1 - Shortness of Breath Flashcards
What is shortness of breath also known as?
Dyspnea
What are the common causes of dyspnea?
Cardiac and pulmonary problems
Almost two-thirds of dyspnea cases are due to these issues.
What are some non-cardiac and non-pulmonary causes of shortness of breath?
- Hematologic disorders (e.g., anemia)
- Metabolic disorders (e.g., acid-base disorders)
- Medication
- Infection
- Toxic ingestions
- Psychological causes
- Physical deconditioning
What is the significance of rapid evaluation in cases of dyspnea?
It is crucial for identifying potentially life-threatening conditions.
What is the complete blood count (CBC)?
A test that includes hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), white blood cell count, and platelet count.
Define hemoglobin (Hb).
The amount of hemoglobin in a volume of blood.
What does hematocrit (Hct) measure?
The percent of blood volume composed of red blood cells.
What does mean corpuscular volume (MCV) indicate?
The average size of red blood cells.
What is clubbing and what conditions is it associated with?
A physical sign associated with heart failure, emphysema, and malignancy.
What does cyanosis indicate?
Lack of oxygenation resulting in a bluish discoloration of the skin.
What is glossitis?
Inflammation of the tongue leading to a smooth and shiny appearance.
What does the Romberg test assess?
Balance and proprioception by having a patient stand with feet together and eyes closed.
What does a high mean corpuscular volume (MCV) indicate in a CBC?
Macrocytosis
What findings in the peripheral smear indicate megaloblastic anemia?
- Larger than normal red blood cells (macrocytic)
- Hypersegmented granulocytes
What might a low total protein and albumin level suggest?
A possible malnourished or malabsorptive state.
What are potential causes of vitamin B12 deficiency?
- Poor dietary intake
- Atrophic gastritis (due to H. pylori infection or autoimmune mechanisms)
What does achlorhydria refer to?
The absence of acid production in the stomach.
What is the primary cause of autoimmune gastritis?
Formation of antibodies to intrinsic factor and/or the parietal cell.
What can chronic H. pylori infection lead to?
Loss of parietal cells and diminished acid and pepsin production.
What clinical signs were observed in the patient with shortness of breath?
- Thin and pale appearance
- Flat affect
- Mild interosseous and temporal muscle wasting
- Mild glossitis
What is the role of a chest X-ray in evaluating shortness of breath?
To help exclude cardiopulmonary etiology.
What is the significance of the reticulocyte index?
It measures the amount of immature red blood cells in circulation expressed as a percentage of the total red cell count.
What cells are primarily involved in autoimmune gastritis?
Autoimmune gastritis primarily involves enterochromaffin (ECF)-like cells
Autoimmune gastritis affects the cardia and fundus while sparing the antrum.
What is a key laboratory finding in autoimmune gastritis?
Markedly elevated serum gastrin level
This occurs due to interrupted negative feedback loop of acid on gastrin production.
What antibodies are associated with autoimmune gastritis?
Antibodies to intrinsic factor and/or the parietal cell
These antibodies contribute to the pathophysiology of the disease.
What is the significance of achlorhydria in autoimmune gastritis?
Achlorhydria leads to elevated serum gastrin levels
This is due to the loss of negative feedback regulation on gastrin production.
What is the relationship between autoimmune gastritis and megaloblastic anemia?
Autoimmune gastritis can contribute to megaloblastic anemia due to low intrinsic factor
This results in impaired vitamin B12 absorption.
What is a common complication associated with autoimmune gastritis?
Increased incidence of gastric carcinoma
Both autoimmune and H. pylori-induced chronic gastritis are linked to this risk.
What does an upper gastrointestinal endoscopy reveal in cases of autoimmune gastritis?
Atrophic mucosal lining
Biopsies may support the suspicion of atrophic mucosa.
What are the low serum levels found in patients with vitamin B12 deficiency?
