Block 2 exam Flashcards
Main causes of anemia are what?
Blood loss
Hemolysis
Decreased RBC production
A 32-year-old female presents to her primary care physician with complaints of fatigue, weakness, and shortness of breath for the past several weeks. She reports feeling lightheaded upon standing and has noticed pale skin and mucous membranes. She also reports irregular menstrual cycles. Upon further questioning, she reveals that she follows a strict vegan diet and does not take any supplements. Physical examination reveals pallor and a slightly elevated heart rate. Lab tests show a hemoglobin level of 9 g/dL and serum ferritin of 12 ng/mL. What is the most likely diagnosis?
Iron deficiency anemia
60-year-old male presents to his gastroenterologist with complaints of recent abdominal discomfort, bloating, and constipation. He also reports passing dark, tarry stools, which he attributes to his acid reflux disease. He has a history of peptic ulcer disease and takes daily non-steroidal anti-inflammatory drugs (NSAIDs) for the chronic pain in his hip and knees. Physical examination is unremarkable. Lab tests show a hemoglobin level of 10.5 g/dL and serum ferritin of 15 ng/mL. What is the most likely cause of the patient’s anemia?
iron deficiency anemia
A 45-year-old female presents to her OB-GYN with complaints of heavy menstrual bleeding that lasts for more than a week at a time. She reports feeling weak, dizzy, and short of breath during her periods. Physical examination reveals pallor and tachycardia. Lab tests show a hemoglobin level of 8 g/dL and serum ferritin of 8 ng/mL. What is the most appropriate management for the patient’s anemia?
iron deficiency anemia supplement iron in diet & vitamins
A 70-year-old male presents to his primary care physician for a routine follow-up visit. He reports feeling weak and tired lately, but attributes it to his age. He has a history of gastric bypass surgery and takes daily proton pump inhibitors for his reflux. Physical examination is unremarkable. Lab tests show a hemoglobin level of 9.5 g/dL and serum ferritin of 10 ng/mL. What is the most likely cause of the patient’s anemia?
iron deficiency anemia
A 6-year-old male presents to the emergency department with recurrent abdominal pain, vomiting, constipation, and irritability. His mother reports that his behavior has been increasingly aggressive and he has difficulty sleeping. Physical examination shows pallor and abdominal tenderness. Lab tests show a hemoglobin level of 7 g/dL and a lead level of 40 μg/dL. What is the most likely cause of the patient’s anemia?
lead poisoning anemia
A 30-year-old male presents to his occupational health clinic with complaints of fatigue, muscle weakness, and abdominal pain. He is employed at a battery manufacturing facility and has worked there for 5 years. Physical examination shows mild pallor and mild abdominal tenderness. Lab tests show a hemoglobin level of 10 g/dL and a lead level of 55 μg/dL. What is the most likely cause of the patient’s anemia?
lead poisoning anemia
A 45-year-old male presents to his primary care physician with complaints of fatigue, weakness, and joint pain. He works in construction and reports exposure to lead-based paint dust while renovating an old building. Physical examination is unremarkable. Lab tests show a hemoglobin level of 11 g/dL and a lead level of 60 μg/dL. What is the most likely cause of the patient’s symptoms and anemia?
lead toxicity anemia
Trauma causes ______ blood loss while GI & gynecological bleeds cause ______ blood loss
Trauma = acute blood loss
GI/G = Chronic blood loss
Microcytic
Normocytic
Macrocytic
MCV’s are
less than 80
80-100
more than 100
What stage of erythropoietic cell is see in bone marrow and myeloid leukemia
polychromatic erythroblast
Describe the 5 stages of erythropoiesis
- Proerythroblast
- Basophilic erythroblast
- Polychromatic erythroblast (ML)
- Orthochromatic erythroblast
- Reticulocyte
List the microcytic anemias (TAIL)
- Thalassemia (hemoglobulin defect)
- Anemia of chronic disease (heme syn def)
- Iron def anemia (heme syn def)
- Lead toxicity anemia (heme syn def)
- Hepcidin overload
List the normocytic hemolytic anemias
- Hereditary spherocytosis (membrane def)
- Paroxysmal nocturnal hematuria (membrane def)
- G6PD def (enzyme def)
- PKD (enzyme def)
- Sickle cell
- Hbc (hemoglobinopathies)
A 25-year-old female presents to the hematologist with complaints of fatigue, shortness of breath, and pale skin. She reports a family history of anemia and was recently diagnosed with a microcytic anemia. Physical examination shows mild splenomegaly. Lab tests show a hemoglobin level of 7 g/dL, a mean corpuscular volume (MCV) of 65 fL, and a red blood cell count of 2.5 million/mm3. What is the most likely cause of the patient’s anemia?
B-thalassemia
A 25-year-old female of Southeast Asian descent presents to her obstetrician for prenatal care. She reports a family history of anemia and miscarriages. Physical examination is unremarkable. Lab tests show a hemoglobin level of 9 g/dL and a mean corpuscular volume (MCV) of 60 fL. The patient’s partner is also of Southeast Asian descent. What is the most likely cause of the patient’s anemia?
