Heme Synthesis - Enzyme Deficiencies
A chronic disease of the liver characterized by red to brown urine and painful, blistering skin lesions
What enzymes is associated?
porphyria cutanea tarda (PCT)
Lead interferes with what 2 heme synthesis enzymes?
ALA dehydratase
ferrochelatase
Genetic mutation of sickle cell
point mutation in B-globin
(GAG to GTG; Glu to Val)
The following is representative of what type of jaundice?
increased urine bilirubin
urine color – normal
stool color - normal
pre-hepatic (hemolytic)
Match the Following Types of vWF:
Type 1 decreased vWF-dependent platelet adhesion
Type 2A increased vWF affinity for Gp1b
Type 2B total or near total quantitative deficiency
Type 2M decreased vWF-dependent platelet adhesion
Type 2N partial quantitative deficiency
Type 3 decreased vWF affinity for Factor VIII
Type 1 - partial quantitative deficiency
Type 2A - decreased vWF-dependent platelet adhesion (selective)
Type 2B - increased vWF affinity for Gp1b
Type 2M - decreased vWF-dependent platelet adhesion
Type 2N - decreased vWF affinity for Factor VIII
Type 3 - total or near total quantitative deficiency
PCT can be influenced by what 6 factors?
Timeline of clinical onset?
hepatic iron overload, sunlight exposure, alcohol ingestion, estrogen therapy, Hep B/C, HIV
4th or 5th decade of life
What type of porphyria is associated with RBCs?
How does it present?
erythropoietic protoporphyria
typically presents in early childhood and most commonly involves a hypersensitivity to sunlight and some types of artificial light
Do heterozygotes for sickle cell typically show clinical symptoms?
no
The following is representative of what type of jaundice?
•increased urine bilirubin
•urine color – dark/normal
•stool color - normal
neonatal (transient, physiologic)
What disease is characterized by an elongated bleeding time related to platelets failing to aggregate via fibrinogen bridges?
Inheritance?
How would this affect platelet count?
BONUS: treatment/recommendations
Glanzmann thrombasthenia secondary to GpIIb/IIIa receptor
autosomal recessive
None; normal platelet count
BONUS: avoid NSAIDs, platelet transfusions
A rare genetic metabolic disease characterized by the accumulation of ALA within the RBCs and hepatocytes
--> ALA leaks into plasma and causes toxicity
d-ALA Dehydratase porphyria
How does lead poisoning present? (think labs)
anemia, elevated levels of zinc protoporphyrin
Thalassemia involves which genes?
HBA1 and HBA2
What type of jaundice is associated with the following:
No UDGPT expression. No conjugation. UB above 30 mg/dl. ↑ urinary bilirubin
Crigler-Najjar Type 1
What disorder is characterized by GI symptoms, bleeding, purpura, and anemia?
How would you test for this?
Thrombotic Thrombocytopenic Purpura (TTP) secondary to decreased ADAMTS13 activity
ADAMTS13 activity test or inhibitor assessment
A disease characterized by acute abdominal pain, chest/back pain, constipation or diarrhea, N/V, "port wine urine," polyneuropathy, psychological and neurological disturbances
What enzyme is involved?
BONUS: possible causes
acute intermittent porphyria
uroporphyrinogen I synthase (porphobilinogen deaminase)
genetics or drugs (ex: barbituates, antiepileptics, rifampin, metoclopramide)
What makes lead so toxic to the body?
ability to cross the BBB --> neurotoxic
What type of jaundice is associated with the following:
UDGPT reduced expression. UB below 20 mg/dl, ↑ urinary bilirubin
Crigler-Najjar type 2
What disorder is characterized by high levels of D-Dimer following exposure to procoagulant factor (bacteria, cancer, etc)?
MOA?
Disseminated Intravascular Coagulation (DIC)
systemic coagulation and microthrombi --> widespread fibrinolysis --> consumption of coagulation factors
What disease is characterized by acute attacks beginning in adulthood and presenting similarly to acute intermittent porphyria (+seizures, muscle weakness, etc)?
Associated enzyme?
variegate porphyria
protoporphyrinogen oxidase
Developmental delays, learning disabilities, low IQ, abd pain, constipation, neurologic changes, and irritability can be signs of what pathology?
lead poisoning
Disorder characterized by a reduced platelet lifespan secondary to antibody-mediated destruction in liver and/or spleen?
Presentation?
Primary Immune Thrombocytopenia
genetic or acquired and some may be asymptomatic
*ex: HIV, Hep C, lymphoid malignancies