Term
| 4 ways we can examine blood |
|
Definition
peripherial blood film/smear
bone marrow aspirate
bone marrow biopsy
automated: CBC, RBC, platelets |
|
|
Term
| peripherial blood film: method and 3 things it evaluates |
|
Definition
direct exam of blood smear or red cell induces
examines size, shape, color |
|
|
Term
| automatic Hb evaluation: what does it measure, how, two classifications |
|
Definition
concentration of Hb
measured sphectrophotometrically
hypochromatic: low Hb decreases color
normochromatic: normal Hb and color |
|
|
Term
| automatic HCT evaluation: what does it measure, how can it be calculated |
|
Definition
fraction of whole blood that is red cells
MCVxRBC |
|
|
Term
| automatic RBC count: what does it measure, what are the units, what is a normal count, what is a count in anemia |
|
Definition
particle count of TBC
absolute count: 24000-84000 ul
marrow response to anemia is 3% or 15000ul (%RBC must be corrected for degree of anemia (0.5-1.5%) |
|
|
Term
| how is manual RBC count recorded |
|
Definition
|
|
Term
| what are the 6 RBC shapes |
|
Definition
normal
spherocyte
eliiptocytes
target cells
pikilocytosis
schistocytes |
|
|
Term
| what is MCV, what does the number indicate |
|
Definition
average volume per red cell
microcytic: <80
normocytic: 80-100
macrocytic: >100 |
|
|
Term
| what is MCH, how can it be calcuated |
|
Definition
average mass Hb per RBC
HB/RBC |
|
|
Term
| what is MCHC, how can it be calculated, what are the units |
|
Definition
average Hb concentration in red cells
(Hb/HCT)
g/dL |
|
|
Term
| what is RDW, what does the value mean, how is it calculated |
|
Definition
ratio of volume of RBC
large number when cells are different volumes
smaller when their the same size
(SD/MCV) |
|
|
Term
| what is the differential WBC count |
|
Definition
| percent total WBC of a certian type |
|
|
Term
| what is the absolute WBC count |
|
Definition
| lymphocytes, monocytes, PMN, eosinophils, basophils |
|
|
Term
|
Definition
|
|
Term
|
Definition
| platelet distribution width (simillar to RDW) |
|
|
Term
|
Definition
electrophoresis: quantifies
HPLC
isoelectric focusing |
|
|
Term
| explain what Hb is made of |
|
Definition
Hb = globin tetramete + heme
heme = prophyrin ring + Fe atom |
|
|
Term
| what are the 3 types Hb and their prevelance |
|
Definition
HbA (a2,B2) 97%
AbF (a2,Y2) 3%
HbA2 (a2,g2) 1.5% |
|
|
Term
|
Definition
| decreased circulating RBC MASS (mass is hard to measure so we say decreased RBC NUMBER) leads to reduced O2 carrying capacity of the blood |
|
|
Term
| how is anemia evaluated, what are the lab limits for definition in males and females |
|
Definition
evaluate Hb, HCT, RBC count
Hb <13.5 male
Hb <12.5 female |
|
|
Term
| what are the 3 common presenting symptoms in anemia |
|
Definition
| pallor, fatigue, lassitude |
|
|
Term
| why would someone have a severe anemia with little symptoms |
|
Definition
| slow onset, more time to adapt |
|
|
Term
| what are symptoms of anemia due to premature destruction (hemolytic) 3, why are these the characterizing symptoms |
|
Definition
due to increased fee Hb
hyperbilirubinemia
jaundice
pigment gallstnes |
|
|
Term
| what are 2 symptoms of anemia due to ineffective erythropoiesis |
|
Definition
increased Fe absorption
Fe overload |
|
|
Term
| what are 3 symptoms of anemia due to congenital abnormalities |
|
Definition
growth retardation
skeletal abnormalities
cachexia |
|
|
Term
| what are the 4 microcytic anemias |
|
Definition
Fe deficiency anemia
anemia of chronic disease
sideroblastic anemia
thallasemia |
|
|
Term
| what are the 3 macrocytic anemias |
|
Definition
folate deficiency
B12 (cobalamin) deficiency
alcoholism/liver disease anemia |
|
|
Term
| what are the 5 classifications of normocytic anemia |
|
Definition
extrinsic anemia (extracorpuscular/peripherial destruction): extravascular and intravascular hemolysis
intrinsic hemolytic anemia (intracorpuscular/under production)
immune mediated hemolytic anemia
angiopathic hemolytic anemia |
|
|
Term
| what are the 3 normocytic anemia with extravascular hemolysis predominance |
|
Definition
hereditary spherocytosis
sickle cell anemia
hemoglobin C disease |
|
|
Term
| what are the 2 normocytic anemia with intravascular hemolysis predominance |
|
Definition
paroxysmal noctournal hemoglobinuria
G6PDH deficiency |
|
|
Term
| what are the 3 normocytic immune hemolytic anemias |
|
Definition
IgG intravascular hemolysis
IgM extravascular hemolysis
drug induced |
|
|
Term
| what causes RBC to be microcytic |
|
Definition
with each division erythroblasts get smaller and make RBC
in microcytic anemia they go through extra division because there is a DECREASE IN HB PRODUCTION they try and make normal [Hb] by making cells smaller |
|
|
Term
| what are things that cause a decreased Hb production 4 |
|
Definition
Fe deficiency
Fe stuck in macrophages - anemia of chronic disease
decreased protophyrin - sideroblastic anemia
decreased globin - thallassemia |
|
|
Term
| what 12 things cause Fe deficiency anemia |
|
Definition
