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250 Cards in this Set

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Tounge is smooth, what do you expect to see on peripheral blood smear?
Megaloblastic anemia with hypersegmented neutrophils (b12 or folate needed for DNA turnover, papillae are smooth)
What builds up if you have a pyruvate dehydrogenase deficiency? (2)
Lactate
Alanine
What is the difference between the operator sequence and the repressor gene in an inducible operon?
Operator = Non transcribed regulator
Repressor = Transcribed regulator
Dry conjunctiva, Small gray plaques on conjunctiva, corneal necrosis

What vitamin deficiency?
Vitamin A/retinol
Recurrence rate of multigenic (non-mendelian inheritance) diseases?

Name 3 examples
5%

Hirschsprung's, Pyloric stenosis, cleft lip
Glycosylated 7-TM receptors are?
G proteins
What causes cystinuria?
Defect in transport for COLA (cystine, ornithin, lysine and arginine)
Name as many XLR disease as you can
Hemophilia A and B
G6PD
Bruton's agammaglobulinemia
Wiskot Aldrich syndrome
Fabry's disease
Ocular albinism
Lesch Nyhan
Duchenne's/Becker's muscular dystrophy
Hunter's syndrome
What are the two galactose metabolism diseases and how do they differ?
Galactokinase deficiency = just get cataracts

Galactose-1-phosphate uridyl transferase = death in infants (failure to thrive, GI, Hepatosplenomegaly, bleeding, Hypoglycemia, neuronal loss, fatty change)
Which polymerase is the only one with 3' to 5' exonuclease activity?

Which polymerase has 5' to 3' exonuclease activity for RNA?
3' to 5' exonuclease = Bacterial DNA pol 3 (leading strand proofreading)

5' to 3' exonuclease = Bacterial DNA pol 1 (lagging strand) AND Pol 3 because both have to be able to chew away the RNA primers (1 does it way more often)
Progressive neurodegeneration
Hepatosplenomegaly
Cherry red spot on macula
Foam cells

What storage disease? Enzyme? accumulation?
Neimann Pick disease
Sphingomyelinase
Sphingomyelin
Progressive neurodegeneration
Cherry red spot
Lysosomes with onion skin look

Storage disease? Enzyme? accumulation?
Tay Sachs
Hexosaminidase A
GM2 Gangliosides
Hepatosplenomegaly
Aspectic necrosis of femur
Bone crises
Crumpled tissue paper

Storage disease? Enzyme? accumulation?
Gaucher's disease
B-glucocerebrosidase
Glucocerebrosides
Renal failure
Angiokeratomas/Telangiectasias/Rash
Peripheral neuropathies in hands and feed

What storage disease? Enzyme? accumulation?
Fabry's disease
a-galactosidase A
Ceramide trihexidose
Which Storage diseases are XLR? (2)
Fabry's
Hunter's
Where does alcohol metabolsim occur? What enzymes?

What inhibits the second step?
Alcohol dehydrogenase in the SER/peroxisomes
Aldehyde dehydrogenase in the mitochondria (disulfuram/antabuse inhibits this)
Fasting hypoglycemia, increased blood lactate, hepatomegaly

What biochemical disease?
Von Gierke's
Decreased glucose 6 phosphatase, can't dephosphorylate G6Ps released from glycogen, glucose can't reach blood
WAGR syndrome?
Wilm's tumor
Aniridia (no iris)
Genital abnormalities
MR
RLS of glycogenolysis?
What two things can turn this on?
Glycogen phosphorylase breakdown of glycogen

Glucagon (liver)
Epinephrine (muscle receptors)
Glycogen storage disease that is also a lysosomal storage disease?

Defining symptom? Enzyme deficiency?
Pompei's disease
Lysosomal glucosidase deficiency (acid maltase)
Leads to CARDIOMEGALY and early death
defect in sickle cell anemia?
Glutamate for valine on the B-globin chain
What are shine dalgarno sequences?
Prokaryotic mRNA seq that binds the 30S ribosomal subunit
Gene responsible for HNPCC? What other DNA mutation can occur
Mismatch repair genes (MLH1, MLH2)

Dinucleotide (microsatellite) repeat instability
Difference between sporadic and li-fraumeni retinoblastomas?
Sporadic = later, one eye
Li Fraumeni = early, both eyes
Weakness, hypotonia and a hypoketotic hypoglycemia after fasting

What is the problem? What if there is an increase in dicarboxylic acids?

What if you see Hypoglycemia hyperketosis after fasting?
Carnitine deficiency = inability to transport LCFAs into the mitochondria that leads to toxic accumulation of them in the cytosol

Increase in dicarboxylic acids with hypoketosis and hypoglycemia = Acyl CoA dehydrogenase deficiency

Hypoglycemia hyperketosis means the FA breakdown is fine but you can't utilize glucose (Glycogen phosphorylase deficiency in McArdles or G6PD)
Shuttle for FA synthesis? Breakdown?
Synthesis = Citrate
Breakdown = Carnitine
ApoB48 and ApoB100 loss

What disease? Symptoms?
Abeta = Lose ApoB48 AND ApoB100 (acanthosis, retinopathy, night blindness, steatorrhea) enterocytes are foamy
ApoB100 lost

What disease? Symptoms?
Hypercholesterolemia (Type IIa), increased LDL levels leading to XANTHOMAS and ATHEROSCLEROSIS and corneal arcus but NO pancreatitis (as opposed to hyperchylomicronemia from losing apoC2)
ApoC2 lost

What disease? Symptoms?
Hyperchylomicronemia (type 1) = no lipoprotein lipase activation => increased circulating chylomicrons, leads to PANCREATITIS and pain after fatty meal and xanthomas, no risk of atherosclerosis (as opposed to Hypercholesterolemia due to ApoB100 lost)
What can be made into propinoyl CoA? What is the purpose of this?
Valine, Isoleucine
Methionine, Threonine
Odd chain FAs

All are made into propinoyl CoA, which is then made into methylmalonyl CoA (B7 biotin dependent) which is then made into Succinyl CoA (B12 dependent) so that it can be fed into the TCA cycle for energy
Which TCA cycle reactions are responsible for creation of the energy equivalents?
( ) = Citrate to Isocitrate
NADH = Isocitrate to AKG
NADH = AKG to Succinyl CoA
GTP = Succinyl CoA to Succinate
FADH2 = Succinate to Fumurate
( ) = Fumurate to Malate
NADH = Malate to OAA
( ) = OAA to Citrate
Difficulty in relaxation of hands and feet, disorganized sarcoplasmic masses