A-Thalassemia
A 60-year-old female with a history of rheumatoid arthritis presents to her rheumatologist for a routine follow-up visit. She reports feeling increasingly fatigued and short of breath. Physical examination shows pale conjunctiva and mild hepatosplenomegaly. Lab tests show a hemoglobin level of 8 g/dL, iron studies are normal, and C-reactive protein (CRP) is elevated. What is the most likely cause of the patient’s anemia?
anemia of chronic disease
A 65-year-old female with a history of rheumatoid arthritis presents to her rheumatologist with complaints of fatigue and shortness of breath on exertion. She reports recent exacerbation of joint pain and swelling. Physical examination is notable for decreased range of motion and tenderness in multiple joints. Lab tests show a hemoglobin level of 10 g/dL and a ferritin level of 300 ng/mL. What is the most likely cause of the patient’s anemia?
anemia of chronic disease
- A 25-year-old male presents to the emergency department with abdominal pain, jaundice, and dark urine. He reports a family history of anemia, and physical examination shows splenomegaly. Lab tests show a hemoglobin level of 7 g/dL and elevated levels of indirect bilirubin. What is the most likely cause of the patient’s anemia?
Hereditary spherocytosis
- A 10-year-old female presents to her pediatrician with complaints of fatigue and shortness of breath during physical activities. Her parents report a family history of anemia, and physical examination shows jaundice and splenomegaly. Lab tests show a hemoglobin level of 8 g/dL and an elevated mean corpuscular hemoglobin concentration. What is the most likely cause of the patient’s anemia?
Hereditary spherocytosis
- A 35-year-old female presents to her gynecologist with heavy menstrual bleeding and fatigue. She reports a history of gallstones, and physical examination shows splenomegaly. Lab tests show a hemoglobin level of 9 g/dL and an elevated reticulocyte count. What is the most likely cause of the patient’s anemia?
Hereditary spherocytosis
A 30-year-old female presents to the hematologist with a history of recurrent episodes of hemoglobinuria and intermittent abdominal pain. She reports feeling tired and weak lately, but denies any other symptoms. Physical examination is unremarkable. Lab tests show a hemoglobin level of 9 g/dL, elevated lactate dehydrogenase, and negative Coombs test. Flow cytometry shows absence or decreased expression of CD55 and CD59 on red blood cells. What is the most likely cause of the patient’s hemolysis and anemia?
paroxysmal nocturnal hemoglobinuria
A 28-year-old female presents to the emergency department with severe abdominal pain and dark urine. She reports recent episodes of fatigue, shortness of breath, and chest pain. Physical examination shows jaundice and splenomegaly. Lab tests show a hemoglobin level of 6 g/dL, elevated bilirubin and LDH levels, and positive urine hemosiderin. Flow cytometry of peripheral blood cells shows absence of CD55 and CD59. What is the most likely diagnosis?
paroxysmal nocturnal hemoglobinuria
A 28-year-old male presents to the emergency department with complaints of dark urine, abdominal pain, and fatigue. He reports taking a new medication for a respiratory infection a week ago. Physical examination shows jaundice and abdominal tenderness. Lab tests show a hemoglobin level of 8 g/dL, elevated indirect bilirubin, and decreased haptoglobin. G6PD enzyme activity is also decreased. What is the most likely cause of the patient’s anemia and jaundice?
G6PD deficeiny anemia
A 30-year-old male presents to the emergency department with acute onset of back pain and dark urine. He reports taking a new medication for a recent respiratory infection. Physical examination shows scleral icterus and abdominal tenderness. Lab tests show a hemoglobin level of 9 g/dL and elevated bilirubin and lactate dehydrogenase levels. The peripheral smear shows Heinz bodies and bite cells. Which type of anemia is most likely present in this patient?
G6PD deficiency anemia
A 30-year-old female presents to the hematologist with a history of chronic anemia since childhood. She reports a family history of “fragile blood.” Physical examination shows splenomegaly and mild jaundice. Lab tests show a hemoglobin level of 7 g/dL, reticulocyte count of 8%, and elevated bilirubin levels. A peripheral blood smear shows spherocytes. Further testing reveals a deficiency in pyruvate kinase activity. What is the most likely cause of the patient’s anemia?
PKD deficiency
A 20-year-old female with a history of jaundice and gallstones presents to the emergency department with severe fatigue and shortness of breath. She denies any recent illness or trauma. Physical examination shows pallor and tachycardia. Lab tests show a hemoglobin level of 6 g/dL and a reticulocyte count of 1%. Peripheral blood smear shows spherocytes. What is the most likely cause of the patient’s anemia?
PKD Deficiency
- A 20-year-old African American male presents to the emergency department with severe pain in his extremities and back. He has a past medical history of sickle cell anemia and reports that the pain started a few days ago after participating in a strenuous basketball game. Physical examination shows tenderness and swelling in his joints and normal vital signs. Lab tests show a hemoglobin level of 7 g/dL and reticulocyte count of 10%. What is the most likely cause of the patient’s pain and anemia?
Sickle cell anemia
- A 6-month-old African American female is brought to the pediatrician for a routine well-baby visit. She has a family history of sickle cell anemia, but her newborn screening was negative for the disease. On physical examination, the baby appears well and has normal growth and development. Lab tests show a hemoglobin level of 8 g/dL and a peripheral blood smear shows sickle-shaped red blood cells. What is the most likely diagnosis?
Sickle cell anemia
- A 30-year-old pregnant African American female is being followed by her obstetrician for a high-risk pregnancy due to her past medical history of sickle cell anemia. She is currently in her third trimester and reports feeling more fatigued than usual. Physical examination is unremarkable. Lab tests show a hemoglobin level of 9 g/dL and a fetal ultrasound confirms appropriate growth and development of the fetus. What is the most likely cause of the patient’s anemia and fatigue?
