Clinical Medicine Flashcards
CC: 72 yo white woman presents with fatigue
- Onset: 2 months
- Increases w/ activity, better w/ rest
- Not improved w/ sleep
- ADLs not affected
- Wt loss of 5 lbs in last 2 mo
- HTN (ACEi), mild OA, ibuprofen, APAP
- Appendectomy, tonsillectomy
- No allergies, no alcohol, no smoking
- Fam hx: HTN, Type 2 DM, long lived
- Enalapril, ASA, ibu, APAP
- Sore throat for 2 weeks amoxicillin
- Easily bruises, petechiae, purpura on skin
- Conjunctival pallor (pale), palatal petechiae
Tests?
- Pancytopenia (all WBC down)
- High MCV, MCH
- Retic LOW
- LDH
Next…
- Check B12 & folate=normal
- Bone marrow biopsy (pancyto but hypoproliferative w/ macrocytosis)
-Concern of what?? What causes it? Tx?
-Aplastic anemia
(pancytopenia + aplastic bone marrow)
Causes:
- Parvo B19 (aplastic anemia and pure red cell aplasia)
- Other virus
- Autoimmune (maybe suppress immune sys to tx)
- Meds (know meds that cause marrow hypoplasia/aplasia)
Treatment:
- Transfusion support
- Antibiotics
- Cyclosporin + prednisone
- Thymoglobulin (T3 lymphocyte removal)
- Bone marrow transplant/stem cells
Tests: CBC, CMP (BUN, creatine, bilirubin, LDH), Retic count
Sore throat for 2 weeks amoxicillin (normally 1 wk)
Pos symptoms for anemia
Thrombocytopenia symptoms
Meds that cause marrow hypoplasia/aplastic anemia? (2)
- Chloramphenicol
- Quinacrine
CC: 45 yo white female with fatigue that developed over the last month. Mildly SOB with exertion, no chest pain. No bright red blood in stool or melena, but heavy menstrual periods for a year. Treated for anemia following 3rd pregnancy 10 years ago. No meds. Italian parents died in grade school
- Aspirin for several months (81 mg…GI bleed? Anti-platelet)
- Vegetarian who eats a lot of cereal (no meat)
- NO cravings for starch or talc or craving for ice-pagophagia, celery, carrots, beet-uria (All Fe def)
- Pale
- Pale conjunctiva
- No hepatosplenomegaly
- Grade I systolic ejection murmur
- No masses, heme negative brown stool
- Heart rate and BP normal
SS of anemia?
Labs:
-Low hb, MCV low, MCH low, RDW high, High platelet count, Incr. reticulocyte count, LDH normal (hemolysis)
Causes of microcytic?
What tests are useful in hyperprol and hypoprol?
High TIDC=incr binding of transferrin to Fe b/c less Fe
Dx?
Tx?
SS of anemia?
-Fatigue, heavy menstrual periods, pale conjunctiva, SEM with heart rate/BP normal due to compensation of anemia
Microcytic causes:
- Fe def
- Thalassemia (Italian heritage)
Tests:
LDH, indirect bilirubin, reticulocyte count, transfusion requirement, serum haptoglobin
DX: Iron-def anemia due to vaginal bleeding
Tx: remove fibroid that causes excessive menstrual bleeding, oral iron therapy until Hb normal
What is the key in anemic pts?
History!
A heterogeneous group of disorders in which enzymes in the heme synthetic pathway are absent or defective. This permits a buildup of heme precursors which have toxic effects
Porphyrias
Cutaneous photosensitivity and neurological effects are most assoc. with what disease group?
Porphyrias
Acute Intermittent Porphyria (AIP):
- Most common in peoples of Scandinavian, British, and eastern European descent
- Increased incidence in psychiatric patients
Due to deficiency of what enzyme?

Porphobilinogen (PBG) deaminase
In AIP, resultant excretion of increased amounts of ____ and ____ in urine
ALA and PBG
- No symptoms prior to puberty
- Various severity
- Abd pain
- Occasional attacks followed by clinical improvement
- Sometimes 1 attack in a lifetime
- N/V,constipation
- Tachycardia, HTN
- Neuro changes: peripheral neuropathy, anxiety, insomnia, depression,hallucinations/paranoia (usually worse during attacks), seizures
AIP
What are some precipitating factors of AIP?
