4 Moath Darwish Waseem Alhaj Tareq Adely...Please refer to the slides for pictures. Iron deficiency...
Transcript of 4 Moath Darwish Waseem Alhaj Tareq Adely...Please refer to the slides for pictures. Iron deficiency...
4
Moath Darwish
Waseem Alhaj
Tareq Adely
Please refer to the slides for pictures.
Iron deficiency anemia
Iron absorption and regulation .1
a. only 10% of ingested iron are absorbed
duodenumtion of iron occurs in . absorpb
c. Iron from plants is a nonheme, and poorly absorbed ( vegetabeles are
not good source for iron)
d. Iron from meat is a heme and directly absorbed in the duodenum
e. The amount of iron absorbed is regulated.
(1) Hepcidin is the “master” iron regulatory hormone and determines
whether iron is absorbed or not absorbed in the duodenum and whether
iron is released from macrophages or not released.
(2) A decreased level of iron stores in the body leads to reduced
hepcidin synthesis in the liver.
• This upregulates ferroportin, causing more iron to be reabsorbed in
the duodenum to bind to transferrin and more iron to be released from
bone marrow macrophages to bind to transferrin for erythropoiesis.
(3) An increased level of iron stores In the body leads to increased
hepcidin synthesis in the liver.
• This downregulates ferroportin, causing iron accumulation in
enterocytes, which are eventually shed into the bowel. A reduced level
of ferroportin also causes iron blockade in bone marrow macrophages,
so less is released for binding to transferrin.
Epidemiology .2
a. Most common overall anemia
b. Most common nutritional deficiency worldwide
c. People at increased risk of anemia are:
(1) infants aged 1 to 2 years
• Due to inadequate intake of iron (infant's milk is poor in iron)
(2) elderly
• because they can't digest meat well
(3) teenagers
• Restricted diets with very little meat intake; decreased intake of heme
iron.
(4) low socioeconomic class.
:Pathogenesis. 3
• Decreased synthesis of heme (iron + protoporphyrin) leads to a
decreased synthesis of Hb-
.microcytic hypochromic anemia
causes.4
classification causes discussion
Non heme iron in vegetables is poorly absorbed. Not sufficient to body demand
vegetarians Decreased intake
1)daily requirement for iron on lactation and pregnancy increases. 2) Iron is required for tissue growth and expansion of blood volume in the developing fetus
1)Pregnancy/lactation
2)Infants/adolescence
Increased utilization
Gastrointestinal loss Blood loss
Absence of the villous surface in the duodenum decreases absorption of iron
Celiac, Crohn's Decreased absorption
findings Clinical .5
a. symptoms due to anemia include headache , pallor, fatigue .
b. symptoms specific to iron deficiency:
(1)glossitis and inflammation in the mouth
(2)hair loss
theory ; there is a)picaCNS manifestation (depression, insomnia , and )3(
that some brain’s enzymes contains iron.
(4)spoon nails
findings labratory .6
A. Decreased serum iron and iron saturation
B. Decreased serum ferritin
C. Microcytic and hypochromic are present with increased central area
of pallor
D. Although erythropoietin is high, low iron stores in bone marrow blunt
its effectiveness, so there is no much increase in erythroid cells.
E. Thrombocytosis
-the doctor said that the exact mechanism is unknown, but some
theories say that erythropoietin, which increases in case of anemia,
cross react to activate megakaryocytes too.
- but according to textbooks, thrombocytosis occurs as a reactive phenomenon to
a tendency or craving to eat substances other Pica:
ashes than normal food (such as clay, plaster, or
a tendency or craving to eat substances :Pica
other than normal food (such as clay, plaster, or
ashes
increase blood viscosity and prevent high-output heart failure
.
In peripheral blood smears:
1)Anisopoikilocytosis: anisocytosis RBCs of varying sizes, poikilocytosis
RBCs of varying shapes
2)Target cells: appears in abnormal hemoglobinization( thalassemia,
sickle cell anemia, iron deficiency anemia)
Iron stains blue(left); compare it to iron absence(right)
astic AnemiaMegalobl
overviewvitamin B12
eggsand meatsoluble vitamin present in -Water. 1
2. Vitamin B12 stores in the liver is sufficient to supply the body for
years, so it's deficiency due to loss of storage is rare.