Sickle cell anemia
A 25-year-old African American female presents to her hematologist for a routine follow-up visit. She was diagnosed with HbC disease a few years ago and has been doing well on folic acid supplements. She reports feeling more fatigued than usual lately and has noticed mild jaundice. Physical examination shows jaundice and a palpable spleen. Lab tests show a hemoglobin level of 8 g/dL and an elevated reticulocyte count. What is the most likely cause of the patient’s anemia?
HbC disease
Describe how hepcidin can lead to microcytic anemia
During inflammation or infection the liver makes more hepcidin to get the body to “hide” aka store its circulating iron out of siderophore’s reach. This makes less iron available for RBC & heme production making them microcytic & hypochromic
Describe sickle cell anemia
A mutation in the 6th codon of the B-globin gene causing a replacement of glutamate with valine. This makes RBCs rigid & sickled so they get stuck in blood vessels causing ischemia, pain, anemia, & organ damage
Describe HbC disease
A mutation in the B-globin gene that causes abnormal hemoglobin C production. This reduces RBC production leading to anemia
List the normocytic and NON-hemolytic anemias
Aplastic anemia
&
Chronic kidney disease
List the macrocytic anemias
Folate def (def DNA syn)
B12 def (def DNA syn)
Orotic acid anemia (def DNA syn)
Fanconi anemia
- A 30-year-old pregnant woman presents with complaints of increasing fatigue and difficulty concentrating. Her obstetrician performed routine blood tests and found that she has a low hemoglobin level and anemic appearance. She has been taking prenatal vitamins but reports a poor appetite and limited intake of fruits and vegetables in her diet. What is the most likely cause of her anemia?
Folate def anemia
- A 55-year-old man with a history of alcoholism presents with worsening fatigue and a persistent red, sore tongue. On examination, his tongue appears swollen with a smooth, shiny appearance. Blood tests show that he has a low hemoglobin level, low serum folate levels, and an elevated mean corpuscular volume (MCV). What is the most likely cause of his anemia?
folate def anemia
- A 20-year-old woman with a history of inflammatory bowel disease presents with fatigue and mild shortness of breath. On examination, she has pale skin and conjunctiva, and her labs show low hemoglobin, low serum folate, and a low albumin level. What is the most likely cause of her anemia?
folate def anemia
- A 60-year-old vegetarian male complains of fatigue, weakness, glossitis, weight loss and numbness and tingling in both hands and feet. What is the most likely cause of his symptoms?
B12 def anemia
- A 35-year-old female with a history of Crohn’s disease presents with fatigue, shortness of breath, and difficulty with balance and coordination. She has lost about 10 pounds in the past few months. Lab tests show elevated mean corpuscular volume, low hemoglobin and hematocrit levels, decreased serum B12 levels, and high levels of methylmalonic acid. What is the most likely diagnosis?
Vit B12 def
- A 70-year-old male with a past medical history of gastric cancer presents with pale skin, fatigue, confusion, and paresthesia in his feet. Lab tests show macrocytic anemia, decreased serum B12 levels, and elevated homocysteine levels. What is the most likely cause of his anemia?
Vit B12 def
- A 28-year-old male presents with a 2-month history of malaise, shortness of breath, easy bruising, and recurrent oropharyngeal infections. He reports no significant past medical or travel history and takes no medications. Physical examination is significant for pallor and petechiae on the skin. Initial laboratory investigations show pancytopenia, and bone marrow biopsy confirms aplastic anemia. What is the most likely etiology for his disease?
Aplastic anemia
- A 65-year-old male with end-stage renal disease presents to the clinic with complaints of fatigue and shortness of breath. He has been undergoing hemodialysis three times a week for the past year. His hemoglobin levels have been consistently low despite erythropoietin-stimulating agent treatment. What is the most likely cause of his anemia?
Kidney disease leading to anemia
- A 50-year-old female with chronic kidney disease stage 3 presents to the clinic with complaints of weakness and dizziness. She has a history of hypertension and type 2 diabetes. Laboratory results show a hemoglobin level of 9.5 g/dL. What is the most likely cause of her anemia?
Kidney disease leading to anemia
- A 4-month-old male infant presents to the emergency department with poor feeding and lethargy. The child was born premature and has been exclusively breastfed. Lab tests show megaloblastic anemia characterized by macrocytosis and a low reticulocyte count. Peripheral blood smear shows megaloblasts, and orotic acid levels are elevated. What is the most likely diagnosis?
Orotic aciduria anemia
- A 6-year-old female presents with growth retardation and developmental delay. Lab tests show moderate anemia with elevated levels of orotic acid in urine and plasma. She has a history of chronic diarrhea, and a colon biopsy is positive for a chronic inflammatory process. What is the most likely cause of this patient’s anemia?
Orotic aciduria anemia
- A 35-year-old male of Jewish descent presents with fatigue and shortness of breath. He has a history of Crohn’s disease and has undergone several surgeries for bowel obstruction. Lab tests show macrocytic anemia with a low reticulocyte count, and elevated levels of orotic acid in the urine and plasma. What is the most likely diagnosis in this patient?
