperseg
B12 deficiency anemia presentation and labs
Decrease Vit b12; increase in homocysteine ; increased mma
Megoloblastic anemia (macrocytic, hyperseg PMNs), glossitis, increased risk of osteoporosis, angular stomatitis, subacute degeneration of the spinal cord, neurological change (mma builds up in the myelin of spinal cord)
Lead poisoning
Inhibition of ALAD and ferrochelatase
Inhibiots rRNA degredation which leaves rRNA aggreagetes in RBCs : Basophillic stippling
LEAD
l: Lean Lines on gingiva / Burton Lines and on metaphyses of long bones
E: Encephalopathy and Erythrocyte basophilic stippling
A: Abdominal colic and sideroblastic anemia
D: Wrist and foot drop, dimercaprol and EDTA are first line treatment
Succimer used for chelation for kids who eat lead paint chips
HbS/ B thalasemia heterozygote
mild to moderate sickle cell disease dpending on the amount of B globin production
Pyruvate Kinase Deficiency
Autosomal Recessive
Defect in pyruvate kinase so a decrease in ATP and rigidity of RBCs
Hemolytic anemia in newborn
Acute intermittent porphyria
porphorbilinogen deaminase deficiency
(Porphorobillinogen –> hydroxymethylbilane in cytoplasm )
5Ps:
1) Painful abdomen
2) Port wine color urine
3) Polyneuropathy
4) Psychological disturbances
5) Precipitated by drugs (CP450 inducers) alcohol, or starvation
Treat: glucose and heme which inhibit ALAS
Porphyria cutanea tarda
uroporphyrinogen decarboylase
uroporphyrin builds up and causes tea color urine
Blistering cutaneous photosensitivity (most common porphyria)
Orotic aciduria
Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) due to defect in UMP synthase
Autosomal recessive
Presents in children as failure to thrive, developmental delay, and megaloblastic anemia refractory to B12 and folate
Ortoric acid in urine
Treat with uridine monophosphotate to bypass the mutated enzyme
Acanthocytes
Spur cells, spiny cell, seen in liver disease and abetalipoproteinemia (states of cholesterol disregulation)
Bilirubin values
Br: Total = 0.1-1mg/dL; Direct = 0-0.3 mg/dL (Indirect = Total- Direct)
Cr
0.6-1.2
Fenton Reagent
Fe2+ + H202 –> Fe3+ + OH(hydroxyl) + OH-
Fe3+ + H202 –>Fe2+ + OOH (radical) +H+
