Mb Diseases & Clinical Relevances

Front 1

Lecithin is a ____

Back 1

phosphatidylcholine

Front 2

Lecithin:sphingomyelin ratio used to assess what?

Back 2

Fetal lung development. Ratio greater than 2 = mature lungs

Front 3

Plasmalogens have this type of phospholipid

Back 3

Phosphatidylethanolamine

Front 4

Rhizomelic chondrodysplasia punctata

Back 4

-Mutations that prevent peroxisomes from making plasmalogens

- Rhizomelia = shortening of bones

- Skeletal defects, distinct facial features, intellectual disability

Front 5

How to detect apoptosis by looking at phospholipids in plasma membrane?

Back 5

If phosphatidylserine flips to outer leaflet of membrane, this indicates cell dying of apoptosis

Front 6

Shingolipidoses

Back 6

Caused by deficiencies in lysosomal enzymes; can't degrade sphingolipids --> lysosomal storage diseases

- Affects CNS

Front 7

Cystic fibrosis is caused by a mutation in _____ which is a _____ membrane protein.

Back 7

Mutation in CFTR which is an integral membrane protein (chloride channel)

Front 8

Specific mutation in CFTR leading to CF

Back 8

Loss of Phe508

Front 9

Spherocytosis

Back 9

-Mutations in RBC membrane proteins --> rigid, misshapen cells --> hemolytic anemia and splenomegaly

Front 10

Spherocytosis is common in people of what ancestry? What is the approx. incidence?

Back 10

1 in 2,000 individuals of Northern European ancestry

Front 11

____________ are phospholipids involved in the synthesis of GPI anchors

Back 11

Phosphatidylinositols

Front 12

Mutations in GPI anchors can result in these two diseases.

Back 12

Mabry Syndrome and Paroxysmal nocturnal hemoglobinuria

Front 13

Mabry syndrome is caused by an accumulation of this substance in the blood.

Back 13

Alkaline phosphatase-- cannot bind to cell due to mutation in its GPI anchor --> hyperphosphatasia

Front 14

Paroxysmal nocturnal hemoglobinuria is caused by mutations in GPI anchors of these proteins, and is characterized by ________________ caused by RBC breakdown

Back 14

Mutations in GPI anchors of the complement-regulating surface proteins. Without these anchors, the complement cascade destroys RBCs unchecked.

RBC breakdown --> hemoglobin released into urine.

Front 15

This integral membrane protein transports glucose in/out of cell. Deficiencies in this protein can lead to what?

Back 15

GLUT-1 is an integral membrane protein. Glut-1 deficiency --> decreased glucose concentration in CSF --> seizures and mental retardation

Front 16

Osmotic diuresis causes intracellular dehydration how?

Back 16

In the blood, increased [glucose] and ketone bodies travel to glomerular filtrate --> urine

Increased osmolarity of glomerular filtrate --> increased water output in urine

The loss of water leads to transfer of water from ICF to ECF --> intracellular dehydration

Front 17

What is edema and how is it caused?

Back 17

Edema is the excessive accumulation of fluid in interstitial space. It is caused by an increase in the flow of fluids from blood to tissues, and a decrease in their return.

Front 18

3 causes of hypoproteinemia

Back 18

1. liver disease - failure to synthesize plasma prots like albumin

2. kidney disease/glomerulonephritis - protein loss in urine

3. starvation - not enough amino acids ingested to synthesize proteins

Front 19

Diabetic ketoacidosis

Back 19

When intake of insulin is inadequate, body goes into fasting state despite food intake.

Liver metabolizes fatty acids into ketone bodies which are weak acids.

Ketone bodies dissociate, producing H+ protons thereby lowering the blood and cellular pH.

Front 20

Cystinuria

Back 20

An amino acid absorption disease.

Kidney cannot resorb/intestine cannot absorb cystine from urine --> cystine stones in urogenital tract

Treatment with alkaline pH

Front 21

Creatine kinase / creatine phosphokinase levels are used to detect what?

Back 21

Myocardial infarctions

When MB > 5%, patient has had an MI.

Peaks 12-24 hours after MI.

Front 22

What is the specific point mutation of sickle cell disease/HbS?

Back 22

Glu6 --> Val6

Goes from a negative charge to neutral charge.

Front 23

HbS mutation leads to what?

Back 23

HbS polymerizes in RBCs, producing the sickle shape. The inflexible RBCs block capillaries --> anoxia and pain crises.

Sickle cells are destroyed by splenic macrophages --> hemolytic anemia

Front 24

What is the lifespan of HbS sickle cell RBCs?

Back 24

20 days (compared to 120 days for normal RBC)

Front 25

Symptoms of HbS/ sickle cell disease

Back 25

- Elevated bilirubin (which is a degradation product of heme)

- increase in reticulocytes

- organ dysfunction

- dactylitis (hand/feet sweeling)

- splenomegaly

- increased infections due to dysfunctional spleen

Front 26

Recombinant insulin involves changing the protein's ____ structure. Specific changes?

Back 26

Primary structure is changed. Pro28 and Lys29 are exchanged --> less dimer formation, greater absorption and faster action

Front 27

ABO blood type is determined by _____ proteins on RBC surface

Back 27

Glycosylated

Front 28

Glycated Hemoglobin

Back 28

Hb is glycated by glucose (no enzyme required). The concentration of glycated Hb is directly proportional to [blood glucose], so Hba1c can assess patient's compliance with insulin

Front 29

Glucose-6-P deficiency results in this type of damage within cells

Back 29

Oxidative damage due to oxygen free radicals.

Proteins are denatured and precipitate in cells --> Heinz Bodies

Front 30

Precipitation of heinz bodies due to G6P deficiency in cells leads to this.

Back 30

Acute hemolytic anemia

Front 31

Alpha 1 antitrypsin is a ______ inhibitor and is mainly produced in the _____

Back 31

Protease inhibitor mainly produced in liver and secreted into circulation

Front 32

Mutation of a1-antitrypsin (a1-antitrypsin deficiency) leads to?

Back 32

- Aggregation of mutant protein in ER

- decreased secretion of a1-antitrypsin

- liver dysfunction in children and cirrhosis in adults

Front 33

Amyloidosis

Back 33

- Precipitation of various misfolded proteins in different tissues/organs

- Protein precipitation causes organ failure

- Precip. prots. have similar B-sheet rich structures

Front 34

AL Amyloidosis

Back 34

- precipitation of antibody light chain fragments (bence jones proteins)

- frequent in multiple myeloma

Front 35

Bence-Jones proteins are a hallmark of what disease? What are they?

Back 35

They are precipitates of antibody light chain fragments; AL Amyloidosis

Front 36

Alzheimer disease

Back 36

- Precipitation of B-amyloid protein causes brain degeneration

Front 37

Multiple myeloma frequently includes ____

Back 37

AL amyloidosis; Bence-jones proteins

Front 38

Prion diseases

Back 38

Abnormal denaturation of prion protein in brain

Acquired = mad cow disease

Genetic = Creutzfeldt-Jacob disease (mutation)

Front 39

Chain reaction of abnormal prion protein in prion disease

Back 39

PrP(sc) + PrP(c) --> 2 PrP(sc)

--misfolded proteins precipitate in brain and lead to death

Front 40

Mechanism of cholera

Back 40

Cholera toxin transfers ADP-ribose to stimulatory G-alpha-s subunit

GTP cannot be hydrolyzed back to GDP

Adenylyl Cyclase- constantly active --> increased cAMP

extreme efflux of salt and water from gut epithelial cells to lumen --> diarrhea