Part 2 Ilaban Mo Yan!!!!!! Lord, Help Me
Part 2 Ilaban Mo Yan!!!!!! Lord, Help Me
Part 2 Ilaban Mo Yan!!!!!! Lord, Help Me
Most common enzymatic deficiency in red blood cells Tonic water – is a bitter carbonated soft drink made with quinine (malarial medication) it
7.5% of world population deficient is used especially as a mixer with gin and other liquors.
o 60-70% kurdish jews Bitter melon/ampalaya
o 35% prevalence in certain areas of africa
Inherited, x-linked recessive disorder. Rare in female. SYMPTOMS
In severe cases it can lead to kidney failure or death. Do not display any signs of the disease until exposed to certain chemicals in food or medicine.
G6pd enzyme helps red blood cells work properly. Dark tea-colored urine – due to increased level of bilirubin in urine
Too little g6pd leads to the destruction of red blood cells. This process is called hemolysis. When Back pain (kidney damage)
this process is actively occurring, it is called a hemolytic episode. Enlarged spleen
3 main triggering factors: infections, certain foods and certain drugs. Anemic symptoms (fatigue, hypotension, tachycardia and confusion)
CAUSE Rapid heart rate or shortness of breath
G6pd deficiency is cause by mutations in g6pd gene. Yellow skin color (jaundice)
The defective gene that causes this deficiency is on the x chromosome, which is one of the two sex
chromosomes. Men have only one x chromosome, while women have two x chromosomes. In males, DIAGNOSIS
one altered copy of the gene is enough to cause g6pd deficiency. Screening tests
In females, however, a mutation would have to be present in both copies of the gene. Fluorescent spot test (most reliable and sensitive) -it detects the fluorescence of NADPH
PATHOPHYSIOLOGY Methemoglobin reduction test
G6pd is an enzyme involved in the production of nadph in the hexose monophosphate shunt Confirmatory tests - If positive screening test , To asses or check the level of g6pd enzyme and
pathway/pentose phosphate pathway generated nadph
Nadph is necessary for reduced glutathione, which protects hemoglobin from oxidase damage Blood tests
When g6pd is deficient, reduced glutathione is absent Complete blood count (cbc) – Hgb and Hct (decreased)
Without reduced glutathione, hemoglobin is oxidized and forms heinz bodies in rbc Reticulocyte count - Increased
Heinz bodies cause damage to the rbc membrane and these damaged rbcs are removed in the Molecular test - Detection of g6pd gene mutation
spleen, leading to anemia.
Note: Without G6PD there is no NADPH, if there is no NADPH our red blood cells will never be safe BLOOD FINDINGS
CLASSIFICATIONS Anemia (normochromic and normocytic)- Normochromic and normocytic meaning there is no
Class i - <10% of normal; chronic change in rbcs or the rbcs are typically normal.
Anisocytosis – there are different shapes of rbcs ( some are smaller and some are bigger)
Class ii - <10% of normal; intermittent
Poikilocytes – different shapes
- G6pd mediterranean Heinz bodies and bite cells
Class iii – 10-60% normal; intermittent
- G6pd a allele TREATMENT
Class iv – wild type: g6pd b (normal individuals) Avoid/remove known triggers
Class v- 2x normal activity Folic acid supplementation (patients with chronic hemolysis)- 1mg/day
CLINICAL PRESENTATION Blood transfusion (if hemolysis is severe)
Majority asymptomatic - No hemolysis, no anemia
Neonatal jaundice/ hyperbilirubinemia - Appearing 1-4 days after birth
Chronic hemolytic anemia (very rare)
Acute hemolytic anemia
Trigger factors
-red blood cell destruction can be triggered by infections, certain foods and certain
HEMOLYTIC DISEASES OF NEW BORN (HDN)
medicines:
• Is a blood problem in newborn babies it occurs when the baby’s red blood cell breakdown at a fast
o Medication: dapsone – medication for leprosy
rate. It is also called Eythroblastosis fetalis.
nitrofurantoin
primaquine – a malarial medication • It is a condition in which the neonate or the fetus red blood cell (rbc) are destroyed by
methylene blue immunoglobulin G (IgG) produce by the mother.