Orotic aciduria anemia
Key difference between B12 def and folate def anemia is
B12 def has neurological symptoms
In hemolytic anemia the reticulocyte count is _____________
falsely increased
A reticulocyte index of 2/+ means
good bone marrow response to anemia
A reticulocyte index of 2/- means
poor bone marrow response to anemia
List some common symptoms of anemia
Pallor
malaise
weakness/easy fatigue
faintness/headache
Dyspnea on exertion
Tachycardia
Angina
Hypoxia (fatty change)
Describe the features of acute blood loss
decreased intravascular volume means lower BP so the body compensates with more ANF, ADH, & Adrenergic hormone to increase sodium retention and pull fluid out of the interstitium into the blood (hemodilution)
List the Hb, HcT, & WBC of a patient with acute blood loss induced anemia
- Normal Hb
- Low HcT (watered down blood)
- High WBC (Fluid pulled in & not let out of BV)
What are the initial features of acute blood loss induced anemia
- Normocytic and normochromic anemia
- Reticulocytosis (5-7 days)
- Thrombocytosis
Chronic blood loss is usually cause by _____&_____
Gi lesions & gynecological bleeds
What are the shared features of hemolytic anemia
- Premature RBC destruction (sooner than 120days)
- Increased EPO (Compensatory)
- Increased indirect (aka unconjugated) bilirubin
Describe extravascular hemolysis
Happens when the RBC’s are stiff (membrane deformities)
low plasma haptoglobin indicates hemolysis in the SPLEEN
Describe intravascular hemolysis
Happens when RBC’s are mechanically injured
No haptoglobin
High methemoglobin (brown urine)
List situations that give rise to intravascular hemolysis
- Calcified cardiac valves
- thrombotic narrowing
- Compliment fixation
- Intracellular parasites
- Exogenous toxic factors
NO haptoglobin
HIGH Methemoglobin
Describe erythroid hyperplasia
Compensation: Bone marrow has more erythroid cells than normal. Usually happens with major blood loss or premature RBC destruction.
What is the myeloid/erythroid (M/E) ratio in normal vs erythro-hyperplastic bone marrow
1:1 = erythroid hyperplasia
3:1 = normal
Describe the features of hereditary spherocytosis
AUTO DOM (compound hetero) mutation that causes frameshift mutations or premature stop codons which alter SPECTRIN (band 3 & 4.2) & ankyrin. RBC’s become spherocytes & get hemolyzed by the spleen
Describe the clinical features of hereditary spherocytosis
Normocytic anemia
Jaundice
Splenomegaly
Decreased haptoglobin
High MCHC & RDW
Hereditary spherocytosis has increased susceptibility to the _____________ test
osmotic fragility test
What is the diagnostic tool used for Hereditary spherocytosis
EMA (Eosin-5’ maleimide) flow cytometry
- A 10-year-old child presents to the clinic with fatigue and yellowing of the skin. On examination, the spleen is enlarged. What diagnosis should be suspected?
Hereditary spherocytosis
- A 25-year-old female has a history of anemia and jaundice. Blood film shows spherocytosis and gallstones. What is the likely diagnosis?
Hereditary spherocytosis
- A 40-year-old male with a history of hereditary spherocytosis presents with abdominal pain. Blood tests show a high bilirubin level and an enlarged spleen. What could be the cause of these symptoms?
Hereditary spherocytosis
- A newborn infant is detected to have jaundice and spherocytosis on a blood film. The family history is significant for spherocytosis in the mother. What is the likely diagnosis?
Hereditary spherocytosis
- A 30-year-old male with a history of hereditary spherocytosis presents with shortness of breath and fatigue. Blood tests show severe anemia. What is the most likely cause of these symptoms?
Hereditary spherocytosis
Describe the features of G6PD deficiency
X-REC mutation, common in Afro-American & Mediterranean’s
Causes episodic hemolysis 2-3 days post exposure to things that trigger oxidative stress
What metabolic pathway is effected by G6PD def and ho does it lead to anemia?
Def G6PD enzyme impacts the hexose monophosphate shunt (glutathione metabolism)
No G6PD means less NADPH which lowers the amount of reduced glutathione (protects against oxidative stress)
What are the clinical findings for G6PD def
2-3 days post exposure to oxidative stress causes
- episodic hemolysis
- hemoglobinuria
- hemoglobinemia
- normocytic/chromic anemia
What are the lab findings of G6PD deficiency
- Heinz & Bite cells (intravascular hemolysis)
- Blister cells (extravascular hemolysis in endothelium)
- NORMOCYTIC & NORMOCHROMIC anemia
What are common triggers for oxidative stress for those with G6PD deficiency
FAVA beans*
- Antimalarials (primaquine, trimethoprim-sulfamethoxazole, &chloroquine)
Describe the features of sickle cell disease
Common in Afro-Americans:
A point mutation of the 6th codon of the B-globin HbSS) that replaces glutamate with valine. This promotes polymerization of deoxygenated RBC’s
Describe the clinical features of sickle cell disease
- Osteomyelitis (salmonella para typhi)
- Avascular necrosis of bone
- Hand/foot/mouth disease
- Dactylitis
- Priapism
- Jaundice
- Chronic hemolytic anemia
- Ischemia tissue organ damage
-Non healing ankle ulcers - Mirovasocclusions
- Crewcut skull & chipmunk face
- Aplastic crisis
- Sequestration crisis
-Splenomegaly or asplenia
-Acute chest syndrome
List the common lab findings of Sickle cell disease
- Target cells
- Howell Jowell bodies
- sickled cells
_____________ is a period where doctors can administer O2, Na, & H2O to reduce/prevent a sickling crisis
delayed time before deoxygenated cells form polymers
Patients that are HbSC &VL
HbSC disease essentially the same symptoms as HbSS except the HbS is mutated means their cells are less likely to sickle but there’s lots of target cells
Someone who is HbAA & GG
Normal
Someone who is HbC & LL
HbC disease same point mutation to the 6th codon on th eB-globin except it causes abnormal Hb C which swaps glutamate for lysine leading to decreased RBC production anemia
Someone who is HbAS & GV
Trait/carriers they’re usually asymptomatic or very mild
Someone who is HbSS & VV
The really bad one
Describe acute chest syndrome
Vaso occlusion causes
- Cough
- Chest pain
- Fever
- Pulmonary infiltrates
Acute chest syndrome in sickle cell disease is typically due to _______ in adults and ________& ________ infections in kids
Atypical pneumonia from Vaso occlusions leading to fat emboli in adults
&
Chlamydia & mycoplasmas in children
sequestration crisis in sickle cell disease
can be fatal in 1-2 hrs secondary to hypovolemia look for
- massive splenomegaly
- Hypovolemia
- Shock
Rx. volume resus & blood transfusion or Splenectomy
Sickle cell patients typically get splenectomies around 18-36 months old leaving them susceptible to _____ infections
pneumococci infections
In sickle cell disease dactylitis is marked by
painful swelling of the hands and feet. X-rays are normal but there’s necrosis of the epiphysial plates
In sickle cell disease Howell-jolly bodies indicate what
They are premature RBC’s with DNA meaning there is not spleen because they are not be hemolyzed
- A 30-year-old man with sickle cell anemia is admitted to the hospital with a fever, headache, and confusion. What is the likely diagnosis, and what is the appropriate treatment for this patient?