malnutrition
acute blood loss
chronic blood loss: ulcers, colon cancer, hemorrhoids, hook worm
malabsorption: celiac disease, spruce, gastroectomy
breast feeding
menorrhagia
pregnancy |
|
|
Term
| how does malnutrition cause Fe deficiency anemia (how is it absorbed, transferred, stored) |
|
Definition
consumed as heme (20% absorbed) from meat and veggies (1-2% absorbed)
Fe3+ reduced by ferric reductase to Fe2+
Transported by DMT1 into duodenum enterocytes
Transported on basal side by ferroportin
Regulated by hepcidin (degrades transporter when no Fe is needed)
Some Fe 2+ stays inside the cell when the body dosent need it and is sloughed off with exphoilation of the GI tract
Hephaestin oxidizes Fe2+ to Fe3+
Fe3+ is transported in plasma to store in macrophage on ferritin in liver/bone |
|
|
Term
|
Definition
| prevents fenton Fe reaction from forming free ROS in Fe absorption in duodenum |
|
|
Term
|
Definition
| gate that decides to absorb Fe in duodenum (has to be choosy, we have no Fe elimination process) |
|
|
Term
|
Definition
regulator of ferrportin gate (binds to ferrportin causing degredation)
stops Fe absorption in duodenum |
|
|
Term
|
Definition
|
|
Term
| how long does it take to restore blood volume after acute loss, what anemia will they have until then |
|
Definition
2-3d
normochromic normocytic anemia |
|
|
Term
| what process occurs if someone has had acute blood loss for several days and cannot replenish |
|
Definition
| erythropoetin causes reticulocytosis and more RBC |
|
|
Term
| define chronic blood loss anemia |
|
Definition
| anemia develops when rate of loss > production or Fe stores in body |
|
|
Term
| what disease can caue malabsorption abemia |
|
Definition
|
|
Term
| why does gastrectomy cause anemia |
|
Definition
Fe2+ is easily absorbed and kept charged with acid
less stomach acid means Fe3+ will not be converted and it is less absorbed |
|
|
Term
| what is the most common cause of Fe deficiency in an infant |
|
Definition
| breast milk has little Fe |
|
|
Term
| what is the most common cause of Fe deficiency in a child |
|
Definition
|
|
Term
| what is the most common cause of Fe deficiency in a adult male and female |
|
Definition
peptic ulcers - male
menorrhagia and pregnancy - female |
|
|
Term
| what is the most common cause of Fe deficiency in elderly 2 |
|
Definition
colon polyps - western
hook work - 3rd world |
|
|
Term
| what are the 4 stages of Fe deficiency anemia |
|
Definition
storage Fe depleted, decreased Fe containing proteins
serum Fe depleted
normocytic anemia
microcytic hypochromatic anemia |
|
|
Term
| Fe deficiency anemia: signs of stage 1 Fe storage depletion |
|
Definition
decreased ferritin: less Fe stored, less needed
increased TIBC: macrophages see decreased ferritin and increase transferrin to find Fe |
|
|
Term
| Fe deficiency anemia: signs of stage 2 Fe serum depletion |
|
Definition
decreased serum Fe
decreased percent saturation |
|
|
Term
| Fe deficiency anemia: signs of stage 3 normocytic anemia |
|
Definition
| marrow tries to make more RBC but Fe is low so it makes less, but properlly formed, RBC |
|
|
Term
| Fe deficiency anemia: signs of stage 4 microcytic hypochromatic anemia |
|
Definition
there isnt enough Fe for normal RBC anymore so now RBC have less Hb (and thus less color) and are smaller to keep [Hb] a little higher
increase MCV, MCHC
decreae platelets
increased RDW: non-unison change from normocytic to microcytic widesn range of RBC size
increased free RBC protoporphyrin: it has less Fe to bind to so some is free now |
|
|
Term
| 4 ways to diagnose Fe deficiency anemia |
|
Definition
serum Fe: 3 transferrin hold 1 Fe in blood
total Fe binding capacity (TIBC): measures how much transferrin
percent saturation: how many transferrin-Fe to transferin-X (normally 1/3)
serum ferritin: how much Fe stored |
|
|
Term
| 3 symptoms of mild Fe deficiency anemia |
|
Definition
asymptomatic
weakness
listlessness |
|
|
Term
| plummer vinsin syndrome: cause, 3 signs |
|
Definition
| Fe deficiency anemia with eosphageal web causes dysphagia, atrophic flossitis, beefy red tonge |
|
|
Term
| TX Fe deficiency anemia 2 |
|
Definition
ferrous sulfate
treat cause |
|
|
Term
| 7 causes of anemia of chronic disease |
|
Definition
chronic microbial infection: osteomyelitis, bacterial endocarditis, lung abscess
chronic immune disorders: RA, regional enteritis
neoplasm: hodgkins lymphome, carcinoma of lung and breast |
|
|
Term
| normal Fe vales: intake, loss, total body in men and women |
|
Definition
intake 10-20mg
loss 1-2mg
2g in women
6g in men |
|
|
Term
|
Definition
80% function: 20% catalase, cytochromes. 80% Hb
20% storate as hemoserdin and ferritin in liver, spleen, marrow, muscle |
|
|
Term
| 8 symptoms of severe Fe deficiency anemia |
|
Definition
anemia: pallor
alpplecia
tongue/gastric mucosa atrophy
malabsorption
PICA
kolionychia: spoon shaped nails
hypovolemia: CV collapse, shock, death
plummer vinsin syndrome |
|
|
Term
| pathology of anemia of chronic disease |
|
Definition
