Pathoma

Doctor notes
Exactly from essential
From books but my notes
Goljan
My notes from internet
IMP Terminology to know :
Hematopoiesis: Hemato(blood), poiesis (production) : Production of all types of blood cells
Myelopoiesis: Myloid cells (all cells except lymphoid cells)
Dyserythropoiesis: disorders erythropoiesis
Anisopoikilocytosis: Aniso(different size) , Poikilo(different shape) , Cytosis: cells
Normoblast: Normal erythroblast (still has nucleus ) Eryhtroblast only means erythroid cells, it
does not tell normal or abnormal.
Pancytopenia: (a drop in red cells, granulocytes and platelets) which suggests a more general
marrow defect .
Erythropoiesis : Production of red blood cells (RBCs) in the bone marrow.
Erythropoiesis
-To make all types of blood cells we start with pluripotent hematopitic stem cell (PHSC), as
they reproduce a small portion remains the same to be retained in the bone marrow.
- The stem cells would give two lineage of cells ( either lymphoid stem cell ) or myloid lineage
also known as : colony forming unit grnulocytes, erythroid, monocyte, megakaryocyte (CFU-
GEMM). Then we get committed stem cells which give specific types of cells.
-Now, for red cells we start with : 1. Burst forming unit erythroid (BFU-E) which I think is the
same as (CFU-B). 2. Colony forming unit erythroid (CFU-E).
- Then we get the pronormoblast (proeryhtroblast) : This is a large cell with dark blue
cytoplasm, a central nucleus with nucleoli and slightly clumped chromatin.
*With more divisions They also contain progressively more haemoglobin (which stains pink) in
the cytoplasm; the cytoplasm stains paler blue as it loses its RNA and protein synthetic
apparatus while nuclear chromatin becomes more condensed*
-After the proeryhtro we get Basophil erythroblasts (EARLY) – Polychromatophil
(INTERMEDIATE) eryhtrhoblast (erthroblast is the same as normoblast) - Orthochromatic
(LATE )erythroblast - reticulocyte and finally erythrocyte ( for more details look at physiology)
*A single pronormoblast usually gives rise to 16 mature red cells*
In developing eryhthroid cells the sign of maturation is loss of nucleus .

Pyknotic is to describe
the nucleus chromatin
condensation

Look at smear pic in

essential page 13
 Erythropoietin (EPO)
- Erythropoiesis is regulated by the hormone erythropoietin (by increasing the number of
progenitor cells committed to erythropoiesis). The erythropoietin gene contains a hypoxia
response element at its 3' end.
- Normally, 90% of the hormone is produced in the peritubular interstitial cells (in the renal
cortex) of the kidney and 10% in the liver and elsewhere.
- The stimulus to erythropoietin production is the oxygen (02) tension in the tissues of the
kidney.
When erythropoietin production increase?
1. Anemia 2. When atmospheric O2 is low 3. In defective cardiac or pulmonary function 4.
Damage to renal circulation that affects O2 delivery to the kidney. 5.Hypoxemia (low arterial
PO2). 6.left-shifted O2-binding curve (OBC), 8. high altitude. 9. decreased O2 saturation
(SaO2; carbon monoxide poisoning, methemoglobinemia)
- Conversely, increased 02 supply to the tissues (because of an increased red cell mass like in
polycythemia vera (canver) or because hemoglobin is able to release its 02 more readily than
normal) reduces the erythropoietin drive.

Other EPO sources: renal

In anemia related to renal failure or
cell carcinoma,
chronic disease or chemotherapy we
hepatocellular carcinoma
usually give a form of erythropoietin
called epoitin alpha made by
recombinant DNA technology . this
epoitin alpha is also abused by some
athletes to increase energy.
Reticulocytes and the reticulocyte count
The reticulocyte count is imp to measure effective erythropoiesis, effective erythropoiesis
refers to having a good bone marrow response to anemia ( which is to increase the
reticulocytes synthesis and release ), RBC maturation needs help from splenic macrophages.

The reticulocyte count is a percentage (normal is less than 3%) and so it could falsely increased
in anemia and that is why we need to correct it. To calculate the reticulocyte count we take
the nb of reticulocytes and divide it by the nb of RBC where the reticulocytes where found,
that is why if we have two people both with the same nb of reticulocytes but one of them has
anemia, since the one with anemia will have less RBCs his percentage will be falsely high so
we correct it !