Disease?
Myotonic dystrophy
Color blindness inheritance?
XLR
Defect in copper transporting P-type ATPases leads to what disease? Why are they hyperpigmented?
Ehlers Danlos type IX, Lysyl oxidase requires copper

Tyrosinase also requires copper (no melanin from L-DOPA)
Black urine on exposure to light, bad arthritis. What builds up?
Alkaptonuria
Homogentisic oxidase mutation

Homogentisic acid and Tyrosine builds up (can't make it into fumurate)
What amino acid can be made directly into Acetyl CoA? Propinoyl CoA?
Leucine into Acetyl CoA

Val, Ile, Met, Threonine into propinoyl CoA into methylmalonyl CoA into succinyl CoA
16S rRNA and 23S rRNA are located where? Function?
16S rRNA is on the 30S bacterial ribosome, responsible for binding shine dalgarno sequences upstream or AUG start codons

23S rRNA is located on bacterial 50S ribosomal subunits and have PEPTIDYL TRANSFERASE activity to transfer AAs to growing peptide (23S rRNA targetd by linezolid, Peptidyl transferase targetd by chloramphenicol)
What is a kozac sequence? Disease association?
3 bases upstream of AUG mRNA start codons, mutation can lead to Thalassemia minor (with a hypochromic microcytosis)
Triad in plummer vinson syndrome?
Dysphagia (esophageal web)
Koilonychias
Glossitis
Iron deficiency anemia (microcytic hypochromic anemia)
Heterochromatin vs Euchromatin

Modification that causes this?
Methylatin/Alkylation => Heterochromatin => SILENT

Acetylation => Euchromatin => ACTIVE
Which enzyme activates the pancreatic proenzymes? How is THAT enzyme activated?
Enteropeptidase located in the duodenum activates protrypsin into trypsin which then activates all the rest of the pancreatic enzymes for protein digestion (carboxypeptidase, elastase and chymotrypsin)
Ureas nitrogens are from what two sources? What about its carbon?

What transports ammonia from the periphery to the kidney?
Ammonia and aspartate = Ns
CO2 = C

GLUTAMINE is the shuttle for ammonia from the periphery to the kidney where it is excreted
RLS for urea cycle? What activates it?
Carbamoyl phosphate synthetase 1 (makes carbamoyl phosphate out of ammonia and CO2)

N-acetylglutamate activates it
What processes of collagen synthesis occur intracellularly? Extracellularly?

Which part is scurvy targeting? Ehlers danlos? OI?
IC = Hydroxylation (vit C, scurvy), glycosylation, assembly of triple helix (OI, type 1 collagen)

EC = N/C terminal propeptide cleavage (peptidase), Cross linkage (Lysyl oxidase, copper req) => deficiency in any of these two leads to Ehlers danlos (type 3 collagen)
Which sugar is rapidly metabolized and why?
FRUCTOSE, it is phosphorylated in the liver and enters glycolysis AFTER the regulatory PFK sttep
Where is glycerol kinase located and what is its purpose?
Only in the liver, makes glycerol from TG breakdown into G3P which can be shunted into glycolysis
HbS vs regular Hb, what will be seen on protein electrophoresis?
moves LESS, loss of glutamic acid leads to less negative charge, doesn't move as much toward anode (+)
What causes methemoglobinemia? What cures it?
Nitrates (ferrous to ferric)
Methylene Blue
Enzyme responsible for making sugars into osmotically active molecules

Name the four cells that this is a problem for

Name two cells that have this enzyme but can address this problem
Aldose reductase (glucose into sorbitol, galactose into galacticol, fructose into frucitol...)

Schwann cells, Lens, Retina and kidneys (causes swelling in these cells)

Liver and seminal vesicles have SORBITOL DEHYDROGENASE to elimate it
Lead has a strong affinity for what kind of chemical groups? Big two enzymes it inhibits?
Sulfhydryl groups

Ferrocheletase and ALA dehydratase
Triad of Wernicke's encephalopathy? What makes it into Korsakoffs?

What is the pathophysiology of WHY this occurs? Diagnostic test?
Ataxia, Ophthalmoplegia, confusion

Confabulation, memory loss and personality change= Korsakoff's

B1 deficiency leads to inability to utilize glucose (dehydrogenase enzymes) in cerebral cells, increased levels of erythrocyte TRANSKETOLASE activity/levels is diagnostic
Deletion/Addition of base pairs that is NOT a multiple of 3 indicates what?
FRAMEshift mutation must have occured
Lung opacities in the superior region of the lower lobes = suscpicion for what? (name some other factors)
Aspiration pneumonia or abscess

Elderly, alcoholic, decreased muscle tone
Splenomegaly has the same pathophys as what heart condtion?
hypertensive hypertrophy

Both lead to hypertrophy of cells (NOT hyperplasia like in benign prostatic hyerplasia)
Which portions of mRNA are NOT transcribed from DNA?
3' Poly A tail
5' 7-MG cap
Describe the process of base excision repair
1) Glycosylases cleave altered base
2) Endonuclease cleaves 5' end
3) Lyase cleaves 3' end
4) DNA pol and Ligase clean up
Deletion/Addition of base pairs that is NOT a multiple of 3 indicates what?
FRAMEshift mutation must have occured
Lung opacities in the superior region of the lower lobes = suscpicion for what? (name some other factors)
Aspiration pneumonia or abscess

Elderly, alcoholic, decreased muscle tone
Splenomegaly has the same pathophys as what heart condtion?
hypertensive hypertrophy

Both lead to hypertrophy of cells (NOT hyperplasia like in benign prostatic hyerplasia)
Which portions of mRNA are NOT transcribed from DNA?
3' Poly A tail
5' 7-MG cap
Describe the process of base excision repair

What could cause defects that this process would be required for?
1) Glycosylases cleave altered base
2) Endonuclease cleaves 5' end
3) Lyase cleaves 3' end
4) DNA pol and Ligase clean up

SINGLE base defects (like NITRATES that cause deamination of bases)
CF mutation?

Most abundant AA in collagen?
Phe deletion

Glycine
An apparently healthy person excreting fructose or galactose in urine. What is the problem? What if they were real sick
healthy = Fructokinase or Galactokinase

not healthy = Aldolase B or Galactose uridyl transferase)
What is the overarching purpose of the HMP shunt?
provide source of NADPH for anabolic reductive reactions like glutathione reductase, FA and cholesterol synthesis
4 irreversible enzymes of gluconeogenesis?