dimercaperol
o Foods to avoid CAUSES OF HDN:
Fava beans (abitsuelas, garbanzos, kadyos, munggo) 1. Rh Incompatability
- Fava beans is a type of legumes consumed worldwide that contains high amount • HDN is occurred when a mother with Rh-negative blood becomes pregnant with Rh-
of divicine, convicine, and isouramil-chemicals that are suspected to be highly positive baby that inherited from a Rh-positive Father
oxidative. • It occurs when anti-D is stimulated in mother plasma due to mother’s immune response
Red wine to the antigen D on fetal red blood cell
Blueberry
• This is due to the Anti-D that capable to cross placenta hence delivered to fetal • Coombs test
circulation • Percutaneous umbilical cord blood sampling
• Rh caused HDN in less common but more severe. - AKA: Fetal Blood Sampling
2. ABO incompatability - This is done to check if your baby needs an intrauterine blood transfusion.
• HDN is aroused when a mother of blood type O become pregnant with a fetus with
different blood types A, B or AB. PREVENTION:
• ABO caused HDN is common but less severe. • Determine Rh status of the mother
• If the mother is not sensitized, reduce the risk of future sensitization
LESS COMMON CAUSE: • If the mother is sensitized, determine whether the fetus is at risk and monitor accordingly
3. other unexpected immune antibody (other than anti-D)
- Other Rh Antibodies
Anti- E (second most common, mild disease)
Anti- c (third most common, mild to severe)
Anti- C and Anti- e (Rare)
- Other Antibodies
Kell system antibodies (uncommon causes)
Duffy, MNSs and Kidd system antibodies (rare causes)
SYMPTOMS:
note: during pregnancy you won’t notice any symptoms
DURING PRENATAL TEST:
• Yellow coloring amniotic fluid
• The baby may have big liver, spleen or heart
• Hydrops fetalis
AFTER BIRTH SYMPTOMS:
• Pale looking skin
• Jaundice- Yellow coloring of the baby’s umbilical cord, skin and the white of
his/her eyes
• A new born with hydrops fetalis
• Kernicterus
KERNICTERUS
- is a rare neurological disorder characterized by excessive levels of bilirubin in the blood
during infancy results from high levels of unconjugated bilirubin in the fetus blood which HODGKIN DISEASE
is more than 20 mg/dl First described in 1832 by Dr. Thomas Hodgkin. It is also called Hodgkin lymphoma.
- Because the unconjugated bilirubin are lipid soluble and toxic it can crosses the blood a type of blood cancer that develops when white blood cells called lymphocytes(B cells) grow out of
brain barrier and it will penetrates neuronal and glial membrane thus causes toxicity control.
- Patients surviving kernicterus have severe permanent neurologic symptoms such as: These lymphocytes divide in an abnormal way or do not die when they should.
- Choreoathetosis It most often spreads through the lymph vessels via lymph nodes but can invade the bloodstream and
- Spasticity metastasize to areas including the liver, lungs, spleen, and bone marrow.
- Muscular rigidity The most common sites of occurrence are in the chest, neck, groin, or armpit.
- Ataxia Bimodal peak: 25-30 yrs. Old and 55 yr. old and above.
- Deafness
Slightly predominance in male. Rare in children younger than 10 years.
- Mental retardation
There are two types of Hodgkin lymphoma
HYDROPS FETALIS
classical Hodgkin lymphoma
• As the fetus anemia got worsen the fetus accelerates red cell production
Nodular lymphocyte- predominant Hodgkin lymphoma (NLPHL)
• Liver and spleen increase in size due to increase of rbc
1. Classical Hodgkin lymphoma
• As a result, portal hypertension occurs, causing the liver to reduce its albumin production
- contains particular cells called Reed–Sternberg cells. These are large, abnormal lymphocytes that
• This turn result in edema
look a bit like owl eyes under a microscope.
• Edema- is an abnormal accumulation of fluid beneath the skin
- It also contains Hodgkin cells, which have similar proteins and DNA to Reed–Sternberg cells but
don’t look like owl eyes
DIAGNOSIS:
Four subtypes of CHL:
• Blood test
• Nodular sclerosis – most common in female
• Ultrasound
• Mixed cellularity- eosinophil's, plasma cells, histiocytes
• Amniocentesis
• Lymphocyte rich classical- very good prognosis Stage 2 – involves a minimum of two lymph node regions on the same side of the body (determined by
• Lymphocyte depleted – has poorest survival their location relative to the diaphragm), or the spread of cancer from one lymph node into one nearby.
2. Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) Stage 3 – involves affected lymph node regions on both sides of the body with further characterization
- Around 1 in 10 people with Hodgkin lymphoma have NLPHL. contains variants of Reed–Sternberg dependant on the affected areas.
cells called lymphocyte-predominant cells (LP cells). They are sometimes known as ‘popcorn cells’ Stage 4 - involves both spread in areas outside the lymphatic system (metastasis), and lymphatic system.
because they look a bit like pieces of popcorn under a microscope. LP cells make a protein called ‘CD20’. Staging can also be determined by the presence or absence of some symptoms.
This is more commonly found in non-Hodgkin lymphomas. Asymptomatic (A) - No fever, night sweats, or weight loss.
RISK FACTORS Symptomatic (B) - Symptoms include fever, night sweats, or weight loss.
