BECOM Exam #4 Flashcards
Cystinuria
Poor resorption of acidic AAs, high Cys in urine, kidney stones; treated by urinary alkalinization with citrate or acetazolamide, dietary salt & Met restriction.
Cystinosis
(Pediatric)Lysosomal accumulation of cystine (oxidized cysteine); treated with cysteamine to form cysteamine-Cys for excretion. Can lead to Fanconi syndrome.
Homocysteinuria
Defects in CbS (usually). Displacement of lens (down and in)*, cognitive defects (variable), long limbs, increased thrombosis
Sideroblastic anemia
Enough iron but it isn’t incorporated due to problems with red cell maturation. -Serum Iron: High -Increased ferritin levels -High transferrin saturation
microcytic hypochromic
-nucleated RBC
low stomach acid
low Fe absorption
pregnant women Fe levels
Brain mitochondrial Fe-S proteins
Fetal brain development
Causes of microcytic
anemias
thalassemia
Fe def
chronic disease
sideroblastic anemia
Fe def anemia
often associated with chronic blood loss
- low iron and ferritin
- high TIBC
Thalassemia anemia
normal Fe serum
-high iron and ferritin
A high UIBC, TIBC, or transferrin normally indicates
iron deficiency
hemochromatosis
Too much Fe
-High serum ferritin
non essential AA
alanine, aspartate, cysteine, glutamate
Ketogenic AA
leucine and lysine
ALT and AST cofactor
B6 (plp) (pyridoxal phosphate)
Non oxidative deamination enzymes
threonine, serine, cysteine, histidine
Ammonia as neurotoxin
high NH3+, high glutamate, low glutamate, low alpha ketoglutarate, low atp
NH3+ + HCO- = Carbonyl phosphate enzyme and cofactor
CPS-1 (NAG)
Urea amine donation
first: aspartate second: glutamate
Defects of urea cycle & treatment
phenylbutyrate (glutamate + NH3+ = glutamine ->
Maple syrup urine disease
- branched chain amino acids
- defective Branched chain alpha ketoacid dehydrogenase
Maple syrup urine disease amino acids
-Leu, Ile & Val
Phenylketonuria (PKU)
Deficiency of phenylalanine hydroxylase
-PKU may be mimicked by deficiencies of enzymes that synthesize tetrahydrobiopterin (BH4), the PAH cofactor
Alkaptonuria
Mutation in homogentisic acid oxidase
-Homogentisic aciduria
Tyrosinemias
enzyme mutation in phenylalanine pathway
Folate and babies
High folate may mask peripheral indications of B12
deficiency, allow cryptic CNS effects
“Unmetabolized” folic acid may interfere with DHFR,
MTHFR
anti-folates (e.g. methotrexate) block
DHFR
-Note: Blocking DHFR inhibit purine and thymidine synthesis, slow rapid cell division. Can cause megaloblastic anemia.
Fluorodeoxy-uracil
TS (dUMP->dTMP
main source of carbon for Folate cycle
serine
B12 used by 2 mammal enzymes
MS & methyl malonyl CoA-
Succinyl CoA mutase (uses
adenosyl cobalamin)
-Deficiency -> Methyl malonic acid accumulation, weakens myelin. Methyl malonic acidemia
Transsulfuration pathway enzymes
CBS (B6), CyL (B6)
RBC glycolysis specific pathway
- NADPH -> Fe3+ -> Fe2+ (metHb)
- 1,3 BPG -> 2,3 BPG
1,3 BPG -> 2,3 BPG enzyme
bisphosphoglycerate mutase
microcytic, hypochromic
- Fe def.
- Thalassemia
- Lead poisoning
macrocytic, normochromic
- B12/Folate acid def
- erythroleukemia
Normocytic, normochromic
acute bleeding
sickle cell
metabolic defects
All carbons and nitrogen in the porphyrin ring are derived from
glycine and succinyl CoA (all nitrogens from glycine).