Name cofactors/energy each enzyme require. Which ones are in the mito and which ones are into cytosol?
Pyruvate carboxylase (pyruvate into OAA), MITO, requires Biotin, ATP and is actiavted by Acetyl CoA

PEP carboxykinase (cytosol), OAA back to PEP, requires GTP

Fructose 1,6,bisphosphatase

Glucose 6 phosphatase
Allosteric activator of gluconeogenesis?
Acetyl CoA on Pyruvate carboxylase (Mitochondria, Biotin and ATP)
Tryptophan deficiency could lead to what two other deficiencies?
Niacin (requires B6, leads to pellegra)

Seratonin/Melatonin (requires BH4)
Name 3 causes of pellegra
Niacin Deficiency
B6 deficiency (isoniazid for ex., required to make niacin from tryptophan)
Hartnup's disease (decreased tryptophan absorption)
Vomiting, lethargy and failure to thrive after breast feeding

What disease?

Discern between the two types of this disease
Galactosemia

Classic = GALT deficiency, will have cataracts, juandice, hepatosplenomegaly and MR

Galactokinase deficiecny = will only have cataracts with maybe an initial failure to track objects/develop a social smile, galactose appears in the blood/urine
Which lysosomal storage disease presents with skin lesions?

Name other symptoms
Fabry's disease (angiokeratomas + peripheral neuropathies, renal fail, CV disease)

A-galactosidase
Build up of ceramide trihexoside
When would you want to induce methemoglobinemia and how do you do this?
Cyanide poisoning, induce metHb with nitrates to cause ferrous into ferric, this binds CN- and prevents it from binding cytochrome oxidase and screwing with ETC (also use hydroxycobalamin and thiosulfate for antidote)
Name inhibitors of ETC and uncoupling agents
1 = Amobarbitol, Rotenone
2 = Antimyin
4 (cytochome oxidase) = CN and CO
ATPase = Oligomycin

Uncouplers = 2,4 DNP, Aspirin, thermogenein in brown fat
Antidotes

1) APAP
2) Salicylates
3) Amphetamines
4) AChesterase inhibitors, organophosphates
5) Antimuscarinics, antiACh, Jimson weed
1) N-acetylcysteine
2) NaHCO3 (sodium bicarbonate, alkalinize urine)
3) NH4Cl (ammonium chloride, acidify urine)
4) Atropine and Pralidoxime
5) Physostigmine
Antidotes

1) BBs
2) Digitalis
3) Iron
4) Lead
5) Copper
1) Glucagon
2) Stop, normalize K+, Lidocaine, Anti dig Fab, Mg2+
3) Deferoxamine
4) Dimercaperol, EDTA
5) Penicillamine
Antidotes

1) Cyanide (3)
2) Methemoglobin (2)
3) CO
4) Methanol, Ethylene glycol
5) Opioids
1) Nitrates, Hydroxycobalamin, thiosulfate
2) Methylene Blue, Vitamin C
3) 100% O2
4) Ethanol (dialysis, fomepizole = competitive inhibitor of alcohol dehydrogenase)
5) Naloxone/Naltrexone
Antidotes

1) BZDs
2) TCAs
3) Warfarin
4) Heparin
5) tPA, streptokinase
6) Theophylline
1) Flumazenil
2) NaHCO3 (serum alkalinization, Na for arrythmias?)
3) Fresh frozen plasma, vit K
4) Protamine sulfate
5) Aminocaproic acid
6) BBs
MCC of homocystinuria? Symptoms? (2)
Cystathione synthetase deficeincy (B6, homocysteine to cystathione to cysteine)

Leads to thromboembolic disease and marfan's habitus
Orotic acid uria leads to what kind of symptoms?

How do you treat? Name 3 enzymes that can cause this and the way you can tell the difference between them
Orotate phosphoribosyl transferase and OMP decarboxylase (both on same polypeptide) ==> required for creation of pyrimidines ==> causes megaloblastic anemia with neurological abnormalities and growth retardation

OTC1 deficiency, can't take ornithine and make it into citrulline, ornithine is shunted to orotic acid leading to orotic aciduria. These patients will have HYPERAMMONEMIA and have hyperammonemic encephalopathy.

Treat the first one with URIDINE (inhibits carbamoyl phosphate synthetase II AND replaces deficient UMP)
4 types of reactions that B6 is used for?
Transamination
Deamination
Decarboxylation (carboxylation is B7)
Condensation
How does glucose cause insulin release? What drug works the same way?
Glucose enters GLUT2 channels on the B-cells of the pancreas, this increases ATP/ADP ratio leading to closure of KATP channels, this depolarizes the cell leading to an increase in IC clacium and a release of insulin

Sulfonylureas (Glipizide, glyburide...) act by binding to KATP channels and causing them to close (increasing insulin release)
Increase in what enzyme activity would cause increased synthesis of purines AND pyrimidines? Disease exacerbation?
PRPP synthetase

Exacerbates Gout (hyperuricemia)
Fructose absorbed in proximal small bowel by what channel?
GLUT-5
Green color in bruises is caused by what?
Heme oxygenase breaking down heme into BILIVERDIN (green)
What do Homeobox DNA seq code for?
DNA binding transcription factors that are usually involved in MORPHOGENESIS
Which of the adrenergic receptors are Gs? Gi? Gq?
Gq = a1 = IP3/DAG, increase IC calcium, increase PKC

Gs = B1, B2 = increase AC, increase cAMP, increase PKA

Gq = a2 = decrease AC, decrease cAMP, decrease PKA
Breast milk lacks which 2 vitamins that must be supplied to infants?
Vitamin D and K (sunlight and IM injection at birth)
What is the P50 of the oxygen saturation curve?
partial pressure of O2 where Hb is 50% saturated.
In the lac operon:

What are the effects of glucose?
What are the effects of lactose?
Glucose = decreases AC, cAMP and causes poor binding of CAP to DNA binding domain, this leads to DECREASED expression of the structural genes

lactose = Normally binds and sequestors the repressor protein what normally binds to the operator, thus lactose INCREASES operon gene production
If gibbs free energy is positive? Negative?
Positive = substrate favored
Negative = product favored
Name as many conditions that would cause sickled cells to sickle more
Anything that INCREASES O2 unloading

Acidic state (increased H+, decreasd pH)
Increased 2,3 BPG
Low blood volume
Increased temperature

(ALL RIGHT SHIFTS)
What is the purpose of lactate dehydrogenase?
in Anaerobic conditions where you can't oxidatively decarboxylate pyruvate into acetyl CoA, thus you create lactate to RESTORE NAD+
How do RBCs increase O2 release at tissues? (with an enzyme)
Phosphoglycerate mutase, changes 1,3 BPG into 2,3 BPG, releases that which causes right shift and O2 release
Painful abdomen, urine is pink, polyneuropathies and mental changes.