Hormones, drugs, etc
- Hormones: AIP in women over men, attacks w/ pregnancy
- Drugs: anticonvulsants (Dilantin, Tegretol, Valproic acid), barbiturates, sulfonamides, alcohol
- Low caloric intake—carbohydrate reduction can increase ALA and PBG levels and precipitate an attack
- Infection
- Surgery
How do we treat acute attacks of AIP?
- Hydration with carbohydrate solutions (D5 or D10)
- Hemin infusion—similar molecule to heme which decreases porphyrin production (negative feedback effect) and terminates an attack
- Beta blockers—for tachycardia and hypertension
- Analgesics
How do we treat chronic long-term management of AIP?
- Avoid medications known to precipitate attacks
- Avoid fasting or caloric deprivation
- Prompt treatment of intercurrent diseases or infections
What is the most common of porphyrias?
Porphyria Cutanea Tarda (PCT)
PCT is due to deficiency of what enzyme in the liver?
Uroporphyrinogen decarboxylase
TQ
What is the major clinical feature of PCT?
Which pt population does it tend to occur in?
Cutaneous photosensitivity
Alcohol consumers
T/F: We see neuro effects in PCT
FALSE
Pt presents with…dx?
Cutaneous bulla formation on sun-exposed areas of skin:
-occur after minor trauma
-skin may tighten diffusely —”pseudoscleroderma”
-Exacerbations after alcohol ingestion in some
-Occasional outbreaks after exposure to petrochemicals—dioxin, trichlorophenols
PCT
TQ What are the clinical features that are assoc with PCT? (Increased risk for?)
- May occur in end stage renal dz
- Increase risk for hepatoma
TQ: When may you have a PCT outbreak?
After alcohol ingestion!
What may you see in PCT lab work?
- Abnormal liver function tests—due to buildup of porphyrins in liver
- Increased iron buildup in liver
- Increased porphyrins in urine—ALA primarily; only slight increase
- Increased porphyrins in stool (buildup in liver)
Tx of PCT?
- Discontinue exacerbating factors—alcohol, suspicious drugs
- Phlebotomy for iron overload
- Chloroquin—may complex with excess porphyrins and facilitate excretion
TQ
- A group of disorders resulting from an inherited abnormality of globin production
- The major focus is a decreased rate of production of a specific globin molecule
Thalassemias
-Microcytic hypochromic anemia
-Hypoproliferative, pale target cells
-Decreased reticulocyte count
-Decreased levels of Hb A1 with increased levels of Hb A2
-May have increased levels of Hb F in some cases
-In homozygous cases:
chronic tissue hypoxia, disordered iron metabolism, expansion of marrow mass causing skeletal deformities
-Transfusion dependent
-Abnormal Hb electrophor.
β thalassemia
How do we manage homozygous B thalassemia?
Die of disease in mid-20s
- Transfusions are the mainstay of tx— decr. erythropoiesis & avoids disfiguring complications
- Tx for iron overload (desferrioxamine) is required in most cases
- Genetic counseling
- Bone marrow transplantation
In alpha thalassemia, 2 genes are inherited per halpotype
So, we have __alpha genes, two genes are active during fetal development, and go off- line as the other two genes become active at the time Hb A is produced
4
this leaves 4 chances to go bad
- Complete absence of α chain production (α° thalassemia) or reduced α chain production (α+ thalassemia)
- In fetal life, homozygous α° thalassemia results in γ chain tetramers resulting in what?
Hb Barts or hydrops fetalis.
TQ:
-In adult life, homozygous α° thalassemia results in β chain tetramers resulting in what disease?
Hb H disease
TQ
- These patients have a clinical course similar to β thalassemia major with lifelong anemia, skeletal changes, splenomegaly, and transfusion dependence
- What is seen on electrophoresis?