Medical conditions that weaken the immune system
Immunosuppressant medications TREATMENT
Certain viral infections – there is a positive correlation seen between Hodgkin disease and Classical Hodgkin lymphoma
infection by viruses such as the Epstein-Barr virus (responsible for Infectious Chemotherapy
radiotherapy
mononucleosis), and human immunodeficiency virus (HIV)
NLP Hodgkin lymphoma
EBV- is very common virus that cause glandular fever. Surgery
There’s a higher risk of developing HL if the person have been infected with the Radiotherapy
virus. Chemotherapy combined with antibody therapy
Family history - if a first-degree relative (such as a parent, child, or sibling) has suffered the
condition.
SYMPTOMS IRON DEFICIENCY ANEMIA (IDA)
Nontender lymph nodes enlargement (localized) A common type of anemia
neck and supraclavicular area As the name implies, it is due to insufficient iron.
Lymphodenopathy(painless) IDA occurs when the body doesn't have enough iron to produce haemoglobin, a part of RBCs that gives
B symptoms blood its red color and enables the RBCs to carry oxygenated blood throughout the body.
fever SIGNS AND SYMPTOMS
night sweats
Initially, iron deficiency anemia can be so mild that it goes unnoticed.
unexplained weight loss
other symptoms As the body becomes more deficient in iron and anemia worsens, the signs and symptoms intensify.
fatigue, weakness, pruritus o Extreme fatigue
cough , chest pain, shortness of breath, vena cava syndrome o Weakness
abdominal pain, bowel disturbances, ascites o Pale skin
bone pain o Chest pain, fast heartbeat (tachycardia) or shortness of breath
o Headache, dizziness or lightheadedness
DIAGNOSIS o Cold hands and feet
Lymph node biopsy o Inflammation or soreness of the tongue
is the only way to tell for certain whether or not a lump is lymphoma. This means taking a sample o Brittle nails
from a swollen lymph node to be examined in a lab. o Unusual cravings for non-nutritive substances, such as ice, dirt or starch
The exact procedure depends on where the swollen lymph node is. o Poor appetite, especially in infants and children
There are different types of biopsy. CAUSES
• Excision biopsy iron loss, iron intake, iron absorption
- involves a minor operation to remove a swollen lymph node. If the lymph node is very large, only Iron deficiency anemia will eventually develop when
part of it might be removed. One is losing too much iron
• Needle core biopsy One doesn’t consume enough iron
-a small sample of the cells in a swollen lymph node is taken using a special needle. The body can't produce enough haemoglobin
It is often done at the same time as an ultrasound or CT scan under local anaesthetics. BLOOD LOSS
Blood tests - Blood contains iron within the RBCs. Losing blood means losing some iron.
Computed tomography (CT) scans - Heavy menstrual periods
Positron-emission tomography (PET) scans - Slow, chronic blood loss (peptic ulcer, a hiatal hernia, a colon polyp or colorectal cancer)
Ultrasound scans- use to examine swollen lymph node that are near the surface of skin. - Medications- Gastrointestinal bleeding can result from regular use of some over-the-counter
pain relievers, especially aspirin.
X-rays –use to assess what parts of the body are affected by lymphoma.
LACK OF IRON IN THE DIET
Magnetic resonance imaging (MRI) scans - The body regularly gets iron from the food we eat.
Bone marrow biopsy - Consuming too little iron, over time the body can become iron deficient.
Staging is a process in which the extent of cancer spread is determined - this is useful in indicating what - Examples of iron-rich foods include meat, eggs, leafy green vegetables and iron-fortified
level of treatment will be most appropriate. foods.
- For proper growth and development, infants and children need iron from their diet.
METHOD OF STAGING HODGKIN LYMPHOMA IS THE FOLLOWING: INABILITY TO ABSORB IRON
Stage 1 – involves one affected lymph node region. - Iron from food is absorbed into the bloodstream in the small intestine.
- An intestinal disorder, such as celiac disease, affects the intestine's ability to absorb
nutrients from digested food.
- If part of the small intestine has been bypassed or removed surgically, it may affect the PREVENTION
ability to absorb iron and other nutrients. Foods rich in iron include:
PREGNANCY- Without iron supplementation, iron deficiency anemia occurs in many pregnant women Red meat, pork and poultry
because their iron stores need to serve their own increased blood volume as well as be a source of Seafood
hemoglobin for the growing fetus. Beans and Peas
Dark green leafy vegetables, such as spinach
Dried fruit, such as raisins and apricots
Iron-fortified cereals, breads and pastas
The body absorbs more iron from meat than from iron-rich plant-based foods.
Enhance the body's absorption of iron by drinking citrus or orange juice or eating foods rich in
vitamin C.
RISK FACTORS Broccoli, Grapefruit, Kiwi, Leafy greens, Melons, Peppers, Strawberries, Tangerines, Tomatoes
These groups of people may have an increased risk of iron deficiency anemia:
Women - They lose blood during menstruation, women in general are at greater risk of iron deficiency
anemia.