What disease is this? What can be found in the blood? Treatment?
Acute intermitten porphyria

Caused by alcohol, barbituates, hypoxia that increase ALA synthase leading to a build up of ALA and Porphobilinogen

Porphobilinogen deaminase is deficient

Treat with glucose and heme that inhibit ALA synthase
Patient comes in with blistering cutaneous photosensitivity and tea colored urine

What disease? found in blood?
Porphyria cutanea tarda

Deficiency in Uroporphyrinogen decarboxylase

Uroporphyrin builds up in the blood and urine
Neutral AAs in the urine

vs

Generalized AAs in the urine

What diseases?
Neutral = HARTNUPs disease (no tryptophan, PELLEGRA)

Generalized = FANCONI'S SYNDROME
Encephalopathy (Chorea, spastic paresis) + high levels or ARGININE

What is the issue?
Arginase deficiency, required for urea formation

get rid of arginine from diet
MAP kinase is the end effect of what signaling pathway?
Tyrosine kinase => Ras => Raf => Map Kinase

Insulin, PDGF, IGF-1, FGF
What step of glycolysis needs NAD+?

what are the two ways you can restore NAD+ after it is reduced?
G3P to 1,3 BPG

use lactate dehydrogenase or pyruvate dehydrogenase to go into TCA to restore NAD+
Skeletal muscle contraction is coupled with what process? (think glucose) Explain the process
Glycogen degredation, calcium activates muscle glucogen phosphorylase to release glucose from glycogen (Calcium mediated myophosphorylase activation), this does NOT contribute to blood levels of glucose
Where are DNA promotor regions usually located?
25-70 basepairs upstream (TATA or CAAT)
Hormones that act on surface receptors are synthesized where in the cell? What if they act on nuclear receptors?
Surface receptors = peptides = RER production

Nuclear receptors = steroid hormones = SER production
Main transporter of ammonia from liver to kidneys or periphery to kidneys?

Describe this process, What is the main amino acid that is used in the LIVER
Glutamate! Glutaminase breaks it down for ammonia excretion in the kidneys

Amino acids are transaminated with AKG into alpha ketoacids and glutamate. Glutamate then delivers the ammonia to the kidneys, ALANINE is the main amino acid used in the liver to make glutamate and thus shunt the ammonia to the kidney or the urea cycle
Brain, RBCs, Kidneys, Skeletal muscle, Liver and Cardiac muscle

Which ones can utilize ketones? Which cannot?
Brain, Kidneys, Skeletal and Cardiac muscle can use ketones

RBCs and Liver cannot
atrophic glossitis, shuffling gait, pain/temp/vibration sense gone

What disease?
B12 deficiency
Why do you get photosensitivity in porphyria cutanea tarda?
Build up of porphoryin/uroporphyrins leads to superoxide mediated free radical formation when exposed to the sun
Name the cycles that occur in mito
TCA, Parts of Heme synthesis, parts of Urea cycle, FA oxidation/Ketogenesis
What causes wrinkles?
decreased collagen/elastin PRODUCTION
Vitamin with the longest storage in the liver?
B12
Hydroxylation of collagen occurs where?
RER
Difference between elastin and collagen structure?
Elastin has glycine, alanine, valine and proline/lysine but they are NOT hydroxylated

Tropoelastin fiber (NOT a triple helix like collagen) is made, secreted and interacts with FIBRILLIN, lysine sidechains from a covalend DESMOSINE crosslink (stretchy properties
What are the ketogenic amino acids? When could you give them to someone as treatment?
Leucine, Lysine

give em to someone suffering from LACTIC ACIDOSIS to shunt products away from lactate
Build up of limit dextrins

What disease? Enzyme deficiency?
Cori's disease
Debranching enzyme deficiency

Can't transfer a(1,6) branches onto ends of long strand, builds up
how soon does glycogen run out? What takes over after that
hours, gluconeogenesis takes over after that
ApoA-1 is responsible for what? Deficiency leads to what?

ApoE3/E4 are responsible for what?
Apo A-1 = LCAT activation (cholesterol esterification in HDL, deficiency leads to low HDLs and increased free cholesterol)

Apo E3/E4 = VLDL and chylomicron remnant uptake by liver (deficiency leads to elevated serum TG and cholesterol)
What enzyme deficiency would also present like G6PD? Why?
Glutathione reductase deficiency, each leads to inability to restore glutathione which protects RBCs from oxidative damage
Compare hemoglobin to myoglobin curves
Remember the hemoglobin is four myoglobins

Myoglobin has a parabolic curve with a Low P50

Hemoglobin has a sigmoidal curve with a higher P50

Remember that if hemoglobin was split up they would all have parabolic myoglobin curves, this is due to the cooperative binding and dissociating of hemoglobin
Compare and contrast glucagon/Epinephrine and insulin's effects on glycogen metabolism
Glucagon/Epi = activate AC, cAMP and PKA, causes phosphoarylation of glycogen phosphorylase, activates it, leads to glycogenolysis and release of glucose (This is also activated by CALCIUM which activates a kinase that is coordinated with calcium influx from muscle contraction)

Insulin = tyrosine kinase dimerization activates a protein PHOSPHATASE that dephosphorylates glycogen phosphorylase, this decreased glycogen breakdown and decreased blood glucose

Glucagon = Liver
Epi = Liver and muscle
Foamy histeocytes + hepatosplenomegaly

Crumpled paper + hepatosplenomegaly

What disease?
Neimann Pick's disease = Foamy

Gaucher's disease = Crumpled
upregulation of serine kinase instead of tyrosine kinase can lead to what?
Insulin resistance
What kinds of FAs cannot be broken down in the mitochondria? Where do they have to go instead?

