Erythrocyte Function and Anemia

Erythrocyte Function Alterations

• Erythrocyte function alteration involves insufficient or excessive numbers of erythrocytes circulating or numbers of erythrocytes with abnormal components.
• Anemia means too few erythrocytes or an inadequate volume of erythrocytes in blood.
• Polycythemia denotes erythrocyte number or volume is excessive.
• Leukocyte disorders include increased leukocytes (leukocytosis) from infection, or proliferative disorders like leukemia or decreased leukocytes numbers (leukopenia).
• Hematologic and nonhematologic malignancies metastasize to bone marrow and affect leukocyte production.
• Clotting (hemostasis) halts bleeding through endothelium, platelets, and clotting factors.

Anemia: Classification and Characteristics

• Anemia signals a reduction in total circulating erythrocytes or poor hemoglobin quality/quantity.
• Anemia is a true decrease in erythrocyte number, not a relative decrease from increased plasma volume (hemodilution).
• Anemia prevalence is 40% for men and 22% for women over age 85.
• Anemia arises from blood loss (acute or chronic), impaired erythrocyte production, increased erythrocyte destruction, or a combination.
• Anemias are classified by cause (acute blood loss or anemia of inflammation [AI]) or changes affecting erythrocyte's size, shape, or substance.
• The most common classification is on cell size and hemoglobin content, using "-cytic" for size and "-chromic" for hemoglobin.
• Additional terms: anisocytosis (varying sizes) and poikilocytosis (varying shapes).

Anemia: Clinical Manifestations

• The reduced oxygen-carrying capacity, leads to tissue hypoxia.
• Symptoms vary based on the body's ability to compensate for reduced oxygen.
• A gradual onset of mild symptoms that's easier to compensate, it may cause problems with exertion.
• Red cell reduction causes pronounced symptoms and organ changes with compensation in cardiovascular, respiratory, and hematologic systems.
• Decreased blood cells reduce the consistency and volume of blood.
• Initial compensation involves interstitial fluid moving into the blood which maintains volume, but decreasing the thickness and increasing blood flow rate, causing a hyperdynamic state.
• The hyperdynamic state increases stroke volume and heart rate and may cause cardiac dilation and valve insufficiency if uncorrected.
• Low blood oxygen causes arteriole, capillary, and venule dilation, increasing flow, further contributing to cardiovascular dysfunction.
• Low blood oxygen and increased flow raise heart rate and stroke volume to meet oxygen demand and prevent cardiopulmonary congestion.
• Compensatory mechanisms lead to heart failure.
• Tissue hypoxia increases breathing rate/depth and oxygen release from hemoglobin.
• Anemia may cause shortness of breath (dyspnea), rapid heartbeat, dizziness, and fatigue.
• Symptoms are present only with exertion in mild cases, but even at rest with severe anemia.
• Manifestations of anemia include pale/jaundiced skin, mucous membranes, lips, nail beds, and conjunctivae.
• Anemia with tissue hypoxia impairs skin healing/elasticity.

Nervous System, GI Tract, Compensatory mechanisms, Therapies and Anemia

• Vitamin B12 deficiency anemia impacts the nervous system and degenerates myelin, causing paresthesia (numbness), gait issues, weakness, spasticity, and reflex changes.
• Decreased oxygen to the GI tract can produce abdominal pain, nausea, vomiting, and anorexia.
• Acute/severe anemia (hemorrhage) causes blood vessel constriction to preserve blood flow to vital organs.
• Low blood flow is detected by kidneys, activating renin-angiotensin, causing salt/water retention to increase blood volume.
• Acute situations require immediate intervention to correct the underlying problem and prevent long-term compensatory mechanisms.
• Therapies consist of diet changes, vitamin/iron supplements, toxin removal, interventions for sickle cell disease, and blood transfusion for severe anemia.

Blood Loss Anemia: Acute Blood Loss

• Posthemorrhagic anemia is normocytic-normochromic resulting from acute blood loss.
• Acute blood loss mainly involves intravascular volume loss, based on hemorrhage rate.
• Rapid blood loss leads to cardiovascular collapse, shock, and death.
• A major cause of acute blood loss is trauma, where uncontrolled bleeding is the primary preventable death.
• Trauma patients with bleeding develop coagulopathy upon admission.
• Coagulopathy indicates increased risk of organ failure and death.
• Within 24 hours of acute blood loss, plasma is replaced as water and electrolytes from tissues enter the intravascular system, lowering hematocrit because of hemodilution.
• Normocytic and normochromic RBCs (normal MCV and MCHC).
• Circulating neutrophils rapidly elevate due to bone marrow release.
• Platelet count can rise during recovery from acute blood loss.
• Reduced tissue oxygenation stimulates erythropoietin, increasing bone marrow production of erythrocytes which may deplete iron stores.
• Saline, dextran, albumin, or plasma can be used to restore blood volume, while fresh whole blood is used in major blood losses.
• Red blood cell transfusions can be used to address both acute and chronic blood loss, but may worsen the outcome and increase morbidity and mortality in critically ill individuals.
• Stored red blood cells undergo harmful structural and metabolic changes, advancing thrombotic complications like DVT post-infusion.