chronic inflammation increases HEPCIDIN which sequesters Fe in macrophages and RBC precursors cannot make heme
hepcidin and inflammation also decrease erythropoetin and RBC production
thought is that hepcidin is hiding Fe from being consumed by bacteria |
|
|
Term
| what type of anemia is anemia of chronic disease |
|
Definition
| normocytic normochromatic --> microcytic hypochromatic |
|
|
Term
| 5 lab signs of anemia of chronic disease |
|
Definition
decreased Fe
increased ferritin: inability to store and use Fe
decreased TBIC: transferrin not needed
decreased percent saturation
increased FEP: not enough Fe means increased protophyrin unbound
increased hepcidin: due to pro-inflammagory cytokines |
|
|
Term
| how can anemia of chronic disease and Fe deficiency anemia be distinguished |
|
Definition
Ferritin is low in Fe deficiency and TIBC is high
it is opposite in anemia of chronic disease |
|
|
Term
| explain the normal production of prophyrin |
|
Definition
| succinylCoA + amino lovonic A synthase > aminolobonic acid > + ALAS > prophyrin > + Fe + ferochetylase > heme |
|
|
Term
| cause of hereditary spherocytosis |
|
Definition
defect in ALAS used in heme production
acquired: alchiism (mitochrondia damage), lead poisoning (denatures enzymes), B6 deficiency |
|
|
Term
| pathology of hereditary spherocytosis |
|
Definition
| Fe shows up at mitochondria of monocytes and there is no heme so it gets stuck in ring around mitochondria making RINGED SITEROBLASTS |
|
|
Term
| lab signs of hereditary spherocytosis |
|
Definition
increased ferritin: Fe damages and kills cells releasing Fe into serum whichis eaten by macrophages and attached to ferritin
decreased TBIC
increased serum FE: cells release Fe into serum when they die
increased percent saturation |
|
|
Term
| general cause and purpose of thalassemias |
|
Definition
AR decrease synthesis of globin decreases Hb causing microcytic anemia
derived for protection from PLASMODIUM FALVIPARUM |
|
|
Term
| a-thalassemia: who it effects, what type of Hb, cause |
|
Definition
DELETION of a-globin on CH16
affects ALL Hb types (HbF, HbA, HbA2)
common in southeast asia, african americans |
|
|
Term
|
Definition
silent carrier - 1 deletion
a-thalassemia trait - 2 deletions
HbBart (b4) disease - 3 deletions
HbBart (Y4) disease - 4 deletions |
|
|
Term
| signs of silent carrier a-thalassemia |
|
Definition
| asymptomatic carrier, normal RBC |
|
|
Term
| signs of a-thalassemia trait |
|
Definition
mild anemia
INCREASED RBC count |
|
|
Term
| 2 types of a-thalassemia trait and their population affected, which is worse |
|
Definition
cys (--/aa): asians, high risk of transfer to offspring
trans (a-,a-): more in african americans |
|
|
Term
| 4 lab signs in a-thalassemia trait |
|
Definition
decreased MCV, Hb, HCT
increased RBC count |
|
|
Term
|
Definition
|
|
Term
| signs of HbBart (B4) in utero and after birth, why |
|
Definition
utero: HbF works fine, asymptomatic
birth:
B chains for tetrametes (HgB) causing RBC damage and macrophage consumption
ineffective erythropoesis
severe anemia |
|
|
Term
| how is HbBart (B4) diagnosed |
|
Definition
| HbB seen on electrophoresis |
|
|
Term
| signs of HbBart (Y4), why |
|
Definition
lethal in utero
Y chains form tetrameres (HbB) that damage RBC and have high affinity for O2 but cannot deliver it to tissues |
|
|
Term
| how is HbBart (Y4) diagnosed 3 |
|
Definition
| HbB, HbH, HbPortland on electrophoresis |
|
|
Term
|
Definition
|
|
Term
| B-thalassemia: population, cause, Hb affected |
|
Definition
AA, greeks, italians
MUTATION in B-globin promoter region, coding sequence, splice site (most common) on CH11
affects HbA only |
|
|
Term
|
Definition
(B/B+) B-thalassemia minor (B-thalassemia trait)
(B0/B0) B-thalassemia major (cooley's disease) |
|
|
Term
| signs of B-thalassemia minor |
|
Definition
|
|
Term
| 8 labs supporting B-thalassemia minor |
|
Definition
decreased MCV, HbA, Hb, HCT
increased RBC, HbA2, HbF |
|
|
Term
| pathology of B-thalassemia minor |
|
Definition
target cells have decreased Hb and RBC volume
this allows for excess membrane and blebing
target cells have Hb darkening in central clearing |
|
|
Term
| signsof B-thalassemia major |
|
Definition
6mo after birth (when HbF decreases) severe anemia
HbF often extends beyond normal time |
|
|
Term
| pathology of B-thalassemia major: how does it damage, what are the effects |
|
Definition
a2 chains dimerize with eachother and percipitate (INEFFECTIVE ERYTHROPOESIS: RBC membrane damage and popotosis why bring made)
poorly made cells get EXTRAVASCULAR HEMOLYSIS
massive erytheroid hyperplasia |
|
|
Term
| what is erythroid hyperplsaia |
|
Definition
hematopossis in skull bones causes bone remodeling making crew cut x-ray and chipmunk face
extramedullary hematopoesis and HSM
risk of aplastic crisis with parvo B19 which infects erythroblasts |
|
|
Term
| 9 labs signs supporting B-thalassemia major |
|
Definition
microcytic
hypochromatic
target cells
nucleated RBC
increased RDW, RBC, HbA2, HbF
decreased HbA |
|
|
Term
| treatment of B-thalassemia major |
