pathoma

Both: When membrane damage is severe, such as that seen when helmet cells are formed, intravascular hemolysis can occur. When bite cells are formed and RBC's are destroyed by macrophages in the spleen, this is extravascular hemolysis occurring.

Does G6PD lead to intravascular or extravascular hemolysis?

1. Right shift 2. Left shift 3. Right shift 4. Left shift 5. Left shift 6. Right shift Increased dumping of oxygen

Does the following lead to a left shift or right shift in the oxyhemoglobin dissociation curve? 1. Reduced pH 2. Decreased temperature 3. Increased BPG 4. Increased pH 5. Decreased BPG 6. Increased temperature Does a right shift cause an increased dumping of oxygen or binding of oxygen?

Osteoid osteoma Young, teens to early 20s. In the cortex of the long bones such as the femur. Small tumors release cytokines which lead to pain and the area is typically well innervated.

A patient comes to your office complaining of nocturnal bone pain that is relieved when the patient takes aspirin. What is the first tumor you should suspect? What age would you expect this patient to be? Where does this type of bone tumor typically arise? What causes the associated pain?

After a nuclear accident there increased levels of radioactive iodine. Massive doses of iodine inhibits the uptake of iodine by the basolateral Na+/I- cotransporter. By taking high levels of non-radioactive iodine the patients inhibit the uptake of the radioactive iodine until it is cleared from their system sparing them these effects.

After the nuclear meltdown in Japan the stores had very little iodine left on the shelves. Why?

Hyper - patient has increased amounts of sex binding globulin which leads to decreased levels of free sex hormones for binding Hypo - patient has low levels of TSH or TH which stimulates increased release of TRH which continues. TRH also stimulates the release of prolactin which inhibits ovulation through decreased secretion of GnRH.

Amenorrhea occurs in both hyper- and hypothyroid conditions. Why does it occur in each condition?

Giant Cell Tumor of Bone Soap bubble appearance showing the expanding lytic lesion.

An X-ray of what condition is seen here and what is the characteristic name of the radiological appearance?

Multifocal Morphology or immunohistochemistry can help to determine or provide a strong suggestion for the site of origin.

Are metastatic tumors of the bone commonly unifocal or multifocal? How do we determine the original site from which the tumor metastasized?

In Graves disease the antibodies for the TSH receptors act as simulators of the receptor leading to excessive secretion of thyroid hormone. In Hashimotos disease the antibodies block the TSH receptor leading to hypothyroidism.

Both Graves disease and Hashimoto's disease are involved as an autoimmune antibody target. What is the difference between the two disease?

Under TSH stimulation the colloid is taken up by the follicular cell into a lysoendosome and T3 and T4 is secreted out the basolateral membrane leaving MIT and DIT to be deiodinized and recycled back to the colloid.

Describe the normal process of thyroid hormone secretion.

Thyroglobulin, synthesized in the follicular cell is moved to the follicular lumen (colloid). On the basolateral membrane of the follicular cell a Na+/K+ ATPase maintains a Na+ gradient that allows for the cotransport of Na+ and I- (against its electrochemical gradient) into the follicular cell. Iodine then diffused through a channel in the apical membrane and enters the follicular lumen. TPO causes oxidation of the I- and also catalyzes its attachment to thyroglobulin which forms MIT and DIT. TPO then synthesizes the conjugation of MIT & DIT to form T3 and T4.

Describe the normal process of thyroid hormone synthesis.

In the bone marrow erythroid precursors are stimulated to grow from stimulation by erythropoietin and progresses through various stages of nucleated RBC until the cell nucleus becomes pyknotic nad disappears and the cytoplasm gets large (5-7 days). The cell is released from the bone marrow as a reticulocyte then matures into a mature RBC (1-2 days) 120 days; destroyed in the spleen

Describe the production and life cycle of a RBC. What is the average life span of a RBC and where is it destroyed?