Deficiency in this process?
Very long chain FAs or Branched fatty acids (Phytanic acid from plants)

Deficiency = ZELLWEGER syndrome (infants can't make myelin in CNS leading to hypotonia, seizures, hepatomegaly, MR and early death)
THey go to PEROXISOMES instead to get spcial oxidation
What disease should you avoid chlorophyll in your diet? Why?
Refsum disease

Inability for peroxisomal alpha oxidation of branched chain FAs (build up of phytanic acid and neurological symptoms)
HbS vs HbC

think about electrophoresis
HbC is less severe form of sickle cell

HbS = valine where glutamate should be (neutral for negative)
HbC = Lysine for glutamate (positive for negative)

HbC will travel LESS distance than HbS due to repelling from positive anode
Compare glucokinase to hexokinase and where they are located

Talk about Km, Affinity, Capacity, VMax, insulin induction and feedback inhibition
Glucokinase = Liver and B-cells of pancreas
HIGH Km, low affinity
High capacity, high vMAX
Induced by insulin
NOT feedback inhibited

Hexokinase = ubiquitous
Low Km, High affinity
Low capacity, Low Vmax
Uninduced by insulin
Feedback inhibited by GP6
Someone eats a lot of eggs and gets lactic acidosis. What happened?
Biotin binds to Avidin in egg whites, without biotin you can't carboxylate (pyruvate carboxylase needed to deplete pyruvate, excess shunted to lactate)
Septate fungal hyphae at acute angles?

Wide angled non septate hyphae?
Aspergillus

Mucor mycosis or Rhizopus (Diabetics!)
Pseudohyphae and oval budding yeast on LM?
Candida (germ tubes, pseudohyphae)
Why is IgM better at activiting the classical complement pathway?
C1 must bind the Fc portion (near the hinge) of TWO different antibodies which is why IgM is so much better than IgG
Diabetic ketoacidosis, Facial Pain, headache with a black necrotic eschar in the nasal cavity.

What is this? WHY does it occur in these patients?
Mucormycosis (mucor, rhisopus or absidia), Rhizopus has high affinity for ketones and high blood glucose (has ketone reductase)

Treat with amphotericin B
What organisms are able to transform DNA from the environment?
SHiN capsular organisms
What hypersensitivity is Post strep glomerulonephritis? What two things will you find deposited?
Type 3

C3 and immunocomplexes, subepithelial deposits
Which antibody does NOT fix complement and is a weak opsonin
IgA
Describe hyperacute, acute and chronic rejection and their appearance microscopically
Hyperacute = preformed antibodies, immediate organ dysfunction
Acute = B and T cell infiltrates, present after 1-2 weeks
Chronic = scant inflammatory cells, fibrosis, months to years after
Measles four MC symptoms? What virus causes and it and from what family?
Measles = Rubeoloa = Paramyxovirus

CCCK
Cough, Coryza, Conjunctivitis
Koplik's spots (Small blue/white spots on buccal mucosa)

maculopapular rash on face and moves down (differential with rubella which has posterior cervical lymphadenopathy)
Th1>Th2, which leprosy? Symptoms?
Tuberculoid, Th1 holds it in check, causes hypopigmentation, and decreased sensation in patches on the skin
Th2>Th1, which leprosy? SYmptoms?
Lepromatous, leonine facies, M. leprae gathers at temps lower than body (skin, superficial nerves, eyes and testes)
Staph gets a beta lactamase, what abx do you use?

Staph changes its PBPs, what abx do you use?
Methicillin, Oxacillin, Nafcillin

Vancomycin
What Abx

RNA pol mutation resistance
Efflux pump resistance (2)
Altered DNA gyrase resistance
Rifampin
Tetracycline, Sulfa
Fluoroquinolones
What bacteria is not a good vaccine canditiate due to antigenic variation of their mucosal attachment pilli
Neisseria gonorrhea
Which Hepatitis viruses are naked and what does this imply?
A and E, hit your bowels because they are not destroyed in the gut
Black eschar on skin with central necoris

What organism? Where is it found?
Anthrax, animal products or biological warfare
High IgE levels and eosinophilia in patients with asthma or CF

What causes this? Repeated exacerbations of this leads to what?
Aspergillus! = Allergic bronchopulmonary aspergillosis

Repeated = transient pulmonary infiltrates and proximal bronchiectasis
Which cells have MHC class 1? Class 2? How are they produced and transported to cell surface?
MHC class 1 = located on ALL nucleated cells, single heavy chain with a B2 microglobulin that assists in transport to cell surface

MHC Class2 = on APCs (dendritic cells, macrophages, B cells), formed by Alpha and beta subunits
Thayer martin media?

Chocolate agar?

How do they work?
Thayer martin = VCN (vanco gets rid of gram +, Colistin or Polymixin gets rid of gram - and Nystatin gets rid of fungi), Used for NEISSERIA GONORRHEA

Chocolate = has factor V (NAD+) and Factor X (Hematin), used for HAEMOPHILUS INFLUENZAE
Which of these agar are differential? Enrichment? Selective?

MacConkey
VCN thayer martin
EMB
Chocolate
Chocolate = Enrichment
VCN = Selective
MacConkey = Differential and selective (Bile salts selects for Gram - bacteria, differentiates between lactose fermenters/pink from non lactose fermenters)
EMB = Differential and selective (eosin methylene blue)
Which pneumoconioses increases risk for both TB and bronchogenic CA?

HOW does it increase TB risk?
Silicosis

decreases macrophage arm of cell mediated defence needed for TB
Th1 and Th2 differ how?
Th1 = CELL mediated
Th2 = Humoral immunity
Gram - curved rod

MCC of what?
Campylobacter jejuni

MCC of gastroenteritis in industrialized countries
Custard and Mayo can have toxins from what bacteria?

Fomites in daycare centers?

Steamed fried rice?

Contaminated shellfish?
Staph = Mayo/custard

Daycare fomites = SHIGELLA

Steamed fried rice = Bacillus cereus

Shellfish = Vibrio parahaemolyticus
MSM transmission

Which hepatitis?
Hep B
East of the mississippi, immunocompetent, granulomas in the lung, broad based buds with double refractive walls

What bug?
Blastomycoses
CD14 is a marker for? CD20? CD7?
CD14 = monocyte macrophage
CD20 and 19 = B-cell
CD7 = T-cell
ssDNA virus, What are you thinking?