Blood Loss Anemia: Chronic Blood Loss and Diminished Erythropoiesis

• Anemia arises if the blood loss exceeds the bone marrow capacity to keep up.
• Slow and sustained hemorrhage can cause iron deficiency anemia.
• Unexplained IDA should be evaluated for sources of blood loss like ulcers or malignancies.
• Diminished erythropoiesis anemias can be classified by their underlying mechanism.
• Iron deficiency anemia (IDA) is the world's most common anemia.
• Other anemias with diminished erythropoiesis result from deficiency in cobalamin or folate.
• IDA causes microcytic anemia; B12/folate deficiencies cause macrocytic anemias.

Macrocytic/Megaloblastic Normochromic Anemias

• Characterized by large stem cells (megaloblasts) in the marro, developing into unusually large erythrocytes with elevations in MCV, volume, and thickness.
• B12 or Folate deficiencies are the most common underlying cause and cause macrocytic anemias.
• Vitamin B12 relies on dietary intake.
• Plants and vegetables contain little to no cobalamin, where vegetarian and/or macrobiotic diets do not provide adequate amounts though folate can be found in vegetables, fruits, nuts, eggs and meats
• Vitamin B12/Folate levels are affected by disorders reducing their intestinal absorption, or by high demand in pregnancy, hyperthyroidism, chronic infection, and cancers.
• DNA synthesis-interfering medications such as chemotherapeutic drugs can contribute.
• Defective megaloblastic erythrocytes die sooner, decreasing count and causing anemia.
• Premature death of damaged erythrocytes, called eryptosis, is a cellular loss mechanism in deficiencies, infections, chronic/genetic disease, and myelodysplastic syndrome.
• Blocked/Delayed DNA synthesis and cell division in megaloblastic anemias causes unequal growth causing overproduction, with a smaller nucleus as the cell divides.

Pernicious Anemia

• Pernicious anemia is a megaloblastic anemia caused by malabsorption from B12 deficiency
• The main disorder is the absence of intrinsic factor which is essential for absorbing B12 in the ileum.
• Pernicious indicates the condition was highly detrimental and deadly.
• Most commonly impacts the Northern European population > age 30, but appears in all groups.
• IF deficiency may be congenital but most often acquired by autoimmune reactions or the damage to the gastric mucosa.
• Congenital IF deficiency is an autosomal recessive genetic pathology.
• Most likely caused by autoimmune activity targeted for parietal or IF cells -- and is possibly a factor of endocrine diseases like thyroiditis or type-1 diabetes

Pernicious Anmeia Continued...

• Pathology is also linked to chronic H. pylori infection, surgical removal of the stomach/lower ilium, and tapeworms.
• Environmental factors might involve increased alcohol and/or tobacco consumption.

Pernicious Anemia: Pathophysiology

• Individuals commonly possess two antibodies; one to parietal cells, the other to IF ( or its binding site) in the small bowel.
• IF deficiency is often connected to autoimmune atrophic gastritis with subsequent autoantibody distraction of parietal and/or enzyme cells leading to gastric atrophy.
  • Infection from H. pylori may raise antibody action which commonly target the gastric H+-K+ ATPase which provides the primary components to parietal cell membranes.
  • The submucosae become infiltrated with inflamed cells, especially autoreactive T-cells.
  • Gut Mucosal injury, and finally Atrophy, induces inadequate excretion of acid (Achlorhydria), pepsin, and the IF itself.
  • With low IF, Vitamin B12 does not effectively process and be absorbed where it needs.
  • Low Vitamin B12 is vital for DNA and the maturation of Nuclear actions, causing deficiencies and abnormal cells present in marrows (megaloblasts) and maturely enlarged components within the bloodstream.
• Increased risk for GI cancer often takes place.
• 40-60 % have antibodies targeted towards intrinsic factor for B12 absorption in the ilium, often appearing with prior history of IDA and even gastric Achlorhydria.
• People with unknown Iron deficiencies should be checked for autoimmunities and Pernicous Anemia.