1. Decreased 2. Increased 3. Increased 4. Increased 5. Decreased 6. Increased 7. Decreased

Does the following lead to an increased or decreased amount of sickling in a patient with sickle cell? 1. HbA + HbS 2. HbC + HbS 3. Acidosis 4. Hypoxemia 5. HbF + HbS 6. Dehydration 7. Coexisting α-thalassemia

1. Intravascular 2. Extravascular 3. Extravascular 4. Intravascular 5. Intravascular

Does the following lead to intravascular or extravascular hemolysis? 1. Infections like malaria and clostridium perfringens 2. RBCs are less deformable through some pathological condition 3. Immune mediated destruction by coating with antibodies 4. Complement fixation 5. Mechanical injury by traveling through cardiac valves or microvascular thrombi

Ollier's or Mafucci's disease. Marfucci's disease is Ollier's disease with multiple hemangiomas. Chondrosarcoma Developing another extraskeletal malignancy such as breast cancer, ovarian cancer, or lung cancer.

Enchondromas are most commonly solitary. When they are seen in in multiples they are associated with which syndromes? What is the difference between the two disease? If associated with these conditions they have a 20% chance of developing into what? Patients with Marfucci's disease have a 100% chance of what?

Malignant proliferation of poorly differentiated cells derived from the neuroectoderm. Small blue cells that grow in sheets. t(11;22) & t(21;22) Poor without treatment but treatment with chemo significantly improves survival.

Ewing Sarcoma is what type of tumor? What is the appearance of the tumor cells? They are associated with what mutation? What is the prognosis for patients with this condition?

1. Glucose-6-phosphate 2. 6-phosphogluconate 3. NADP 4. NADPH 5. GSSG 6. GSH 7. H₂O₂ 8. H₂O

Fill in numbers 1-8

Due to iron overload from increased iron absorption, increase RBC breakdown, and regular transfusions of blood. Heart - heart failure Liver - cirrhosis Pancreas - diabetes mellitus

How does β-thalassemia minor lead to hemosiderosis and secondary hemochromatosis? What organs are affected if this occurs and what can this lead to?

Through a negative feedback system. T3 and other thyroid hormones feeds back negatively on the hypothalmic release of TRH and the anterior pituitary release of TSH.

How is the release of thyroid hormones regulated?

Site: Intravascularly - RBC's broken down in the vessels Extravascular - RBC's broken down in the spleen Cause: Intrinsic - Caused by something being wrong with the RBC Extrinsic - Caused by something else being wrong besides the RBC Extravascular

Hemolytic anemia can be classified by site (intravascularly or extravascularly) or by cause (intrinsic or extrinsic). Describe each. Is the majority of hemolytic anemia sites intra- or extravascular?

Family history, identification of sickled cells on a peripheral blood smear, hemoglobin electrophoresis, and mixing blood with oxygen consuming agents to induce sickling for microscopic peripheral smear identification.

How can we diagnose sickle cell disease?

Both are microcytic anemia β-thalassemia minor: May have a somewhat normal Hb level leading to normochromic appearance Iron deficiency anemia: MCV will follow the level of hemoglobin reduction.

How can we differentiate between β-thalassemia minor and iron deficiency anemia?

TRH binds to cell surface receptors, Gq, which causes increased Ca2+ levels which leads to exocytosis of TSH and increased synthesis of TSH.

How does TRH lead to its function on thyrotrophs?

The lifespan of the RBC's is normally 120 days but the abnormal shape and decreased flexibility of the spherocytes leads to an average lifespan of 10-20 days. Extravascular Family history, evidence of hemolysis, peripheral blood smear examination and osmotic fragility test.

How does hereditary spherocytosis lead to anemia? Is this an intravascular or extravascular hemolytic anemia? How is this condition diagnosed?

T3 directly enters the cell and binds to a receptor on which enters the nucleus to modulate gene expression. T4 is acted on by 5'-deiodinase and is converted to T3 which then enters the cell, binds to a receptor, and modulates gene expression.

How does thyroid hormone timulate the modulation of gene expression on target tissues?

Beta - 2 genes (one on each chromosome) found on chromosome 11 Alpha - 4 genes (2 on each chromosome) found on chromosome 16

How many α & β genes does each non-pathological person have and what chromosome are they located on?

90% T4 9% T3 1% rT3 T3 is the most potent. Biological activity is obtained as a result of the location of the iodine which is why T3 has high activity (very potent) and rT3 is minimally or not potent.

How much of each thyroid hormone does the thyroid gland produce? Which is the most potent? What give the hormone its biological activity?

Hypochromic, microcytic anemia

How would you describe a patient whose CBC indicated a low HGB, low MCV, and decreased HCT?