Infants and children - Infants, especially with low birth weight or born prematurely, who don't get
enough iron from breast milk or formula may be at risk of iron deficiency. Children need extra iron during
growth spurts.
Vegetarians- People who don't eat meat may have a greater risk of iron deficiency anemia if they don't eat
other iron-rich foods.
Frequent blood donors- People who routinely donate blood may have an increased risk of iron
deficiency anemia since blood donation can deplete iron stores. Low hemoglobin related to blood
donation may be a temporary problem remedied by eating more iron-rich foods.
DIAGNOSIS
Complete Blood Count
Red blood cell size and color. With IDA, red blood cells are smaller and paler in color than normal.
Hematocrit. This is the percentage of the blood volume made up by the RBCs. Normal levels are
generally between 35.5 and 44.9 percent for adult women and 38.3 to 48.6 percent for adult men.
These values may change depending on the age.
Hemoglobin. Lower than normal hemoglobin levels indicate anemia. Male: 13-18g/dL. Females:
12-16g/dL
Mean Corpuscular Volume (MCV). Lower than normal when RBCs are too small. This condition
is called microcytic anemia. Microcytic anemia may be caused by: iron deficiency.
Ferritin. This protein helps store iron in the body, and a low level of ferritin usually indicates a low
level of stored iron.
ADDITIONAL DIAGNOSTIC TESTS TO IDENTIFY AN UNDERLYING CAUSE
Endoscopy. A thin, lighted tube equipped with a video camera is passed down the throat to Preventing iron deficiency anemia in infants
the stomach to view the esophagus and stomach to look for sources of bleeding from a hiatal hernia FIRST YEAR- Feed the baby breast milk or iron-fortified formula.
or an ulcer in the stomach.
UNDER 1 YEAR- Cow's milk isn't a good source of iron for babies and isn't recommended for
Colonoscopy. To rule out lower intestinal sources of bleeding. A thin, flexible tube equipped
with a video camera is inserted into the rectum and guided to the colon to view inside some or all of infants.
the colon and rectum to look for internal bleeding. Patient is sedated during this test. AFTER AGE 6 MONTHS, start feeding the baby iron-fortified cereals or pureed meats at least twice
Ultrasound. Pelvic ultrasound for women to look for the cause of excess menstrual bleeding, a day to boost iron intake.
such as uterine fibroids. AFTER ONE YEAR, children should not drink more than 20 ounces (591 milliliters) of milk a day.
Too much milk often takes the place of other foods, including those that are rich in iron.
COMPLICATIONS OF IDA
TREATMENT
Mild iron deficiency anemia usually doesn't cause complications.
Blood transfusion in severe cases - If iron deficiency anemia is severe, iron maybe given intravenously
If left untreated, IDA can become severe and can lead to the following:
or a need for blood transfusion to help replace iron and hemoglobin quickly.
Heart. IDA may lead to a rapid or irregular heartbeat. The heart must pump more blood to compensate for
Iron supplementation
the lack of oxygen carried in the blood. This can lead to cardiomegaly or heart failure.
- Correct dosing to replenish the iron stores in the body.
Pregnancy. Severe iron deficiency anemia has been linked to premature births and low birth weight
babies. It is preventable by iron supplements as part of the prenatal care. - Iron is available in liquid form for infants and children.
Growth problems. In infants and children, severe iron deficiency can lead to anemia as well as delayed - To improve the chances that the body will absorb the iron in the tablets
growth and development. IDA is associated with an increased susceptibility to infections. Take iron tablets on an empty stomach. May need to take iron tablets with meals if it upsets the
stomach.
Don't take iron with antacids. Medications like antacids can interfere with the absorption of iron. Take Halt cell division causing the cell lysis which increases apoptosis resulting in peripheral
iron two hours before or four hours after you take antacids. pancytopenia.
Take iron tablets with vitamin C. Vitamin C improves the absorption of iron. It is recommended to take Pancytopenia: a decreased in all blood cell types
Some of the erythroid progenitor cells may manage to survive and continue abnormal
iron tablets with a glass of orange juice or with a vitamin C supplement. Generally, patients start to feel
maturation then released into circulation.
better after a week or so of treatment. Blood is rechecked after treatment to measure iron levels. CAUSES OF MEGALOBLASTIC ANEMIA
Two most common cause:
TARGET is to TREAT UNDERLYING CAUSE OF IRON DEFICIENCY 1. Vitamin B12 deficiency
- If iron supplements don't increase blood-iron levels, it's likely the anemia is due to a source of bleeding 2. Folate deficiency
or an iron-absorption problem that has to be investigated and treated. These two nutrients are needed for the production of thymidine nucleotides for DNA synthesis to be
- Depending on the cause, iron deficiency anemia treatment may involve: able to generate normal erythropoiesis.