Reticulocyte count

Example calculation: Read about

(1) Hct 15%, reticulocyte count 18% polychromasis in goljan
(2) Corrected reticulocyte count is 6% (15/45 . 18% = 6%)

-If the corrected is more than 3 % it is effective erythropoiesis , like in hemolytic anemia (sickle
cell ) or after you treat some one with iron deficiency anemia

- if the corrected is less than 3 % it is ineffective erythropoiesis, which indicates bone marrow
response to anemia, this happens in cases of aplastic anemia (deficiency of all types of blood
cell caused by failure of bone marrow development.) also happens in folic acid deficiency also
in chronic anemia and untreated iron deficiency anemia.
Read about Extramedullary
hematopoiesis in goljan
 Remember than in anemia PO2 and
SaO2 are normal because exchange
in the lungs is normal, but the O2
content in the RBC would be low
Complete Blood Cell Count and Other Studies
What do we measure from CBC: Hb – Hct – RBC count – RBC indices – RDW – WBC count (with
differential count ) – platelets count – peripheral blood morphology

Anemia classification and laboratory findings

Anemia Definition: Reduction in red cell mass OR Reduction in the hemoglobin concentration
of the blood, less than 13.5 g/dl in males and less than 11.5 g/dl in females (less than 12.5
g/dl) .
Normal Hb values Males : 13.5-17.5 g/dl Females : 12.5-16 g/dl . in newborns it should not
be less than 14g/dl.
Anemia is decrease in red blood cell mass BUT it is difficult to measure it so we use 3 other
surrogates : HB and Hematocrit and Red cell count so anemia could be defined as decrease in
Hb,Hct OR Hb concentration. ( we say surrogates because they are not always equal) For
example :
When Plasma volume increase like in splenomegaly or pregnancy even though mass is same,
Hct and Hb go down due to dilution which cause anemia . Or when plasma volume decrease
like in dehydration will mask anemia or even cause (pseudo) polycythemia.
Also after acute major blood loss anemia is not apparent immediately apparent because the
total blood volume is reduced. It takes up to a day for the plasma volume to be replaced and
so for the degree of anaemia to become apparent.

Symptoms: related to hypoxia

-shortness of breath (dyspnea )+ lethargy (fatigue )+ weakness + inability to concentrate +
dizziness + palpitations + headaches + lightheadedness + angina + intermittent claudication +
confusion + Visual disturbances because of retinal haemorrhages may complicate very severe
anaemia, particularly of rapid onset.

Signs: related to hypoxia

pale conjunctiva and skin and palmer creases (if less than 9 or 10 g/dl) pallor indicate severe
anemia + Pulmonary valve &ow murmur, due to decreased blood viscosity in severe anemia +
High-output cardiac failure Due to decreased blood viscosity in severe anemia (<5 g/dL)
Iron deficiency anemia: koilonychia 'spoon nails'
Hemolytic or megaloblastic anemia : jaundice
Sickle cell and other hemolytic anemias : leg ulcers
thalassemia major and other severe congenital haemolytic anaemias : bone deformities
The association of features of anaemia with excess infections or spontaneous bruising suggest
that neutropenia or thrombocytopenia may be present, possibly as a result of bone marrow
failure
I skipped RBC indices since I have najeeb notes
+ Mature RBC Characteristics
 Iron studies
(Serum ferritin – Serum iron – TIBc- Iron saturation%)

1-Serum ferritin :
Ferritin is the protein that controls the process of releasing iron according to our body needs.
Ferritin is stored and found in many areas of our body like our bone marrow macrophages and
liver (hepatocytes) and spleen cells and skeletal muscles.
Although ferritin is found in these areas, it is also found in in our blood . the definition of
serum ferritin is : soluble iron-binding storage protein. It is imp because the serum levels
directly correlate with the ferritin stores in macrophages : 1 μg/L of serum ferritin correlates
with 8 mg of storage iron. We use this In diagnosis of anemia, if you don’t have iron then you
cannot store it (storage form is ferritin ).
“Ferritin functions as an intracellular site of iron storage. Clinically significant concentrations are
found in serum, and the concentration of serum ferritin is directly related to total body iron
stores.”
So when serum ferritin decrease this means person has iron deficiency, if serum ferritin
increase this could be chronic disease or iron overload.