Low serum vitamin B12 and folate levels
Methylmalonic acid levels are also assessed to support the diagnosis.
What biochemical role do vitamin B12 and folate play in erythropoiesis?
They are crucial for DNA synthesis and amino acid formation
This process is known as single-carbon metabolism or transmethylation.
What is the mechanism by which vitamin B12 deficiency leads to anemia?
Prevents conversion of 5-MTHF to THF, causing a functional folate deficiency
This is referred to as the folate trap.
What neurologic damage can result from vitamin B12 deficiency?
Neurologic symptoms due to accumulation of methylmalonic acid
Vitamin B12 is a cofactor for the enzyme methylmalonyl CoA mutase.
What is the primary method of vitamin B12 absorption?
Vitamin B12 binds to intrinsic factor in the ileum for absorption
R-protein protects vitamin B12 from degradation in the stomach.
What are common manifestations of vitamin B12 deficiency?
Macrocytosis, neurologic symptoms, atrophic glossitis
Neurologic symptoms may include paresthesia and gait problems.
What is pernicious anemia?
Anemia due to lack of B12 absorption from loss of intrinsic factor
This is caused by autoimmune targeting of parietal cells.
How can vitamin B12 deficiency be distinguished from folate deficiency?
Elevated methylmalonic acid level is a more reliable marker
Serum vitamin B12 levels can be unreliable for diagnosis.
What can cause malabsorption of vitamin B12?
Excess antacids, bariatric surgery, Crohn disease
These conditions may disrupt vitamin B12 absorption.
What are the high-yield concepts regarding vitamin B12 and folate?
- Vitamin B12 deficiency can create a concomitant folate deficiency by trapping folate in its reduced form
- Macrocytic anemia and neurologic symptoms suggest vitamin B12 deficiency
- Nutritional deficiency must be considered as a primary cause of low vitamin B12
Additional high-yield concepts include the roles of B12 in DNA synthesis and its relationship with gastric conditions.
What is the primary cause of low vitamin B12 and folate levels?
Nutritional deficiency must be considered as a primary cause.
Other causes include structural/surgical or pathologic changes in the stomach and terminal ileum.
What does a fecal occult blood test (FOBT) detect?
It detects occult blood in the stool.
Commonly used for colorectal cancer screening.
What are the notable physical findings in the 44-year-old woman presented in Case 1.2?
Pale conjunctiva and nail beds; soft systolic murmur; hemoccult positive stool.
Suggests anemia with possible chronic gastrointestinal blood loss.
What is the significance of hemoccult-positive stool tests?
Indicates possible gastrointestinal bleeding.
Important to rule out other causes of anemia.
What dietary changes were recommended for the patient in Case 1.2?
Increase iron intake and take a supplement containing iron and vitamin C.
Dark green vegetables are a good source of iron.
What are the potential causes of iron deficiency in the patient from Case 1.2?
Heavy menstrual bleeding, gastrointestinal blood loss, low iron intake, low bioavailable iron.
Patients on vegan diets may have decreased bioavailability of iron.
What is the structure of mature red blood cells (RBCs)?
Lack organelles, contain over 600 million hemoglobin molecules, have a flexible biconcave disc shape.
RBCs have a lifespan of approximately 120 days.
What is the composition of hemoglobin A (Hb A)?
Tetrameric protein with four polypeptide chains: 2α globin and 2β globin.
Each globin subunit has a heme prosthetic group.
What happens during iron deficiency regarding hemoglobin synthesis?
Decreased hemoglobin synthesis results in hypochromic and microcytic RBCs.
The last step of heme synthesis is inhibited.
What is hemosiderin and when is it formed?
A storage protein for excess iron formed when iron concentration is high in circulation.
Protects the body against the toxicity of free iron.
What are common causes of iron deficiency anemia?
Iron-deficient diet and gastrointestinal blood loss.
Populations at risk include menstruating females and those with malabsorption diseases.
What are the key indicators of hemolysis in laboratory tests?