Medications, such as oral contraceptives to lighten heavy menstrual flow Other Causes of megaloblastic erythrocytes: Dysplastic erythroid cells in Myelodysplastic syndrome
Antibiotics and other medications to treat peptic ulcers (MDS)
Surgery to remove a bleeding polyp, a tumor or a fibroid Vitamin B12 Folate
- Vitamin B12 is known as cobalamin. - A vitamin B9
- A water-soluble vitamin found in some - Folic acid: synthetic form of
foods like meat, fish, eggs, dairy supplements.
products as wells as fortified cereals - Folate: They are naturally found in
and supplements. foods.
ADDITIONAL NOTES: - Vitamin B12 is not destroyed by - Source: leafy green vegetables, dried
DO NOT self-diagnose or treat. cooking. beans, fortified breakfast cereals, some
If a person develops signs and symptoms that suggest iron deficiency anemia, seek medical - It is coabsorbed with intrinsic factor, a fruits like oranges
attention. product of stomach parietal cells, - Folate are heat labile and overcooking
Self- medication may lead to overloading with iron which can be dangerous, excess iron absorb by the terminal ileum after being of foods can diminish their nutritional
accumulation can damage the liver and cause other complications. extracted by gastric acid. value.
Iron supplements can cause constipation; a stool softener is also recommended.
Iron may turn stools black, which is a harmless side effect. ABSORPTION OF VITAMIN B12 AND FOLATE
Iron deficiency can't be corrected overnight. Take iron supplements for a month or longer to
replenish iron reserves. • Dietary intake of Vitamin B12 and Folate
• Intrinsic Factor is a glycoprotein secreted by parietal cells of stomach mucosa.
• Cobalamin splits from dietary protein & combines with IF to form vitamin-IF complex.
• Vitamin-IF complex remains stable and unabsorbed until it reaches the ileum
• In ileum, vitamin-IF complex attaches to specific receptor sites present in the microvillus
membrane
• Release of this complex from the mucosal cells with subsequent transport to the tissue depends
on the Transcobalamin II
• TC II is a plasma polypeptide synthesized by the liver, bone marrow and probably other
tissues. TC II acts as the acceptor and principal carrier of the vitamin to the liver & other
tissues
WHAT CAUSES THE DEFICIENCIES?
A. Vitamin B12 Deficiency
1. Decreased intake in strict vegetarian
2. Malabsorption
Lack of Intrinsic factor: IF is produced in the gastric parietal cells of the stomach,
its secretion parallels that of hydrochloric acid
Lack of intrinsic factor can be due to immune system producing antibodies that mistakenly attacks
gastric parietal cells of the stomach leading to pernicious anemia.
MEGALOBLASTIC ANEMIA
Pernicious anemia
Characterized by impaired DNA synthesis and distinct megaloblast in the bone marrow. Hereditary intrinsic factor deficiency, a rare autosomal recessive disorder characterized by the absence or
Impaired DNA synthesis: due to deficiency of vitamin B12 or folate. nonfunctionality of intrinsic factor.
Impaired DNA synthesis leads to depletion of thymidine nucleotide which leads to retarded mitosis. Post gastrectomy: a surgical removal of stomach parts which results in removal of intrinsic factor-
There is a delayed nuclear maturation→resulting in megaloblasts →macrocytes producing parietal cells
Megaloblast: abnormally large nucleated erythroid precursors Celiac disease
Macrocytes: RBCs are larger than normal Ileal resection
It affects all rapidly dividing cells of the body including skin, epithelium of GI tract, and Crohn disease: a type of inflammatory bowel disease which causes inflammation in the digestive tract.
hematopoietic tissues. Bacterial or parasitic competition for vitamin B12
Ineffective erythropoiesis occurs: where in megaloblast precursors undergo intramedullary Bacterial overgrowth: Helicobacter pylori infection resulting in loss of parietal cells.
destruction
Infestation of fish tapeworm Diphyllobothrium latum is able to split vitamin B12 from intrinsic Neuropsychiatric symptoms may also be present, Including personality changes and psychosis
factor. (delusions and hallucinations). These symptoms seem to be the result of demyelinization of the
3. Increased Demand: pregnancy, lactation, infants and children growth due to vigorous cell spinal cord and peripheral nerves, but the relationship of this demyelinization to vitamin B12
replication deficiency is unclear.
B. Folate Deficiency In folate deficiency
1. Decreased intake: Especially old age, poverty, poor diet Depression, Folate levels appear to influence the effectiveness of treatments for depression.