Stage Grade Metastasis

Is grade or stage of a malignant bone tumor important in predicting the clinical outcome? Predicting the behavior? What indicates that a bone tumor is at the highest stage?

3 - it is a tripeptide It has a short half life, approximately 5 minutes, which means in order to maintain systemic levels it is secreted at a constant rate.

Thyrotropin releasing hormone is how many amino acids long? As a result, how long is its half life and what does this mean for the secretion of TRH?

The apical surface. Calcitonin

On what aspect of the follicular cell of the thyroid is the colloid found? What hormone is secreted by the parafollicular cells?

Hyperthyroidism. It treats this condition by inhibiting TPO required for thyroid hormone synthesis.

PTU is used to treat what condition? How?

1. Chronic state of RBC breakdown leading to a chronic hemolysis, hyperplastic bone marrow, skull bone changes, autosplenectomy, etc. 2. Caused by the small vessel obstruction that occurs when the cells sickle and become sticky leading to a sickle cell crisis 3. Can lead to aplastic anemia if the patient is exposed to parvovirus B19 infection. Also prone to infection by encapsulated bacteria.

Patients with sickle cell anemia are prone to some very particular conditions. Describe each: 1. Chronic hemolytic anemia 2. Microvascular obstruction 3. Infection vulnerability (what can this lead to)

Thyroid enlargement, bulging eyes with top of sclera exposed, pretibial myxedema. Leads to a thyroid storm.

What are some signs of Grave's disease? If untreated what does it lead to?

1. Mean cell volume - average volume of a RBC (in femtoliters) 2. Mean cell hemoglobin - average content of Hb per RBC (picograms) 3. Mean cell hemoglobin concentration - average concentration of Hb in a given volume of packed RBCs (g/dL) 4. Red Cell Distribution Width - coefficient of variation of RBC volume 5. Hematocrit - percent of centrifuged serum that is RBC 6. Hemoglobin count It is an indicator of the variation in the size of RBCs in the serum.

Seen here is a CBC printout. Define the following: 1. MCV 2. MCH 3. MCHC 4. RDW 5. HCT 6. HGB What is RDW an indicator of?

1. Normal (high amounts of HbA with a small amount of HbA2 and unidentifiable amounts of HbF) 2. β-thalassemia (high HbF with no HbA indicative of this condition) 3. Sickle cell trait (patient has one normal HbA and one HbS containing chromosome)

Show in the photo is an electrophoresis of 3 different patients. What condition does each patient have and why?

Osteosarcoma: Codman triangle - triangle peaks of growing bone lifting the periosteum Sunburst appearance - tiny bone fragments coming off of the area of tumor growth Hereditary: Li Fraumeni (p53 mutation) & Rb mutation (retinoblastoma gene) Sporadic: p53, MDM2, and Rb mutation (although this is rare) Rb mutation

Two characteristic features of what condition are seen here? Name and describe the characteristics. This condition can be associated with hereditary condition or sporadic development. Name the mutations. If the tumor is associated with heredity, what is the most common mutation?

Increased glucose absorption and motility in the GI tract, increased use of glucose, fats, and proteins for energy, and increased effects of the hormone that increases metabolic rate. This can lead to decreases in weight.

What are the metabolic effects of TH?

1. Painful crisis requires aggressive pain management 2. Crisis can be caused by dehydration 3. Get out sickled cells and give normal RBCs 4. Can speed new RBC production as folic acid is needed for DNA synthesis and rapid cell division 5. Treat possible infection if the spleen is poorly functioning or autosplenectomy has occurred 6. Increases the amount of HbF and inhibits HbS polymerization (inhibiting sickling) 7. Permanent treatment

The clinical treatment of sickle cell disease involves many treatments. Give a reason for each: 1. Analgesics 2. Rehydration 3. Exchange transfusions 4. Folic acid supplementation 5. Penicillin 6. Hydroxyurea 7. Bone marrow transplant

1. The heart is trying to keep up with the needs of the body despite low RBC count 2. The lungs are trying to provide the oxygen needs of the body despite the low RBC count 3. The heart is trying to keep up with the needs of the body despite low RBC count 4. The heart eventually becomes unable to keep up with the needs of the body and cardiac failure occurs.