Increased reticulocytes, elevated LDH, elevated indirect bilirubin.
These suggest a hemolytic process.
What is the normal life expectancy of red blood cells?
Approximately 120 days.
What is the effect of iron deficiency on the color of RBCs?
RBCs become pale (hypochromic) and small (microcytic).
What is the role of haptoglobin in hemolysis?
Haptoglobin levels decrease during hemolysis as it binds free hemoglobin.
This helps to assess the severity of hemolysis.
What condition is indicated by an increase in serum alkaline phosphatase (ALP)?
Cholestasis, where the flow of bile from the liver is slowed or blocked.
What is a common genetic cause of hemolysis in Mediterranean descent?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
What must be considered when evaluating a patient for nutritional iron-deficiency anemia?
Gastrointestinal blood loss should always be considered in the workup.
What are the expected laboratory findings in a case of iron deficiency anemia?
Hypochromic microcytic RBCs, low hemoglobin, low ferritin levels.
What medication is associated with drug-induced liver disease (DILI) in the 16-year-old boy?
Sulfur-based antibiotic.
What symptoms did the 16-year-old boy present with?
Fatigue, acute dyspnea on exertion, darkening urine, slight yellow tinge to sclera.
What happens to bilirubin levels in hemolytic conditions?
Unconjugated bilirubin levels increase in the blood
This increase may spill over to saturate peripheral tissues and lead to elevated urobilinogen levels in urine and blood.
What tests are ordered to confirm a hemolytic process?
Tests include:
* Fractionation of bilirubin
* Measurement of haptoglobin level
* Reticulocyte count
* LDH
* Urinalysis for hemoglobin
These tests help assess the presence of hemolysis.
What clinical symptom is indicated by elevated indirect (unconjugated) bilirubin?
Jaundice
This suggests a ‘prehepatic’ problem rather than a pathologic process within the liver.
What are the three reasons for elevated unconjugated bilirubin?
Reasons include:
* Hemolysis
* Gilbert syndrome
* Neonatal jaundice
In this case, hemolysis is the most likely cause.
What role does haptoglobin play in hemolysis?
Haptoglobin binds free hemoglobin in serum and prevents renal damage
Near-zero haptoglobin levels indicate a possible hemolytic event.
What is the significance of dark urine in a hemolytic process?
Dark urine is likely due to free hemoglobin saturating haptoglobin and entering the urine
This is further evidence for acute intravascular hemolysis.
What is the most common enzyme deficiency causing hemolysis worldwide?
G6PD deficiency
It is often triggered by certain medications or foods.
What is the function of the hexose monophosphate pathway (HMP) in RBCs?
The HMP pathway synthesizes NADPH
This pathway is crucial for protecting RBCs against oxidative damage.
How is NADPH synthesized in RBCs?
NADPH is synthesized through the hexose monophosphate pathway
G6PD is the rate-limiting enzyme in this pathway.
What is the consequence of superoxide formation in RBCs?
Superoxide leads to membrane lipid peroxidation and accumulation of methemoglobin
This reduces the oxygen-carrying capacity of RBCs.
What happens to RBCs in G6PD deficiency?
RBCs become more susceptible to oxidative damage and undergo hemolysis
G6PD deficiency leads to the formation of Heinz bodies.
What are Heinz bodies?
Heinz bodies are small inclusions formed from oxidized hemoglobin molecules
They indicate oxidative damage in RBCs.
What are common triggers for hemolysis in individuals with G6PD deficiency?
Triggers include:
* Infections
* Antimalarial medications (e.g., primaquine)
* Fava beans
* Sulfur-containing drugs
These factors increase reactive oxygen species in RBCs.
What laboratory findings indicate a hemolytic disorder?
Findings include:
* Elevated indirect (unconjugated) bilirubin
* Low haptoglobin
* Elevated LDH
* Elevated reticulocyte count
These results support a diagnosis of hemolysis.