Sickle cell anemia
- A 24-year-old African American male presents with severe pain in his hands and feet. What is the likely diagnosis, and what is the cause of his symptoms?
sickle cell anemia
- A 25-year-old African American male reports experiencing frequent episodes of fatigue and muscle pain. Upon examination, his blood work reveals a hemoglobin level of 9.5 g/dL with moderate anisocytosis and microcytosis. What is the most likely diagnosis?
HbSC disease
- A 30-year-old African American female presents with a history of recurrent painful crises in the arms and legs, particularly during times of stress or exercise. Her peripheral blood smear shows numerous target cells, polychromasia, and occasional sickle cells. What is the most likely diagnosis?
HbSC disease
- A 40-year-old African American male presents to the clinic with abdominal pain, nausea, and vomiting. Imaging studies reveal multiple gallstones. He also reports a history of recurrent episodes of painful swelling of the fingers and toes. What is the most likely diagnosis?
HbSC disease
- A 20-year-old African American female presents to the emergency department with severe chest pain and difficulty breathing. She reports a history of frequent episodes of pain in the legs and arms. Her blood work shows moderate anisocytosis and microcytosis. Chest x-ray reveals Consolidation in the left lower lobe. What is the most likely diagnosis?
HbSC disease
Splicing mutations to the _______ lead to B+ Thalassemia minor
Intron (B-globin production is reduced)
Splicing mutations to the _______ lead to B- Thalassemia major
Exons (NO B-globin production)
Mutations to the __________ lead B+ Thalassemia minor
&
mutations to _______ lead to B- Thalassemia major
minor: promoter region mutation
&
major: chain terminator mutation
Describe the features of B-thalassemia minor
Due to a splicing mutation in the intron or a mutation in the promotor region:
It causes MILD anemia with normal iron levels.
Hct is between 28-40%
MCV is between 55-75fL
RBC & Reticulocyte counts are normal or elevated
Increase in HbA2
Describe the features of B-thalassemia major
Due to splicing mutations in the exon or mutations in the chain terminator:
HbF is the dominant Hb so
No B-globin = erythropoiesis is ineffective in the bone marrow. This causes abnormal RBC’s and reduces the RBC count leading to extravascular hemolysis and microcytic anemia.
Body compensates with iron reabsorption (iron overload) & high EPO (hepatosplenomegaly & bone deformities)
Describe the clinical features of B-thalassemia major
- Prone to secondary hemochromatosis (iron overload in the heart & liver)
- Microcytic anemia
- Erythroid hyperplasia (crewcut skill & chipmunk face)
- High EPO
- Low MCV
- Low Hb
14-year-old patient diagnosed with _________, who has severe anemia, hepatosplenomegaly, high ferritin levels, and has been receiving chronic blood transfusions?
B-thalassemia major
Describe the features of HbH disease
an alpha thalassemia deletion of 3 a-globins:
Usually in asians, older kids and adults for stable HbH tetramers from excess B-globins which cause ineffective erythropoiesis.
Their HbH has a high O2 affinity (hypoxia and extravascular hemolysis)
Describe the clinical symptoms of HbH disease
- Anemia
- Jaundice
- Fatigue
- Shortness of breath
- Fainting or dizziness
- Growth retardation
- Enlarged spleen or liver
- Bone deformities
- Delayed puberty
- Gallstones
Describe the features of Hydrops fetalis (Bart’s disease
An alpha thalassemia deletion of all 4 a-globins leaving only y-globin (Hb Bart) which hogs all O2
Describe the clinical features of hydrops fetalis (Bart’s disease)
- Severe tissue hypoxia (leading to death in utero or soon post birth)
- Severe pallor
- Anasarca
- Massive hepatosplenomegaly
Describe the features of Paroxysmal nocturnal hemoglobinuria
An acquired mutation in the PIGA gene needed to make GPI so CD59 & 55 can inactivate compliments and protect RBC’s.
