Lecture 2: Clinical Relevance of Cell Membranes and Transport Flashcards
What is Niemann-Pick Disease?
- causes deficiency in Acid-Sphingomyelinase (A-SMase) which normally breaks down sphingomyelin
- defective enzyme = SM accumulation in: liver, spleen, CNS, and bone marrow LYSOSOMES
What are the symptoms of Niemann-Pick Disease?
- enlarged liver and spleen (hepatomegaly and splenomegaly)
- neurological damage, “cherry red spot” in the eye
How does A-SMase cute sphingomyelin?
cuts the phosphate-choline off from the sphingosine backbone
- creates: ceramide and phosphoryl-choline
Why is phosphatidyl serine (PS) a marker for apoptosis?
- normally found in INNER LEAFLET of bilayer
- apoptosis occurs when PS is found on OUTER LEAFLET (phagocytes recognize and remove)
What is the role of Annexin V and FITC in PS apoptosis?
- Annexin V binds to PS on apoptotic cell (in OUTER leaflet)
- FITC acts as fluorescent marker of Annexin V
What blood types are distinguished as the Universal Donor and the Universal Acceptor, and why?
Universal Donor = TYPE O
- RBC’s have NO blood group antigens
- can only receive from Type O (A/B antibodies)
Universal Acceptor = Type AB
- plasma has NO A/B antibodies
What is the Rh incompatibility between newborns and their mothers? (Erythroblastosis fetalis)
- refers to D antigen (Rh+) –> autosomal dominant
Erythroblastosis Fetalis - incompatibility between mother (Rh-) and fetus (Rh+) blood
- mother produces antibodies that attack fetus by crossing placenta
What is the importance of cholesterol in membranes?
- INCREASES fluidity in RIGID membranes
- prevents close packing of saturated fatty acids)
- DECREASES fluidity in FLUID membranes
- fit in gap between kink of unsaturated fatty acid tails)
What is Spur Cell Anemia?
- type of hemolytic anemia, elevated cholesterol levels bound to RBC membranes
- excess cholesterol from impaired liver cholesterol metabolism (Chronic Liver Dysfunction)
- spiky RBC’s called ACANTHOCYTES
What are the symptoms of Spur Cell Anemia?
- impaired RBC deformability = lyse as they pass through capillaries of spleen
- prognosis poor, median survival = months
- Liver Transplant = only potential curative option
What is Cystinuria and what are the symptoms associated with it?
- autosomal recessive disorder
- cause: defect in transporter (uptake) of Cysteine (and other dibasic AA’s –> Arginine, Lysine, Ornithine)
- results in: cystine crystals in kidney
- patients present with Renal Cholic (kidney stone-linked waves of abdominal pain)
What is Hartnup Disease and what are the symptoms associated with it?
- autosomal recessive disorder
- cause: defect in non-polar/neutral AA transporter (alanine, valine, threonine, leucine, TRYPTOPHAN)
- results in: intermittent cerbellar ataxia (no muscle coordination), nystagmus, photodermatitis, photosensitivity
What are Cardiotonic Drugs and what do they act on?
- contraction-inducing drugs (ouabain and DIGOXIN) –> CARDIAC GLYCOSIDES
- inhibit Na/K-ATPase pump (cardiac myocytes) = INC. intracellular Na
- impairs Sodium Calcium Exchanger (NCX) –> 2nd transport coupled it Na/K-ATPase pump
- NCX impairment = Ca INC in sarco-endoplasmic reticulum
What is the effect of cardiotonic drugs?
- increased sarcoplasmic Ca = INC cardiac contractile force
- used for: Congestive Heart Failure, atrial fibrillation, dysrhythmias
- cardiac glycosides EXTREMELY POTENT (become toxic over long periods of use)
What is Digitoxigenin?
- cardiotonic drug
- slowly reduces neuron resting potential to 0
- side effects: disturbed vision, confusion, delirium