What are the signs of chronic hemolytic anemia?
Signs include anemia and splenomegaly
Splenomegaly indicates chronic hemolysis due to damaged RBC removal.
What is the primary role of glutathione in RBCs?
Glutathione protects RBCs from oxidative stress and damage
It helps prevent hemolysis.
What happens to the spleen in chronic hemolytic anemia?
The spleen enlarges due to the removal of damaged RBCs
This is a cardinal manifestation of chronic hemolytic anemia.
What is the significance of elevated reticulocyte count in hemolysis?
An elevated reticulocyte count indicates a normal bone marrow response to the loss of RBCs
It shows that the body is attempting to compensate for the hemolysis.
Why is G6PD deficiency considered an X-linked recessive disorder?
G6PD deficiency affects predominantly males, as they have only one X chromosome
Females would need mutations on both X-chromosomes to exhibit symptoms.
What is the geographical correlation with G6PD deficiency?
G6PD deficiency prevalence correlates with malaria distribution
It is thought to provide some protection against malaria.
What is the typical management for a patient with G6PD deficiency after a hemolytic event?
Management includes hydration and supportive care
The clinical situation usually resolves spontaneously.
What is the significance of measuring G6PD levels after a hemolytic event?
G6PD levels are measured to confirm the diagnosis once steady-state levels are reestablished
This is done after the hemolytic event resolves.
What are the primary symptoms observed in the 4-year-old male patient?
Acute fatigue, severe shortness of breath, severe back pain, pain in the lower extremities, myalgia, arthralgia, and fever.
The patient also has a nonproductive cough and mild shortness of breath.
What significant medical history is noted for the patient?
No medical care since birth and no vaccinations received.
Parents report episodes of crying in pain for no apparent reason.
What were the findings from the physical examination of the child?
Poorly nourished but well-developed, in distress, fever of 100 °C, pulse of 90 beats/min, respiratory rate of 20 breaths/min, pO2 of 94% on ambient air, and scattered wheezes in lungs.
The spleen is easily palpable and there is diffuse mild tenderness in the back.
What does a low reticulocyte count indicate in this patient?
A low reticulocyte count of 0.8% suggests inadequate red blood cell production.
This can indicate an aplastic crisis or a response to hemolytic anemia.
What is the clinical impression for this case?
The child has sickle cell anemia due to the presence of sickle cells on the peripheral smear.
The parents’ description of painful episodes indicates possible sickle cell crises.
What are common triggers for a sickle crisis?
- Infection
- Dehydration
These factors can lead to vascular obstruction and ischemic pain.
What is acute chest syndrome in sickle cell disease?
A condition presenting with chest pain, fever, hypoxemia, and pulmonary infiltrates.
It can occur during a sickle crisis.
What is the role of Parvovirus B19 in sickle cell disease?
It is associated with acute drops in hemoglobin and can cause transient red cell aplasia.
Infection can trigger a sickle crisis.
What is autosplenectomy in sickle cell disease?
Gradual destruction of the spleen due to multiple infarctions from sickle crises.
This condition is more typical in adults.
What characterizes an acute splenic sequestration crisis (ASSC)?
The spleen traps massive amounts of sickle cells, leading to a rapid drop in hemoglobin and hypoxia.
This is a medical emergency, especially in infants and young children.
What laboratory studies might support the clinical impression of sickle cell anemia?
Hemoglobin levels, reticulocyte count, parvovirus B19 titer.
Transfusion and fluid replacement can help manage the patient’s condition.
How does oxygen bind to hemoglobin in the lungs?
Oxygen binds cooperatively to hemoglobin, increasing the affinity for subsequent oxygen molecules.
This results in a sigmoidal oxygen saturation curve.
What is the Bohr effect?
The process where elevated levels of H+ and CO2 promote the release of oxygen from hemoglobin in peripheral tissues.
This is due to the acidic environment found in those tissues.