The symptoms of anemia can be mild including weakness, easy fatigability, headaches, fainting, & SOB on exertion. Describe the reason for the signs listed below: 1. Increased pulse 2. Increased respiratory rate 3. Increased stroke volume 4. Eventual cardiac failure

Increased protein breakdown to amino acids. Increased lipolysis of TAGs to fatty acids and glycerol. Increased use of free fatty acids and amino acids for glucose production and increased glucose production. The liver leads to increased glucose levels which leads to increased insulin secretion from the pancreas and increased glucose uptake by cells with an increased metabolic rate.

What are the effects of TH on muscle? What are the effects of TH on adipose tissue? What are the effects of TH on the liver? What effects does this lead to from the pancreas and general cells?

1. There is a reduced β chain production as a result of a mutation in the promotor region of the gene 2. There are no β chains formed form this gene as a result of a mutation leading to abnormal splicing or a non-sense mutation.

There are about 100 β-gene mutations resulting in two pathological genes. Describe each: 1. β+ 2. β⁰

1. Increased metabolic rate 2. Increased metabolic rate 3. Increased amounts of sex binding globulin which leads to decreased levels of free sex hormones for binding 4. Increased activity of the cardiac muscle 5. Increased GI motility 6. Increased metabolic rate 7. Overactivity of the heart

There are many symptoms to hyperthyroidism. Why does each of the following occur? 1. Irritability 2. Weight loss 3. Amenorrhea 4. Palpitatiosn 5. Increased bowel movements 6. Heat intolerance/sweating 7. CHF in the elderly

G6PD A-: Seen in about 10% o the American Black population leading to a milder form of this condition G6PD Mediterranean: Seen in the Middle Eastern population and causes a severe form of this condition It provides a protection against malaria which led to a natural selection for heterozygous individuals and higher prevalence in populations that were exposed to malaria.

There are many variants of G6PD deficiency but only 2 cause clinically significant hemolysis. What are they and who do they most commonly affect? Why is a G6PD deficiency likely seen in these populations?

1. Normochromic (for normal, pink RBCs) and hypochromic for cells that are very light pink 2. Normocytic, macrocytic (too big), and microcytic (too small) 3. Biconcave (normal), spherocytes, sickled, etc. If they don't contain enough RBCs

There are three morphological classification so anemia. What are the terms used to describe the following classifications? 1. Degree of hemoglobinization 2. Cell size 3. Cell shape What causes RBCs to be hypochromic?

It binds to cell surface receptors which causes increased cAMP levels and modulation of cellular processes.

Through what pathway does TSH exert its effects on the thyroid gland?

Tyrosine molecules group together in thyroglobulin.

Thyroid hormone is made through the iodination of what molecule?

BLT & Kosher Pickle Breast Lung Thyroid Kidney Prostate It can be either or both. Axial skeleton on the vertebrae and diaphysis of some bones. Older patients

What are the most common primary sites for a metastatic tumor of the bone? Is this type of tumor blastic or lytic? What area of the skeleton is most often involved? What age group is associated with metastatic bone tumors?

1. Elevated (likely becoming the major Hb in these patients) 2. Normal, low or high 3. Very low to absent 1. Normal or elevated 2. Elevated 3. May be normal

What are the typical levels of the following in a patient with this condition? 1. HbF 2. HbA2 3. HbA What would the expected levels of the following be in patients with β-thalassemia minor? 1. HbF 2. HbA2 3. HbA

Usually asymptomatic Pain, fractures, and metastasis.

What are the typical symptoms of a benign tumor? Malignant bone tumors are aggressive. What are some symptoms?

Iodine deficiency and placental transfer of TSH antibodies. It has major effects on normal bone growth and an even larger effect on mental development. Patients with untreated congenital hypothyroidism after treatment with thyroxine catch up to normal bone and growth development but after a certain age a critical period is reached for mental age development in which thyroxine treatment will not improve patients mental age.

What are two causes of hypothyroidism in newborns? How does hypothyroidism effect growth in children? What is important about the effect on mental development?

Giant cell tumor of bone (osteoclastoma) - osteoclastic giant cells mixed with mononuclear histiocytes. Benign The ends of long bones and the pelvis.