2. Malabsorption: due to tropical sprue Folate deficiency during pregnancy can result in impaired formation of fetal nervous system
3. Excessive loss of folate: Hemodialysis resulting in neural tube defects such as spinal bifida. Pregnancy requires an increase in folate to
Renal dialysis, however patients are routinely provided with supplemental folic acid fulfill the requirements related to rapid fetal growth, uterine expansion, placental maturation, and
to prevent megaloblastic anemia. expanded blood volume.
4. Increased demand: Pregnancy, Lactation, Infants LABORATORY FINDINGS
Markedly increased in hematopoiesis SCREENING TEST
5. Impaired utilization due to: 1. Complete Blood Count
Drugs that are folate antagonist: Hemoglobin and hematocrit (PCV): reduced
o anticonvulsant such as carbamazepine, phenytoin Normal Hgb values for Male: 13-18g/dL. Females: 12-16g/dL
o anti-cancer such as methotrexate, hydroxyurea Red cell indices
Mean Corpuscular Volume (MCV): increased, above 100 fL (Normal MCV 82-98 fL)
Mean Cell Hemoglobin (MCH): increased (normal 27-32 pg)
Mean Cell Hemoglobin Concentration (MCHC): normal (31-36 g/dL)
2. Reticulocyte count: decreased
3. WBC Differential Count: hypersegmented neutrophils with 6 or more lobes, bands can also be seen
4. Bilirubin and Lactate Dehydrogenase Levels
Serum total and indirect bilirubin – increased
Serum lactate dehydrogenase (LDH) – increased
NUCLEAR CHANGES
Poikilocytosis - Poikilocytosis is the medical term for having abnormally shaped red blood cells (RBCs)
HYPERSEGMENTATION
in your blood. Abnormally shaped blood cells are called poikilocytes.
- also referred as macropolycytes
Morphology:
Larger than normal
Different types of poikilocytosis; With 5 lobes or more
A. Spherocytes Found in:
B. Stomatocytes • Megaloblastic anemia
C. Codocytes/Target cells • Iron deficiency
D. Leptocytes • Chronic infection
E. Sickle cell • Liver disease
F. Elliptocytes • Uraemia
G. Ovalocytes ______________________________________________________________________________
H. Dacryocytes/Teardrop cell HYPOSEGMENTATION
I. Acanthocytes - Pelger Huet Nucleus
J. Echinocytes Morphology:
K. Schizocytes Bilobed (pince-nez spectacles) nucleus
More condensed chromatin
Found in:
Anisocytosis is the medical term for having red blood cells (RBCs) that are unequal in size. Normally, a • Pelger Huet Anomaly
person's RBCs should all be roughly the same size. Anisocytosis is usually caused by another medical • Idiopathic myelofibrosis
condition called anemia. • Chronic granulocytic leukemia
• Inherited Myelodysplastic syndromes
Different types of anisocytosis; • Severe infection
- Macrocytosis – the red blood cells are larger than the normal.
Cytoplasmic Swelling
______________________________________________________________________________
BARR BODY - caused by actual osmotic swelling
Morphology: of the cytoplasm or by increased adhesion to the glass
Appear as small drumstick-like projection on one of the lobes of the neutrophil in females slide by stimulated neutrophils. Regardless of the cause, the result is a variation in neutrophil size or
Attached to the nuclear lobes by a single narrow stalk neutrophil anisocytosis
Are the morphological expression of inactivated X-chromosome
It is non-pathological unless associated with rare chromosomal disorders
_____________________________________________________________________________
___________________________________________________________________________
PYKNOTIC NUCLEI
- indicate imminent cell death CYTOPLASMIC INCLUSIONS:
Morphology: Döhle body
Nuclear water is lost Morphology:
Chromatin is dense and dark Irregular shaped pale blue cytoplasmic inclusions
Filaments can still be seen between segments often in the periphery of the cell.
these inclusions represent remnants of free ribosome or Rough Endoplasmic
Neutrophil that has died Reticulum (RER)
Found in:
• Infective and inflammatory states
______________________________________________________________________________ • Severe burns
• Tuberculosis
CYTOPLASMIC CHANGES • Post chemotherapy
TOXIC GRANULATION
- hypergranulation
Morphology:
______________________________________________________________________________
Increased granulation
May-Hegglin body
More basophilic
Morphology:
Larger than normal
multiple or single blue or pinkish inclusion
darkly staining bluepurple
Dohle like bodies but are larger and more defined
coarse granules in the cytoplasm of neutrophils.
the difference is that they contain glycogen and RNA, methyl green pyronine positive
Found in:
Found in:
• Severe bacterial infection
• May-Hegglin Anomaly
• Therapy with cytokines
- rare autosomal inherited dominant platelet disorder
• Chemical poisoning
____________________________________________________________________________
______________________________________________________________________________
HYPOGRANULATION
Alder-Reilly granules
- degranulation
Morphology:
Morphology:
Large, purple or purplish black and coarse azurophilic granules that covers the nucleus.
