Anemias - Hertz - SRS Flashcards
An unbelievably skinny woman comes in with the attached CBC results. What do you think?
Severe anemia, high MCV indicates likely a B12 or folate deficiency
What are the most common/important anemias associated with red cell underproduction?
Top 3
- Nutritional deficiencies
- Renal failure
- Chronic inflammation
What do aplastic anemia, primary hematopoietic neoplasms, and infiltrative disorders have in common?
Lead to generalized marrow failure
What is the common theme among the megaloblastic anemias?
Impairment of DNA synthesis leading to ineffective hematopoiesis and distinctive morphological changes including abnormally large erythroid precursors and red cells.
What is a term we should associate with megaloblastic anemia?
Asynchrony
What are the major causes of megaloblastic anemia?
- B12 deficiency
- folic acid deficiency
What are examples of impaired absorption derived megaloblastic anemia?
- Intrinsif factor deficiency (pernicious anemia and gastrectomy)
- Malabsorption states
- Diffuse intestinal disease (lymphoma, systemic sclerosis
- Ileal resection, ileitis
- Bacterial overgrowth in blind loops and diverticula of bowel
What are the two causes of intrinsic factor deficiency Hertz talked about?
Which one did he emphasize?
Pernicious anemia
gastrectomy
Decreased intake can cause megaloblastic anemia, what are the big examples of this Hertz emphasized with big stars?
3
What are two other causes of decreased absorption of folic acid that were incorrectly formatted in the table hertz gave us?
- Inadequate diet
- Alcoholism
- infancy
- anticonvulsants
- oral contraceptives
What is an example of an impaired utilization megaloblastic anemia causitive agent?
Folic acid antagonists - methotrexate!
What does the presence of these nuclear hypersegmentation and macro-ovalocytes indicate?
B12 or foloate or myelodysplastic syndromes
What is pernicious anemia caused by?
Autoimmune gastritis that impairs the production of intrinsic factor
What is intrinsic factor important for?
B12 uptake from the gut
Your patient with anemia comes in for you to do endoscopy and gastric biopsy, this is what you find. What is going on?
On the left, the stomach should not be smooth like that. The histology image shows decreased glands and loss of normal villous structure.
These findings indicate that autoimmune gastritis is causing pernicious anemia in your patient.
How is the shillings test performed?
Radioactively tagged cobalamine given to patient will rule out intrinsic factor deficiencies.
Where does B12 come from?
Meat, specifically the bacteria in/on meat
What produces intrinsic factor?
Parietal cells of the fundic mucosa
What are B12 and folate needed for?
DNA synthesis
Pernicious anemia involves an autoimmune attack on the gastric mucosa. What do you find grossly/histologically?
Chronic atrophic gastritis
What are the three types of antibodies that can be involved in pernicious anemia?
Type I
Type II
Type III
Roughly 75% of pernicious anemia cases are due to type I antibodies. What does this antibody type do?
Blocks the binding of vitamin B12 to intrinsic factor
Where are type I antibodies found?
In both plasma and gastric juice
What do type II antibodies do?
Prevent binding of the intrinsic factor-vitamin B12 complex to its ileal receptor.
Type III antibodies are present in 85% to 90% of patients with pernicious anemia. What do these antibodies do?
Bind the alpha and beta subunits of the gastric proton pump, which is normally localized to the microvilli of the canalicular system of the gastric parietal cell.
Describe the findings shown, and identify what disease process they are associated with.
- Left: Fundic gland atrophy
- Right: Intestinalization (of the stomach, it now looks histologically like intestine)
- Pernicious anemia
Describe what is going on in the attached image and identify the disease process it is associated with.
- Silver stain reveals demyelination of the dorsal and lateral spinal tracts - leading to sensory deficits.
- Pernicious anemia
What are the four diagnostic clinical features of pernicious anemia?
- Moderate to severe megaloblastic anemia
- leukopenia with hypersegmented granulocytes
- Low serum vitamin B12
- Elevated serum levels of homocysteine and methylmalonic acid
How is the diagnosis of pernicious anemia confirmed?
2
- By an outpouring of reticulocytes and a rise in hematocrit levels beginning about 5 days after parental administration of vitamin B12.
- Also, serum antibodies to intrinsic factor are highly specific for pernicious anemia.
What do patients with pernicious anemia have an increased risk level for developing? (three things)
Gastric carcinoma
Atherosclerosis
thrombosis
Interpret this CBC.
Moderate macrocytic anemia
What two things does this peripheral smear bring to mind?
Folate and B12 deficiencies, both look the same on peripheral smear
What is the common denominator of B12 and folate deficiency, and what does this cause?
Suppressed DNA synthesis
Immediate cause of megaloblastosis
What are the three main causes of anemia of folate deficiency?
- decreased intake
- increased requirements
- impaired utilization
How long does the body store B12? Folate?
