T2 - Neoplasia 11 - Nutritional Anemias And Hemolytic Anemias

Front 1

Define anemia:

what general things can lead to anemia?

Back 1

decrease in the oxygen carrying capacity of RBC's due to a decrease in their mass.

things that lead to anemia:
decreased production of RBC's

increased destruction of RBC's

loss or RBC's (bleeding)

Preggers - babies steal iron during pregnancy/lactation.

rare in men, common in women (they have higher daily requirements due to aunt flo)

Front 2

where in the gut is iron absorbed, and why is malabsorption so common?

Back 2

malabsorption is really uncommon. absorbed in the dupdenum - happens only in patients with duodenal resection or random malabsorptive conditions.

Front 3

so what is the most common source of iron deficiency?

Back 3

blood loss (chronic). likely from the gut - need to think about colon carcinomas.

Front 4

talk about the blood smear appearance and the lab tests that indicate iron deficiency anemia - and how do you fix it?

Back 4

MICROCYTIC and HYPOchromic cells - so they're small and pale. Think that you need to fill up the RBC's with heme, and you aren't able to do it.

MCV (mean cell volume) = low

lots of anisocytosis and poikilocyotiss (bad size/shape)

serum FERRITIN is LOW

TIBC (total iron binding capacity) is HIGH, due to there not being enough iron.

fix if possible with oral iron - it's cheap, give with Vit C to help improve absorption. Can also give IV and with transfusion.

Front 5

how long does it take B12 deficiency to show up? what's the most common cause? go over the typical route of B12 absorption.

Back 5

years! we have a decade or so of B12 stores. Vegans have to keep at their bullshit to get sick.

more commonly, see pernitious anemia - this is autoimmune destruction of the parietal cells that release intrinsic factor.

usually, eat b12, it gets bound up and protected by R factor in the saliva/stomach, then by intrinsic factor in the alkaline part of the small intestine.

then it's absorbed with the intrinsic factor in the distal ilium.

Front 6

what symptoms do you see in b12 deficient people?

Back 6

nervous system problems - loss of proprioception and vibration, dementia, psychosis, peripheral neuropathies

Front 7

what are the smears/lab tests like in B12 deficiency?

Back 7

here, see MACROCYTIC RBC's - remember that b12 is necessary for cell division, and without it, cells swell up and can't separate.

also see HYPER-SEGMENTED neutrophils (PMN's) - >5 segments. Again, can't divide.

Also see results of increased hemolysis: increased indirect bilirubin, maybe.
LDH is up (lactate dehydrogenase)
Homocystine is UP
Methylmalonate is UP.

Front 8

how long does it take folate deficiency to show up and where does it come from? what condition should you think of when you hear folate deficiency?

Back 8

green leafy vegetables - and note that you DO NOT have big stores of folate, so deficiency can show up fast.

ALCOHOLISM is where you see most folate deficiency. Gets in to the cell when it's MONOGLUTEMATED, alcohold stops the deglutination reaction. So can have normal stores of folate but unable to use it when boozing.

Front 9

what does the smear/lab values for folate deficiency look like?

Back 9

smear looks JUST LIKE B12 deficiency - macrocytic RBC's, extra segments in the PMN's.

lab values are like b12 deficiency, except that the methylmalonyl is NORMAL.

so, MCV is high
homocystine is HIGH
methylmaolnyl is NORMAL.

Front 10

back to iron deficiency - if you are suspecting that there's a lack of production, what are possible causes?

Back 10

maybe ERYTHROPOETIN deficiency - this is the hormone that gets it all started. Recall that erythropotein comes FROM THE KIDNEY - so look at kidney function tests. Can supplement with erythropoetin.

Front 11

what does the reticulocyte count tell you in the context of anemia?

Back 11

it should be elevated if the patient is anemic - this is the body's normal response to anemia (make more RBC's).

Reticulocytosis should kick in within 4 days.

if it's normal or low in the face of anemia, something's wrong with the bone marrow.