|
Definition
dependent on chronic transfusion
marrow transplant |
|
|
Term
| SE of tx for B-thalassemia major |
|
Definition
| secondary hematochromatosis (cannot get rid of Fe from transfusions) |
|
|
Term
| what is the cause of macrocytic RBC |
|
Definition
erythroblast does not divide enough due to delay in nuclear DNA maturation, cell division making giant metamyelocytes with NUCLEAR ASYNCHRONY (cytoplasm synthesis > normal rate)
could undergo apoptosis (INEFFECTIVE HEMATOPOESIS) |
|
|
Term
| how is foate acquired and used |
|
Definition
| green veggies > jejunum > tetrahydrofolate methylated > B12 demythelyates > B12 transfers methyl to homocystine > methionine + THF > DNA purine and thymidine production |
|
|
Term
| how does folate deficiency cause anemia, what are some complications |
|
Definition
deficiency causes decreased DNA synthesis and cell division cessation
increased levels of homocystine
body has little stores so anemia develops in months
cause megaloblastic anemia: RBC and other rapidly dividing cells (INTESTINES) become large due to decrease in DNA components
pancytopenia: not isolated anemia, some cells live and some die, but total RBC output decreases |
|
|
Term
| causes of folate deficiency 8 |
|
Definition
poor diet: alcoholic, elderly
increased demand: pregnancy, cancer, hemolysis
folate antagonists: methotrexate
malabsorption: contraceptives, phenytoin |
|
|
Term
| 5 signs of marrow changes in folate deficiency |
|
Definition
thrombocytopenia
megaloblastic: enlarged erythroid precursors
megakaryocytes with large nuclei
metamyelocytes: large granulocyte precursors
granulocytopenia (hypersegmented neutrophils in blood): before anemia develops |
|
|
Term
| 4 signs in blood in folate deficiency |
|
Definition
hypersegmented neutrophils
RBC with egg shaped macro-obalocytes
decreased folate
increased homocystine
normal methylamalonic A and B12 |
|
|
Term
| symptoms of folate deficiency 3 |
|
Definition
flossitis: sore tongue
chlirosis
often complicated with other vitamin deficiencies |
|
|
Term
| explain normal production, absorption, and storage of B12 |
|
Definition
| B12-protein > B12-haptocorrin (from salive) > small intestine > protease cleaves haptocorrin > B12-intrinsic factor (from parietal cells) via cuvulin > ileum > B12-plasma transcovalamin > liver and cells |
|
|
Term
| how does B12 deficiency cause anemia, what are the complications in blood |
|
Definition
onset is long term B12 stores can last 5y
B12 cannot demythelate THF or transfer it to homocystine halting DNA synthesis and causing cell division cesation
causes megaloblastic anemia: RBC and other rapidly dividing cells (INTESTINES) become large due to decrease in DNA components
causes subacute combined degeneration |
|
|
Term
| why does subacute combined degeneration occur with B12 deficiency |
|
Definition
B12 convers methylamolnic A to succinyl CoA
when it dosent methylamonic A builds up on posterior and lateral columns |
|
|
Term
| how can you use degree of subacute combiined degeneration to estimate the anemia levels |
|
Definition
|
|
Term
| cause of B12 deficiency 6 |
|
Definition
pernicious anemia- autoimmune
destruction of parietal cells in stomach
pancreas insufficiency (cannot cleave B12 from carriers)
damage to terminal ileum
dietary deficiency
gastric atrophy in elderly interferes with pepsin production so B12 isnt released |
|
|
Term
| explain why pernicious anemia leads to B12 deficiency |
|
Definition
| autoimmune reaction to parietal cells and intrinsic factor make it so B12 isnt absorbed |
|
|
Term
| what antibodies can cause B12 deficiency 3 |
|
Definition
B12 blocking antibodies: prevent binding fo cubulin
parietal canicular antibodies: attack parietal cells
ileal receptor blocking antibodies |
|
|
Term
| what conditiosn is pernicious anemia associated with 3 |
|
Definition
hashimotos thyroiditis
addisons disease
DM1 |
|
|
Term
| what are some marrow signs that support B12 deficiency 5 |
|
Definition
megaloblastic: enlarged marrow erythroid precursors
megakaryocytes with large nuclei
metamyelocytes: large granulocytic precursors
granulocytopenia: hypersegmented neutrophils in the blood before anemia develops
thrombocytopenia |
|
|
Term
| what are some blood signs that support B12 deficiency 6 |
|
Definition
auto-antibodies in serum and gastric juice
hypersegmented neutrophils
RBC with egg shaped macro-ovalocytes
decreased B12 (folate normal)
increased homocystine
INCREASED METHYLMALONIC A |
|
|
Term
| what are some symptoms of B12 deficiency 6 |
|
Definition
glossitis
chilosis
burning, tingling, numbness in hands and feet
ataxia
decreased position sense (esp toes)
jaundice |
|
|
Term
| treatment of B12 deficiency |
|
Definition
reticulocyte response in 2-3d to parentrail B12
WILL RESPOND TO FOLATE THERAPY BUT THAT WILL ONLY CORRECT THE ANEMIA NOT CORD DEGENERATION |
|
|
Term
| how can alcoholism and liver disease caused anemia be distinguished from B12 or folate deficiency anemia |
|
Definition