3. Intrinsic factor which is released from parietal cells of the stomach
is important to absorb vitamin B12 in the ileum
4. Important in myelination of nerves.
5. It's an important Coenzyme in thymidine synthesis
encycicauses of vitamin B12 defi a.
classification causes discussion
The stages of iron deficiency in sequence are as follows: absent
iron stores; decreased serum ferritin; decreased serum iron, then
microcytic hypochromic anemia appears.
Vitamin B12 is absent in vegetables
Pure vegan diet Malnutrition Decreased intake
-Autoimmune destruction of parietal cells: this occurs in pernicious. -gastrectomy decrease intrinsic factor -Crohn disease, celiac disease interfere with the vitamin absorption.
↓Intrinsic factor
↓Terminal ileum absorption
Impaired absorption
Folic acid overview .C
and meat lesvegetabound in is f Water soluble vitamin that. 1
2. The liver contains small amount of folic acid, so deficiency due to
loss of storage is quick.
3. It's coenzyme important in thymidine synthesis
encycicauses of folic acid defib.
classification causes discussion
Low vegetables intake Malnutrition Decreased intake
In celiac disease, villi in the jejunum may be destroyed, leading to folic acid deficiency.
Celiac disease Malabsorption
1)This drug inhibits thymidine synthesis in the cell. 2)inhibits uptake of folic acid from the intestine
1)Methotrexate
2) anti-convulsant, Oral contraceptives, alcohol
Drug inhibition
There is increased utilization of folic acid in DNA synthesis
Pregnancy Increased demand
1)folic acid could be lost from serum in renal failure and
dialysis which lead to it's deficiency
2) methotrexate and vitamin b12 deficiency impair
utilization of folic acid synthesis .
anemia megaloblastic of pathogensis
1. Impaired DNA synthesis delays nuclear maturation.
this Causes a block in cell division in all rapidly dividing cells, leading
to large, immature, hematopoietic cells with a pale inactive
chromatin
2. Ineffective hematopoiesis
a. Megaloblastic precursors outside the bone marrow sinusoids are
phagocytosed and destroyed by bone marrow macrophages.
b. Megaloblastic precursors undergo apoptosis, causing
pancytopenia (anemia, neutropenia, and thrombocytopenia).
Clinical findings in vitamin B12 deficiency
1. Pernicious anemia (PA)
• there is Abnormal autoreactive T-cell response initiates direct
gastric mucosal injury also triggers formation of autoantibodies
include :
A)Type 1 antibody: antibodies block Vit B12 from binding to intrinsic
factor
B) Type 2 antibody: Antibodies that prevent the binding of vitamin
B12–intrinsic factor complexes to ileal receptors
C)type 3 antibody: Antibodies directed against the proton pump in
parietal cells( to understand this point read the extra box below)
2. Neurologic disease associated with demyelination
(A) Peripheral neuropathy with sensorimotor dysfunction
(B) weakness in the muscle that is supplied by the nerve.
findings in vitamin B12 deficiencyLaboratory
1)peripheral blood findings include
A. Pancytopenia
b. Oval (egg-shaped) macrocytes
C. Hypersegmented neutrophils
Hypersegmented neutrophils have more than five nuclear lobes•
D. giant metamyelocyte
E. large,hyper lobulated Megakaryocytes:
in vitamin B12 deficiency Bone marrow findings. 4) 2
• Megaloblastic immature nucleated cells are present with a pale
inactive chromatin pattern
•as a result of increased erythropoietic level, bone marrow cellularity
, but because impaired DNA synthesis in the cells, increase initially
decrease they undergo apoptosis and Bone marrow cellularity will
too
Clinical findings in folic acid deficiency
to vitamin B12 deficiency with the exception of neurologic Similar•
disease
Laboratory findings in folic acid deficiency
to vitamin B12 similarPeripheral blood and bone marrow findings •
deficiency
: Anemia of chronic diseases
overview-
persistentwith chronic diseasesthis condition is associated with
inflammation like tuberculosis , HIV infection, rheumatologic diseases
and malignancies
NOTE :malignancies are associated with chronic inflammation because
malignant cell activate the immune system when they go necrosis
: Pathogenesis
nt inflammation , is released during persiste atth6,-interlukin
activate hepcidin, leading to decrease iron transfer from stores and
from macrophage to erythroid cells.
:findings Laboratory
serum ferritin is increased)1
Iron stores in BM are markedly increased )2
it becomes with time, normochromic normocytic anemia, llyiatIni) 3
hypochromic microcytic anemia.
iency anemia and anemia of icbetween iron def iateHow to different
In anemia of chronic diseases, serum ferritin and ?chronic diseases
iron stores in bone marrow are high, unlike in case of iron deficiency
anemia.
iron iency anemia, we don't give icunlike iron def Treatment :
supplement , instead, we treat the underlying cause.
