Erythrocytic Disorders PDF

PATHOLOGY LDCU MEDICINE-2 Dr. Casio & Dr. Rana MAIN TOPIC: ERYT...

PATHOLOGY LDCU MEDICINE-2 Dr. Casio & Dr. Rana MAIN TOPIC: ERYTHROCYTIC DISORDERS bound largely to transferrin, is central in this scheme. It ANEMIAS completely turns over several times a day in supplying iron Anemia is present if the: for heme synthesis. Each day, about 1% of total circulating =& hemoglobin (Hb) concentration or the↳hematocrit (Hct) is red cells are destroyed, and the same number of new red below the lower limit of the 95% reference interval for the cells is delivered to the blood. That proportion of the total individual’s age, sex, and geographic location. erythron iron enters the plasma from the site of hemoglobin  Conversely, an individual whose Hb falls within the (Hb) degradation, the macrophages of the reticuloendothelial 12 - reference intervals for age and sex yet significantly& - below (RE) system, and travels (bound to transferrin) to the Standard - his or her own usual values should be considered normoblasts in the marrow. Storage iron largely resides also Divisio - T anemic. in the macrophages of the RE system. Absorbed iron enters  Anemia may be absolute, when red blood cell mass is - the plasma pool, bound to transferrin. Iron is largely excreted -decreased, or relative, when associated with a higher by loss of cells. (Data from Hillman RS, Finch CA: Red cell plasma volume. = manual, ed 4, Philadelphia, 1974, FA Davis. plasma's a - - fault Causes of absolute anemia  Very little iron is lost from the body; this small iron loss occurs mainly as loss of cells from the gastrointestinal este. ampalaya ! impaired red blood cell production /impaired erythropoiesis -  ↳ LOSS IN EXCESS OF (GI) tract and to a lesser extent from the skin and - THE ABILITY OF E  increased erythrocyte destruction (premature) through the urine. ROW TO REPLACE  Increased blood loss (bleeding/hemontages)  About & 1 mg is lost each day, except in menstruating /maynotbe & THESE LOSSES. - = - females, whose iron loss averages about 2 mg/day. Relative anemia a em 1 AdditionaFind - May occur with pregnancy, with macroglobulinemia, and in 3 1.IRON DEFICIENCY ANEMIA (IDA) < postflight astronauts. [prolonged exposure to weightlessness When iron loss exceeds iron intake for a time long enough to and return to sea level after a period of high altitude deplete the body’s iron stores, insufficient iron is available for acclimatization are associated with selective loss of young red normal Hb production. blood cells - neocytes, as a result of erythropoietin (EPO)  characterized by a hypochromic microcytic anemia. ↳ withdrawal - neocytolysis (Risso et al, 2014) te smallersize Results: When anemia- develops slowly in a patient who is not A) when the need for iron is increased (e.g., during rapid growth ( pt was able to otherwise severely ill, Hb concentrations as low as⑥ 6 g/dL in infancy and childhood, during pregnancy) cope up whe may develop without producing any discomfort or physical B) when excessive loss of blood has reduced the body’s slowly lowing of signs, as long as the patient is at rest reserves of iron (e.g., following repeated hemorrhages, e hemoglobin excessive menstruation, or multiple pregnancies). # Anemic patient complains f More common physical  most common cause of anemia affecting at least one of: (symptoms) findings: (signs) third of the world’s population in usually women's ( # of RBL ~ ↓ B volume Y easy fatigability ~ pallor, licmpensation ) Marrow ↑ Active making of RBC Erythroid hyperplasia occurs early, but in later stages the limiting menstration & Adyspnea on exertion, ~ a rapid bounding pulse, - A faintness, - low blood pressure, effect of severe iron deficiency restricts erythropoiesis to the vertigo, - slight fever, basal level. ①palpitations, ~ some dependent edema,  The erythroblasts are smaller than normal, deficient in Sheadache. ~systolic murmurs the amount of Hb in the cytoplasm, and irregular in shape with frayed margin IMPAIRED PRODUCTION of RBC RBLS I young. small Slacking - Onene d O O - 80kg a man different in sizes spochrom L URINE recycle/d reabsorb t peen Baseline TESTS TO BE DONE 1) Serum Iron. (NV - 50 to 160 μg/dL (9 to29 μmol/L) in adults. 2) Serum (Total) Iron-Binding Capacity. (NV 250 to 400 μg/dL (45 to 72 μmol/L).)  In iron deficiency anemia, the serum TIBC is increased. Scheme of iron metabolism  It is normal or decreased in the anemia of chronic The upper figure in each position is average for an 80-kg disease. man; the lower figure is for a 65-kg woman. The plasma iron, Vance | MD 2024 1  TRANS: ERYTHROCYTIC D/O & HEMOGLOBINOPATHIES  If chronic infection coexists with chronic blood loss, the  The major abnormality is the diminished capacity for TIBC may not be increased, even though the patient is deoxyribonucleic acid (DNA) synthesis. [cobalamin or - iron deficient. folate deficiency] 3) Percent Saturation of TIBC. The ratio of serum iron to TIBC (NV 20% to 55%) = values below 15% indicate iron-deficient fee I erythropoiesis. ovalony less # of fat 8 "How much p - 4) Serum Ferritin(NV 12 to 300 μg/L) = in equilibrium with tissue. cells Iron is still ferritin and is a good reflection of storage iron in normal subjects & ~ remaining... and in most disorders micro FOLIC ACID DEFICIENCY MANAGEMENT Intake of Folate = Inadequate [ Ferrous iron is given orally—200 mg/day—in three doses - between meals. - - - &  Provides 40 to 60 mg of absorbed iron per day, which, Defective Production of Defective Production of for easy will be sufficient to increase production to two or three - Intrinsic Factor = most Intrinsic Factor = most from - absorption. - times normal. - Stomach common cause of common cause of Patients refractory to treatment need to be investigated for /resistant cobalamin deficiency cobalamin deficiency continued underlying diseases, particularly chronic gastritis and Helicobacter pylori Gastritis. Ccausative - agent) & Iron-Refractory Iron Deficiency Anemia (IRIDA) This is a recently-described hereditary recessive microcytic anemia, which does not respond to oral iron therapy. -  IRIDA patients have inappropriately high hepcidin levels preventing iron absorption and release. Patients may show a slow or partial response to parental iron (De Falco et al, 2013) > 2. MEGALOBLASTIC ANEMIA "many large RBCs i Macrocytosis with Normoblastic Marrow. large marrow" new RBC in Macrocytic anemias that are not megaloblastic may be due to other causes: a) O early release of erythrocytes from the marrow, “shift - = reticulocytes.” b) also found in - hypothyroidism, in individuals with - excessive alcohol intake, and inE  Some cases of FOLATE ACID DEFICIENCY may be - liver disease associated with marked red cell fragmentation Megaloblastic Anemia simulating microangiopathic hemolytic anemia. Blood  Severe folate deficiency in pregnancy may G mimic Oval-shaped  macro-ovalocytes and giant hypersegmented the syndrome of hemolysis, elevated liver enzymes, ~ & - and low platelets (HELLP syndrome) - Appeared to be large ·- neutrophils are present in the blood = =  Pancytopenia is the rule. everything is -- 33 Pernicious Anemia(PA) ( me Lack of intrinsic factor  anemia is macrocytic with an elevated MCV absorb  a “conditioned” nutritional deficiency of cobalamin w/c you cannot B12 your Vitamin Characteristics of MEGALOBLASTIC ANEMIAS that is caused by failure of the gastric mucosa to BLOOD: macro-ovalocytes and often extreme degrees of secrete intrinsic factor. anisocytosis and poikilocytosis, including red blood cell  less than& 10% of cases occur in persons younger than fragments. 40 years of age.  Microcytes and-dacrocytes are common. tear drop cells  Positive family history is obtained in approximately  Basophilic stippling, multiple Howell-Jolly bodies, O30% of patients - nucleated red cells with -monuclei karyorrhexis, and even don't Clinical Features  have megaloblasts may be seen in the peripheral blood. - fine edges. skin pallor and jaundice with lemon yellow appearance  - Leukopenia is present. Granulocytes have increased to the skin numbers of lobes, as a result of abnormal nuclear  atrophic glossitis & acute glossitis).=> Inflammation of becauseOTongue maturation. 18.5 g/dL for men, inherit: = >16.5 g/dL for women, A defective gene from one of your parents (autosomal dominant - pattern) Absolute polycythemia refers to an increase in the total red Defective genes from both parents (autosomal recessive cell mass in the body; pattern) Vance | MD 2024 8  TRANS: ERYTHROCYTIC D/O & HEMOGLOBINOPATHIES Acquired forms Risk factors: Porphyria cutanea tarda (PCT) typically is acquired rather than In addition to genetic risks, environmental factors may trigger inherited, although the enzyme deficiency may be inherited. the development of signs and symptoms in porphyria. Certain triggers that impact enzyme production — such When exposed to the trigger, your body's demand for heme as too much iron in the body, liver disease, estrogen medication, production increases. smoking or excessive alcohol use — can cause symptoms. This overwhelms the deficient enzyme, setting in motion a process that causes a buildup of porphyrins Examples of triggers include: Exposure to sunlight Certain medications, including hormone drugs I pills Recreational drugs /drugs for pleasure Dieting or fasting Smoking * Autosomal- dominant inheritance pattern Physical stress, such as infections or other illnesses In an autosomal dominant disorder, the mutated gene is a Emotional stress dominant gene located on one of the nonsexchromosomes Alcohol use # (autosomes). You need only one mutated gene to be affected Menstrual hormones ― acute porphyria attacks are rare O by this type of disorder. A person with an autosomal dominant before puberty and after menopause in women disorder — in this case, the # father — has a 50% chance of having an affected child with one mutated gene (dominant gene) Complications and a 50% chance of having an unaffected child Possible complications depend on the form of porphyria: with two normal genes (recessive genes) Acute porphyrias  can be life-threatening if an attack isn't promptly treated.  During an attack = dehydration, breathing problems, - - seizures and high blood pressure. - -  Episodes often require hospitalization for treatment.  Long-term complications with recurrent acute attacks may include chronic pain, chronic kidney failure and - - liver damage. Autosomal - recessive inheritance pattern - Cutaneous porphyrias - organs many be safe > To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. These disorders are  permanent skin damage. usually passed on by two carriers. Their health is rarely affected,  skin blisters can become infected. but they have one mutated gene (recessive gene) and one  abnormal healing, or colored, or fragile scars normal gene (dominant gene) for the condition. Two carriers have a 25% chance of having an unaffected child with O two Clinical manifestations normal genes (left), a 50% chance of having an unaffected Skin lesions accompany acute attacks in ½ of people with child who also is a carrier (middle), and a 25% chance of having caruegate porphyrias and 1/3 of those with hereditary 10 an affected child with two recessive genes coproporphyhrin. (right). examine - Vance | MD 2024 9