Summative 2 Review Flashcards
Where do injuries that cause hemianopia occur?
either at (bitemporal hemianopia) or after the optic chiam
anything before optic chiasm is optic nerve problem
Signs of ischemic optic neuropathy
Acute vision loss in ONE eye
what is ischemic optic neuropathy?
stroke of the optic nerve
signs of retinal detachment
Monocular vision loss that occurs gradually
Described as a curtain being drawn down
Optic neuritis vs. ischemic optic neuropathy
ischemic optic neuropathy is sudden
optic neuritis is subacute
Occipital stroke vs. ischemic optic neuropathy
both occur quickly
occipital stroke happens in both eyes (homonymous hemianopsia)
Retinal artery occlusion vs. ischemic optic neuropathy
Both occur quickly and monocularly
retinal artery occlusion has a cherry red spot on macula
ischemic optic neuropathy has swollen optic nerve
Pituitary adenoma
compression of optic chiasm
subacute timing
results in bitemporal hemianopsia due to damage of optic chiasm
Th1 response normally targets …
intracellular pathogens
Th2 response normally targets …
extracellular pathogens (worms)
How do Th1 trigger an immune response?
they secrete IFN-y which activates macrophages
Th17 normally targets …
extracellular bacteria + fungi
What is the cell type that Th1 targets?
macrophages
What is the cell type that Th2 targets?
Eosinophils and mast cells
What is the cell type that Th17 targets?
neutrophils
Defining cytokines of Th1
IFN-y
Defining cytokines of Th2
IL-4, IL-5, IL-13
Defining cytokines of Th17
IL-17 and IL-22
What is the main function of CD8 cells?
works on intracellular pathogens
cytotoxic T-cell
What would defects in TLR-4 result in?
defective response to LPS and bacteria
What would defects in CD28 result in?
T-cells could not bind B7 on APCs
this would result in an ineffective immune response
STAT-3
important transcription factor in differentiation of Th17 cells
Glatiramer acetate
MS medication
prevents activation of autoreactive cells by mimicking the self-antigen
called a “myelin” mimic
T-cells will not recognize myelin, they will recognize the mimic
How do cyclosporin and FK506 work?
they inhibit calcineurin which then inhibits NFAT
without NFAT (transcription factor), IL-2 will not be produced and T-cell response will dampen
What is activation of NFAT dependent on?
calcium activation
you actually dephosphorylate NFAT to activate it
HLA DR2
important in the pathophysiology of MS
presents a putative myelin peptide to autoreactive T-cells
Why are MHC alleles important factors of autoimmune disease?
because they can present self-peptides needed to activate self-reactive T-cells
Which element does an MRI work on?
hydrogen
How does BOTOX work?
proteolysis of proteins required for acetylcholine release
prevents excitatory state
What happens when you go from sitting to standing?
BP drops
therefore, you want to increase HR, cardiac output and peripheral vascular resistance (all sympathetic stimulation)
Why do we give epinephrine to patient’s in anaphylactic shock?
stimulates B2-adrenergic receptors and subsequent bronchodilation
a1-adrenergic receptor bladder
constricts the urethra to prevent peeing
What 2 things induce peeing?
urethra relaxes
detrusor contracts
What channels play a role in neuronal repolarization?
both K+ and Na+ channels
nicotinic acetylcholine receptors
these can be adrenal/sweat glands or muscles
if at neuromusclar junction (NMJ), you know they are referring to the muscle receptors
Carbamazepine
antagonist of Na+ channels
this decreases firing of neurons and controls excitatory state
use in seizures
What is the function of CD4 cells?
work on extracellular pathogens
expressed by Helper T-cells and macrophages
Where is the LGN? What does it divide?
