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Path Anemia
KYCOM Block 14
205
Pathology
Graduate
02/18/2014

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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
number RBC per 100 cells
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
what is MPV
Definition
mean platelet volume
Term
what is PDW
Definition
platelet distribution width (simillar to RDW)
Term
how is Hb measured 3
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
define anemia
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
function of ferritin
Definition
prevents fenton Fe reaction from forming free ROS in Fe absorption in duodenum
Term
function of ferrportin
Definition
gate that decides to absorb Fe in duodenum (has to be choosy, we have no Fe elimination process)
Term
function of hepcidin
Definition
regulator of ferrportin gate (binds to ferrportin causing degredation)
stops Fe absorption in duodenum
Term
define acute blood loss
Definition
>20% volume
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
celiac disease
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
poor diet
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
Fe storage: locations
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
4 types of a-thalassemia
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
tx a-thalassemia trait
Definition
none
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
TX HbBart (Y4)
Definition
intrauterine transfusion
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
2 types of B-thalassemia
Definition
(B/B+) B-thalassemia minor (B-thalassemia trait)

(B0/B0) B-thalassemia major (cooley's disease)
Term
signs of B-thalassemia minor
Definition
mild, asymptomatic
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
you cant!
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
what is dactylitis
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
what is a pain crisis
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
vasooclusion of the lung
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
55% HbA
45% HbS
2% HbA2
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
sympgoms of HbC, why
Definition
mild anemia due to extravascular hemolysis
Term
how is HbC diagnosed
Definition
HbC crystals on smears
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
TX of aplastic anemia
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
define polychthemia
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
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