-Homozygous α° thalassemia
- Electrophoresis shows Hb A as major component, with Hb H levels varying from 5-30%;
- May be small levels of Hb Barts as well
-Patients with __________ α° thalassemia usually have a much milder disease course with a trace of Hb Barts or Hb H found on electrophoresis
heterozygous
Patients with ___________ α+ thalassemia have a thalassemic picture with 5-10% Hb Barts at birth and findings similar to _________ α° thalassemia in adult life
homozygous
heterozygous
A group of diseases in which the structure of the globin molecule is altered such that conformational changes in RBC morphology occur with deoxygenation
Sickling Syndromes
What are the 4 sickling syndromes?
Sickle cell anemia
Sickle cell trait
Hemoglobin C disease
Hemoglobin D disease
Sickling:
- Hemoglobin normally exists in two conformations—oxy (relaxed, R) and deoxy (tense, T).
- Amino acid substitutions cause conformational changes in globin morphology resulting in hemoglobin molecules that tend to aggregate when ___________–>sickled RBCs overtime
deoxygenated (T)
TQ
- Symptoms begin early in life, levels of Hb F protect newborns
- Due to homozygous state for hemoglobin S (SS)
- What is the mutation involved in this dz?
Sickle cell anemia
Valine is substituted for glutamic acid at the 6th amino acid residue on the β globin chain
Glu–>Val
Even though most sickle cell anemia patients are in reasonably good health much of the time, this may be suddenly interrupted by a crisis which is usually severe and often fatal
What is the most common form of the crisis? What is it due to? What is the result?
- Infarctive crises are the most common form of crisis
- Due to obstruction of blood flow by sickled cells
- Results in tissue hypoxia and death
What is the primary manifestation of an infarctive crisis? What are the primary organs involved?
- Pain=major manifestation
- Bone
- Lung: occasional infiltrates and fever (“acute chest syndrome”)
- Spleen: many pts asplenic after age (“autosplenectomy”)
- CNS (CVAs not unheard of in children!)
What are aplastic crisis of sickle cell anemia pts usually associated with?
-Parvovirus suppressing erythropoiesis
May also be substrate deficiency (folate during pregnancy)
What are is the major cause of death of infants and young children with sickle cell anemia?
hint: serum Hb<6gm
Sequestration crises due to massive pooling of RBCs in spleen
(Major crisis: serum Hb < 6gm or drop > 3gm from baseline)
TQ
Growth abnormalities may occur in sickle cell children where they may be shorter than peers, but catch up in late adolescence
What other abnormalities might be seen?
Bone abnormalities!
- Sickle cell dactylitis: swelling of the dorsal surfaces of the hands and feet (infants/young children)
- Medullary expansion w/ thinning of bone cortex
- Infarctive crises–>osteosclerosis
TQ
For sickle cell anemia pts, there is an increased rate of what infections in necrotic bone marrow?
Salmonella
What lab results may we see in sickle cell anemia pts?
- Anemia: Hb 5-11gm/dl; normocytic normochromic
- Signs of hemolysis: incr. serum bilirubin &retic. count, nucleated RBCs on smear
- Sickled RBCs on PS
- Pos. sickle cell test: suspend RBCs in oxygen poor environment and observe for sickling
- BEST: Hb electrophoresis-Hb S comprises >50% of Hb in the RBC
What situations should a person with sickle cell anemia avoid?
-changes in oxygenation (if going in for surgery, give transfusion 1 wk prrior to decr. sickled cells); airplanes!!
How should you treat a sickle cell pt with an infection?
- Aggressive antibiotics
- Pneumococcal vaccine (during infancy b/c need spleen)
- Prophylactic penicillin
How do we handle painful infarctive crises of sickle cell pts? Splenic sequestration crises?
- Hospitalization, hydration, and analgesics (try nonnarcotics first) to alleviate pain
- Splenic sequestration should be managed by transfusion
What are some experimental sickle cell anemia treatments?
- Antisickling agents such as Hydroxyurea but is myelosuppressive & pt compliance required
- Bone marrow transplantation
- Hypertransfusion—transfuse to keep Hb S levels <50% to reduce sickling (Fe overload risk)
Sickle cell trait:
- Represents carrier state for sickle cell anemia
- <50% of Hb in RBC is Hb S
- No clinical abnormalities
- Patients should still avoid high altitude
Tx?