What bone tumor is seen here and what gives it away? is this type of tumor benign or malignant? What bones does this type of tumor typically occur on?

1. Destruction of bone and extreme pain 2. Lung infarcts 3. Strokes 4. Blindness 5. Kidney damage (might not be observed until later in life 6. Ulcers

What can occur during a sickle cell crisis if there is a microvascular obstruction to the following organs? 1. Bones 2. Lungs 3. Brain 4. Retina 5. Kidneys 5. Legs

The hypothalamus secretes TRH which causes the anterior pituitary to release TSH which binds to receptors on the thyroid follicular cell and causes release of thyroid hormone.

What causes secretion of thyroid hormone?

β⁰/β⁰, β⁰/β+, β+/β+ β⁰/β, β+/β Milder variant of major, more severe variant of minor or major combined with α-thalassemia.

What combination(s) leads to β-thalassemia major? What combination(s) leads to β-thalassemia minor/trait? What combination(s) leads to β-thalassemia intermedia?

Chondrosarcoma showing lots of cartilagenous matrix with many cells in different stages of growth. Pain in the bone It entraps and invades the pre-existing bone.

What condition is seen here and what helps to identify it? What is the typical clinical presentation of a patient with this condition? What does this type of tumor do to pre-existing bone?

Osteosarcoma - pleomorphic cells that are producing osteoid The distal femur or proximal tibia (the knee area) 1. Low grade 2. Low grade or High grade 3. High grade

What condition is seen here? In teens this condition typically arises in the metaphysis. Where is it most commonly seen? Most osteosarcomas are high grade and require chemo and extensive treatment. Identifying the area of the bone affected helps to identify the grade. Based on the following location, name the grade of the tumor. 1. Intramedullary 2. Juxtacortical 3. Intracortical

Enchondroma - punctate and ring like calcifications Hyaline and myxoid cartilage Medullary cavity which may cause erosion of the cortex but not invasion (as it is benign). Most commonly affected bones are those of the hands and feet.

What condition is seen here? It is a benign tumor of what type of cartilage? What area of the bone is most commonly affected and what bones are most commonly affected in solitary tumors?

Chondrosarcoma Older adults Pelvis, ribs, humerus, and proximal femur.

What condition is seen here? What age group is typically affected by this condition? Which bones are typically affected by this condition?

Osteosarcoma It is a bimodal age distribution with the largest peak at an early age (children & young adults) and a second smaller peak in the elderly. Youth: Metaphysis of long bones Elderly: Flat bones Paget's disease of the bone and radiation.

What condition is seen here? What age is typically affected by this condition? It typically occurs where in youth and where in the elderly? What conditions are associated with development of this condition in the elderly?

Howell-Jolly bodies Inclusions are small amounts of clumped nuclear chromatin that failed to be expelled from the RBC during maturation. Splenic damage, megaloblastic anemia, and hereditary spherocytosis.

What condition is seen here? What is found in the inclusions? What is an important condition you should think of when you see this presentation on a peripheral blood smear?

Hereditary spherocytosis In 75% of cases it is caused by an autosomal dominant condition. It is a defect in, most commonly, ankyrin but can also be a defect in band 3, spectrin, and band 4.2.

What condition is seen here? What is it caused by?

Basophilic stippling Inclusions are composed of rRNA/ribosomes. Lead or arsenic poisoning, anemia involving impaired Hb synthesis, and megaloblastic anemia.

What condition is seen here? What is the composition of the inclusions? What is an important condition you should think of when you see this presentation on a peripheral blood smear?

Dehydration, acidosis, exposure to low oxygen tension.

What conditions put a person with sickle cell disease at risk of having a sickle cell crisis?

5'-deiodinase

What enzyme breaks down T4 to T3?

In the patients, deoxygenated HbS molecules form a linear aggregate which results in the RBC forming a needle like shape (sickling). This can be reversible initially but if this occurs repeatedly the sickling becomes permanent and the RBC's become sticky entering small vessels, sticking and aggregating and leading to a sickle cell crisis

What leads to the sickling seen in patients with sickle cell disease and the small vessel thrombosis?

Hereditary spherocytosis The RBCs in 65% of patients with this condition lyse early as a result of their membrane already being stretched and unable to accommodate additional swelling when placed in a hypotonic solution. The cells become smaller with the same amount of Hb within the smaller space. The treatment is a splenectomy which corrects the anemia (as the spleen was causing the quick breakdown of the spherical RBCs) but it does not correct the condition.