Pernicious Anemia: Clinical Manifestations

• Develops slowly, usually over 20 to 30 years
• Common initial symptoms may involve infection, mood swings, and kidney/gut ailments.
• As HGB levels decrease to 7-8 g/dL, weakness symptoms occur, with fatigue, difficulty walking, loss of satiety, abdominal pains, beefy red tongue and sallow (jaundiced) skin-tones.
• Conditions such as right-heart failure, hepatomegaly or splenomegaly, might take place for people who are elderly. Neurological symptoms that result from demyelination could be neuronal death where its more commonly Sensory Neurophathy is a deficit resulting in losing ability to possess vibrational sense which appears within feet leading to Ataxia
• Vision, the spinal cord, and other normal function may become impaired.
• Long-term treatment improves recoveries, though most improvements occur within small windows.
• Brain function with issues, primarily relating to depression,
• Low levels of vitamin B12 were linked to to neurocognitive disorders and Alzheimer's

Folate Deficiency Anemia

• Shows similar responses/symptoms of what b12 shows where deficiencies take effect
• Folate is a vital vitamin (as Folic acid) and must effectively function with RNA and DNA production; humans must take daily doses of 50-200 mg
• Incidences did go lower since introducing fortified substances and supplements for Folate levels
• Lactic and pregnant women hold requirements, which could further imply tube defects to future fetus
• Folate deficiencies appear more significantly to the others primarily with alcoholics along with malnutritioned subjects, ulcerative colitis in relation to the absorption, and sulphates
• Folate is absorbed in the upper section of the intestines and doesnt require different elements (IF) to facilitate absorption, and then moves throughout liver circulation to be stored
• All the versions of Folate are coenzymes for synthesizing thy mine and purines for homozygotines.
• Insufficiencies in thymine productions effect division process (with Bone Marrow functions) causing megaloblastic precursors and microcytic anemia to take effect.

Folate Deficiency Manifestation

• Shows symptoms close to conditions of Pernicious Anemia like Cheilosis (scales within mouth, inflammation) with painful ulcerations/burning inside it.
• The Burning mouth symptoms may show by others (dry mouth, nutritional or autoimmune influences) which doesnt diagnose Folate deficiencies.
• Possible Dysphagia, flatulency, diarrhea, and histological damages take effect too within G.I tract.
• Those who are greatly malnutrition may show neurological disturbances because of deficiencies in thiamine too
• Symptoms may go away with folate administration within 1-2 weeks

Megaloblastic Anemia with Medication Influence

• Certain drugs that do greatly influence Dna will interfere with cell production that produce megaloblastic anemia
• Immunodulators and other chemo effects will further lower the effect
• Further medicines tend to inhibit effective B12 or folate absorption

Microcytic-Hypochromic Anemias

• Display abnormally small erythrocytes, containing smaller Hemoglobin compositions
• Sideroblastic anemia possibly may lead to both which can be rare, but most commonly IDA

Iron Deficiency Anemia (Microcytic-Hypochromic)

• The world's main nutritional issue, taking place mostly within underdeveloped regions
• Resulting from improper nutrition, impairments to proper absorptions, elevated demand and prolonged ailments
• Most typically showing across US between infant ages, teenagers, childbearing or generally within individuals of poverty and even restricted nutrition
• Rising instances among individuals of eating/weight issues, teenagers etc
• Increasing iron demands with monthly premenstrual factors and in pregnancies

Further and Detailed Factors and Results

• Additional needs will primarily attribute to IDA across children's development.
• Medical implications from surgeries can impact stomach pressure thus also causes IDA
• Both biological genders can attain d/t through erosions stemming through esophagus, hiatus, etc
• Unknown sources of Iron Deficiency in both biological cases should indicate potential GI diseases
• Parasitic attacks are commonly linked together from less fortunate territories increasing both blood loss amount from dietary intakes.
• H. Pylori causes Iron intake to be impaired stemming across unknown origins across adults
• Exposure to unsafe toxicity levels is related to poorer conditioned children, which effects Microcytic anemia since both prevent additions of Heme Associated to pica resulting in contact with contaminants or contaminated soils as for lead.
• Actions between lead/iron- deficiency may act together synergistically within Anemias
• Bone marrow and then into normal circulation for significant amounts in acute losses
• Reduction from oxygenations promotes production and rises bone marrows erythrocythes.
• Stores commonly deplete because the bodies lost erythocytes and erythrothythes are impeded.
• Typically it is advised to restore blood, volume, saline, dextrose, albumin, etc., and huge blood defects make it necessary to transfusion all blood stores. Transversions provide good access for acute/chronic issues and the opposite can be true especially in seriously defective

PathoPhysiology of IDA

Hypocythmia Microcytic occurs when resources then deplete; inadequate intake then reduces levels affecting Hemoglobin production affecting Tissues

• When sufficiency lacks, those sources might suffice however its insuffient in terms of heme creations which may be a secondary affect.