Without CD59&55 RBCs are lysed via the alternative pathway via C3 convertase and activation of the MAC (C3b-C9)
Describe the clinical features of Paroxysmal nocturnal hemoglobinuria
- Hemosiderinuria (iron deficiency + red-brown pee)
- Thrombosis (leading cause of death in people with PNH esp hepatic, portal, and cerebral veins)
- Eventual myeloid leukemia
What are the 2 tests used for PNH (not including Ham’s cause we don’t use that anymore)
Flow cytometry (Negative CD55&59 bottom left)
&
Coombs test (Negative because there’s no antibody, only C3B mediated hemolysis)
Describe the features of Budd-Chiari syndrome
- Sudden severe abdominal pain
- Ascites
- Paroxysmal nocturnal hemoglobinuria
What would be the presentation of a 34-year-old female patient with Paroxysmal nocturnal hemoglobinuria who presents to the emergency department with severe abdominal pain, dark urine, and shortness of breath?
Budd-Chiari syndrome
A 35-year-old male presents with a history of recurrent episodes of dark urine and fatigue. On examination, he has signs of hemolytic anemia with elevated bilirubin and LDH levels. CBC shows decreased hemoglobin and hematocrit with normal platelet and leukocyte counts. Coombs test is negative. What is the likely diagnosis and what further tests would you order?
Paroxysmal nocturnal hemoglobinuria
Describe the features of Immune Hemolytic anemia WARM Ab
warm IgG antibodies coat RBC’s and bind to Fc receptors on phagocytes triggering premature & partial hemolysis. This can be primary (idiopathic) or secondar (SLE or drugs)
What drugs cause warm Ab Immune hemolytic anemia reactions
- Antibiotics (penicillin’s & cephalosporins)
- Hydralazine
-a-methyldopa
Describe how a-methyldopa causes warm Ab immune hemolytic anemia
a-methyldopa is given to lower BP in pregnant women. A side effect is if mom is Rh- & baby is Rh+ IgGs will form against Rh and cross the placenta to attack baby’s RBC’s
Describe how Hydralazine causes warm Ab immune hemolytic anemia
Used to lower BP in pregnant women it can lead to IgGs against RBC’s that can cross the membrane causing SLE
List the differences between warm vs cold Ab type in immune hemolytic anemia
Warm:
Spherocytes
IgG (Ab)
Common IgG chain (pathogenic opsonin)
Cold
Agglutination
IgM (Ab)
C3 (Pathogenic opsonin)
Describe the features of Immune Hemolytic anemia COLD Ab
Following infection with EBV (mono) or mycoplasma pneumoniae IgM binds and fixes compliment when temperature is below 37 degrees
Hemolysis tends to happen in exposed areas like fingers, toes, ears
Describe the clinical features of EBV (preceding immune hemolytic anemia)
Dry cough (no sputum)
Fever
Sore throat
Pale mucus membranes
Describe the features of vitamin B12 deficiency anemia
Without Vit B12 haptocorrin (precursor for thymidine synthesis & CH3-malonylCOA isomerization) can’t be absorbed by cells. This causes ineffective hematopoiesis causing fewer and large RBC that don’t function properly
Describe the features of megaloblastic anemias
Vitamin B12, Folate deficiency, & Orotic aciduria cause impaired DNA synthesis leading to ineffective hematopoiesis producing fewer but larger RBC’s which don’t function properly
Neurological symptoms
List the lab features of Vitamin B 12 megaloblastic anemia
-High Homocysteine
- High Methyl-Cbl (Methyl cobalamin)
- High Methyl malonyl-CoA
- Hypersegmented neutrophils
- Neurological symptoms
Describe the absorption of haptocorrin
1.Ingest haptocorrin
2.binds Intrinsic factor in gastric mucosal (parietal cells)
3. bins Vit B12 to form complex
4. absorbed in terminal ilium via ileal enterocytes with cubilin (IF receptors)
5. proteases cleave haptocorrin-B12 complex
6. Intrinsic factor and trans-colbalamin form complex & bind/enter ilieal cells
List instances of impaired absorption in vit B12 def
- Pernicious anemia (intrinsic factor def)
- Gastrectomy (Intrinsic factor def)
- Ileal resection
- Ileitis (infection)
- H.pylori (infection)
- Tape worm
- Chronic alcohol gastritis
Describe the features of mechanical hemolysis
Synthetic cardiac valves cause trauma to RBCs turning them into schistocytes, helmet cells, & spherocanthocytes
Describe the features of pernicious anemia
Common in older white/Scandinavians. It’s caused by autoimmune gastritis (Ab’s vs a & b subunits of pumps) which reduces parietal cell count & Intrinsic factor levels leading to B12 deficiency
Describe the clinical features of pernicious anemia
- Megaloblastic anemia
- Neurological symptoms of dorsolateral tract
-Achlorhydria (no HCL) - High homocysteine
- High methyl malonic acid
- Positive schilling test
What are the neurological symptoms associated with Pernicious anemia
- Spastic paraparesis,
- Sensory ataxia, severe
- Paresthesia of lower limbs
(Dorsolateral spinal tract degeneration)
Describe the features of folate deficiency induced megaloblastic anemia
lack of leafy greens (aka folylpolyglutamates) which can’t be absorbed in the duodenum. Can be from hemodialysis, diet (greens) pregnancy or infancy
Describe the clinical features of folate def megaloblastic anemia
low folate
high homocysteine
NORMAL methyl malonate
Schilling’s test:
Normal urine excretion of radiolabeled B12 means
decreased intake of B12
Schilling’s test:
Less urinary excretion of radiolabeled B12
Impaired B12 absorption
Schilling’s test:
Normal excretion of radiolabeled B12 after step 3 (added intrinsic factor)
intrinsic factor deficiency like Pernicious anemia
Schilling’s test:
Less urine excretion of radiolabeled B12 after step 3 (added intrinsic factor)
Malabsorption
Describe anemia in the first 18 months of life
If baby is only breast feed they will lack Vit D & B12 causing;
Anemia
&
Weight loss (RARE)
Describe the clinical features of iron deficiency anemia
- Esophageal webs (diff swallowing food but not drinks)
-Microcytic & hypochromic anemia - Atrophic glossitis
- Angular stomatitis (sores at corner of lips)
-Koilonychia (spooning nails)
Describe the Plummers triad of iron deficiency anemia
- Microcytic & hypochromic anemia
- Esophageal webs
- Atrophic glossitis
List the lab findings for Iron deficiency anemia
Low Hb
Low Hct
Low iron
Low ferritin
Microcytic hypochromic anemia
Moderate poikilocytosis (Squished RBCs)
HIGH TIBC
What is ferrous
free iron
What is transferrin
iron binding protein
What is ferritin
macrophage stored/laden iron
What is Hemosiderin
inhibitor of transferrin
the features of anemia of chronic disease (inflammation)
3 main types lead to less proliferation of erythroid cells and poor iron usage.