| causes megaloblastic anemia too but only RBC become large NOT other rapidly dividing cells like intestines |
|
|
Term
| how is extrinsic hemolytic anemia diagnosed |
|
Definition
in anemia reticulocyes >3% due to increased erythropoetin and reticulocytosis
RBC are large, blue cytoplasm due to residual RNA |
|
|
Term
| causes of extrinsic hemolytic anemia 3 |
|
Definition
immune mediated
mechanical destruction
infection |
|
|
Term
| patholog of extrinsic hemolytic anemia, what changes does it cause in the body, how is it started |
|
Definition
RBC damaged or immunologically rargeted
reticuloendothelial system destories RBC
globin breaks into AA
heme: Fe is recycled and protophorin turned into unconjugated bilirubin which binds albumin and sits in blood (jaundice) until it can be conjugated in liver
liver conjugates and makes bile with too much bilirubin which makes gall stones |
|
|
Term
| 5 signs of extrinsic hemolytic anemia |
|
Definition
reactive hyperplasia; marrow and spleen hyperplasia (HSM)
anemia
jaundice
pigmented gall stones
haptoglobin decreased because some Hb leaks from macrophages onto plasma so lactate DH is increased when it binds |
|
|
Term
| cause or intravascular hemolysis, process of destruction |
|
Definition
RBC lysed in serum due to mechanical damage (valve, complement, toxins, heat)
Hb in serum binds to haptoglobin, floats around in blood
evuntally removed in spleen |
|
|
Term
| signs of intravascular hemolysis |
|
Definition
hemoglobinemia
hemoglobinuria
hemosiderinuria
heptoglobin is used to bind Hb so its decreased and releases lactte DH which increases ins erum
unconjugated hyperbilirubinemia
acute tubular necrosis of kidney: Hb and RBC membrane stroma is toxic
reactive hyperplasia: marrow and spleen hyperplasia (HSM) |
|
|
Term
| howis intrinsic hemolytic anemia diagnosed |
|
Definition
in anemia reticulocytes will not rise >3% because the marrow cannot produce them
NOTE: reticulocytes can seem elevated in anemia falsly, must use correction factor formula
%reticulocytes = HCT/45) |
|
|
Term
| cause of intrinsic hemolytic anemia |
|
Definition
inherited membrane abnormalities
enzyme deficiencies
Hb synthesis dosorders |
|
|
Term
| howis intrinsic hemolytic anemia diagnosed |
|
Definition
in anemia reticulocytes will not rise >3% because the marrow cannot produce them
NOTE: reticulocytes can seem elevated in anemia falsly, must use correction factor formula
%reticulocytes = HCT/45) |
|
|
Term
| cause of intrinsic hemolytic anemia |
|
Definition
inherited membrane abnormalities
enzyme deficiencies
Hb synthesis dosorders |
|
|
Term
| cause of hereditary spherocytosis, pathology, how it causes problems |
|
Definition
AD (most common) AR more severe
deformed spectrin, ankyrin, or band 3/4.2 in cytoskeleton of RBC weakens vertical interaction between membrane and cytoskeleton and causes blebs which get eaten in spleen and deform so the cell becomes SPHEROCYTE
evuntally their so small they cannot manuever in spleen so it consumes them via extravascular hematopoesis
some intravascular hematopoesis occurs due to abnormal RBC shape
this happens at all different stages of RBC so their is a wide range in RBC size |
|
|
Term
| 3 lab signs of hereditary spherocytsis |
|
Definition
spherocytes: round cells with loss of central palloe
increased RDW
increased MCHC: cells decrease in size but still have same Hb content increaseg [Hb] |
|
|
Term
| 6 symptoms of hereditary spherocytosis and why |
|
Definition
anemia: 30% asymptomatic
splenomeagly: work hypertrophy (500-1000g) and congestion of splenic cords with macrophages
hemolytic crisis: spleen destruction due to intercurrent event (like mono)
jaundice: increased RBC destruction causes more bilirubin conjugation in liver and a back up of unconjugaed bilirubin in blood
pigment gall stones: (chorlelithiasis) increase in bilirubin processing puts more into bile causing stones
aplastic crisis: parvo B19 invades erythroid precursors worsening anemia
hemosiderosis: excess heme from RBC destruction is taken up into tissues
erythroid hyperplasia of marrow and reticulocytes |
|
|
Term
| diagnosis of hereditary spherocytosis |
|
Definition
osmotic fragility test
RBC + hypotonic solution causes spherocyte (normal)
spherocyte + hypotonic solution causes lysis |
|
|
Term
| treatment of hereditary spherocytosis, prognosis and complications |
|
Definition
splenectomy: spherocytes persist but are not depleted
see howell jolly bodies (spleen isnt there to remove DNA gragments from new RBC so the persist) |
|
|
Term
| cause of sickle cell anemia |
|
Definition
AR mutation in B0Hb (glutamic acid - hydrophillic --> valine - hydrophobic)
derived for protection from FALCIPARUM MALARIA |
|
|
Term
| what are the 2 types of sickle cell |
|
Definition
1 gene mutation - heterozogoys
2 gene mutation - homozygous |
|
|
Term
| what are the RBC changes in heterozygous sickle cell, the symptoms, and why |
|
Definition
55% Hb and 45% HbS: you need 50% HbS to cause sickle except in renal medulla where it is low O2 and hypertonic which allows sickle and causes microinfarcts
