Anemia of Chronic Renal Failure

1
Anemia of Chronic Renal Failure

• Etiology
• Metabolic Red Blood Cell Dysfunction
• Decreased Erythropoietin production
• Hemolytic Ureamic Syndrome
• Marrow Suppression ( ureamic inhibitors )
• Hyperthyroidism

2
Metabolic Red Cell Dysfunction

• ATP is high possibly due to a high serum
  phosphate
• 2,3 DPG is increased in response to anemia and
  hyperphosphatemia
• ATPase, Na-K pump are decreased in ureamia and
  resulting in shortening life span (more rigidity
  and cell shape changes), HMP decreased response
  renders excessively sensitive to Oxidant drugs
  and Chemicals
• (???? ???????????????????????????)

3
Glucose
G-6-PD
6-Phosphoglycerate (HMS)
Glucose-6-Phosphate
NADP
NADPH
GSSG
GSH
Lactate (EMP)
4
Decreased Erythropoietin (EPO) Production

1. Glycoprotein MW 36,000 daltons.
2. Eschbach showed that the patient with renal
   failure even there was anemia but normal EPO
   level. However, it was lower than the anemia from
   other causes.

5
Hemolytic Ureamic Syndrome

1. Pathology of renal endothelial cell forming
   fibrin clot and platelet thrombi resulting in
   microangiopathic hemolytic anemia
2. Decreased platelet mass, mildly lower platelet
   count and MPV
3. Reduced platelet adhesion such as high molecular
   weight multimers of von Willebrand are reduced,
   GP Ib has been reported to be defective
4. Defective platelet activation and aggregation
   (reduced synthesis of thromboxane A2). Platelet
   functions defected due mainly to toxic substances
   e.g. Guanidinosuccinic acid, phenol.

6
Marrow suppression (Ureamic inhibitors)

1. Experiment found that serum from ureamic patient
   can suppress the growth of CFU-E and burst
   forming unit- erythroid ( BFU-E)
2. After hemodialysis or continuous ambulatory
   peritoneal dialysis can increase Hb level.
   Anyway, hemodyalysis may cause iron and folate
   deficiency.

7
Hyperthyroidism

1. Hyperparathyroidism is a complicated condition in
   renal failure
2. Increased PTH resulting in suppression of RBC
   production in BM

8
Anemia of endocrine disorder

1. Anemia of Pituitary deficiency
2. Anemia of thyroid dysfunction
3. Anemia of adrenal dysfunction
4. Anemia of gonadal dysfunction
5. Anemia of pregnancy
6. Anemia of parathyroid dysfunction

9
Anemia of pituitary deficiency

1. Hypophysectomy in animal causes severe erythroid
   hypoplasia and anemia (???????? GH)
2. It has been proposed that the pituitary gland
   produces a specific erythropoietic hormone
3. Growth hormone has been shown to be capable of
   stimulating red cell production in vitro
4. It has been claimed that hypothalamic injury may
   affect erythropoietin release, the rate of red
   cell production or both
5. Hypophyseal dysfunction is often associated with
   leukopenia and a normochromic, normocytic anemia
   (??? GH ???????????)
6. The red cell life span is normal and relative
   marrow failure

10
Anemia of Thyroid dysfunction

1. Kocher reported that thyroidectomy is followed by
   a reduction in the red cell count
2. Anemia is normocytic, microcytic, macrocytic
3. Lack of thyroid hormone is complicating of iron,
   Vitamin B12, folic acid
4. T3, T4 potentiate the effect of erythropoietin on
   the formation of erythroid colonies
5. Many hypothyroid patients have a hypoplastic
   anemia ( Hb 8 9 g/dl)
6. Normochromic, normocytic anemia is the
   characteristic form of hypothyroidism

11
Anemia of Adrenal Dysfunction

• Adrenalectomy in animal causes a mild anemia and
  respond to therapy with adrenal glucocorticoid or
  erythropoietin
• Normochromic, normocytic anemia has been observed
• (?????????????????? ??????????????????)
• The erythropoietic effect of ACTH or adrenal
  cortical hormone are unclear

12
Anemia of Gonadal Dysfunction

1. Androgens extensively utilized in the treatment
   of patients with various types of refractory
   anemia. It has been shown to stimulate red cell
   production by increasing the production of
   erythropoietin (??????????????????????)
2. Castration of animal causes a decrease in the
   rate of red cell production until the Hb and red
   cell volume stabilized at levels the same as
   those of the normal female
3. Right now the recombinant human erythropoietin is
   used in place of androgens. Even now, androgens
   is used to reduce the cost of such therapy.

13
Anemia of Pregnancy

1. Anemia in pregnancy is thought due to changes in
   hormonal environment
2. In mice even progressive decrease in the Hct, the
   red cell volume, erythropoietin secretion and
   rate of red cell production increase during
   pregnancy. Placental lactogen may in part be
   responsible for the erythropoietic stimulation.
3. In human, anemia is aggravated by dietary
   restrictions resulting in iron deficiency
   sometimes folic acid deficiency
4. Anemia will be manifested about the 8 th wk
   progresses slowly until the 32-34 wk. This is
   so-called a dilution anemia the red cell volume
   increases by 20 while the plasma volume
   increases by 30 .

14
Anemia of Parathyroid Dysfunction

1. Anemia in hyperparathyroidism will disappear
   after parathyroidectomy
2. Parathyroidectomy in renal disease results in
   some improvement in the anemia
3. One report says that parathyroid hormone can
   suppress normal red cell production but in fact
   these hormones may cause either renal
   calcification resulting in reduction of
   erythropoietin formation or marrow sclerosis
   resulting in reduction of erythroid proliferation