: Aplastic Anemia
causes)1
classificiation discussion and example
Most cases Idiopathic
Rheumatoid arthritis and viral infection Inflammation
Like chloramphenicol and gold that occur rarely drug reactions :idiosyncratic reaction
and unpredictably amongst the population
Idiosyncratic reaction to drugs
2)pathogenesis
A) due to Immunologic alterations occur in the myeloid stem
(progenitor) cells, causing T-cell activation and release of cytokines
that suppress or destroy the myeloid stem cells .
B) or due to acquired or genetic mutation that overlap with PNH.( to
understand how read the below extra box)
findings laboratory)3
a. Pancytopenia
This is due to Mutations in TERT, the gene for
the RNA component of telomerase, cause
short telomerases in congenital aplastic
anemia
b. Reticulocytopenia
c. Hypocellular bone marrow (bone marrow is filled with fat)
D.no splenomegaly
:Myelophthisic anemia
: overview
it's an infiltrative disease that cause secondary bone marrow failure
:causes
1) most commonly due to bone marrow cancer like leukemia.
2)also, it could less commonly be caused due to granuloma, which is
an aggregation of macrophages that could destroy normal bone
marrow cells.
: laboratory findings
pancytopenia)1
no splenomegaly)2
chronic renal failure
pathogenesis
Low erythropoietin level decreases erythropoiesis
bleedingUremia impairs platelet function, leading to
labtratory findings
anemia normochromic normocytic) 1:
ich RBC's have small cytoplasmic ha condition in w ,echinocytes) 2
projection (spines)
: Hypothyroidism
since Thyroxin is essential for cell metabolism, it's deficiency causes
bone marrow's cells maturation to decrease, leading to macrocytic
anemia
chronic liver diseases
laboratory findings :
A)since clotting factors are synthesized in the liver, it's diseases leads
to bleeding
B)since liver is the major organ where lipids are synthesized, it's
diseases causes impairment in lipid synthesis , which lead to
)acanthocytes( abnormal RBC's with long projection
Myelodysplastic syndrome
in blood cells in which immature cancers up ofare a gro
do not mature and therefore do not become bone marrow the[.healthy blood cells
: sisepathogen
exposure to an agent known to cause DNA damage and
.smutation
: laboratory findings
1)megaloblastic immature erythroid, myeloid and megakaryocyte.
2)hyper cellular bone marrow , with low peripheral blood count,
they become unable defective in their functionsince these cells have
to exit from bone marrow
3) Aggregates of iron in the nucleus, this condition called ring
sideroblasts; ring because they are found around the nucleus.
:Polycythemia
. of RBCs, which is full of hemoglobin massIt’s an increase in the
.of RBCs numberErythrocytosis is an increase in the
(aka primary polycythemia and rubra vera) Polycythemia vera:
Neoplastic disease of erythroid cells
:Pathogenesis
JAK-2 mutation, which is erythropoietin receptor, become very
sensitive to erythropoietin. Also there are other mutations.
.ary erythropoiesis on ita result of extramedull Splenomegaly
an increased erythropoiesis, granulopoiesis and Panmyelosis
megakaryopoiesis ( because there precursor cells also contains JAK-2)
By negative-feedback there will be a decrease in erythropoietin level.
:Clinical symptoms
Plethora, cyanosis and itching( plethora is a red skin / itching occurs
due to increased WBCs numbers and increased histamine and other
cytokines)
Sluggish circulation predisposes to thrombosis
Bleeding can also occur because platelets aren’t functioning well
Hypertension
Gout occurs when RBCs die they release uric acid which forms
crystals
:Lab findings
High HB, Hct, RBC count reticulocytes count.
High WBCs and platelets (panmyelosis)
:Secondary polycythemia
An adaptive change with no mutations
Causes:
a.chronic hypoxia, the body respond by increasing erythropoietin,
examples include : chronic lung and heart diseases, alcoholism,
smoking and high altitude.( alcohol suppresses normal respiration,
also it increases urination with subsequent high blood concentration)
b.Renal cell carcinoma: cells secrete erythropoietin
c.surreptitious: when athletes take certain drugs to increase there
performance
Secondary polycythemia is reversible and characterized with high
erythropoietin with no splenomegaly