microscopic hematuria and decreased ability to concentrate urine |
|
|
Term
| signs of homozogous sickle cell 11 |
|
Definition
sicking of cells
extravascular hemolysis/target cells
extramedullary hematopoesis/massive erythroid hypoplasia
aplastic crisis
intravascular hemolysis
microvascular vasooclusion
stroke
seizure
aseptic necrosis of femur head
leg ulcers
Ca bilirubin gall stones |
|
|
Term
| give two reasons sickle cell could be benificial to the patient |
|
Definition
protection from falciprum malaria
coexistance with a-thalassemia decreaes Hb and reduces sickling |
|
|
Term
| give 7 reasons that cause sickling and why |
|
Definition
acidosis: inflammation and infection
inflammation: causes cells to be more sticky
low O2: sluggish capillary flow and sickling esp in spleen and marrow
increases in HBS: more stuck together. sickling causes influx of Ca and efflux of K and water. DEHYDRATION damages membrane skeleton and causes sticking and sickling
HbS interacts with HbA weakly
HbF INHIBITS HbS polymerization - no sickling
HbC aggregates with HbS
increased MCHC (Hb) causes more sickling (decreased MCHC like in a-thalassemia causes less) |
|
|
Term
| why do sickle cells go through extravascular hemolysis, explain the process |
|
Definition
they continously sickle and desicle as they go through normal oxygenation/deoxygenation which slowly damages the cells
the spleen removes them or they lysis releasing haptoglobin and making TARGET CELLS (membrane damages causes dehydration and the membrane blebs creating bleb in center with Hb in it) |
|
|
Term
| why is there massitve erythroid hypoplasia and extramedullary hematopoesis in sickle cell, what are the signs of this |
|
Definition
RBC are destoried and non-functional so their is less effective RBC in circulation so bone tries to make more but the normal long bones can't keep up so other bones help out
this causes chipmunk facies and cerw cut xray |
|
|
Term
| why do people with sickle cell get aplastic crisis |
|
Definition
| when infected with parvo B19 it infects the little RBC precursors they have decreasing oxygenation even more |
|
|
Term
| why do people with sickle cell get intravascular hemolysis |
|
Definition
| minor, due to mechanical fragility of sickled cells |
|
|
Term
| what are 5 effects of vasoocclusion in sickle cell |
|
Definition
infarct and fibrosis of spleen
dictylitis
vasoocclusion of lung
renal papillary necrosis
pain crisis |
|
|
Term
| what are the complications of vasooclusion in the spleen in sickle cell 4 |
|
Definition
decreased antibody formation allows infection of encapsulated microbes (MOST COMMON COD IN KIDS)
autosplenectomy: fibrosis of spleen causes regression (CHRONIC ERYTHROSTASIS) leading to formation of HOWEL JOLLY BODIES in RBC (spleen no longer removes residual RNA from new RBC)
sequestration crisus: rapid enlargement due to entraped RBC causing HYPOVOLEMIC SHOCK |
|
|
Term
| what microbes can infect when the spleen stops working in sickle cell, what is a common infection complication |
|
Definition
encapsulated microbes: pneumococcus, H. influenza)
salmonella osteomyelitis |
|
|
Term
| what is the most common COD in kids with sickle cell |
|
Definition
| spleen damage due to vasoocclusion causes decreased antibody formation and allows infection with encapsulated microbes |
|
|
Term
|
Definition
| swelling and infarct of bones in hands and feet (common in 6-9mo sickle cell patients) |
|
|
Term
| what are the complications of vasoocclusion in the lung in sickle cell 4 |
|
Definition
acute chest syndrome
CP
SOB
infiltrates
MOST COMMON COD IN ADULTS |
|
|
Term
| what is the cause and signs of acute chest syndrome |
|
Definition
| pneumonia causes vasodilation which increases RBC transit and dehydration, acidemia, and deoxygenation of cells increasing sickling |
|
|
Term
| what are the complications of renal papillary necrosis in sickle cell 2 |
|
Definition
hematuria
loss of concentrating ability |
|
|
Term
|
Definition
| hypoxic tissue injury and infarct due to clogging of sickle cells in small vessels causes severe pain |
|
|
Term
| what is the most common COD in adults with sickle cell |
|
Definition
|
|
Term
| treatment for sickle cell, MOA |
|
Definition
hydroxyriua after 6mo
gentile inhibitor of DNA synthesis increases HBF and decreases leukocytes which decreases inflammation
increases MCV and MCHC due to decreased DNA synthesis
causes NO production leading to vasodilation and inhibition of clotting |
|
|
Term
| 3 types of screening for sickle cell |
|
Definition
prenatal screen: fetal DNA detection of point mutations
metabolisulfite screen: causes sticking of ANY HbS (even heterozygous)
Hb electrophoresis: thicker band means more of that type of Hb |
|
|
Term
| what is the distribution of Hb in homozygous sickle cell disease |
|
Definition
90% HbS
8% HbF
2% HbA2
0% HbA |
|
|
Term
| what is the distrubution of Hb in heterozygous sickle cell trait |
|
Definition
|
|
Term
| cause of hemoglobin C disease |
|
Definition
| AR mutation in Hb B-chain (glutamic acid --> lysing) making HbC |
