Anemia Flashcards
The transport and storage of iron are largely mediated by three proteins they’re?
transferrin, transferrin receptor 1 (TfR1)
and ferritin.
Some iron is stored in the macrophages as ___&___
What’s the difference ?
ferritin and
haemosiderin
Ferritin is a water-soluble protein–iron complex and hemosiderin is not
What are the causes of a hypochromic microcytic anaemia.
.
These include lack of iron (iron deficiency) or of iron release
from macrophages to serum (anaemia of chronic inflammation
or malignancy), failure of protoporphyrin synthesis (sideroblastic
anaemia) or of globin synthesis (α- or β-thalassaemia). Lead also
inhibits haem and globin synthesis
At the end of their life, red cells
are broken down in the macrophages of the reticuloendothelial
system and the iron is released from haemoglobin, enters the
plasma and provides most of the iron attached to transferrin.
Only a small proportion of plasma transferrin iron comes from
dietary iron, absorbed each day through the duodenum and
jejunum. Iron in excess of that needed for haemoglobin synthesis is also released from erythroblasts and erythrocytes to
plasma transferrin.
What’s the distribution of iron in the body?
Hemoglobin 65
Ferritin & hemosiderin 30
Myoglobin 3.5
Haem enzymes 0.5
Transferrin bound fe 0.1
This tissue iron is less likely to become depleted than haemosiderin, ferritin and haemoglobin in states
of iron deficiency, but some reduction of these haem-containing
enzymes may occur
What’s the major hormonal regulator of iron homeostasis and how fore it work?
When it’s raised I’m the blood it indicates?
Hepcidin is a polypeptide produced by liver cells. It is the
major hormonal regulator of iron homeostasis
. It inhibits iron release from macrophages, from intestinal
epithelial cells and from other cells by its interaction with
the transmembrane iron exporter, ferroportin
. It accelerates degradation of ferroportin protein. Raised hepcidin levels
therefore profoundly affect iron metabolism by reducing its
absorption and its release from macrophages.
Factors Influencing Hepcidin Production
High iron levels increase hepcidin production to lower iron in the blood.
Low iron levels and increased red blood cell production reduce hepcidin production to allow more iron absorption.
i.e during erythtopiosis: Early red blood cells (erythroblasts) produce erythroferrone, a protein that suppresses BMP signaling for hepcidin.
Hypoxia suppresses hepcidin, leading to more iron absorption.
Inflammation increases hepcidin, reducing iron to limit bacterial growth.
During inflammation, cytokines like interleukin-6 (IL-6) increase hepcidin production.
Factors Influencing Hepcidin Production
High iron levels increase hepcidin production to lower iron in the blood.
Low iron levels and increased red blood cell production reduce hepcidin production to allow more iron absorption.
i.e during erythtopiosis: Early red blood cells (erythroblasts) produce erythroferrone, a protein that suppresses BMP signaling for hepcidin.
Hypoxia suppresses hepcidin, leading to more iron absorption.
Inflammation increases hepcidin, reducing iron to limit bacterial growth.
During inflammation, cytokines like interleukin-6 (IL-6) increase hepcidin production.
Factors Influencing Hepcidin Production
Iron Status:
Iron Overload (High Iron Levels):
Process:
When iron levels are high, a protein called diferric transferrin (which carries iron) signals the liver cells.
This signal causes liver cells to produce bone morphogenetic proteins (BMPs), particularly BMP6.
BMP6 binds to receptors (BMPRs) on liver cells, forming a complex with other proteins (TFR2, HJV, HFE)
This complex activates signaling proteins (SMADs) that go to the cell nucleus and stimulate hepcidin production.
Hepcidin then works to reduce iron absorption from the diet and release of iron from storage.
Example: Think of BMP6 as a traffic light turning green, signaling more hepcidin cars to move out from the liver garage to reduce iron traffic in the bloodstream.
What are the factors favouring absorption and those that reduce
Ferrous form (Fe2+)
Acids (hydrochloric acid, vitamin C)
Solubilizing agents (e.g. sugars, amino acids)
Reduced serum hepcidin
Ineffective erythropoiesis
Pregnancy
Hereditary haemochromatosis
Inorganic iron
Reduce
Haem iron
Ferric form (Fe3+)
Alkalis – antacids, pancreatic secretions
Precipitating agents – phytates, phosphates, tea
Increased serum hepcidin
Decreased erythropoiesis
Inflammation
What’s the normal hg and pcv for a
Adult male
Adult female non P
Adult female P
Children 6-12Y
Children 6M to 6Y
Infants 2-6M
Newborn
Adult males
13-17
40-50
Adult females(nonpregnant)
12-15
38-45
Adult females(pregnant)
11-14
36-42
Children, 6-12yrs
11.5-15.5
37-46
Children, 6mths-6yrs
11-14
36-42
Infants, 2-6mths
Newborns
9.5-14
13.6-19.6
32-42
44-60
What are the categories of anemia. Severity with hg figures
Mild : lower limit of normal to 10g/dl
Moderate : 7-10g/dl
Severe : <7g/dl
Clinical evaluation : signs and symptoms of anemia
Signs and symptoms :
easy fatiguability, effort dyspnoea, tachycardia, pallor, ccf in severe cases
Sure, let’s break down this text about determining the cause of anemia into simpler terms with some examples.