NONE! no therapy needed! normal lifepan
In Hb C disease, ______ replaces_____ ____ at position 6 on the β globin chain
Hb C produces fragile RBCs in patients ________ for the trait
> 50% of the Hb in RBCs is Hb C
lysine–> glutamic acid
homozygous
Pt presents with…dx?
- Splenomegaly
- Fleeting abdominal pain on occasion
- Anemia
- Target cells on PS, a few sickled cells may be present
Tx?
Hemoglobin C Disease so no tx needed
Just beware of worsening anemia with infection!
Grade of anaphylaxis?
-Generalize erythema, urticaria,
periorbital edema, angioedema
Mild (Cutaneous only)
Grade of anaphylaxis?
-Dyspnea, Stridor, Wheeze, Nausea, Vomiting, dizziness, diaphoresis, chest or throat tightness, abd pain
Moderate ( Respiratory, CV
or GI involvement)
Grade of anaphylaxis?
-Cyanosis, Sat <90) confusion, collapse, LOC,incontinence
Severe (Hypoxia,
hypotension or neuro
compromise)
What are some indications for IM administration of epinephrine in a cutaneous anaphylaxis rxn?
hint:
Goals include
-Maintain Airway patency
-Reduce Fluid extravasations
- Bronchospasm
- Laryngeal edema
- Hypotension
- Urticaria
- angioedema
What are some indications for I.V. H1 and H2 inhibitors (Diphenhydramine, 25‐50mg and Ranatidine 50mg) in a cutaneous anaphylaxis rxn?
hint: Goals include -Reduce pruritis -Antagonize histamine -Assist in pressure support
- Urticaria
- Hypotension
Which drug reduces late phase rxn in bronchospasm of cutaneous anaphylaxis rxn?
Methylprednisolone
In cardiovascular anaphylaxis rxns, what are some treatments? When is IV fluid indicated?
- Epinephrine/Norepi
- IV ranitidine
IV fluids indicated for hypotension
How long must you observe a pt post anaphylaxis rxn? Why?
-Should be observed for at least 4 hours (90% reactions occur during this time period)
-20%‐28% of cases have recurrence several hours
after treatment
-Can occur after symptoms completely resolved
Fatal anaphylactic events often result from _____ _____ as the primary cause of death
cardiac arrest
(peripheral pooling of
circulating volume or enters the interstitial space. Therefore, Heart has no blood to pump…Empty heart syndrome, Hypotension)
T/F: Blockage ofβ‐receptors decreases effectiveness of
epinephrine
TRUE!
also avoid ACEi
What type of reaction is anaphylaxis?
Type 1 hypersensitivity
4 manifestations of anaphylaxis?
- Mucocutaneous
- Cardiovascular
- Respiratory
- Gastrointestinal
Most common cause of anaphylaxis?
foods! (peanuts, tree nuts, shellfish, gelatin, fish, eggs, milk, soy, wheat, etc)
What is the primary mediator of anaphylatic shock?
histamine! – H1 • Pruritis • Rhinorrhea • Tachycardia • Bronchospasm – H1 & H2 • Headache • Flushing • Hypotension
Richet and Portier in 1902 defined a “super sensitivity” reaction while attempting to
produce tolerance to sea anemone venom in
dogs
-Dogs who completely recovered from initial dose of the toxic venom died a few minutes
after given a second, very small dose
-What is this called?
anaphylaxis
Pt presents with…dx?
- Rash is spreading
- Itches
- Ate peanut butter cupcake after getting kindergarten shots
- Rash is red, raised, itches (erythematous & urticarial)
Dx? Differentials?
Tx?
Peanut allergy
Differentials:
- Immunization shots
- Contact dermatitis
- Vericella
- Latex
- Infx (fever?)
Tx: Histamine antag (diphenhydramine)
WATCH for 4 hours (late phase rxn risk)
Common causes of anaphylatic rashes? Just name a few…
Peanuts (foods) Latex Exercise Insect sting (Hymenoptera) Shots (eggs) Meds Shellfish Cinnamon Plants Detergent
Kindergarten shots?