What hemolytic anemia is tested for using the osmotic fragility test? Why does this test show a patient has this condition? Patients with this condition present with an elevated MCHC. Why? How are these patients treated and how does this alter the condition?

It is an autoimmune disease where the antibodies produce bind to the TSH receptor and act in a stimulatory fashion to increase the release of thyroid hormone. ↓TRH, ↓TSH, ↑TH. This is the result of high levels of TH that send negative feedback signals to the hypothalamus and anterior pituitary to inhibit the release of TSH and TRH.

What is Grave's disease? What would be the typical levels of TRH, TSH, and TH in a patient with this condition and why?

An autoimmune disease where antibodies bind to the TSH receptor and cause endocytosis of the receptors and decrease TH secretion. ↑TRH, ↑TSH, ↓TH. TRH and TSH levels would be high because there would be no negative feedback signals on the hypothalamus or anterior pituitary hormone release.

What is Hashimoto's thyroiditis? What would the typical TRH, TSH, and TH levels be in this patient and why?

Heinz bodies - precipitated hemoglobin on the RBC membrane Supravital stain G6PD deficiency

What is abnormality is seen here and what do they consist of? What stain is being used? What condition is this indicative of?

A benign cartilage tumor of the metaphysis with an overlying cartilage cap. Those that undergo endochonral ossification (ie. long bones). Lateral projections of the growth plate. EXT gene family mutation - gene involved in growth plate regulation

What is an osteochondroma? What types of bones does this develop in? What is seen at the growth plate in this condition? What is the suspected gene associated with this condition?

Reticulocytes It is getting rid of the last bit of highly basophilic nucleus from the cell RBC

What is being pointed at in the picture? What about the picture makes you think it is that kind of cell? What is it a precursor of?

They are inhibitors of the Na+/I- pump on the basolateral membrane of the thyroid follicular cell.

What is perchlorate and thyocyanate?

A: Helmet cell - multiple "bites" taken by macrophages in the spleen to remove Heinz bodies leads to this irreversible damage of the RBC B: Bite cell - macrophages attempt to "bite" the Heinz body off of a RBC leading to this shape

What is seen here at A & B and how do they form?

Hypochromic, microcytic anemias. In iron deficiency anemia

What is the appearance of RBCs in patients with thalassemia conditions? When else would you see hypochromic, microcytic cells?

1. α²γ² 2. α²β² 3. α²δ² Most is HbA (~95%) but a small amount is HbA2 and HbF

What is the chain composition of the following hemoglobin molecules? 1. HbF 2. HbA 3. HbA2 What is the major hemoglobin in adults?

150 μg Below this level there is initial compensation through increased TSH levels which leads to goiter. Below 50 μg the compensatory mechanism fails.

What is the dietary daily requirement of iodine for thyroid hormone synthesis? What occurs below this level?

Hemoglobinopathy is when there is a mutation in a globin gene that leads to the production of defected hemoglobins (sickle cell anemia and HbC disease) Thalassemias are when there is a lesion, or lack, of a globin gene leading to decreased synthesis of the globin chains of HbA (α-thalassemia & β-thalassemia)

What is the difference between a hemoglobinopathy and a thalassemia? Name two of each condition.

A-: Moderately reduced half life Mediterranean: Severely reduced half life

What is the difference in the half life between patients with the G6PD A- variant and G6PD Mediterranean variant?

It increases heart rate and contractility by increasing the activity of the sarcoplasmic reticulum Ca2+ ATPase, increasing the activity of the Na+/K+ ATPase, and by increasing the number of β1 adrenoreceptors. Overall this leads to increased stroke volume, increased heart rate, and increased cardiac output.

What is the effect of TH on cardiac muscle and how does it cause this to happen? Overall, what does this lead to?

Anemia Hemoglobin concentration or packed cell volume/hematocrit.

What is the following: Reduction, below normal limits, of total circulating red cell mass. What is a good measurement of this?

They carry oxygen on their hemoglobin molecules. At the lung capillaries they quickly bind oxygen as a result of the high oxygen tension and at the tissues they release oxygen as the pH decreases from CO2 binding. Hemoglobin

What is the function of RBCs and how do they carry out this function? What is the main protein found within RBCs?