Front 12

what's the most common anemia in the hospital? signs and lab values?

Back 12

the other doctor lady thinks its INFLAMMATORY ANEMIA or ANEMIA OF CHRONIC DISEASE.

here, inflammatory cytokines (IL6) cause release of HEPCIDIN - this lowers iron absorption and stops iron release by macrphages (think that bacteria need iron, so better to not have it floating around).

varries from iron deficiency in that the ferritin is HIGH and the TIBC is LOW (normal iron deficiency is opposite).
MCV can be normal, then goes down.

need to treat the disease, maybe give erythropoetin.

Front 13

if someone has iron deficiency anemia, what's the first thing to do?

Back 13

identify the source of bleeding - it's the most common cause.

Front 14

what's the main cause of b12 deficiency?

Back 14

malabsorption syndromes. pernitious anemia is relatively rare.

Front 15

what generally are the indicators of hemolytic anemia on lab tests? what about physical symptoms?

Back 15

high LDH, high indirect (unconjugated) bilirubin, low haptiglobin (it's degraded when it's free in the cytoplasm).
high urate (uric acid)

more reticulocytes


physical symptoms include PIGMENTED GALLSTONES (from the bilirubin floating around), hepato/spleno megaly, jaundice.

these are the things that show up in tests when RBC's are getting lysed.

Front 16

generally, how can HEMOLYTIC syndromes be divided and subdivided?

Back 16

hemolytic syndromes can be inherited or acquired.

inherited ones include:
heredetary spherocytosis
heredetary elliptocytosis
heredetary stomatocytosis (cytoplasmic mouths).

thalasemias (alpha/beta)

enzyme defects (G6p deficiency)

hemoglobinoathies (sickle cell)

acquired: These are either IMMUNE (warm/cold) or NON-immune (MAHA)

Front 17

details of sickle cell - what kind of hemoglobin is made? what kinds of hemoglobin are there? What do you see on electrophoresis in Trait vs. Disease?

Back 17

recall that hemoglobin A is 2 alpha, 2 beta.

hemoglobin A2 is made of 2 alpha, 2 delta.

Hemoglobin F is fetal and made of 2 alpha, 2 gammas.

sickle cell people make HbSS.

in trait, you see bands in the A and S segments. In disease, one big band in S.

also can do the SOLUBILITY TEST - if you reduce HbSS, get turbid fluid you can't see through.

Front 18

what are targetoid RBC's and when do we see them?

Back 18

these are DACROCYTES - see anytime you're lacking a spleen, after liver disease, or in the hemoglobinopathies.

so that means SICKLE CELL
THALASEMIAS
LIVER DISEASE
ASPLENIA

Front 19

what are the symptoms seen in sickle cell?

Back 19

crises!

vasculoocclusive crisis = pain due to lack of blood

aplastic crises (can be due to co-infection with parvovirus B19)

sequestration crisis (rbc's trapped can lead to lack of circulating RBC's and hypovolemic shock type symptoms)

kill off your own spleen by age 5.

affects stature due to hypoxia and bone infarcts

priopism

gallstones (hyperchromatic) and cholystasis.

high output heart problems

seizures

strep

high maternal mortality.

hemolytic crisis.

Front 20

treatment of sickle cell?

Back 20

vaccinations, FOLATE (using it up all the time from making new cells), hydroxyurea (increases fetal Hb which we remember is Alpha 2, Gamma 2).

frequent eye exam.

Front 21

heredetary spherocytosis - what's messed up, what are the lab values, etc?

Back 21

symptoms are typical for your hemolytic anemias - gall stones, splenomegaly, high bilirubin.

caused by mtuation in the ANKYRIN gene - cell membrane scaffold - so the cell ends up spherical. Gets trapped in the spleen.

see spherical cells on smear.

the MCHC is HIGH in this disease - it's about the only time you see that particular value high.