To find out why someone has anemia, doctors look at the signs and symptoms that might come from the anemia itself or from the illness causing it.
Anemia can cause various symptoms, such as:
- Easy Fatiguability: Getting tired very easily.
- Effort Dyspnea: Shortness of breath during physical activity.
- Tachycardia: A fast heartbeat.
- Pallor: Pale skin.
- CCF (Congestive Cardiac Failure): In severe cases, the heart struggles to pump blood effectively.
Doctors will ask about different aspects of a person’s history, such as:
- Chronic Blood Loss: Ongoing loss of blood, like from heavy menstrual periods or gastrointestinal bleeding.
- Recurrent Pregnancies: Multiple pregnancies can deplete iron stores.
- Pica: A strong desire to eat non-food items, like dirt or ice, which can be linked to iron deficiency.
- Chronic Alcoholism: Drinking a lot of alcohol over a long time can affect the body’s ability to produce healthy blood cells.
-
Drug History: Certain medications can cause different types of anemia. For example:
- Hypoplastic Anemia: A condition where the bone marrow doesn’t make enough blood cells, can be caused by drugs like chloramphenicol.
- Macrocytic Anemia: Caused by drugs like methotrexate, which affect how the body uses folic acid.
- Iron Deficiency Anemia (IDA): Drugs like aspirin can cause stomach bleeding, leading to anemia.
- Hemolytic Anemia: Caused by drugs like methyldopa that make the body destroy its own red blood cells.
- Jaundice or Gallstones: These conditions can indicate issues with red blood cell breakdown, which might contribute to anemia.
- Chronic Illness: Long-term diseases, like kidney disease or cancer, can lead to anemia.
- Prevalent Forms of Anemia in the Area: Certain types of anemia are more common in specific regions. For example, Sickle Cell Anemia (SCA) is more prevalent in some areas and can help guide the diagnosis.
Imagine a patient named Jane who goes to the doctor because she feels extremely tired all the time and gets out of breath just walking up a few stairs. The doctor notices she has pale skin and a fast heartbeat. Jane mentions that she has very heavy periods each month and has had three children in the last five years. She also tells the doctor that she sometimes craves and eats ice.
The doctor suspects Jane might have iron deficiency anemia (IDA) due to her history of heavy menstrual bleeding and multiple pregnancies. The craving for ice, a type of pica, also supports this. Further tests would likely confirm the diagnosis and help determine the right treatment.
What are the Causes of Anemia in Chronic Disorders
How Anemia Develops in These Conditions
Treatments and possible complications
Causes of Anemia in Chronic Disorders
Chronic Inflammatory Diseases:
- Infections: Conditions like lung abscesses, tuberculosis, bone infections (osteomyelitis), pneumonia, and bacterial infections in the heart (endocarditis).
- Non-infectious Conditions: Diseases like rheumatoid arthritis, lupus, other connective tissue diseases, sarcoidosis (a disease involving abnormal collections of inflammatory cells), and inflammatory bowel disease (IBD).
Other Chronic Conditions:
- Heart Problems: Congestive heart failure.
- Lung Problems: Chronic pulmonary disease.
- Kidney Problems: Chronic renal disease.
- Obesity.
- Cancer: Including types like carcinoma, lymphoma, and sar
How Anemia Develops in These Conditions
- Iron Handling Issues: The body has trouble releasing iron from certain cells (macrophages) into the blood because of high levels of a protein called hepcidin. Hepcidin levels go up due to inflammation caused by substances like IL-6 and IL-1.
- Poor Red Blood Cell Production: The body doesn’t produce enough red blood cells because of the effects of inflammatory substances (cytokines) like IL-1 and tumor necrosis factor (TNF). These substances directly block the production of red blood cells.
-
Shortened Red Blood Cell Lifespan: Red blood cells don’t live as long because they get targeted and destroyed by the immune system. This happens due to:
- Macrophage Activation: Macrophages are cells that can destroy red blood cells.
- Antibody and Complement Binding: Red blood cells get tagged with antibodies and complement proteins, marking them for destruction.
- Interference with Other Blood Cell Production: A protein called interferon-gamma binds to thrombopoietin (which normally helps produce platelets) and stops it from working properly.
- Treating the Underlying Disease: Fixing the primary health issue usually corrects the anemia.
- Erythropoietin Injections: These can help in some cases by stimulating red blood cell production.
- Iron Therapy: This generally does not work for this type of anemia.
Sometimes, this type of anemia occurs alongside other types of anemia caused by:
- Iron, vitamin B12, or folate deficiencies.
- Kidney failure.
- Bone marrow failure.
- Hypersplenism (an overactive spleen).
