Anemia

Question 1

Q2.
ANEMIA OF CHRONIC DISEASES
1. Cause? What is HEPCIDIN and its role in anemia of chronic disease?

2. Lab findings
3. Treatment

Answer 1

1. Association with chronic infl. e.g:
   - chronic infection - osteomyelitis etc.
   - AIs - SLE, rheumatoid arthritis
   - neoplasms - hodgkin lymphoma etc.

• Most common type in hospitalized patients.
• An acute phase protein released from liver in chronic inflammation/disease to sequester and lock iron in storage sites (so cannot be used) + suppress EPO. Regardless of infection or not e.g. can be AI or cancer but if chronic, still released as a response.

NB. Fe a component required by microbes.

2. • Increased ferritin, Decreased TIBC (Total iron binding capacity, transferrin measure)
     - Decreased serum Fe, % saturation
     - Increased FEP (free erythrocytic protoporphyrin)

NB. early phase - normocytic, then becomes microcytic.

3. underlying cause, exogenous EPO

Question 2

General
4 types of microcytic anemia?

NB. Hb –> Heme + globin

Answer 2

Heme --> Fe + protoporphyrin 
Globin 
1) Iron deficiency anemia (Fe decrease)
2) Anemia of chronic disease (Fe locked in storage)
3) Sideroblastic anemia (protoporphyrin)
4) Thalassemia (globin decrease)

Microcytic anemia = MCV <80 um3 ,an extra division (from erythroblast) to maintain low Hb conc –> small cells…

Question 3

Q2. Anemias of diminished erythropoiesis; pernicious anemia

Classify, what?

Answer 3

1. Lack of substances required for hemato/erythropoiesis:
   - Iron = Iron deficiency anemia, Anemia of chronic disease
   (Protoporphyrin = Sideropblastic anemia)
   - Folic acid anemia
   - Pernicious anemia (B12 deficiency)
   - Deficiency in pyridoxine, thiamine (less frequent)
2. Anaplastic anemia (BM failure)
3. Myelophthisic anemia (BM replacement by tu or infl. cells)

Question 4

Q2. IRON DEFICIENCY ANEMIA

1. Causes

(know mechanism of iron absorption and regulation. NB. no regulated pathway for excretion except a little via skin ep/ mucosal turnover and menstruation).

2. Lab findings
3. Clinical
4. Treatment

Answer 4

1. Infants - breastfeeding, children - poor diet, malabsorption e.g. celiac, pregnancy (increased demands), menstruation, chronic loss e.g. peptic ulcers (esp. males), polyps&colonic cancer (elderly), hookworm (developing countries), gastrectomy (acid maintains Fe2+, absorbed easier) etc.
2. 1) Dec ferritin, Inc TIBC
   2) low serum iron, saturation
   - Inc FEP & RDW (red cell distribution width)
   NB. 3) fewer normocytic anemia in early phase 4) microcytic
3. fatigue, pallor, dysphagia, koilonychia (spoon shaped nails), pica (chew on random things), atropy of tongue ep.
4. Supplement iron (ferrous sulphate)

Question 5

(Q2/extra info)

SIDEROBLASTIC ANEMIA

Answer 5

• defective protoporphyrin synthesis
• synthesis in cytoplasm and last stage in mitochondria –> +Fe to make heme
• If deficient - Fe builds up in mitochondria of erythroblasts forming ring around nucleus = ‘ringed sideroblasts’.
• congenital e.g of ALAS rate-limiting enzyme or ..
• .. acquire e.g. alcoholism (poision mitochondria), lead poisoning + vitB12 def - required for synthesis
• Inc ferritin, Dec TIBC, high serum iron (iron-overload as free radicals of Fe eventu destroys cell releasing iron).

Question 6

Q1. POST-HEMORRHAGIC AND HEMOLYTIC ANEMIAS

classification, what?

Answer 6

1. Post hemorrhagic anemias - blood loss

2. Hemolytic anemias:
Predominantly Intravascular:
1. Glucose-6-phosphate-dehydrogenase deficiency 
2. Paroxysmal nocturnal hemoglobinemia 
3. Immunohemolytic anemias
4. Mechanical trauma --> microangiopathic hemolytic anemia
5. Malaria 
Predom Extravascular:
1. Hereditary spherocytosis
2. Sickle cell anemia 
3. Thalassemia

Question 7

Q2.

CAUSES OF MEGALOBLASTIC ANEMIA (MACROCYTIC)?

Answer 7

Folic acid deficiency –> folic acid anemia
B12 deficiency –> pernicious anemia

review these!

Question 8

Q2.

MYELOPHTHISIC ANEMIA

Answer 8

Replacement of BM by tumors (metastatic cancers) or lesions.

Can –> pancytopenia

Question 9

Q2

ANAPLASTIC ANEMIA

Answer 9

Results in BM failure –> pancytopenia (leukopenia, anemia, thrombocytopenia).