What is 2,3-BPG and its role in regulating hemoglobin?
2,3-BPG is formed during glycolysis and decreases hemoglobin’s affinity for oxygen, promoting oxygen release.
It helps adapt to conditions like high altitude.
What is the genetic basis of sickle cell disease?
A single nucleotide substitution from A to T in the β-globin gene, changing glutamate to valine, termed HbS.
This results in polymerization of deoxygenated hemoglobin.
What are the negative allosteric effectors of hemoglobin?
- Low pH
- Increased temperature
- 2,3-BPG
- Decreased oxygen availability
These factors promote the sickling process in sickle cell disease.
What is the relationship between sickle cell disease and malaria?
Sickle cell gene confers protection against malaria infection.
Sickling is believed to be incompatible with the life cycle of the malaria parasite.
What management strategies were initiated for the child?
- Supplemental oxygen
- Rehydration
- Analgesia
- Hydroxyurea therapy
Hydroxyurea promotes the production of fetal hemoglobin, which has a higher affinity for oxygen.
What is the condition characterized by a stable but enlarged spleen supporting the diagnosis of ASSC?
Splenomegaly
ASSC stands for acute splenic sequestration crisis.
What therapy is initiated to reduce the occurrence of infections, transfusion requirements, and vaso-occlusive events in sickle cell anemia?
Hydroxyurea
Hydroxyurea induces the production of fetal hemoglobin.
What is the effect of fetal hemoglobin in sickle cell anemia?
Higher affinity for oxygen and reduced morbidity and mortality
Fetal hemoglobin does not interact with 2,3-BPG.
What are the allosteric regulators of hemoglobin?
O2, H+, CO2, 2,3-bisphosphoglycerate (2,3-BPG), and fever
These molecules influence hemoglobin’s affinity for oxygen.
Fill in the blank: The production of _______ acts as an allosteric effector of hemoglobin.
2,3-BPG
What happens to the oxygen saturation curve when hydrogen ions, carbon dioxide, and 2,3-BPG increase?
Shifts to the right
This encourages oxygen delivery to the tissues.
What condition is characterized by hypoxemia and occurs quickly after sudden climbing to high altitude?
Acute mountain sickness (AMS)
AMS is exacerbated by ignoring acclimatization recommendations.
What are the symptoms of acute mountain sickness (AMS)?
Headache, nausea, vomiting, disturbed sleep, fatigue, dizziness
These symptoms develop in response to hypoxia at altitude.
What laboratory studies are reasonable to request for a patient suspected of AMS?
Electrolytes, renal function, chest X-ray, electrocardiogram
These studies help assess the patient’s condition.
What is the primary stimulus to breathe at high altitudes?
Hypercapnia
An increase in CO2 levels in the blood.
What is the Bohr effect?
Right shift in the O2 saturation curve due to decreased pH
This enhances O2 release from hemoglobin.
What action does acetazolamide perform in the kidneys?
Increases bicarbonate excretion
This helps alleviate respiratory alkalosis.
What happens to the pH during hyperventilation at high altitudes?
Increases
This leads to respiratory alkalosis.
Fill in the blank: The oxygen saturation curve shifts to the _______ due to respiratory alkalosis.
Left
What is the most likely diagnosis for a patient with low hemoglobin and elevated methylmalonic acid and homocysteine levels?
Vitamin B12 deficiency
This is indicated by the laboratory results.
Which factor is most likely to be decreased in a patient with vitamin B12 deficiency?
Intrinsic factor
It is essential for vitamin B12 absorption.
What mechanism is likely involved in primaquine causing hemolysis in patients?
Inhibition of glucose-6-phosphate dehydrogenase
This leads to oxidative stress in red blood cells.
What is the most likely finding on the peripheral blood smear of a patient with hemolysis due to primaquine?
Heinz bodies
These are indicative of oxidative damage to red blood cells.
What is a common reason for a child’s severe pallor and hepatosplenomegaly after playing soccer?