Reduced granulation
Found in:
in neutrophil cytoplasm
• Alder-Reilly Anomaly
Found in:
- a rare hereditary anomaly of WBC
• Myelodysplastic syndromes
-result of abnormal polyssaccharide metabolism which prevents the formation of secondary
specific-staining granules.
_____________________________________________________________________________
¬¬¬¬¬-_____________________________________________________________________________
Chediak-Higashi granules
TOXIC VACUOLATION
Morphology:
Vacuoles: represents the sites of digestion of the phagocytized material
Red, blue or greenish gray granules of variable size
Sign of Activation of:
These inclusions represents abnormal lysosomes
Active Phagocytosis
Found in:
Bacterial Infection
Chediak-Steinbrinck-Higashi syndrome
Viral Infection, Sepsis or Some Types of Cancers
- hereditary autosomal recessive syndrome
- cells show not only a chemotactic defects but also impaired adhesion to artificial surfaces and
_____________________________________________________________________________
delayed killing of intracellular bacteria because of defective lysosomal emptying into phagocytic vacuoles.
Alpha-thalassemia
Four genes are involved in making the alpha hemoglobin chain. Two from each parent.
______________________________________________________________________________ If one inherits:
Auer Body One mutated gene
Morphology: o no signs or symptoms of thalassemia.
Pink or red o a carrier of the disease and can be passed on to the children.
Round or rod shaped
These inclusions represents agglomeration of azurophillic granules Two mutated genes
Found in: o signs and symptoms will be mild.
• Acute-lymphocytic anemia o This condition might be called alpha-thalassemia trait.
• Promyelocytic leukemia
• Fagot cell: a cell containing multiple Auer rods clumped together in the form of bundle
Three mutated genes
o signs and symptoms will be moderate to severe.
______________________________________________________________________________
REACTIVE MONOCYTE
• Reactive changes may be seen in monocytes in infections, during recovery from bone marrow Four mutated genes
aplasia, and after GM-CSF administration. o Rare and usually results in stillbirth.
• The nucleus can become thin and band-like in areas and may appear to be segmenting. o Babies born with this condition often die shortly after birth or require lifelong
• Reactive changes also include increased cytoplasmic volume, increased numbers of transfusion therapy.
cytoplasmic granules, and evidence of phagocytic activity o In rare cases, a child born with this condition can be treated with transfusions and a
stem cell transplant.
Beta-thalassemia
Two genes are involved in making the beta hemoglobin chain.
One gene is inherited from each parent.
If one inherits:
Prevention
Slowed growth rates In most cases, thalassemia can't be prevented.
Anemia can both slow a child's growth and delay puberty. If the patient has thalassemia, or a carrier of thalassemia gene, a genetic counselor should be
consulted especially if desirous of children.
Heart problems There is a form of assisted reproductive technology diagnosis, which screens an embryo in its
Congestive heart failure and abnormal heart rhythms can be associated with severe early stages for genetic mutations combined with in vitro fertilization.
thalassemia. o This might help parents who have thalassemia or who are carriers of a defective
hemoglobin gene have healthy babies.
Diagnosis o The procedure involves retrieving mature eggs and fertilizing them with sperm in a
Most children with moderate to severe thalassemia show signs and symptoms within their first dish in a laboratory.
two years of life. o The embryos are tested for the defective genes, and only those without genetic
Confirm a diagnosis with blood tests if Thalassemia is suspected in a child. defects are implanted into the uterus.
RISK FACTORS
• Cold
• Lack of oxygen
• Lack of fluid in the body
• Hard exercise
Sickle Cell Anemia • High temperature (fever)
Most severe form of sickle cell disease • Infection
Inherited red blood cell disorder PATHOPHYSIOLOGY OF SCD
A condition where there aren’t enough red blood cells to carry adequate oxygen throughout the Two interlinked mechanism
body 1. Anemia
• Normally, blood cells are flexible, round and move easily through the blood vessels • HbS Polymerization- HbS undergo polymerization under hypotoxic condition
• People with sickle cell anemia has rigid, sticky, and shaped like sickle or crescent moon red • Sickling- HbS distort the shape of the RBs causing them to become dense and sickle shape
blood cells • Hemolysis- inflexibility of sickled RBC contributes to their premature destruction
• Normal lifespan of RBC: 120 days • Anemia- decreased in no. of RBC, due to premature destruction, leads to lower hemoglobin
• Life span of sickled cells: 10-20 days level
o Body may have trouble in making enough new cells to replace one you lost 2. Vaso-occlusion
o Result in red blood cell deficiency known as anemia • Chronic Vascular Damage
• African- American have higher risk of sickle cell anemia than people of other races. Ongoing vascular damage and repeated injury to the blood vessel wall over time result in activation of
Hemoglobin endothelial cells
Made up of four peptide chain • Inflammation and Cell Activation
2 alpha hemoglobin The chronic inflammatory environment within blood vessels leads to increased expression of adhesion
2 beta hemoglobin mediators, resulting in multicellular adhesion
Faulty hemoglobin is called hemoglobin S (HgbS) as it replaces the normal hemoglobin which • Multicellular Adhesion
is called hemoglobin A (HgbA) Activated endothelial cells initiate a complex cascade of interactions with RBCs, white blood cells
In all forms of SCD, at least one of the two abnormal genes causes a person’s body to make (WBCs), and platelets that leads to multicellular adhesion and ongoing vaso-occlusion
hemoglobin S. When a person has two hemoglobin S genes, Hemoglobin SS, the disease is • Vaso-Occlusion
called sickle cell anemia. This is the most common and often most severe kind of SCD. Multicellular adhesion reduces and blocks blood flow to organs
SCD FREQUENCY • Vaso-Occlusive Crises
• Most common in individual of African descents but seen also in Hispanic, Arabians, Indians, Ongoing, silent, vaso-occlusion may result in vaso-occlusive crises (VOCs)-the clinical hallmark of SCD.