|
|
Term
| how does HbC cause anemia |
|
Definition
| HbC has a greater tendancy to aggregate with HbS so even heterozygous sickle cell disease will have sicking |
|
|
Term
|
Definition
| mild anemia due to extravascular hemolysis |
|
|
Term
|
Definition
|
|
Term
| paroxysmal nocturnal hemaglobinuria: cause |
|
Definition
normally RBC protect themselves from complement damage with DAFT and MIRL which is held on by PIG/GIP
ACQUIRED deficit in myeloid stem cell so platelets, RBC, and WBC have no PIG/GPI which allows for complement destruction of RBC |
|
|
Term
| why is paroxysmal nocturnal hemaglobinuria called that |
|
Definition
when we sleep we breathe shallow and retain CO2 causing resiratory acidosis which activates complement increasing RBC lysis
leads to dark urine in morning due to RBC breakdown products |
|
|
Term
| 8 signs of paroxysmal nocturnal hemaglobinuria |
|
Definition
paroxysmal nocturnal hemaglobinuria
hemoglobinemia
hemoglobuinuria (episodic)
hemosiderinuria (days after episode)
VENOTHROMBOSIS
Fe deficiency anemia
APLASTIC ANEMIA in 10%
decreased PMN allowing for infection |
|
|
Term
| why does paroxysmal nocturnal hemaglobinuria get venothrombosis |
|
Definition
| pt is in procoagulable state due to activity of MAC attack |
|
|
Term
| why does paroxysmal nocturnal hemaglobinuria pt get Fe deficiency anemia |
|
Definition
| Fe is lost in urine with Hb |
|
|
Term
| 4 diagnostic tests for paroxysmal nocturnal hemaglobinuria |
|
Definition
sucrose hemolysis test (sugar water test) - screening: sugar enhances complement attachment
acidified serum test (ham test) - conformation: activates alternate complement pathway
peripherial blood: normocytic anemia with pancytopenia (microcytic Fe deficiency develops later)
decreased CD55 (DAFT) on RBC surface |
|
|
Term
| TX paroxysmal nocturnal hemaglobinuria |
|
Definition
| targeted against MAC attack decreasing hemolysis and thrombotic complications but increasing risk of Neisseria infection (esp menngococcal sepsis) |
|
|
Term
| cause of G6PDH deficiency anemia |
|
Definition
RBC in liver undergo much oxidative stress and must protect themselves with glutathione
GSH + peroxide + glutathione > GS-SG + NADPH > GSH > repeat
NADPH comes from glucose-6-P A varient DH reaction
in G6PDH deficiency there is X-linked mutation in G6PDH A varient
derived for protection from FALCIPRUM MALARIA |
|
|
Term
| what are the two types of G6PDH anemia and who gets them, what are their severities, why |
|
Definition
african (A-) variant (in 10% of AA): mildly decreased t1/2 of G6PDH (only older RBC destoried. less severe
mediterranean varient: very short t1/2 G6PDH (any RBC >30d old is destoried, worse disease) |
|
|
Term
| why does G6PDH deficiency cause anemia |
|
Definition
cells destoried during oxidative stress when ROS increases
destruction causes Hb to percipitate leaving HEINZ BODIES in the RBC which partially destoried in spleen making BITE CELLS
bite cell irregular shape makes them sensitive to intravascular hemolysis |
|
|
Term
| what types of oxidative stress can cause a problem in G6PDH deficiency anemia 4 |
|
Definition
infection
drugs: primaquine, chloroquine, sulfonamide
fava beans |
|
|
Term
| signs of G6PDH deficiency anemia 3 |
|
Definition
occur 2-3d after oxidative stress
hemoglobinuria
back pain |
|
|
Term
| why do people with G6PDH anemia get back pain |
|
Definition
| nephrotoxic Hb in kidney 2-3d after oxidative stress |
|
|
Term
| how is G6PDH deficiency anemia diagnosed 2 |
|
Definition
heinz bodies: shows percipitated Hb
enzymatic studies: must do AFTER acute episode or all the cells left over will just be good cells and give no results |
|
|
Term
| causes of warm imune hemolytic anemia 4 |
|
Definition
primary: idiopathic
secondary: leukemia, lymphoma, neoplasm autoimmune (esp SLE) |
|
|
Term
| how does warm immune hemolytic anemia cause anemia |
|
Definition
IgG binds RBC in WARM areas of the body causing complement C3b recruitment
membrane consumption in spleen bit by bit over time makes cells SPHEROCYTE shape
most hemolysis occurs due to opzonixation of RBC by autoantibodies INTRAVASCULAR HEMOLYSIS |
|
|
Term
| signs of warm immune hemolytic anemia |
|
Definition
jaundice
spenomeagly
normocytic anemia with spherocytes
coombs test |
|
|
Term
| explain how a direct and indirect coombs test for wam immune hemolytic anemia works |
|
Definition
direct: checks RBC: antibody against IgG causes agglutination
indirect: checks serum: put RBC in pt serum and add anti-IgG causing agglutination |
|
|
Term
| tx warm immune hemolytic anemia |
|
Definition
steroids
IVIG
remove drug
splenectomy |
|
|
Term
| cause of cold immune hemolytic anemia 4 |
|
Definition
mycoplasma pneumonia
infectious mono
idiopathic
lymphoid neoplasms |
|
|
Term
| how does cold immune hemolytic anemia cause anemia |
|
Definition
in cold (ears, hands, toes) IgM binds RBC and fixes C3b but isn't lysed because its too cold for the rest of the complement cascade
when they get to warmer place IgM is released by C3b stays.