Causes - idiopathic (maybe abnormal T cell activation, cytokine release), chemical - drugs, physical radiation, viruses (- hep, CMV, HZV), metastatic tus, inherited e.g. Fanconi’s anemia(–> pancytopenia).

• hypocellular BM (HSCs replaced by fat cells, ly, plasma cells), marrow biopsy - dry tap (needle)
• granulocytopenia = infections, thrombocytopenia = bleeding (petechiae, ecchymoses), anemia = fatty change in liver (weak, pallor, dyspnea)
• reduced reticulocytes

Treatment - immunosuppression (aimed at T cells esp. in idiopathic cases), BM transplantation.

Question 10

Q1.

POST HEMORRHAGIC ANEMIAS?

Answer 10

Anemia is normocytic and normochromic

ACUTE
- hypovolemia (rapid hemodilution) - recovery by increasing EPO –> reticulocytosis

CHRONIC

• GIT
• Female genital tract
• gradual depletion of iron stores –> chronic anemia of underproduction

Question 11

Q1.

FEATURES OF HEMOLYTIC ANEMIAS?

Answer 11

• Increased rate of RBC destruction
• Accumulation of Hb products e.g. unconjugated bilirubin, (iron and AAs recycled) –> jaundice, increased risk for gallstones (when conjugated, hypersaturation)
• Compensatory increase in EPO (kidney) –> hypercellular BM esp. marked erythroid hyperplasia –> reticulocytosis (hallmark)
• In severe cases –> extramedullary hematopoiesis in spleen, liver, LNs etc. (can - splenomegaly etc.)

Question 12

Q1.

TYPES OF HEMOLYTIC ANEMIAS?

Answer 12

1. INTRAVASCULAR
   RBC destruction within blood vessels:
   - Mechanical injury e.g. macroangiopathy HE
   - Physical and chemical injury damaging memb
   - Complement mediated damage e.g. mismatch transfusion
   - results in hemoglobinemia, hemoglobinuria, hemosiderinuria.
   - decreased haptoglobin
   - unconjugated hyperbilirubinemia –> jaundice
2. EXTRAVASCULAR
   RBC destruction by RES (macrophages of spleen, LNs, liver etc.)
   - Destruction of deformed or immunologically targeted RBCs
   - NO hemoglobinemia, hemoglobinuria… etc.
   - decreased haptoglobin (as some escape), often jaundice, pigmented stones
   - reactive hyperplasia of RES e.g. splenomegaly (deformed RBCs cannot navigate through splenic sinusoids –> phagocytosis).

NB. Chronic hemolytic anemia –> increased iron absorption –> systemic hemosiderosis or secondary hemochromatosis.

Question 13

Q1.

WHAT NORMOCYTIC ANEMIAS ARE WITH PREDOMINANTLY EXTRAVASCULAR HEMOLYSIS?

Answer 13

• Hereditary Spherocytosis (intracopuscular anemia)
• Sickle Cell Anemia (intracorp)
• Thalassemia ? (intracorp, microcytic)

NB.
Intracorpuscular/intrinsic - defect within RBC itself (usu. inherited)
Extracorpuscular/extrinsic - attacked by something outside of RBC (acquired)

Question 14

Q1.

WHAT NORMOCYTIC ANEMIAS ARE WITH PREDOMINANTLY INTRAVASCUAR HEMOLYSIS?

Answer 14

• Paroxysmal Nocturnal Hemoglobinuria - PNH (intracorp)
• Glucose-6-phosphate-dehydrogenase deficiency (intracorp)
• Immune hemolytic anemia - IHA (extracorp)
• Malaria (extracorp)
• Mechanical trauma –> Microangiopathic hemolytic anemia (extracorp)

Question 15

Q3.

POLYCYTHEMIA

• Classifications
• Features and complications

Answer 15

Increased hematocrit, erythrocytosis

• Primary e.g. bng hemoblastosis - decreased EPO
• Secondary - erythroid precursor prolif due to high EPO
• -> Relative - decreased plasma volume e.g. dehydration, stress, hypertensive diseases
• -> Absolute - increased no. of RBCs (in response to EPO) - - appropriate increase e.g. lung disease, hypoxia (high altitude), CO poisoning etc.
• inappropriate irrespective of needs - e.g. EPO secreting tumors, ambnormal myeloid stem cells (increase in all lineages incl.RBCs)–> e.g. polycythemia vera (myeloproliferative sy).

Features & Complications:

• Increased viscosity, Hct –> slow BF
• Decreased perfusion to organs, e.g. kidneys cause - RAAS activation.
• Cyanosis in periphery
• Risk for thrombosis, thromboembolisms
• Hypertensive diseases (increased peripheral resistance)
• Hepatosplenomegaly
• leukemias, osteoporosis