B12: stores last years
Folate = One month
In what patients are folate deficiencies most frequently encountered? 3
- Chronic alcoholics
- the indigent
- Eldery
Malabsorption syndromes can lead to inadequate absorption of folate. What are two examples of this?
Celiac sprue
Infiltrative diseases of the small intestine - noteably MALT/Marginal zone lymphoma
Some drugs can cause impaired folate absorption. What are two examples?
- Phenytoin (anticonvulsant)
- Oral contraceptives
Despite normal intake, a relative deficiency of folate can arise when requirements are increased. What are four examples of this?
- Pregnancy
- infancy
- derangements associated with hyperactive hematopoiesis
- Disseminated cancer
Folic acid antagonists can lead to a deficiency of FH4. What is an important example of this?
Methotrexate
Many chemotherapeutic drugs used in tx of cancer damage DNA or inhibit DNA synthesis through other mechanisms. What type of change can these cause in rapidly dividing cells?
Megaloblastic changes
Do you get neural deficits in anemia of folate deficiency?
Nope
As in vitamin B12 deficiency serum homocystiene levels are increased in anemia of folate deficiency. How about the levels of methylmalonate?
Normal in this one.
If you have a patient with B12 who is exhibiting neurological defects typical of the B12 deficiency state, can you give folate to reduce the symptoms?
No, in fact it may even make it worse.
So, folate can’t help with the neurological symptoms of B12 deficiency… is there a reason we might give it to a patient with a B12 anemia?
Yes, the hematological symptoms of B12 deficiency also respond to folate therapy.
45 yo female with cc of fatigue. You get the attached smear. What does this indicate?
Presence of pencil cells indicates the patient has an iron deficiency.
Interpret the attached CBC
Severe hypochromic microcytic anemia
You work up your 45 yo female patient with hypochromic microcytic anemia and obtain the attached US and biopsy.
Endometrial hyperplasia
What is the most common nutritional deficiency in the world?
What are the corresponding signs and symptoms related to?
Iron deficiency
inadequate hemoglobin production
What amount of iron is absorbed AND lost per day in a normal individual?
1-2mg/day
1-2mg/day
Samesies
If hepcidin is upregulated, how does your absorption of iron change?
It decreases since hepcidin is a ferroportin inhibitor
What is hepcidin released in response to?
Increased intrahepatic iron levels
In the case of anemia of chronic disease, perhaps more acccurately referred to as the anemia of chronic inflammation, what causes increased hepcidin production in this scenario?
Inflammatory mediators
Characterize hepcidin activity in both primary and secondary hemochromatosis, a syndrome caused by systemic iron overload.
inappropriately low in both
Secondary hemochromatosis can occur in diseases associated with ineffective erythropoiesis such as?
give two examples
B-thalassemia major
myelodysplastic syndromes
Give me four causes of iron deficiency anemia.
- Dietary lack
- impaired absorption
- increased requirement
- chronic blood loss
Infants, are at high risk of iron deficiency anemia due to the small amount of iron in milk. Human milk provides only about 0.3 mg/L of iron. Cows milk has twice as much. Is it as good?
Why?
No, because bioavailability is poor.
Apart from infants, what other people are at high risk for dietary iron deficiency?
- The impoverished - suboptimal diets for socioeconomic reasons.
- Older adults - restricted diets with little meat because of limited income or poor mastication.
- Teenagers who subsist on junk food. Also Michael.
We already discussed how sprue decreases iron absorption. Other causes include chronic diarrhea and gastrectomy. What is the problem that gastrectomy causes?
- Impairs iron absorption by decreasing the acidity of the proximal duodenum (reduction of ferric form to ferrous which we can absorb. (Ferrous goes into us)
- Increases the rate that gut contents pass through the duodenum.
Growing infants, children, adolescents and premenopausal women during pregnancy. What patients are at exceptionally high risk for iron deficiency?
Economically deprived women having multiple closely spaced pregnancies.
What is the most common cause of iron deficiency in the western world?
Chronic blood loss
What are the sites where internal chronic blood loss is commonly seen?
- GI tract
- Urinary tract
- Genital tracts
Iron deficiency in adult men and postmenopausal women in the western world must be attributed to what until proven otherwise?
gastrointestinal blood loss (probably mostly colorectal cancer)
What are each of these findings called and what are they indicative of?
Left: Koilonychia
Right: Atrophic glossitis
Iron deficiency (atrophic glossitis can also be B12 deficiency per Hertz says)
What is the finding shown in the barium swallow radiograph attached?
Esophageal web or ring
Your patient with the attached image also has iron deficiency anemia and atrophic glossitis. What does this combination equal?
Plummer-Vinson syndrome
What does the dx of iron deficiency anemia ultimately rests upon what?
laboratory studies.
Describe the levels of serum iron, ferritin and total iron binding capacity (TIBC) in the case of iron deficiency anemia.
Serum Iron = Low
Ferritin = low
TIBC = High
