Patho Ch 13

• Most abundant cell in the body
• Responsible for tissue oxygenation
• Biconcavity and reversible deformity (flexible)
• 120-day life cycle
• No nucleus

Erythrocytes are derived from erythroblasts (normoblasts)

Maturation is stimulated by erythropoietin

• blasts⇢give rise to other cells
• blood cells⇢from bone marrow

erythropoietin⇢made by the kidney that tells the blood cells to grow up! erythroblasts⇀erythrocytes

If kidneys are messed up, not going to have happy healthy red blood cells to carry oxygen = anemia

• Two alpha chains
• Two beta chains
• Each protein chain holds one iron-containing heme group
• oxygen binds to the heme groups

Each heme group (4 chains=4 heme groups) is capable of carrying 1 molecule of oxygen

Read the book to understand!!

Nutritional requirements:

Protein: _{amino acids}

Vitamins: _{Vitamin B12 Cobalomin), B6 (pyridoxine), B2 (riboflavin), E (tocopherol) and C (ascorbic acid); folic acid (B9); pantothenic acid (B5); and niacin (B3)}

Minerals: _{iron and copper}

Folate

All important in the building/needed for blood

Numbers of circulating red cells in healthy individuals remain constant

The peritubular cells of the kidney produce erythropoietin

Hypoxia stimulates the production and release of erythropoietin

• Erythropoietin causes an increase in red cell production and release from bone marrow
• _______________

more red blood cells⇢thicker. ei- dehydration

Hypoxia⇢too little oxygen⇢stimulates erthropoietin⇢increase in red blood cell production⇢blood becomes thicker

Aged red cells are sequestered and destroyed  by macrophages of the MPS (mononuclear phagocyte system), primarily in the spleen

The liver takes over if the spleen is absent

Globin chains are broken down into amino acids

Porphyrin is reduced to bilirubin, transported to the liver, and secreted in the bile

Iron is "recycled" in the body

• bone marrow aspiration (break into bone and test bone marrow)
• bone marrow biopsy
• measurement of bone marrow iron stores
• differential cell count

Erythrocyte life span is normal but erythrocytes are replaced more slowly

possible causes:

• iron depletion
• decreased total serum iron, iron-binding capacity, and intestinal iron absorption

___________

as you get older RBC not replaced as quickly. Kidney function decreases

• RBC Count: number of cells in the blood
• Men: _4.2-5.4
• Women: _3.6-5.0

• Hemoglobin: hemoglobin content of blood
• Men: _14-16.5
• Women: _12-15

• Hematocrit: volume of cells in 100 ml blood (number of cells)
• Men: _40-50%
• Women: _37-47%

Elevated: dehydration (look at BUN and sodium) or polycythemia (COPD, high elevations, cancer)

Low: anemia, hemorrhage, bone marrow suppression

Critical: <5


(BUN: The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain between 6 to 20 mg of urea nitrogen per 100 ml of blood.)

Elevated: dehydration (look at BUN and sodium); or polycythemia

Low: over hydration; hemorrhage; anemia

Critical: <15% or >60%

Decreased blood oxygen⇢kidneys secrete erythropoietin⇢bone marrow stimulated⇢creates new red blood cells

Immature RBCs (nucleated)

Reticulocytes (RBCs that still have their endoplasmic reticulum)

Mature RBCs

______________

They last about 120 days

• -Their membranes become weakened
• -Because they have no nuclei, RBCs cannot make new membrane components
• -Eventually, RBCs break as they squeeze through the capillaries

break in capillaries in the spleen⇢eaten by white blood cells in the spleen, liver, bone marrow, or lymph nodes⇢hemoglobin processed into unconjugated bilirubin

unconjugated bilirubin is toxic

__________

Unconjugated bilirubin in blood⇢bilirubinemia⇢jaundice

Unconjugated bilirubin in blood⇢liver links to gluconuride⇢conjugated bilirubin⇢bile

bile gives poop brown color and urine yellow color.

too much built in the body and not released in waste-bilirubinemia

Hemoglobinemia makes the plasma turn red

Hemoglobinuria makes the urine cola-colored

____________

Malaria called "blackwater fever" because red blood cells are bursting in the plasma and the urine looks dark red/brown because of the RBC

RBC break in capillaries outside the spleen⇢hemoglobin released into the blood⇢hemoglobinemia-hemoglobinuria

Reduction in the total number of erythrocytes in the circulating blood or in the quality or quantity of hemoglobin

• impaired erythrocyte production
• acute or chronic blood loss
• increased erythrocyte destruction
• combination of the above

Causes:

• blood loss
• hemolysis
• impaired RBC production

Size

• identified by terms that end in "-cytic"
• macrocytic, microcytic, normocytic

Hemoglobin content

• indentfied by terms that end in "-chromic"
• normochromic and hypochromic

_______________

Anisocytosis: red cells are present in various sizes

Poilkilocytosis: red cells are present in various shapes

physiologic manifestation: reduced oxygen-carrying capacity

variable symptoms based on severity and the ability for the body to compensate

Classic anemia symptoms: fatigue, weakness (reduced oxygen), dyspnea (difficulty breathing), and pallor (pale)

