Clinical Relevance Of Cell Membranes & Transport

Question 1

Niemann-Pick Disease

Answer 1

• Deficiency in the enzyme Acid-Sphingomyelinase (A-SMase), which breaks down sphingomyelin (SM) into 1) ceramics and 2) phosphorylcholine (KNOW THESE TWO)
• Autosomal recessive trait
• Leads to build up of sphingomyelin in the lysosomes of the liver, spleen, CNS and bone marrow, causing:
  1) Enlargement of liver (Hepatomegaly)
  2) Enlargement of the spleen (Hepatomegaly)
  3) Neurological Damage

Calling card -> “Cherry Red Spot” in eye, by the macula
Prognosis: Death by 18 months

Question 2

What are the two products that form from the breakdown of A-SMase?

Answer 2

1) Ceramide
2) Phosphorylcholine

*Backbone is Sphingosine

Question 3

Explain how Phosphatidylserine is a marker for apoptosis

Answer 3

-In healthy cells, PS is located in the inner leaflet of the bilayer
-PS is moved to the outer layer during apoptosis
-This makes it a tag/label for phagocytes, who will attack and kill cell
Ex. Occurs in RBC replacement when need to get rid of old, create new

Question 4

Explain how to determine difference between Apoptosis and Necrosis

Answer 4

Phosphatidylserine does not move from inner leaflet to outer leaflet until very late in necrotic process. Since the cell membrane deteriotes in necrotic cells, a fluorescent molecule, once it enters the cell, will fluoresce once it binds to DNA, indicating necrosis due t breakdown of cell walls and influx of extra cellular environment.

Question 5

What is the ABO blood system based on (I.e. what give blood its “types”)?

Answer 5

Carbohydrate antigens attached to:

1) Proteins (glycoproteins)
2) Lipids (Glycolipids)

Question 6

What happens during incompatible blood transfusion?

Answer 6

If plasma has blood with antigen of more than one ABO blood group or Rh antigen, there could be:

1) Acute hemolysis (fast destruction of donor RBCs)
2) Renal failure
3) Shock

Question 7

Explain Rh Factor and its relevance to Hemolytic Disease of the Newborn

Answer 7

1) Rh factors are antigens on RBCs
2) Term Rh applies to D-Antigen
- Autosomal dominant
- People who are Rh+ have the D-antigen
3) If mother and fetus are incompatible (I.e mom is Rh- and fetus is Rh+) the mom’s antibodies created during pregnancy will attack fetus, which is called Erythroblastosis fetalis

Question 8

Explain spur cell anemia

Answer 8

1) Hemolytic anemia that results in elevated levels of cholesterol in RBC Membranes
2) Membranes become rigid with “spur-like” projections
3) Results in losing of RBCs as they pass through capillaries - reduced RBC survival
4) Prognosis is death after a few months
5) Common in people with alcoholic cirrhosis

Question 9

Describe Cystinuria

Answer 9

1) Austosomal recessive disorder
2) Defect with the COAL transporter (AA: cystine, ornithine, arginine and lysine
3) Leads to build up of cystine in the kidney (cystine crystals)
4) Prognosis: Renal chalice (abdominal pain that comes and goes, similar to kidney stone)

Question 10

Describe Hartnup Disease

Answer 10

1) Autosomal recessive disorder
2) Results in defect of the transporter protein that moves non-polar or neutral amino acids (alanine, valine, threonine, leucine, tryptophan, etc.). (TRYPTOPHAN is the most important)
- Tryptophan is important for melatonin (sleep), serotonin (mood) and NAD+ (metabolism)
3) Build up of these AA in Kidney and Intestine
4) Prognosis: photosensitivity, cerebellum ataxia (poor muscle coordination) and photodermis

Question 11

Describe Cardiotonic Drugs

Answer 11

1) Cardiac glycosides (digoxin) act as a cardiac-inducing drug (i.e. cardiotonic
2) Drugs inhibit NA/K-ATPase, preventing the movement of Na+ into the cell.
3) Results in ineffectiveness of secondary transporter Sodium Calcium Exchanger (NCX), which pushes Ca2+ out of the cell/sarco-endoplasmic reticulum
4) Excess Ca2+ leads to contractions of heart

Therefore, increase in sarcoplasmic Ca2+ increases contraction of cardiac cells

Important! The window is very small - too much and the heart could stop since these drugs are very potent

Question 12

What is a side effect of digitoxigenin?

Answer 12

Digitoxigenin is a cardiotonic drug, causing a reduction of the resting potentials of neurons.

Too much, side effects would be confusion, disturbed vision

Question 13

Cystic Fibrosis

Answer 13

1) A defect in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) —- responsible for active transport of Cl- (it is an ion channel)
2) Leads to build up of Cl within the airway epithelial cells
3) Results:
- Very salty sweat due to Na+ compensating for Cl-
- Water rushing into cell to compensate for salinity, leading to THICK MUCUOUS
4) Thick mucus leads to bacterial infections
- Can be so bad that mucus completely obstructs airway.