Heme synthesis enzymes and cofactors
ala syntheses (B6), ala dyhydratase (lead inhibits)
acute porphyria
characterized by episodic acute neurovisceral attacks
non acute porphyria
characterized by light-sensitive lesions
van den Bergh’s test
- Total bilirubin = conjugated (direct) + unconjugated (indirect)
- Total bilirubin - unconjugated bilirubin (indirect bilirubin) must be released from albumin by addition of caffeine-benzoate
If direct (i.e. conjugated) bilirubin is normal, then the problem is
an excess of unconjugated bilirubin, and the location of the problem is upstream of bilirubin excretion
If direct bilirubin is elevated,
then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction should be suspected.
Beta-lactam antibiotics (penicillins, cephalosporins, carbapenams) target which offollowing bacterial components which ultimately results in destruction of the bacterium?
prevents peptidoglycan from cross-linking properly in the last stages of bacterial cell wall synthesis
High transferrin means
low iron (deficiency)
Hepcidin
more will degrade ferroportin
will take up less Fe
Ferritin
binds Fe3+ in cell
CD4
helper T cells
CD8
cytotoxic T cells
Adaptive cell
B T NK and antibodies
lymph drainage
afferent, sub scapular sinus, cortex, paracortex, medullary sinus efferent
primary lymph
- made in bone marrow
- B cells mature in bone marrow
- thymus T cells mature
secondary
where white blood cells meet APC
Red pulp of spleen
sinuses filled with MΦ, erythrocytes, & dense network of reticular fibers (reticuloendothelial system is an old term that refers to a dense network of phagocytic cells, predominantly MΦ, in reticular connective tissues); this is where old, fragile RBCs are eliminated by splenic MΦ
White pulp
dense lymphoid tissue; lymphocytes, DCs, MΦ surrounding small branches of splenic artery
Marginal zone
dense lymphoid tissue; lymphocytes, DCs, MΦ surrounding small branches of splenic artery
Marginal zone
surrounds outer perimeter of follicles & contains marginal zone B cells, which make T-independent responses (w/o T cell help) mainly to repetitive bacterial cell wall polysaccharide antigens—these MZ B cells underlie spleen’s effectiveness at opsonizing encapsulated bacteria & fungi; abundant splenic MΦ facilitate elimination of those opsonized pathogens.
Periarteriolar lymphoid sheath (PALS)
Periarteriolar lymphoid sheath (PALS)—
Hapten
molecule that can be recognized by immunoglobulins but incapable of eliciting an immune response by itself; can be coupled to protein carriers to induce immune response
epitope and different types
the specific sequence on an antigen that binds to an antibody
-linear and discontinuous
Characteristics of Pattern Recognition Receptors (PRRs):
- Invariant.
- Germ-line encoded.
- Ever-present and expressed.
- Recognize general structures that share certain characteristics, i.e. broad patterns, not very specific.
- Protein subunits may oligomerize at varying levels & oligomerization can initiate downstream cell signaling.
mast cells
contain histamine granules used during inflammation to cause vasodilation inc vascular permeability
what cytokines does macrophages release?
IL-1 and TNF-a
Th1
macrophages (intercellular pathogen)
Th2
eosinophils (allergies and parasites)
Th17
neutrophils (extracellular pathogen)
G-CSF
neutrophils
M-CSF
macrophages
GM-CSF
dendritic cells
IL-5
eosinophils
where are macrophages and monocytes found
- tissue
- circulation
what cytokines do macrophage release
TNF-α, IL-1B, IL-12
MCHI vs MCHII
- all nucleated cells
- MCHII APC specific
left shift
inc in immature neutrophils (band cells) due to
Non-disease production fungi MAY cause disease in …. host
immunocompromised
unicellular fungi
yeast
multicellular fungi
(molds) which have long branching filaments called “hyphae”
Masses of hyphae are referred to as
mycelium
septate hyphae
crosswalls
aseptate hyphae
no crosswalls
Have cell walls primarily made of
chitin, glucan and mannan
The sterols in the cell membrane are
egosterol
in bacterial cell high glucose means
dec cAMP = low CAP
in bacterial cell high low glucose means
inc cAMP = high CAP
Conjugation
Donor cells transfer genetic information to a recipient cell
Transformation
occurs when a recipient cell takes up a fragment of donor DNA from the surrounding growth medium
Transduction
is the transfer of genetic material from a donor to a recipient cell by way of a bacteriophage
Hfr
plasmid plus some chromosomal genes transferred
F’
plasmid but cant donate