Big fat cells that still look normal and red

Also termed megaloblastic anemias

Characterized by defective DNA synthesis⇢caused by deficiencies in vitamin B12 or folate⇢coenzymes for nuclear maturation and the DNA synthesis pathway

• Large red blood cells (High MCV). Cell looses the dimple in the middle
• Causes: folate or Vitamin B12 deficiency

A macrocytic-normochromic anemia

Lack of intrinsic factor from the gastric parietal cells:

• required for vitamin B₁₂ absorption
• results in vitamin B₁₂ deficiency
• typical anemia symptoms

• neurologic manifestations: nerve demyelinatin; absence of intrinsic factor
• other: <appetite, abdominal pain, beefy red tongue (atrophic glossititis), iceterus (jaundice), spleen enlarged
• treatment: parenteral or high oral doses of vitamin B12 (need an outside source of B12)

_______________

No intrinsic factor from gastric parietal cells of the stomach⇢cannot absorb B12

Megaloblastic anemias

A macrocytic-normochromic anemia

• Absorption of folate occurs in the upper small intestine
• Not dependent on any other factor
• Similar symptoms to pernicious anemia except neurologic manifestations generally not seen
• Treatment requires daily oral administration of folate

Characterized by red cells that are abnormally small and contain reduced amounts of hemoglobin

Related to:

• disorders of iron metabolism (iron deficiency⇢
• pale=less hemoglobin)
• disorders of porphyrin and heme synthesis
• disorders of globin synthesis (Thalassemias)
• lead poisoning

Small cell size (microcytic: low MCV) and low amount hemoglobin makes the cell appear pale (hypochromic: low MCH)

A microcytic-hypochromic anemia

Most common type of anemia worldwide

• Nutritional iron deficiency
• Metabolic or functional deficiency

Progression of iron deficiency causes:

• brittle, thin, coarsely ridged, and spoon-shaped nails
• a red, sore, and painful tongue
• Low MCV; Low MCH

_____________

Do not have enough iron

Vitamin C⇢help to absorb iron

___________

• Hypochromic and microcytic erythrocytes
• Poikilocytosis (irregular shape)
• Anisocytosis (irregular size)

A microcytic-hypochromic anemia

• group of disorders characterized by anemia
• altered mitochondrial metabolism causing ineffective iron uptake and resulting in dysfuntional hemoglobin synthesis

Ringed sideroblasts within the bone marrow are diagnostic

sideroblasts are erythroblasts that contain iron granules that have not been synthesized into hemoglobin

_____________

Problems with mitochondrial metabolism⇢not able to take up the iron or use it in the hemoglobin

Cells right size and right color but bone marrow is not making enough

Characterized by red cells that are relatively normal in size and hemoglobin content but insufficient in number

Aplastic anemia (bone marrow does not make enough new blood cells); acute blood loss; prosthetic heart valves; sepsis (severe response to bacterial or germs); tumor

Sickle cell anemia

Anemia of chronic inflammation:

Mild to moderate anemia seen in- AIDS, rheumatoid arthritis, lupus erythematosus, hepatitis, renal failure, and malignancies

Normocytic-normochromic 

• Accelerated destruction of red blood cells
• Autoimmune hemolytic anemias
• Immunohemolytic anemia
• Warm antibody immunohemolytic anemia
• Drug-induced hemolytic anemia
• Cold agglutinin (causes coagulation)  immunohemolytic anemia
• Cold hemolysin hemolytic anemia

________________

Hemolytic-being destroyed. Red blood cells bust

Membrane disorders: _{-hereditary spherocytosis; -acquired hemolytic anemias and hemolytic disease of the newborn}

Hemoglobinopathies: _{-Sickle cell disease; -Thalassemia (alpha, beta)}

G6PD deficiency

(Pernicious Anemia)

• Megaloblastic anemia
• erythrocytes are large, often with oval shape
• poikilocytosis and teardrop shaped
• neutrophils are hypersegmented (6-10 lobes as opposed to 3-4)

Small cell size (microcytic), but normal amount of hemoglobin in the cell (normochromic)

Causes: erythropoietin deficiency from chronic renal failure (CRF)

Mutations in beta chains of hemoglobin

When hemoglobin is deoxygenated, beta chains link together⇢forming long protein rods that make the cell "sickle"

Recessive inheritance

Hypoxia, more likely to occur in lung/pulmonary disease, is an exacerbating factor for increased sickling and vessel occlusion

______________

because of its shape, it can get caught on each other and cause a log jam which would hinder the tissue on the other side from getting the blood and oxygen.

• cold, stress, infection, physical exertion=more necessity of oxygen use
• ________________

Heterozygous: sickle cell trait; may not have symptoms enough to know they have it.

Homozygous: sickle cell disease

• Factors associated with sickling: cold, stress, physical exertion, infection, sleep, illnesses that cause hypoxia, dehydration, or acidosis

Sickled cells block capillaries:

• Acute pain (the pain is horrible)
• Infarctions cause chronic damage to liver, spleen, heart, kidneys, eyes, bones
• Pulmonary infarction⇢acute chest syndrome
• Cerebral infarction⇢stroke

Sickled cells more likely to be destroyed: Jaundice

___________

The blood on the other side is not going where it needs to be.