this causes cell to be eaten by macrophages, EXTRAVASCULAR HEMOLYSIS, and causes agglutination with other cells |
|
|
Term
| signs of cold immune hemolytic anemia 7 |
|
Definition
hepatosplenomeagly
raynauds phenomenon
positive DAT for C4b
intravascular hemolysis: hemoglobinuria, hemoglobinemia, decreased haptoglobin
positive coombs test |
|
|
Term
| how can penicillin cause immune hemolytic anemia |
|
Definition
| absorbs into RBC and antibody binds cell leading to extravascular hemolysis |
|
|
Term
| how can quinidine cause immune hemolytic anemia |
|
Definition
| makes drug-Ab complexes that are absorbed into RBC causing complement fixation and intravascular/extravascular hemolysis |
|
|
Term
| how can a-methyldopa cause immune hemolytic anemia |
|
Definition
| induces RBC autoantibody (same as warm/IgG but self limiting in a few mo) |
|
|
Term
| how can cephalosporin cause immune hemolytic anemia |
|
Definition
| causes RBC membrane to become stickly and IgG and complement adhere non-specificially |
|
|
Term
| what are the two types of angiopathic hemolytic anemia |
|
Definition
macroangiopathic hemolytic anemia (in large vessels)
microangiopathic hemolytic anemia (in capillaries) |
|
|
Term
| causes of macroangiopathic hemolytic anemia 2 |
|
Definition
calcified stenotic aortic valve: sheer forces due to turbulent flow and abnormal pressure gradients
artificial mechanical heart valves |
|
|
Term
| causes of microangiopathic hemolytic anemia 6 |
|
Definition
DIC - most common
thrombotic thrombocytopenic purpura
hemolytic uremic syndrome
malignant HTN
SLE
disseminated cancer |
|
|
Term
| how does how is angiopathic hemolytic anemia diagnosed |
|
Definition
| small vessel thrombosis partially blocks vessels and sheers RBC causing SCHISTOCYTES (HELMET/TRIANGLE/BURR RBC) |
|
|
Term
| what are the causes of anemia due to underproduction 6 |
|
Definition
microcytic and macrocytic anemia causes decreased reticulocytes
renal failure decreases erythropoetin and thus reticulocytes
damaged progenitor cells
drugs and chemicals
viruses
autoimmune / idiopathic 50% |
|
|
Term
| what are the causes of damaged RBC progenitor cells 2 |
|
Definition
parvovirus B19
aplastic anemia |
|
|
Term
| how does parvovirus B19 effect RBC |
|
Definition
stops erythropoesis and causes anemia in pt with preexisting marrow stress
self limited |
|
|
Term
| drugs that cause aplastic anemia |
|
Definition
antioneoplastic
benzene
chlorphenicol reaction or hypersensitivity |
|
|
Term
| viruses that cause aplastic anemia, how can you tell cause is viral |
|
Definition
community acquired viral hepatitis (not ABC)
aplasia for several months after |
|
|
Term
| 2 autoimmune causes of aplastic anemia |
|
Definition
familial telomere defect causes premature senescence of hematopoetic stem cells
autoreactive T cells: associated with paroxysmal nocturnal hemoglobinuria, T cells may target PIG/GIP |
|
|
Term
| blood changes in aplastic anemia 7 |
|
Definition
marrow failure/hepatocellular/fatty marrow: 10% cellularity only WBC and plasm a(dry tap)
pancytopenia: normocytic normochromatic anemia with decreased reticulocyte count
anemia
thrombocytopenia
granulocytopenia
hemorrhage
bacterial infection |
|
|
Term
| symptoms of aplastic anemia 4 |
|
Definition
petechiae and echimosis
palor, weakness, listless
chills and fever
infections |
|
|
Term
|
Definition
stop drug
transfusion
marrow stimulation
immune supression
transplant is curative |
|
|
Term
| cause of myelophtisic process |
|
Definition
| pathological process replaces marrow causing decreased hematopoesis and pancytopenia |
|
|
Term
| what conditiosn is myelophistic process associated with 7 |
|
Definition
breast, lung, prostate, and other cancer
TB
lipid storage diseases
osteosclerosis |
|
|
Term
| changes in blood in myelophistic process 3 |
|
Definition
misshaped RBC resemble teardrops
immature granulocytic and erythrocytic precursors (leukoerythroblastosis)
thrombocytopenia |
|
|
Term
|
Definition
| increase in blood concentration of RBC usually correlated with increased HB concentration |
|
|
Term
| definition and causes of reactive polycythemia |
|
Definition
| hemoconcentration due to decreased plasma volume caused by dehydration |
|
|
Term
| define absolute polychthemia |
|
Definition
| increase in total RBC mass |
|
|
Term
| 4 causes of primary absolute polycyhemia |
|
Definition
autonomous proliferation of myeloid stem cells
abnormal proliferation of myeloid stem cells
normal/low erythropoetin levels (polychthemia vera)
inherited activating mutations of erythropoetin receptor (rare_ |
|
|
Term
| 3 appropirate causes of secondary absolute polychthemia |
|
Definition
| lung disease, high altitude, cyanotic heart disease |
|
|
Term
| 4 inappropirate causes of secondary absolute polychthemia |
|
Definition
erythropoetin secretin tumor
carcinoma hepatoma
cerebellar hemagiioblastoma
renal cell carcinoma |
|
|
Term
| in general, what is the cause of secondary absolute polycythemia |
|
Definition
| response to increased erythropoetin |
|
|