It promotes thyroid growth and stimulates the steps of thyroid hormone synthesis. Both trophic and tropic, respectively.

What is the function of thyroid hormone on the thyroid gland?

Thyroxine-binding globulin. Pregnancy and increased estrogen levels. Liver disease.

What is the majority of T3 and T4 bound to in blood plasma? What increases levels of this protein? What decreases levels?

Metastatic Osteosarcoma Osteochondroma

What is the most common tumor of the bone? What is the most common bone sarcoma? What is the most common benign bone tumor?

There is a point mutation in position 6 of the β globin gene leading to glutamic acid (a polar AA) to be replaced with valine (a non-polar AA). Heterozygosity (HbA/HbS) provided a selective advantage for

What is the mutation leading to sickle cell anemia? What led to a high prevalence of this condition in the African American population?

Increase in metabolic rate.

What is the overall effect of thyroid hormone on target cells?

Because there are higher levels of α-chains in the cells they aggregate and lead to membrane damage and reduced survival of RBCs.

What leads to RBC and RBC precursor membrane damage in patients with β-thalassemia?

These patients have a deficiency of glucose-6-phosphate dehydrogenase in their RBC's which leaves them prone to oxidative injury as a result of their inability to convert H₂O₂ to water.

What occurs in patients with a G6PD deficiency that leads to hemolytic anemia?

90% and 50% respectively. Infection

What percent of sickle cell disease patients survive to age 20 and age 50 if proper crisis treatment is given? What is the major cause of death in children under 5 with this condition?

People of Mediterranean, Asian, and African decent.

What populations are thalassemias seen in?

Oxidation of iodine, attachment (organification) of iodine to thyroglobulin, and formation of T3 and T4 from MIT and DIT.

What steps of steroid hormone synthesis require TPO?

Garner's syndrome The craniofacial bones. This is mature bone growing in an abnormal place as this type of bone should only be seen in the shaft of long bones.

What umbrella condition is associated with an osteoma? Where do osteoma's typically develop? This condition presents with cortical type bone growing in the craniofacial bones. Why is this a problem?

Parvovirus B19 Anemias (hereditary spherocytosis & G6PD deficiency)

What viral infection can cause an aplastic crisis? What condition is associated with an aplastic crisis?

1. a. Elevated (more in intravascular hemolysis) b. Elevated (more in intravascular hemolysis) c. Elevated d. Decreased or absent (because of elevated Hb levels binding to it) 2. a. Elevated b. Could be elevated 3. Erythroid hyperplasia 4. Normochromic normocytic anemia or macrocytic with polychromasia if the reticulocyte count is extremely high.

What would be seen in the following areas in a patient with hemolytic anemia? 1. Plasma serum: a. Bilirubin b. Free Hb c. LDH d. Haptoglobin 2. Urine levels of: a. Hemosiderin b. Hemoglobin 3. Bone marrow aspiration appearance 4. What type of anemia seen in peripheral blood smear

The patient will likely be jaundiced from increased Hb being broken down to bilirubin within the serum. Hb breakdown products would increase.

When RBC's are broken down intravascularly what will we likely see in the patient?

6-9 months as prior to this time the primary hemoglobin would be HbF which does not contain β-chains

When would β-thalassemia major first present and why?

1. Metaphysis 2. Epiphysis 3. Metaphysis 4. Diaphysis 5. Metaphysis/diaphysis 6. Metaphysis Young

Where in the bone does the following tumor occur? 1. Osteosarcoma 2. Giant cell tumor 3. Osteochondroma 4. Ewing's Sarcoma 5. Enchondroma 6. Chondrosarcoma The typical patient with a primary bone tumor is in what age group?

Males, because it is a X-linked recessive condition. 1. Viral infection leading to increased oxidant formation by phagocytes 2. Foods with high oxidants like fava beans (causing fauvism) 3. Certain drugs such as anti-malarials, sulfa drugs, and large doses of aspirin.

Who is most commonly affected by a G6PD deficiency and why? What leads to an acute hemolytic presentation in these patients?

Because there are large colloidal stores in the thyroid gland.

Why would we be unaware of a thyroid deficiency for about 2-3 months?