It has alpha chains and gamma chains

This means it cannot sickle (because sickle is related to beta chains)

Person with some fetal hemoglobin are partially protected from sickle cell disease

Heterogenous group of inherited disorders caused by mutations that decrease the rate of alpha or beta-globin chains.

Inherited as a Mendalian trait. May be heterozygous and have mild case or homozygous and have severe form. (Not sex-linked; inherited)

Beta-thalassemia sometimes called Cooley anemia or Mediterranean anemia.

Beta in Italians and Greeks; Alpha in Asians; both in Africans and African Americans

__________

Both have deficiency in hemoglobin due to decreased synthesis of the affected chain, with excess production of unaffected chain

Results in hypochromic, microcytic anemia

Accumulation of unaffected chain leads to problems with RBC maturation, lead to hemolysis and anemia

Alpha:

Defective gene for alpha-chain synthesis

May have 1-4 defective genes

Affects both fetal and adult Hb

In fetus, gamma₄ Hb may form; in adult, beta₄ Hb may form

_______________________

Beta:

Defective gene for beta-chain synthesis

May have 1-2 defective genes

Affects only adult Hb

Alpha₄ Hb may form

Lots (abnormal amount) of cells in blood

Abnormally high total RBC count with hematocrit >50% (number of RBC in blood)

Categorized as relative or absolute

Relative (relative to amount of fluid): hematocrit rises because of loss of plasma volume without a decrease in RBCs. Causes: water deprivation; excess diuretics (promote increase of flow of water out of body), GI losses.

Absolute (more RBC to be created): rise in hematocrit due to increase in total red cell mass; classified as primary or secondary

_______________

• loss of plasma volume w/o decrease in RBC.
• Everything is more concentrated⇢dehydrated

Primary polycythemia (polycythemia vera)

Neoplastic disease of pluripotent cells (problem with top level in bone marrow so increase in all types of blood cells) of bone marrow.

Absolute increase in RBC mass; increase WBC; increase platelets

Manifestations are variable

Viscosity interferes with cardiac output and blood flow.

Hypertension, headache, dizziness, problems with concentration, difficulty with hearing/vision

Venous stasis (vein blood just sitting there; no movement) =dusky redness

May have cyanosis of lips, fingernails, mucus membranes

May have itching, pain (bc blood flow not efficient) in fingers, toes; night sweats, weight loss

Thromboembolism (clots occur) and bleeding are problems

Treatment: therapeutic phlebotomy _{(making an incision in a vein with a needle-need them to be well hydrated and pull out some of the cells)} to decrease hematocrit to <42%; low-dose aspirin _{(prevents platelet aggregation)}; chemotherapy.

Secondary: results from physiologic increase in level of erythropoietin

Commonly as compensation for hypoxia

Causes: high altitudes, chronic heart/lung disease, smoking, anabolic steroids

May be caused by neoplasm secreting erythropoietin

Treatment focuses on relieving hypoxia

Increased level of serum bilirubin

Common cause of jaundice in newborn

Usually benign; self-limited; rarely pathological

If remains elevated may cause kernicterus

• Kernicterus = accumulation of unconjugated bilirubin in brain cells; serious brain injury
•  
• Factors that contribute to elevated bilirubin: breast-feeding, hemolytic disease in newborn, hypoxia, infections, acidosis

Risk factors: prematurity, Asian, maternal diabetes, breast-feeding

Treated with phototherapy or exchange transfusion (when s/sx kernicterus)

Exposure to fluorescent light in the blue range converts bilirubin to isomer that is easily exceted in stool and urine

= Erythroblastosis fetalis

Occurs in Rh-positve infants of Rh-negative mothers who have been sensitized

First Rh-positive infant usually not affected

Infants with Rh-negative blood have no antigens to react with maternal antibodies and are not affected

____________________

After being sensitized, Rh antibodies from mother's blood are transferred to subsequent fetuses through placental circulation

Antibodies react with red cell antigens of the Rh-postive fetus causing agglutination and hemolysis

Results in severe anemia with compensatory hyperplasia (increased cell production) and enlargement of spleen and liver

Liver function is impaired, decreased production of albumin causing massive edema called hydrops fetalis

Injection of Rh immune globulin prevents sensitization in Rh-negative mothers who have given birth to Rh-positive infants if given at 28 weeks gestation and within 72 hours of birth or maternal-fetal bleeding

After sensitization has developed immune globulin is of no value

Hemolysis in fetuses can be treated with intrauterine transfusions; after birth with exchange transfusions

Anemia is common problem of elderly

Highest prevalence in men >= 85 years old. 

If undiagnosed/untreated, associated with > risk mortality, cardiovascular disease, self-care deficits, cognitive disorders, increased risk of fractures (<bone density)

RBCs not replaced as quickly in elderly

Diagnosis: exam, CBC (including reticulocyte count and index), rule out comorbidities (simultaneous presence of two chronic diseases) and problems (bleeds)

Correct underlying cause; orally administered iron is poorly used in the elderly; may require administration of erythropoietin