NOTE - this has HUGE spleens, often leading to SPLENECTOMY. So if a question stem mentions a gigantic spleen, you know they're talking about spherocytosis.

Front 22

what's G-6-p deficiency and who has it?

Back 22

also confers resistance to malaria - seen in africans and mediteranians.

important in the glutathione pathway - this protects against oxidative damage. see hemolytic anemia after exposure to drugs, fava beans, infection.

Front 23

Thalasemias - what chromosomes have our hemoglobin genes, and generally what's the problem?

Back 23

C/some 16 has 2 copies of the alpha gene, c/some 11 has the beta, delta, and gamma genes (recall that HbA1 is 2 alphas, 2 betas. HbA2 is two alphas, two deltas, and HbF is two alphas, two gamms).

thalasemias come from messed up hemoglobin molecules - alpha from messed up alpha chains, beta from messed up beta chains.

Front 24

talk about alpha thalasemia, who's typically affected, disease course and variations: diagnosis?

Back 24

africans at greatest risk.

4 alpha genes - two on each c/some 16. With one or two mutated, you're generally asymptomatic. With 3, you have bad symptoms, and with 4 = hydrops fetalis (incompatible with life).

note that because you're still making at least one alpha and your betas are normal, YOU CANNOT DIAGNOSE WITH ELECTROPHORESIS (it will appear normal).

generally, alpha thalasemia is less severe than the betas (you have so many alpha copies and if you don't have any, baby dies before birth).

POST NOTE - 3 out of 4 alphas messed up SHOULD be diagnosable by electrophoresis.

Front 25

who gets beta thalasemias? symptoms/diagnosis?

Back 25

beta thalasemia is more mediteranian, india/pakistan/southeast asia.

here, only two copies of the gene present on c/some 11: remember that if you can't make enough beta, you'll try to make more hemoglobin A2 (2 alphas, 2 DELTAS) - so that's DETECTABLE by electrophoresis. Also more Hemoglobin F (2 alphas, 2 gammas) - recall that normally, there is NO hemoglobin F in people (3% is usually HbA2)

the product here is cytopathic and can cause MICROCYTIC ANEMIA, so not just iron deficiency causes that.

Front 26

so we talked about inherited hemolytic diseases. Which are acquired, generally?

Back 26

Acquired hemolytic diseases are divided into IMMUNE and NON IMMUNE.

Immune includes WARM and COLD.

Non-immune includes MAHA - microangiopathic hemolytic anemia.

Front 27

compare COLD and WARM hemolytic anemia

Back 27

in WARM, the offender is IgG (wear a G string when it's warm). They attack the Rh style markers on the RBC's. Not from complement fixation.
destruction in the SPLEEN. from drugs/infections/cancer.
glucocorticoids effective. Maybe antiCD20 rituximab.
splenectomy, maybe.
COOMB'S TEST positive.
see SPHEROCYTES (think of G string and boobs).

COLD hemolytic anemia: IgM (wear mittens), against I antigen of the ABO group. Complement fixation killing.
Agglutination on the glass side, see CLUMPING.
Maybe from cancer.
treat by KEEPING WARM.

Front 28

what's the main non-immune acquired hemolytic anemia?

Back 28

MAHA. Microangiopathic Hemolytic Anemia.

This is a condition seen in other diseases.

This is the water balloons through piano wire - the platelets are going crazy and putting up fibrin deposits in the blood vessels.

see sheared up RBC's on smear (schistosomes)

Seen in HUS, TTP (thrombotic thrombocytopenic purpura, preeclampsia, malignant hypertension).

cells on smear look cut in half= SCHISTOCYTES.

Front 29

just for fun, what's the coomb's test?

Back 29

it's a test to see if IgG or C3 are bound to the RBC's.

incubate RBC's with antibodies to the IgG or C3 and see if they clump. Might be positive in both warm and cold hemolytic syndromes, but for sure positive in warm.