What disease does it cause? Major symptoms?
parvovirus B19

Erythema infectiosum (fifth's disease)
Slapped cheeks!
Aplastic crisis (tropism for RBCs, marrow), hydrops fetalis... etc.
Which 3 bacteria have LOW infectious doses
Shigella, EHEC and Campylobacter
How many organisms of entamoeba histolytica or Giardia does it take for infection?
1
Meningitis in a HIV (+) patient, CD4 < 50
Cryptococcus

India ink of CSF, Antigen as well
Fever + vesiculoulcerative lesions of oral mucous membranes + local lymphadenopahy
PRIMARY HSV1 (first infection is the worst)
How can you inactivate naked viruses? (how do you kill them?)
Chlorination
Bleach
UV
Boiling to 85 degrees C

(Acid, drying and ethers do NOT damage them)
PIP and MCP joints painful and stiff, pain gets better with use

What disease? What markers? What hypersensitivity?
RA
RF (IgM against IgG = forms immunocomplexes and deposits in joints, TYPE 3)
Anti Mitochondial antibody
Primary biliary cirrhosis
LPS is found in what kind of bacteria? What portion of it is toxic? What does it cause?
LPS = gram - bacteria
Lipid A = toxic, causes septic shock and DIC by causing release of TNF-a, IL-1 and IFN-y, C3a, C5a

LPS is NOT secreted
K1 capsular antigens, bug?

Heat stabile/labile exotoxins, bug?
E.coli, neonatal meningitis

ETEC, travelers diarrhea
Causes of aspectic meningitis?

2 MC causes of bacterial meningitis in adults?

MC cause of meningitis in HIV?
Enteroviruses (coxsackie, echovirus, polio or other enteroviruses)

Adults = Strep pneumoniae, then Neisseria meningitidis

Cryptococcus MC in AIDS (look india ink or antigen in CSF)
Primary HIV receptor? What are the two other ones? mutation to which one leads to resistance
Primary = CD4
Macrophage = CCR5
T-cell = CXCR4

Mutation to CCR5 = resistance
Where are B-cells made? Where do they isotype switch?
Made and mature in the bone marrow, then go to lymph nodes for exposure

Isotype switch and activated in the GERMINAL CENTERS
Discern between central and peripheral tolerance
Central = in the thymus, negative selection, if a maturing T-cell reacts to a self MHC antigen, it is destroyed

Peripheral = develops by CLONAL ANERGY, if a T-cell reacts to self antigens it is inactivated and becomes ANERGIC
2 stains used for cryptococcus neoformans
India Ink
Mucicarmine (appears red)
How do you form vaccines for the SHiN organisms?
Conguate a protein (diphtheria or tetanus toxoid) to the capsular carbohydrate to allow for better T-cell uptake and response.

Carbohydrate capsules are much worse at being taken up by APCs
PRP (polyribose ribotol phosphate) capsule

What bacteria?
H. flu
Ovoid bodies in macrophages, hilar lymphadenopathy

What bug? What does it present like?
Histo!

Histo, Blasto and Coccidio present like TB
MC pathogen causing cystitis and pyelonephritis?

2nd MC in sexually active women?
MC = E. coli

2nd MC in women = Staph saprophyticus
Nitroblue tetrazolium

What is this used for?
Chronic granulomatous disease

No NADPH oxidase leads to no blue color formation in neutrophils (inability to make reactice oxygen species, recurrent pyogenic infections)
3 MC organisms for OM? Recurrent OM indicates what kind of deficiency?
Strep pneumo, H. flu, Moraxella

Recurrent = Humoral deficiency
C5-C9 deficiency = what bug infection?
Neisseria
3 functions for IL-4? IL-5?

IL10
IL12 functions?
IL4 = B-cell growth, IgE switch, Th2 promotion

IL5 = B-cell differentiation, IgA switch, Eosinophil for parasitic infections

IL10 = Th2 (humoral)
IL12 = Th1 (cell mediated)
Which two bugs have A-B toxins that ADP ribosylate EF-2 to decrease protein synthesis
Diphtheriae
Pseudomonas

(also the function of Rb tumor supressor)
Which two bugs inactivate human 60S ribosomal subunit?
EHEC
Shigella
3 MC cause of pneumonia?

What paves the way for pneumonia?
Strep pneumonia, Staph aurues, H. flu

Viral infection (influenza A)
Pneumonia in alcoholics/IVDAs
Nosocomial UTIs/pneumoina

What bug?
Klebsiella
MCC of reiter's syndrome? What is it also called? What is the triad?
Usually post Nongonococcalurethritis (chlamydia or ureaplasma)

Reiter's syndrome = Reactive arthritis
1) Conjunctivitis/Uveitis
2) Urethritis
3) Arthritis (asymmetric)
Repeated 2nd/3rd trimester miscarriages, Recurrent DVTs and a false positive syphillis test

Whats wrong? What lab test is weird...
SLE ==> Lupus anticoagulant ==> Antiphospholipid syndrome

Hypercoagulable with a paradoxical elongation of PTT time
5 organisms with lysogenic phage transducing toxins?
ABCDE

shigA toxin
Botulinum toxin
Clostridium toxin
Diphtheria toxin
Erythrogenic toxin of GAS
Fimbrae, UTIs and pyelonephritis

What bug?
E. Coli

Use fibrae to adhere to uroepthelial cells, P-fimbrae can lead to pyelonephritis

K1 capsular antigen of E. coli causes meningitis
Metronidazole used for which bugs?

Mebendazole
Albendazole
Thiabendazole
Praziquantel
Metro = GET (Giardia, Entaemeba histolytica, trichimonas vaginalis, Gardnerlla vaginitis, anaerobic bacteria)

Mebendazole = Nematodes aka roundworms (non invasive, enterobius, necator/anclyostoma, ascaris, trichiruria)

Albendazole = (echninococcus and taenia solium cystercircossis, also used for invasive nematodes like trichinella, anisikiasis, cutaneous and visceral larva migrans)

THiabendazole = Strongyloides nematode (roundworm)

Praziquantel used for taenia saginata, diphyllobothorium (cestode tapeworms), all flat worms (Schistosoma, paragoniums and chlonorchis sinensis)
Killed vaccines?
Live vaccines?
Toxoid vaccines?
Conjugate?
Killed = RIP Always (Rabies, Influenza, Salk Polio, Hep A) ==> only HUMORAL immunity
Live = Small yellow chicken Sabin Polio, MMR
Toxoid = dTAP (Diphtheria, pertussis, Tetanus)
Conjugate = HBV, HPV
Organism for the following agar:

Cysteine tullurite
Mackonckees
Thayer martin
Blood agar
Bordet Gengou
Charcoal yeast
Cysteine tullurite = Loeffler's media = C. diphtheriae
Mackonckees = Enteric bacteria
Thayer martin = VCN = Neisseria gonorrhea
Blood agar = Eneterococci culture (differentiates enterococci from group D strep)
Bordet Gengou = Bordetella pertussis
Charcoal yeast = Leigonella
bacteria that causes hemolytic anemia? Pathophys?
Mycoplasma pneumoniae (cold agglutinins, IgM, causes intravascular/extravascular hemolysis, mimicry?)
rose spots on the abdomen + fever + diarrhea

Organism? virulence? sites of infection?
Salmonella typhi (typhoid fever)

Infects through M-cells in the peyer's patches, macrophages then carry organism to liver spleen and bone marrow (can sit in gallbladder for seeing of the GI tract)
purulent cervical discharge

organisms? treatment? if disseminates to peritoneum?
PID
N. gonorrhea, C. trachomatis
3rd gen ceph + Azithro/Doxy

Fitz Hugh curtis if disseminates to peritoneum or liver capsule
Firm dome shaped umbilicated papules on skin

Organism?
Molluscum contagiosum
Pox virus
Posterior lymphadenopathy + rash on face moving downwards

Organism? What if it was congenital?
Rubella (german measles)

Congenital = PDA, deafness and cataracts
Three organisms that cause papular rash from the palms/hands spreading toward the trunk
Coxsackie A
Secondary syphilis
Ricketssia
CD21, what is it used for?

P antigen?
B-cell thing that EBV attaches to for infectious mononucleosis

P-antigen = thing that B19 parvovirus attaches to on RBCs
Tumbling motility

What bug? What does this bug require for infection?
Listeria

Requires cell mediated immunity to enter cells that phagocytose it
What two disease can cause a positive Nikolosy's sign
Pemphigus vulgaris
Scalded Skin syndrome (staph aureus exfoliatin toxin)
Which organism has protein A? IgA protease?
Protein A = Staph, binds Fc portion of igG at complement binding site (hinge region) and doesn't let complement activate

IgA protease = SHiN orgnaisms (allows for penetration of mucosa, neisseria needs this to cause meningitis, gets across and then goes through the choroid plexus)
Oral thrush, interstitial pneumonia and severe lymphopenia in a newborn

What happened? how do you prevent?
HIV vertical transmission, give mom zidovudine (RT inhibitor to prevent transmission)
What drug blocks fusion of HIV (penetration)?
Enfuviritide, blocks gp41
IFN alpha is indicated for what 5 disease?
Hep B
Hep C
Hairy cell leukemia
Condyloma acuminatum (genital wart)
Kaposi's sarcoma
what organism still causes OM even though we vaccinate? Why?
H. flu B, we vaccinate to prevent meningitis, epiglottits and pneumoina

only against type B, there are other strains that still cause OM
Eczema, thrombocytopenia (purpura, petichiae), recurrent infections

What disease? Defining features?
Wiskott Aldrich disease, X linked

Combined B and T cell due to progressive B and T cell deletion (leads to infections)

IgM is down but IgE and IgA may be up
Albinism + peripheral neuropathies + immunodeficiency

What disease? Pathophys?
Chediak higashi

MT dysfunction leading to inability to form the phagolysosome
Recurrent sinopulmonary and GI infections

What disease? Blood transfusion?
IgA deficiency

Can lead to hypersensitivity reaction to IgA in blood transfusions
Recurrent cutaneous infections without pus formation, umbilical stump does not fall off

What disease? Pathophys?
Leukocyte adhesion deficiency (CD18 integrin mutation)

Poor wound healing
Anti Jo1, increased serum CK

What disease? pathophy? main symptom?
Polyomyositis/Dermatomyositis

Grottons papules (MCP, PIP, DIP)
CD8 T-cells destroy muscle
Proximal muscle weakness
Bilateral stiffness of shoulder/girdles, fever, weight loss and increased ESR

What disease?
temporal arteritis with Polymyalgia rheumatica
Recurrent fever, chills and sweats, episodic hematuria

what disease? Treatment? (2)
Malaria

Plasmodium

Chloroquine (blood stream), Primaquine (get rid of liver vivax/ovale, prevente recurrence)
Hypopigmented/hyperpigmented skin patches/papules that are NOT anesthesized

Who did this? Characteristic microscopic view? What if they were anesthesized?
Tinea versicolor caused by Malessezia furfur (cutaneous mycoses, spaghetti and meatbulls appearance on KOH, hyphae look like cigar butts, treat with antifungals or selenium containing shampoo)

Anesthesized = Tuberculoid leprosy (Th1>Th2)
toxin that screws up actindepolymerization

What bug
C diff (cytotoxin B, also has toxin A = enterotoxin)
Serpentine growth of thick ropelike cords

What is this, what bug? What does it mean?
TB, CORD FACTOR (virulence factor of TB, inactivates neutrophils and damages mitochondria and releases TNF)
Migratory polyarthritis

What disease?
Rheumatic ferver (JONES)
Child, Lethargy, Oliguria, Bloody diarrhea, elevated urea and creatinine, shitocytes

What disease
HUS, undercooked beef, E. coli O157:H7
Custard mayo, what bug?
Fried rice, what bug?
Raw oysters? (2)
Raw eggs?
Canned beans?
Contaminated food?
Daycares with fomites?
Custard mayo = Staph (enterotoxin and TSS toxin)
Fried rice = bacillus cereus
Raw oysters = Vibrio and Hep A
Raw eggs = Salmonella
Canned beans = Clostridium
Contaminated food = Listeria
Daycares with fomites = Shigella
shallow painful ulceraltion on genitals with swollen regional lymph nodes, requires chocolate agar to grow

What bug?
Haemophilus ducrei, chancroid, requires X factor (hematin) like H. flu
Serpentine growth of thick ropelike cords

What is this, what bug? What does it mean?
TB, CORD FACTOR (virulence factor of TB, inactivates neutrophils and damages mitochondria and releases TNF)
Migratory polyarthritis

What disease?
Rheumatic ferver (JONES)
Child, Lethargy, Oliguria, Bloody diarrhea, elevated urea and creatinine, shitocytes

What disease
HUS, undercooked beef, E. coli O157:H7
Custard mayo, what bug?
Fried rice, what bug?
Raw oysters? (2)
Raw eggs?
Canned beans?
Contaminated food?
Daycares with fomites?
Custard mayo = Staph (enterotoxin and TSS toxin)
Fried rice = bacillus cereus
Raw oysters = Vibrio and Hep A
Raw eggs = Salmonella
Canned beans = Clostridium
Contaminated food = Listeria
Daycares with fomites = Shigella
shallow painful ulceraltion on genitals with swollen regional lymph nodes, requires chocolate agar to grow

What bug?
Haemophilus ducrei, chancroid, requires X factor (hematin) like H. flu
Serum mixed with cardiolipin, cholesterol and lecithin. Aggregation/flocculation of the sample occurs

What is this test? explain it? What bug? confirmatory test? explain it
RPR (rapid plasmin reagin test), along with VDRL is used for high sensitivty screening for TREPONEMA bugs (syphilis, yaws).