and white There is tissue and organ damage.
• In united states the incidence is 1 in 635 live births to African- American is affected with sickle
cell anemia.
GENETICS OF SCD
• Changes in cell structure arises from a change in the structure of hemoglobin
Adhesion Mediators
• A single change in amino acid causes hemoglobin to aggregate.
P-selectin on activated endothelial cells and platelets
• Mutation in beta globin at 6th position (glutamic acid is replaced by valine)
• Mediates the capture and tethering of WBCs and sickled RBCs to the activated endothelium
• Expressed on platelets causing them to bind to WBCs that are clustered together
E-selectin on activated endothelial cells
• Binds WBCs to activated endothelial cells and promotes the capture of sickled RBCs
INHERITANCE PATTERN
L-selectin on the surface of WBCs
• If Each parent has normal A gene and one Hemoglobin S, which mean each children has:
• Mediates the recruitment and adhesion of additional WBCs to endothelial cells
25% chance of inheriting two normal hemoglobin A gene, then child does not have sickle trait
or disease
SYMPTOMS
50%- one normal A gene and one hemoglobin S gene- child has sickle cell trait
• Usually appear around 5 months of age
25%- two hemoglobin s genes- child has sickle anemia
• Vary from person to person and change over time
• SCA is diagnosed in infants through newborn screening.
Sickle cell traits Sickle cell disease
1. Anemia
Carrier Affected • Sickle cells break apart easily and die leaving you with too few RBC.
Carry only one copy of the altered hemoglobin Carry two copies of altered hemoglobin genes • Shortage of RBC (anemia)
genes • Without enough RBC, your body can’t get enough oxygen, causing fatigue
SCD individual have both normal and some sickled Two copies of altered genes destroy RBC rapidly 2. Episodes of pain
Periodic episodes of pain called pain crisis (major symptoms of sickle cell anemia) o fatal
Pain develop when sickled RBC block blood flow to chest, abdomen, and joint • Splenic Sequestration (Pooling)
Pain can also occur in bones (avascular necrosis) o spleen helps filter the blood of infection
Pain varies in intensity and severe crisis requires hospital stay o Pooling of sickled cells causes spleen to enlarge and painful
Chronic pain results to bone and joints damage, ulcers and other causes among o Become permanently damaged and become scarred due to repeated episodes
adolescents and adults o Symptoms: sudden weakness, pale lips, rapid breathing, excessive thirst, belly pain
3. Frequents infection and rapid heartbeat
Sickle cell can damage spleen, leaving you more to vulnerable to infection o Requires emergency medical care
Non-functional spleen- susceptible to encapsulated bacteria such as S. pneumoniae, H.
• Leg ulcer
influenzae, Neisseria meningitidis and Salmonella spp.
o open sores
Infants and children are given vaccination and antibiotics to prevent life threatening infection
such as pneumonia
4. Delayed growth or puberty
• Gallstone
RBC provide the body with oxygen and nutrient needed for growth
o Break down of RBC produces of bilirubin
Shortage of RBC can slow the growth in infants and children, delay puberty in teenagers
5. Swelling of hand and feet o High level of bilirubin can lead to gallstone
Dactylitis (inflammation of the digits) • Pregnancy Complication
happens when sickled RBC blocks blood flow to hands and feet o SCA increases risk of high blood pressure and blood clot during pregnancy
First symptoms in babies o Increases of miscarriage, premature and low birth weight babies
• Priapism
6. Sickled cells can also be stock in other bones causes sickle cell crisis which lead to o Sickle cell that block the blood vessels in the penis can lead to impotence over time
avascular necrosis of the bone o Painful, long-lasting erection