- Endocrine (hormonal) abnormalities.
- Leucoerythroblastic anemia (where immature blood cells appear in the bloodstream).
What’s the normal, micro and macro value of rbc i.e MCV
Microcytic, hypochromic
Normocytic, normochromic Macrocytic
MCV <80fL
MCV 80–95fL
MCV >95fL
Macrocytic anemia can be either ___or__
Megaloblastic or non megaloblastic anemia
What’s megaloblastic anemia
It’s causes and
Morphological xteristic
What is Megaloblastic Anemia?
Megaloblastic anemia is a type of anemia where the developing red blood cells (called erythroblasts) in the bone marrow show a specific abnormality. The problem lies in how these cells mature:
Nuclear Maturation Delay: The nucleus (control center of the cell) matures slower than the cytoplasm (the fluid part of the cell).
Common Causes
Vitamin B12 Deficiency: Vitamin B12 is essential for DNA synthesis. Without enough B12, red blood cells can’t develop properly.
Folate Deficiency: Folate (another B vitamin) is also crucial for DNA synthesis. A deficiency leads to the same problem as with B12.
Less Common Causes
Metabolic Issues: Problems with how the body processes these vitamins (sometimes caused by drugs or genetic issues) can lead to the same type of anemia.
Inherited DNA Synthesis Defects: Genetic conditions affecting DNA synthesis.
Morphological Characteristics
When you look at the erythroblasts under a microscope, you see:
Chromatin: This is the material inside the nucleus containing DNA. In megaloblastic anemia, the chromatin remains open and loosely organized, indicating the nucleus hasn’t matured properly.
Cytoplasm: Despite the nucleus lagging behind, the cytoplasm shows signs of hemoglobinization, meaning it takes on the appearance typical of more mature red blood cells.
BIOCHEMICAL BASIS OF MEGALOBLASTIC ANEMIA
What are the causes of severe md mild vitamin B13 defiency?
Pernicious Anemia**: This is the most common cause in developed countries. It is an autoimmune disease where the body’s immune system attacks the stomach’s lining, leading to poor vitamin B12 absorption.
-
Dietary Deficiency:
- Vegans: People who follow a strict vegan diet without supplements may lack vitamin B12, which is mostly found in animal products.
- Poor-Quality Diet: People who eat a diet very low in B12-rich foods might develop a deficiency, though their body’s recycling system (entero-hepatic circulation) often prevents severe deficiency.
-
Surgical and Medical Conditions:
- Gastrectomy: Removal of part or all of the stomach can impair B12 absorption.
- Intestinal Lesions: Damage or diseases in the small intestine can affect absorption.
-
Other Factors:
- Nitrous Oxide: Can rapidly inactivate vitamin B12 in the body.
- Inadequate Diet: This is the most common cause worldwide.
-
Malabsorption Conditions:
- Atrophic Gastritis: Particularly in the elderly, where the stomach lining thins and reduces B12 absorption.
- Medications: Proton pump inhibitors (reduce stomach acid), metformin (diabetes medication), and cholestyramine (lowers cholesterol) can affect B12 absorption.
- Chronic Pancreatitis: Inflammation of the pancreas.
- Gluten-Induced Enteropathy: Celiac disease.
- HIV Infection: Can interfere with nutrient absorption.
- Zollinger-Ellison Syndrome: Causes low pH in the duodenum, interfering with the enzymes that help release B12 from food.
- Pregnancy: Temporary drop in B12 levels in some women, usually returning to normal after delivery.
- Autoimmune Attack: The immune system attacks the stomach’s lining, leading to its thinning and reduced function.
- Atrophic Gastritis: The stomach lining becomes thin and inflamed, with immune cells infiltrating the area.
- Loss of Parietal Cells: These cells normally produce stomach acid (leading to achlorhydria) and intrinsic factor (IF), a protein essential for B12 absorption. Without IF, B12 cannot be absorbed properly.
- Increased Gastrin Levels: The hormone gastrin levels rise as a response to low stomach acid.
- Helicobacter pylori Infection: This bacterial infection can trigger autoimmune gastritis, leading to PA.
- Parietal Cell Antibody: Found in 90% of PA patients, it targets the cells that produce stomach acid. However, it’s not specific to PA and can appear in older adults without PA.
- Intrinsic Factor (IF) Antibody: More specific to PA, found in 50-70% of PA patients. It inhibits IF from binding to B12, preventing B12 absorption.
- Blocking Antibody: Less common, it prevents IF from attaching to its binding site in the small intestine.
Pregnancy causes both micro and macro anemia depending of the nutrient deficiency
What are the clinical features of megaloblastic anemia
Mildly jaundice ( due to excess break down of hemoglobin)
Glossitis ( beafy-red sore tongue)
Angular cheilosis
Loss of weight
Purpura
Neuropathy
Sterility
How does maro/megaloblastic anemia causes neuropathy
Due to deficiency in folate or B12
Affecting the neural tube causing spinal bifeda & anancaphale