RPR and VDRL tests for anticardiolipin antibodies (positive in lupus antiphospholipid syndrome)


Diagnose with FTA-abs (antibodies directed against treponema)
3 markers of active HepB infection?

What gives lifelong immunity to Hep B? What differs if its from a vaccine
HBV DNA
HBsAg
HBeAg

Infection then immunity = IgG anti HBsAg as well as IgG anti HBcAg

Vaccine = only HBsAg IgG
IgG HepC core antigen gives immunity

True or false
FALSE

relapsing and remitting hepatitis
High fever, smoker, diarrhea, hyponatremia, confusion, cough and chest pain

What bug? What disease? Diagnosis? where is the bug found?
Leigonella, Leigonnaire's disease

Urine antigen
Water
Indwelling catheters, prosthetic heart valves or orthapedic hardware can lead to what bug? What sequallae? Tx?
Staph epidermidis

Endocarditis, sepsis

Vancomycin (most are resistant to penicillins and other beta lactams)
MC neonatal sepsis/meningitis?
GBS, strep agalactiae
Bronchitis, pneumonia in elderly patients with COPD (3rd MC OM)

What bug
Moraxella
Virulence factor for N. meningitidis?
LOS, analagous to LPS of gram - rods, acts as an endotoxin leading to toxic meingococal disease

LOS can be released in outer membrane vesicles that cause sepsis as well as waterhouse friedrichsen syndrome
Difference between positive and negative selection
Occurs in the thymus. T-cells that are made must be able to bind to self MHC, only those survive. After that, they are tested against binding to self ANTIGENs, if they bidn to those they are destroyed (negative seelction
Hydrocephalus, intracranial calcifications, encephalitis, necrotizing brain lesions and white yellow chorioretinal lesions in both eyes

What caused this in baby? What should you tell the mother to avoid?
Treatment?
Congenital toxoplasmosis

avoid CAT LITTER

Sulfadiazene and pyrimethamine
How do IFN A/B work?

Do they upregulate innate or adaptive immune system?
decrease viral replication, increase synthesis of antiviral proteins that impair translation of viral mRNA without impacing cellular mRNA

INNATE
Tumbling motility, Can survive in cold refrigerated temperature

What bug?
Listeria!
CNS lymphoma

What usually causes this? (disease and bug)
HIV patients, EBV, causes a B-cell lymphoma in the brain
MC viral meningits?

Meningitis with accompanied lower leg weakness?
Enteroviruses (cox, echo, polio)

POLIO (damages anterior horn cell bodies, anterior horn cell bodies = LMN, also seen in werdnighoffman in kids)
Penetrating injury ==> crepitus

What happened? What bug? What toxin?
C. perfringens, alpha toxin or phospholipase, gas gangrene
Which Hepatitis virus is DNA material?

Which hepatitis virus has no envelope?
DNA = Hep B
Unenveloped = A and E
Endocarditis after genitourinary procedures?

Endocarditis after colonic malignancy?

How do you tell between these bacteria with a lab test
GU procedures = Enterococcus faecilis or Poststreptococcus (survives in 6.5% NaCl)

Colonic malignancy = Strep Bovis (can't survive in 6.5% NaCl)

Both are Gram +, cocci, catalase -, gamma hemolysis (none)
Pseudoappendicitis

What bug? Why?
Yersinia enterolitica, penetrates bowel mucosa and gains access to lymphatics and proliferates in the mesenteric nodes (RLQ pain)
Two causes of green diarrhea?
C diff
Yersinia enterolitica
Gram - rods, lactose -, oxidase -

How do you use lab tests to discern
Shigella, salmonella and proteus

Salmonella produces H2S
Shigella does not
IFN-y is essential for defence against what disease?
TB and other granuloma forming disease (required for macrophage maturation and phagolysosome formation)
Clustered gram + bacteria in clumps resembling chinese letters, stain with methylene blue, tonsillar exudates

Bug?
C. Diphtheriae (exudates also seen in GAS and EBV mono)
Serum agglutinates sheep or horse erythrocytes. What test is this? If positive what disease?

what do you see on the blood smear in this disease?
Monospot/Heterophile test

Positive = EBV mononucleosis

If negative with symptoms think CMV

Atypical lymphocytosis (big blue tinged cytoplasm)
Where do you usually get monospot + mono?

monospot - mono?
+ = EBV, close contact, kissing disease

- = CMV, usually from blood transfusions
Latex particle agglutination positive CSF

What bug
Cryptococcus, more specific than india ink
What abx do you use for bacterial meningitis caused by H. flu or strep pneumo?

Listeria?
Ceftriaxone

Listeria = Ampicillin
What bug has preformed toxin that is released via lysis? (2)
Clostridium BOTULINUM, STAPH aureus enterotoxin

(tetani is not preformed)
Trouble swallowing, trouble seeing, trouble hearing, trouble moving joints

What disease?
Botulinum neurotoxin!
Cutaneous/superficial candida infections is caused by what kind of dysfunction?

What about disseminated candida?
Cutaneous = T-cell mediated (prevents localized spread)
Disseminated = neutrophil dysfunction (usually prevents hematogenous spread)
Antibodies against cell outer covering causes it to swell

What test is this and what is it positive for?
Quellung test, positive for capsullar bacteria (SHiN
Person has GAS pharyngitis, early antibiotic treatment prevents which sequellae?
Prevents rheumatic fever but does not prevent post strep glomerulonephritis which may still occur
Increased CD4/CD8 ratio indicates what disease process?
Granuloma formation (Sarcoid, TB.. etc.)