Playing soccer at a high altitude
This can lead to hypoxia and other complications.
What is likely to improve symptoms in a patient with hypoxia at high altitudes?
Increased concentration of 2,3-BPG
This enhances oxygen release to tissues.
What mechanism would be initiated in a person experiencing severe headache and light-headedness at high altitude?
Increased cerebral blood flow due to low CO2 levels
This is a compensatory response to hypoxia.
What condition is likely in a patient with macrocytic anemia and low vitamin B12 and folate levels after ileum resection?
Vitamin B12 deficiency due to malabsorption
The ileum is crucial for vitamin B12 absorption.
What marker would most likely be elevated in a patient with macrocytic anemia after ileum resection?
Methylmalonic acid
This supports the diagnosis of vitamin B12 deficiency.
What laboratory marker is most likely elevated in a patient with macrocytic anemia due to vitamin B12 deficiency?
Methylmalonic acid
Methylmalonic acid accumulates in the absence of vitamin B12 due to its role in metabolism.
What is the most likely laboratory finding in a patient with iron deficiency anemia?
Increased total iron binding capacity
This is a typical finding in iron deficiency anemia.
What type of anemia is indicated by high methylmalonic acid levels?
Vitamin B12 deficiency
High methylmalonic acid levels differentiate vitamin B12 deficiency from folate deficiency.
What is the effect of losing a significant portion of the stomach during bariatric surgery on vitamin B12 absorption?
Disturbed vitamin B12 digestion and absorption
The loss affects gastric secretions necessary for vitamin B12 digestion.
What is the major iron storage protein in the body?
Ferritin
Ferritin levels can indicate iron deficiency when low.
What condition is indicated by oxidative stress on red blood cells due to primaquine?
Hemolytic anemia
G6PD deficiency can lead to hemolytic anemia when oxidative stress occurs.
What are Heinz bodies?
Precipitated hemoglobin polymers
They result from the oxidation of sulfhydryl groups in hemoglobin due to reactive oxygen species.
What factors favor the sickling of hemoglobin S (HbS)?
- Low pH
- Increased temperature
- Decreased availability of oxygen
These conditions shift Hb from the relaxed state (R) to the tense state (T), promoting sickling.
What is the effect of respiratory alkalosis on oxygen binding to hemoglobin?
Increases oxygen binding
This is undesirable in cases where increased oxygen delivery to tissues is needed.
What autoimmune condition is characterized by atrophic gastritis affecting the body of the stomach?
Autoimmune-mediated atrophic gastritis
It leads to the loss of parietal cells and intrinsic factor, affecting vitamin B12 absorption.
What is the relationship between the ileocecal valve and diarrhea in short gut syndrome?
Without the ileocecal valve, small bowel contents can enter the colon more freely, causing diarrhea
This overwhelms the colon’s absorptive capacity.
What is the expected serum ferritin level in a patient with iron deficiency anemia?
Decreased
Low ferritin indicates reduced iron stores in the body.
What laboratory finding would be expected in a patient with G6PD deficiency experiencing oxidative stress?
Increased oxidized glutathione levels
Due to low NADPH, reduced glutathione levels would be low.
What is the most likely cause of a patient experiencing weakness, fatigue, and mild dyspnea with low hemoglobin levels?
Iron deficiency anemia
Symptoms can arise from chronic blood loss or dietary deficiencies.
What is a typical laboratory finding in megaloblastic anemia?
Hypersegmented neutrophils
This finding is characteristic of megaloblastic anemias, including those caused by vitamin B12 or folate deficiency.
What is the primary role of intrinsic factor in the gastrointestinal system?
Vitamin B12 absorption
It is necessary for the absorption of vitamin B12 in the terminal ileum.
What is the expected effect of dehydration on sickle cell disease?
Increases sickling due to higher intracellular hemoglobin concentration
This promotes polymerization of deoxygenated HbS.