Polio Diphtheria Pertusus Tetanus Hep B Varicella Measles, Mumps, Rubella
The mucosa is sky blue in the back of throat/nose is due to..
mast cells
74 yo obese male admitted to ER w/ hypertensive crisis. Complains of pressure in chest and can’t breathe. Pt also cannot talk and has swollen lips and tongue
- Meds: B-blocker, alpha-blocker, simvastatin (sulfa), lisinopril to help with HTN
- HR, BP, RR, Pulse ox low
- Cant see veins, cant hear breath sounds, abd distended, pitting edema, cool to touch
1st priority? Secure airway via intubation
What caused his tongue to swell?
Tx:
-Epi, albuterol, diphenydramine, ranitidine, IV fluids, norepinephrine, glucagon
Epi (to incr HR but on B-blocker…give glucagon)
ACEi–>bradykinin angioedema!!!!
Hypersegmented neutrophils. Think:
Megaloblastic anemia
Acanthocytes on peripheral smear can be attributed to:
Chronic kidney dz
3 RBC morphologies in megaloblastic anemia:
- Macro-ovalocytes
- Cabot rings – remnants of the mitotic spindle apparatus
- Howell-Jolly bodies – nuclear remnants
Pernicious anemia (Abs specifically directed at intrinsic factor in the stomach) impairs absorption of nutrients, such as vitamin B12, leading to what type of anemia?
Megaloblastic macrocytic
Clinical presentation:
- Fatigue, lethargy, and exercise intolerance
- Some pts will note unusual craving for ice chips, carrots, or other foods having a crunchy consistency when eaten
- Pts may also crave dirt (pica)
Iron deficiency anemia
What are some lab features in iron deficiency anemia?
- Microcytic hypochromic anemia
- Decreased serum iron
- Decreased serum ferritin
- Increased TIBC (transferrin is relatively unsaturated and available for iron binding)
What are 4 pieces of evidence that hemolysis is occurring?
- Decreased haptoglobin
- Increased LDH and bilirubin
- Urine hemosiderin elevated in some
- Plasma Hb elevated if hemolysis severe
- Common in individuals of Northern European descent
- Inherited defect in RBC cytoskeleton-membrane tethering proteins
- Normocytic anemia with predominant extravascular hemolysis
- Extravascular hemolysis leads to splenomegaly, jaundice, and increase risk of bilirubin gallstones
- Increased for aplastic crisis w/ parvovirus B19 infection of erythroid precursors
Hereditary spherocytosis
What is the test called to diagnose hereditary spherocytosis?
Osmotic fragility test
How do you treat hereditary spherocytosis?
Splenectomy
Blood smear shows:
-Normocytic, hypochromic, with prominent basophilic stippling in young polychromatophilic cells.
Lead intoxication
- MC cause of hemolytic anemia in the world
- Transmitted by the bite of an infected female Anopheles mosquito
- Hemolysis results from erythrocytic infestation by Plasmodium organisms
Malaria
- Protozoan infection through transmission by the bite of a tick
- Infection leads to clinical syndrome of fever, lethargy, malaise, hemoglobinuria 1-4 weeks after the bite
- Intravascular hemolysis occurs
- Protozoa appears inside RBCs as “Maltese cross”
Babesiosis
How do you treat babesiosis?
Atovaquone + Azithromycin
or clindamycin + quinine, but Hubbard doesn’t like quinine
- An acquired clonal hematopoietic stem cell disorder cause by a somatic mutation of the PIG-A gene that results in a lack of GPI anchor proteins (CD55 and CD59) ***
- Complement-mediated lysis of RBCs
- Patients may experience chronic hemolytic anemia, cytopenias, and/or thrombotic tendency
- Occurs in both children and adults
Paroxysmal nocturnal hemoglobinuria (PNH)
What is the treatment for autoimmune hemolytic anemia?
Prednisone
Bite cells are a clinical feature of what?
Enzyme deficiency (both G6PD and PK)
