Lecture 47 + 48 + DLA Flashcards
what gene encodes for AAT?
alpha 1 anti-trypsin
SERPINA1 gene
serine protease inhibitor
what is the target for AAT?
elastase
what is the role of AAT?
protect lung tissue from the elastase released from neutrophils during infection
also protects from non-specific damage
different alleles of the AAT gene?
PiMM
PiMZ
PiSZ
PiZZ
M = functional Z = most common deficiency S = deficiency, but not as bad as Z
COPD and ATTD
autosomal recessive disorder
caused by a loss of function
what is common in those with the PiZZ deficiency?
liver disease
protein product will accumulate in the cell and will not be secreted
forms aggregates
‘attainment of new function’
how to treat AATD?
IV administration of A1AT protein
what are the four regulators of the effective circulating volume (ECV)?
RAAS
sympathetic NS
starling forces
ANP (atrial natriuretic peptide)
all these increase total body sodium
movement of the proteins in serum protein electrophoresis?
albumin moves the furthest (most negative) Alpha-1 Alpha -2 Beta Gamma moves the least (most +)
what are the proteins in the Alpha-1 globulin bands?
Alpha 1 antitrypsin
alpha fetoprotein
transcortin
Retinal binding protein
What are the proteins in the alpha-2 globulin bands?
Alpha2 macroglobulin
Ceruloplasmin
haptoglobin
what are the proteins in the beta band?
transferrin
hemopexin
LDL
what are the proteins in the gamma band
immunoglobins
IgG, IgM, IgA, IgD, and IgE
functions of albumin?
maintenance of osmotic pressure
transport Ca and whatnot
general function of alpha and beta globulins
enzymes, transport, and inhibitor proteins
general functions of immunoglobins
immune function
Congenital analbuminemia?
appear normal and do not get edema
other proteins regulate osmotic pressure early on
what happens during decreased synthesis of albumin?
Kwashiorkor - deficiency of protein, thus less albumin
liver cirrhosis - liver damage impairs protein synthesis
increased loss of albumin??
Kidney disease - loss in urine due to basement membrane damage in the glomerulus
severe burns - loss of serum
Alpha 1 antitrypsin deficiency (alpha-1)
alpha 1 antitrypsin is a protein released by the liver to inhibit neutrophil elastase in the lung alveoli
this deficiency leads to degradation of elastin in the lung tissue, thus emphysema
hereditary?
due to a defective N-glycosylation, thus reduced release from the liver
can lead to pulmonary and liver disease
alpha Fetoprotein (alpha-1)
is found in a large amount during fetal life
low levels of albumin
fetoprotein levels are low in adults, normally, but can increase if one has liver cancer
during pregnancy AFP levels can mean what??
high level of maternal AFP can lead to a neural tube defect
lows levels of maternal AFP can point at down syndrome
Transcortin (alpha-1)
transports cortisol in the blood
RBP (retinal binding protein) (alpha-1)
transports retinal in the blood from the liver to the tissues
Alpha-2 macroglobulin (alpha2)
function?
clinical?
inhibits many kinds of proteases
found in high amounts in those with Nephrotic syndrome due to damage the BM of the glomerulus
Ceruloplasmin (alpha2)
function?
used for copper transport in the blood
also ferroxidase activity = prevents radical damage done by ferrous ion by forming ferric iron that can bind to transferrin for transport
Wilsons disease?
have very low levels of ceruloplasmin as hepatic copper binding is decreased
thus, the liver releases aceruloplasmin, without copper, and is degraded in the blood
have a copper transporting ATPase deficiency
damage due to copper accumulation occurs
hepatic dysfunction, neurological and psychiatric symptoms
Kayser-Fleischer rings can be seen!
Heptoglobin (alpha2)
function?
binds to free hemoglobin dimers in the blood and prevents loss of Hb in the urine
heptoglobin-hemoglobin complex is taken up by macrophages; this explains why acute hemolysis leads to low levels of free heptoglobin
Transferrin (beta) function and clinical?
transports ferric iron in the blood
transferrin can bind two atoms for transport
clinical:
low saturation = seen in those with iron deficiency
high saturation = iron overload
Hemopexin (beta) function and prevention?
binds to free heme in the blood and prevents the loss of heme-iron
heme-hemopexin can be taken up into heptacytes and the iron is bound to ferritin (storage protein)
prevents:
heme-induced damage to PM
heme usage of microbes
LDL (beta)
only have B-100
+ charge
The immunoglobins? (gamma)
functions?
IgM = first antibody to be produced
IgG = produced by multiple exposures to same antigen; passive immunity to fetus
IgE = allergic reaction
IgA = main antibody found in human milk
IgD = role is not known
multiple myeloma?
A tumor of the plasma cells and an example of monoclonal gammopathy
on the chart the gamma protein wave spikes!
Hepatic acute phase?
+ and - reactions?
overall positive response that prevents damage
positive: expressed in higher amounts since they reduce inflammation and deprive microbes
- alpha-1 antitrypsin
- ceruloplasmin
- heptoglobin
- hemopexin
negative: reduced expression
1. albumin
2. transcortin
3. RBP
4. transferrin
C-reactive protein
synthesized and released during inflammation
acute inflammation (Densitometry)
smaller albumin peak
higher alpha 1 and 2 peak
Liver cirrhosis (densitometry)
smaller albumin peak
beta2-gamma bridge (both increase)
alpha2 peak is smaller
multiple myeloma (densitometry)
high spike in gamma
Nephrotic syndrome? (densitometry)
very low albumin
Very high alpha 2
hypogamma globulinemia (densitometry)
no gamma peak
Alpha 1 antitrypsin deficiency (densitometry)
very low alpha1 peak
prolonged inflammation (densitometry)
Wide gamma peak
Osmoregulation?
retainment or excretion of water
can be dilute or concentrated
depends on ADH
ADH effect on V1 and V2
ADH effect on osmolarity?
V1 = vasoconstriction V2= water retention
the higher the ADH concentration, the higher the plasma osmolarity
High ADH/ high osmolarity = thirst
what happens during low protein states in the nephron?
limited ability to concentrate the urine
low urea / age below 1
how can the urine concentrate to 1200 mOsm
By urea!
vasa recta movement?
descending = salt in and water out
ascending = water in and salt out
matches descending LOH to prevent backtracking
collecting duct during low and high ADH
Low:
collecting duct is impermeable to water
no urea reabsorption
slightly hyperosmotic
high: dehydrated
permeable to water by AQP-2
urea reabsorption
highly hyperosmotic
Diabetes insipidus?
types?
This is due to a ADH deficiency
nephrogenic DI:
V2 receptor mutation; AQP-2 mutation
acquired by lithium therapy
central DI:
congenital lack of ADH
acquired by head trauma
How to test for the type of DI?
No water to drink for 4 to 6 hours.
central and nephrogenic will have no increase in urine osmolarity
give ADH
central DI: large increase in osmolarity
nephrogenic: still no change
clearance equation?
clearance = rate of excretion / plasma excretion
osmolar clearance equation?
Cosm = urine osmolarity x flow rate / plasma osmolarity
free water clearance equation
water clearance = V - (Uosm x V / Posm)
water clearance = V - Cosm
0 = iso-osmotic \+ = hypo-osmotic - = hyper-osmotic