- Microbial infections (lung abscess, osteomyelitis, & bacterial endocarditis)
- Chronic immune disorders (Rheumatoid arthritis & Chron’s)
- Neoplasms (breast & lung cancer, & Hodgkin lymphoma)
describe the clinical features of anemia of chronic disease
Low iron
Low TIBC
Low EPO
High ferritin
Describe the pathogenesis of anemia of chronic disease
Inflammatory mediators IL6 increase hepcidin release from the liver to reduce iron absorption and increase iron storage in bone marrow macrophages, less available iron means poor hematopoiesis
Describe the features of aplastic anemia
Chronic primary hematopoietic failure & pancytopenia (anemia, neutropenia, and thrombocytopenia)
It can be idiopathic or follow viral infections, drug use, or radiation treatment
What are the drugs that may lead to aplastic anemia
Chloramphenicol
Carbamazepine
Penicillamine
What viral infections may lead to aplastic anemia
Hepatitis A, B, & C
Describe the features of inherited aplastic anemia aka Fanconi anemia
An AUTO REC (rare) defective multiprotein complex needed for DNA repair that leads to
- Hypoplasia of kidneys & spleen
- No thumbs or radii
- Hypocellular bone marrow with fat globules
Describe the features of anemia due to chronic renal failure
Damaged kidneys means less EPO (low RBC prod)
&
uremia (mean corpuscular def, iron def, platelet dsy) both of which lead to anemia
Describe the clinical findings of anemia due to chronic kidney disease
Low Hb (below 10)
Normocytic & Normochromic anemia
Describe the general features of polycythemia
typically has
High Hb, Hct, & RBC #
Describe the features of relative polycythemia
Less plasma volume which can be from diuretic use or dehydration. Bone marrow production of RBC’s is fine:
- Normocytic anemia
- Normal EPO &SaO2
- High Hb & Hbt
Describe the general features of secondary appropriate polycythemia
An increase in bone marrow’s production of RBCs which can be due to
- high altitude adaptation to hypoxia
-Eisenmenger’s syndrome
- Smokers polycythemia
Describe the features of secondary appropriate polycythemia High altitude response
People who live at higher altitudes have more bone marrow production of RBCs (High EPO) to deal with chronic tissue hypoxia
Describe the features of secondary appropriate polycythemia Eisenmenger’s syndrome
Patients with cardiac/intrapulmonary hunts or ventilation defects (COPD) have right to left shunting & produce more RBC’s to combat tissue hypoxia
Describe the features of secondary appropriate polycythemia Smokers polycythemia
Heavy smoking makes carboxyhemoglobin which has a high affinity for O2 causng tissue hypoxia in response bone marrow makes more RBCS;
High EPO
More RBCs
Low SaO2 (Carboxyhemoglobin stiff has higher O2 affinity)
Normocytic anemia
Describe the features of inappropriate polycythemia
Can be due to paraneoplastic EPO conditions like renal or liver tumors, or cerebellar hemangioma
Normal SaO2
High EPO
High RBC count
More RBC mass
Normal plasma volume
Describe the features of primary polycythemia
Late onset (60yrs) of a somatic Janus type V617F gene mutation in the exon 14 of pluripotent hematopoietic stem cells causing a hyperactive JK2 Kinase causing excess erythrocytes, granulocytes, and platelets
Describe the clinical features of Primary polycythemia
Splenomegaly
Erythromelalgia
Thrombotic episodes
Budd Chiari syndrome
List the lab findings of primary polycythemia
High RBC count, mass, & plasma vol
Low EPO
Normal SaO2
Hypocellular bone marrow with fibrosis
Describe primary malnutrition
dietary insufficiency of nutrients/vitamin
Describe secondary malnutrition (conditional)
Lack of protein
Describe the features of Marasmus
Not enough calories
No edema (normal albumin)
thin
Anemia
Immunodeficiency
Describe the features of Kwashiorkor
not enough protein
Anasarca (hypoalbuminemia)
Desquamation (flaky skin)
areas of hyper/po pigmentation
hypopigmented hair
Enlarged fatty liver
Apathy & lost appetite
Vitamin/immunodeficiencies
Sufficient fat
Describe the features of Cachexia
lack of protein in patients with cancer, usually death due to respiratory failure
Tumors secrete
- PIF (Degrades myosin aka muscle atrophy)
- LMF (increases fatty acid metabolism)
- TNF & IL6 (Activate NFkB signalling pathway to increase ubiquitin)
- Dystrophin-glycoprotein complex (increase proteosomes)
Describe the features of Obesity
- Insulin resistance (type 2 diabetes)
- Hypertension
- Hypertriglyceridemia & low HDL (Coronary artery disease)
- non-alcoholic fatty liver disease
- Cholestasis (gallstones)
- Obesity hypoventilation syndrome
- Osteoarthritis
- Cancer risk
Describe the features of Obesity-hypoventilation syndrome
Hypoventilation
Hypersomnolence (day time sleepiness)
Polycythemia
Hypoxia