• Inflammation withholds it from Plasma especially through peptide process limiting iron transfer to properportin- degrading it endocyctostically.

• While recycleable, its commonly required by the body with HGB present and Iron in storage for later

• Blood loss will typically damage this state by increasing new Iron demands thus then using them to replace iron thats lost from bleeding

• By adjusting selective mechanisms, body contributes to immunity while not taking it is part of its infection defense.

• Most pathogens needs Iron for survival which restricts Hypoferremia as a result

• As opposed, proper Iron function within bodies defenses is needed and also results when Demands outgrow, develops then steadily while shifting

• Bone marrow levels are then decreased affecting its circulation although serum Iron still remains

• Secondary state causes decrease/affects for bone transprotation results resulting to less erthyopholseis

• Its not always obvious and could reach around 7-8 with nonspecific levels.

• Third state reaches is when red types enter circulation and manifestations indicate at its current state with dimished/altered compositions.

• In contrast, neutroplis, and macrophages usually require adequate iron function across Immune responses

Manifestations and Effects

Beginning primarily or consistently/individually and in early stages affecting tissues such for what becomes severe.

• Nail changes show.
• Mouth conditions are common.
• Swallow changes occur.
• More altered symptoms, effects, and pain changes typically lead to rare alterations and cognitive declines affecting cognitive behavior for what ends as irreversibly.

Normochomatic / cythmic Anmeia

• Few situations influence both size color or compositions resulting in AI and Anplastic complications.

Alterations Anemically and Inflammations

• Referred to as CDE/ACD (disease/inflammation, and or chronic) that results in issues for Erthythyrolseis while affecting usage. Its one of the higher cases among medical concerns/hospitilized groups and others predisposed due to their associations while others get genetically predisposed from inflammatory cytokines due to aging.
• Most commonly with elder homes being anemia ridden. Typically shown from a defective syndrome within Utilization and no known factors.

Inflammations Pathothysioogy

• Commonly forms within 1 / 2month and is always linked to underlying situations that hardly advance.
• May stem with shorter lifespans, reduced product and a number altered with some mechanics
• During chronicity, many cytokines get discharged from different sources impacting its reduction or absorptions
• Impairments from Normal processes, are an issue and is mainly for increased levels of Lacterifferin, and Apotofferin.
• Impairments from defects may not rise production as for numbers but failure possibly also impact resposiveness
• Proliferations and interaction/interations may even be impacted.

Bone Marrow Complications

• Hemolysis is a commonly a result as for what causes issues for functions while showing defects leading and causing what it is.
• Manifestions are within mild ranges mostly, with limited signs

Anplastic Anmeia (AA)

Reductions in functioning blood leads to a pancytopenia which is mostly a decrease or absences.

• US cases happen rarely, due to limited exposures.
• Bimodal occurs.
• Equal to gender with many primary issues although several autoimmune issues may take.
• Those secondary are based on toxicity for some components.
• Therapies get targeted based on irradiation, infection or environmental effects.
• Infections are virus related, including Hiv.
• Issues for proper BM function are possibly attributed to a cause.
• AA usually shows from congenital disorder with limited cases, which can affect the functions and results.

Pathos / Physio

Features relate from hypcells relating from fatty actions, and other processes such for Hcs. Mechanisms of immune and abnormal are present, with various T cell effects and declines in levels.

• Elevated Inflammatory Levels get found.
• Triggers may take effect, and even be linked to the body.

Clinical AA

How they initiate/present is based on speed where components are damaged as the body tries to then help for those effects which can relate to other immune defects etc A more gradual approach over a longer time are progressive weaknesses, and even hemorrhaging which may impact other levels. Treatments become difficult with little relief and can cause infections while often leading to mouth issues with possible cell damages and brain impacts although can be seen at any rate and generally comes from more issues present.

Anmeia with Damaged Increases

Haemolytic anemics lead to the destruction of early forms on early levels be it at regular points, or constantly. May stem from vessels issues and other places such like in liver spleen or even Marrows. Macrophages help then by impacting and damaging any issues which then lead. Intravascular commonly appears through antibody fixation etc which makes its difficult, Those compensations provide all the essential nutrients and processes