When ferritin is degraded by lysosomes it gives hemosiderin which is insoluble and stains
blue with Prussian blue stain. Hemossideren levels also correlate with changes in
ferritin stores in macrophages of the bone marrow.

2-Serum iron :
We are talking about iron in the plasma which can’t be left on its own, it needs to bind to
transferrin so we are measuring : iron that is bound to transferrin. It is decreased in iron
deficiency and chronic disease anemia. It is increased in iron overload (like hemochromatosis
and the sideroblastic anemias )
Remember that transferrin carries the ferric form of iron (Fe3) . each transferrin has can bind
2 iron molecules
3-Serum total iron- binding capacity TIBC :
Correlates with the concentration of transferrin (bound or unbound to iron ). Transferrin
takes the ferric iron from the bone marrow macrophages and from the deuodenum (where
iron is reabsorbed) and delivers ferric iron (Fe3+) to erythroid precursors in the bone marrow.
The amount of ferritin in the macrophages has negative feedback on transferrin synthesis in
the liver .

In iron deficiency, ferritin is low , so TIBC in increases .

In anemia of chronic disease and iron overload, ferritin is increased, so TIBC is decreased.

TIBC is not exactly the same as transferrin, remember than transferrin can bind 2 molecules of
iron, so TIBC is the maximum amount on iron that can bind to transferrin molecules so the nb
of transferrin molecules will determine the TIBC ..... this was from a YouTube video

4- iron saturation (%) : AKA transferrin saturation

percentage of binding sites on transferrin that are occupied by iron.
Iron saturation (%) = serum iron/ TIBC × 100 . the normal % saturation is 100/300 × 100, or
33% (one third ).
Low saturation in : iron deficiency + chronic disease
Increased saturation in : iron overload diseases
 Anemia
Classification: based on red cell indices : Microcytic ( > 80) ,normocytic (80-100),
Macrocytic (< 100)
With anemia we expect reticulocyte count to be high due to erythropoietin (If the
reticulocyte count is not raised in an anemic patient this suggests impaired marrow function
or lack of erythropoietin stimulus)
Iron deficiency is the most common cause of anemia in every country in the world. And it is
the most common nutritional deficiency

Iron deficiency
Microcytic Anemia
Anemia of chronic disease ACD

Thalasemia

Sideroblastic Anemia
All are defects in Hb synthesis
• Hemoglobin = heme + globin chains. Heme is : iron + Protoporphyrin

Iron : iron deficiency + ACD

Protoporphyrin : Sideroblastic anemia
Defects in globin : Thalasemia ( alpha and Beta )

1- Iron deficiency anemia

(Ancylostoma duodenale and Nieator americanus) in the developing world

breast-feeding (human milk is low in iron)

Like in gastrectomy
 Clinical and laboratory findings
a. Chronic iron deficiency
(1) Esophageal web (Plummer-Vinson syndrome) : Produces dysphagia for solids but not liquids
(2) Achlorhydria : Absence of hydrochloric acid in the stomach
(3) Glossitis and angular cheilosis : Inflammation of the tongue and corner of the mouth, respectively
(4) Spoon nails (koilonychias)
b. Pallor of the conjunctivae and palmar skin creases
c. Craving (pica) for ice (Pica is an abnormality in which patients begin to chew on things abnormaly like
dirt and ice, it is like a psychological drive to get iron from any source possible .)

The stages of iron deficiency in sequence are as follows: absent iron stores; decreased serum ferritin; decreased serum
iron, increased TIBC, and decreased iron saturation; normocytic normochromic anemia (Bone marrow makes fewer, but
normal-sized, RBCs,); and microcytic hypochromic anemia.( Bone marrow makes smaller and fewer). A normal rbc has
central area of pallor which becomes expanded and more area has less Hb in the rbc .

laboratory findings
hypochromic microcytic RBC – low ferritin – low serum iron – low % saturation – high TIBC –
high free erythrocyte protoporphyrin FEP (since iron is low some protoporphyrin in the rbc
will not be bound to iron and just floating around free) – low MCV – high RDW (because the
initial phase of the bone marrow response is to try to produce as many normal cells as
possible but once the anemia progress it will make smaller cells and there will be a spectrum
of normal cells and small cells )

also thrombocytopenia may be there in chronic iron deficiency to increase blood viscosity and
prevent high output heart failure. Wbc count is normal but eopsinophilia may be there In
hookworm infestations .