Describe the features of metabolic syndrome
Systolic BP 130+
Diastolic BP 85+
Fasting glucose 100+
Triglycerides 150+
HDL below 40 women 50 men
Waist 88cm women 120 men
Describe the role of adiponectin in obesity
Moves fatty acids to muscle oxidation via ApoR1/2 in skeletal muscle and liver. Obese plp have lower Adiponectin
Describe the role of leptin in obesity
in obesity, the body becomes resistant to the effects of leptin, leading to leptin resistance. This means that even if a person has high levels of leptin, their brain does not receive the signal to stop eating, and they continue to consume more calories than they need
Mutated leptin receptors or melanocortin receptors cause
super obesity
Describe the clinical features of vitamin A deficiency
- Xerosis conjunctivae
- Nyctalopia (night blindness)
- Xerophthalmia
- Squamous metaplasia
- Bitot’s spots
- Keratomalacia
- Blindness
Describe Xerosis conjunctivae
occurs in vitamin A deficiency causing dryness and inflammation of the membranes lining the eyelids and conjunctiva
Describe Bitot’s spots
Patches of foam and a thickened conjunctiva it’s a precursor to Xeropthalmia.
Describe Xerophthalmia
Severely dry eyes causing corneal damage which eventually leads to blindness
Describe keratomalacia
the cornea is soft & opaque eventually leading to blindness
What can lead to vitamin A deficiency
Malnutrition
Malabsorption (celiac, chrons, colitis)
Using mineral oil as a laxative
Vitamin A is used in the treatment of what condition?
Acute myeloid leukemia
Describe how retinol and B-carotene are absorbed into the body
Bile helps absorb Vit A & B-carotene into the lymph as chylomicrons to get taken to the liver. Apolipoprotein E facilitates their storage and they can be re-uptaken when bound to RBB to cells with RBBR. In cells they’re oxidized into retinoic acid
to maintain normal vision rods have _______- & cones have 3 ________
Rhodopsin & 3 iodopsin
Describe how retinol is converted in the eye
Photon causes oxidation making all-trans retinol, which is then isomerized into 11-cis retinol, which is finally covalently modified with 7 transmembrane rod protein opsin to make rhodopsin (for rods)
Describe the general functions of vitamin A
- vision (rhodopsin & iodopsin)
- cell growth (mucus secreting epi)
- cell differentiation (myeloid cells via RAR)
- fatty acid metabolism (obesity)
- Antioxidant (B-carotene)
Describe the function of retinoic acid receptors (RAR) & retinoic x receptors (RXR) heterodimers in cell growth/differentiation
RAR/RXR heterodimers bind retinoic acid response elements on regulatory genes within cells to activate transcription of cell growth, tumor suppressor, & secreted proteins
Which type of retinoic acid has the highest affinity for RAR
All-trans Retinoic acid which is why it’s used to treat acute myelocytic leukemia because they bind PML-RAR-alpha
Describe how 9-cis Retinoic acid regulated fatty acid oxidation, adipogenesis, and lipolysis
it activated RXR which binds & activates peroxisome proliferator activated receptors (PPARs)- & vitamin D receptors both play a role in fatty acid oxidation, adipogenesis, and lipolysis
Describe the clinical features of Vit A toxicity
Headaches
Dizziness
Blurred vision
Vomiting
Dry + itchy skin
Sparse hairs
Cheilosis
Osteoporosis
Teratogenic effects (preggos)
Carotenoderma (yellow skin)
Who is most at risk of Vit A toxicity
Fishers (Fish)
Hunters (Liver)
& their families
Describe the features of pseudotumor cerebri in vitamin A toxicity
Dizziness
Headache
Blurred vision
Vomiting
BMI under 19
underweight
BMI 19-24
ideal
BMI 25-30
Overweight
BMI 30-34
Obese
BMI 35-39
severely obese
BMI 40-45
Morbidly obese
BMI 50+
Super obese
Obesity is linked to hunger control via the arcuate nucleus in the hypothalamus describe the functions of the weight loss neurons
POMC/CART increase MSH (α-melanocyte-stimulating hormone) & MC3/4R (melanocortin receptors 3 and 4) to stimulate energy expenditure (burn calories)
Obesity is linked to hunger control via the arcuate nucleus in the hypothalamus describe the functions of the weight gain neurons
NYP & AgRP activate Y1/5 receptors in 2nd order neurons to increase MCH (melanin-concentrating hormone) & orexin to stimulate appetite and therefor weightgain
What are the key regulators in weight gain/loss in obesity
Leptin & adiponectin (fat cells)
Ghrelin (stomach)
PYY & GLP-1 (Ileum & colon)
Insulin (pancreas)
loss-of-function mutations in the leptin receptors and Mutations of melanocortin receptor 4 (MC4R) leads to what
obesity
Leptin activates which 2nd order neurons
POMC & CART = weight loss!
Ghrelin activates which 2nd order neurons
NPY & AgRP to increase orexin = weight gain!
PYY & GLP-1
suppress food intake (ileum & colon)