LGN is located on thalamus
before LGN = optic tract
after LGN = optic radiation
What creates contralateral inferior quadrantanopia?
lesion to Baum’s loop
Baum’s loop runs through parietal lobe (superiorly) and synapes on cuneus
What creates contralateral superior quadrantanopia?
lesion to Meyer’s loop
Meyer’s loop runs through temporal lobe (inferiorly) and synapes on lingual
Does Myelin decrease capacitance? What is capacitance?
Yes
Capacitance is the amount of charge needed to propagate a signal
absolute refractory period
Na+ is in inactive state and another potential cannot be fired under any circumstance
relative refractory period
period of hyperpolarization
K+ channels are slower to close
leads to increased outward flow of K+ and decreased cellular charge
Which way do sodium and potassium move in action potential?
salty bannana
Na+ moves inward (depolarizes the cell)
K+ moves outward (repolarizes the cell)
Inhibitory neurons and which toxin prevents them
GABA and glycine
C. tetani
excitatory neurons and which toxin prevents them
acetylcholine and glutamate
C. botulinum
What 2 signals do you need for T-cell activation?
TCR – MHC
CD28 (T-cells) – B7 (APC)
CTLA-4
dampens immune response by binding B7 on APC and blocking it
without B7 you have anergy
cancer upregulates CTLA-4
How do Th1 and Th2 antagonize eachother?
Th1 produces IFN-y to activate macrophages.
At the same time, Th2 produces IL-4 to inactive macrophages.
Which works more with intracellular pathogens Th1 or Th2?
Th1
Nicotinic receptors
acted on by acetylcholine
ex: sympathetic sweat glands, neural, somatic muscle
Adrenergic receptors
acted on by norepinephrine
exclusively part of the sympathetic ANS
Sympathetic nervous system origins and ganglia location
Origin: T1-L3
Ganglia: paravertebral sympathetic trunk
Parasympathetic nervous system origins and ganglia location
Origin: craniosacral distribution
Ganglia: located near target organs
-stigmine drugs
prevent acetylcholinerase and therefore lead to increased acetylcholine
B3-adrenergic receptor effect on bladder
relaxes the detrusor to prevent peeing
M3 muscarinic receptor effect on bladder
constricts detrusor to allow peeing
also relaxes the urethra to allow peeing
what is pyruvate an intermediate of?
intermediate of conversion of glucose to fat
also of the Cori Cycle
fructose 2,6 bisphosphate function + location
increase PFK-1 activity in glycolysis
only found in the liver!
hepatic reciprocal regulation
insulin activates F-2,6-BPG to increase glycolysis
in the absence of F-2,6-BPG, FBPase1 is turned on and glycolysis occurs
FBPase-1
stimulates hepatic gluconeogenesis
Signs of ketoacidosis
nausea / abdominal pain
fruity breath
history of T1DM
Ketoacidosis
normally insulin prevents ketogenesis in the liver
with T1DM, there is no insulin to stop the production of ketone bodies
What actions does metformin stimulate and inhibit
Stimulates hepatic glycolysis (want more glucose uptake)
Inhibits hepatic gluconeogenesis
What cues you in that something is a beta-lactam?
-lin suffix
How does T2DM occur?
insulin resistance occurs AND your body cannot produce enough insulin
pancreatic B-cells can not compensate for insulin resistance
not everyone with insulin resistance is diabetic
Two ways you can determine between T1 and T2 DM
use a C-peptide (if there is C-peptide, you have T2DM)
Islet cell antibodies mark T1DM (remember T1 is an automimmune disease)
What are 2 important components of glomerular filtration barrier?
podocytes
fenestrations
Why are cornea transplants successful?
the cornea is largely avascular so immune system cannot target
Function and location of cornea
clear layer in front of the aqueous humor that helps provide refractive power
Uvea components
iris, ciliary body and choroid
Function of the iris
regulate the amount of light reaching the retina
Function of ciliary body
make aqueous humor, provide multifocal ability to accomodate
Why do we need reading glasses?
the lens hardens and we can no longer accomodate
Where do cataract repairs happen?
at the lens
largely avascular
Ganglion layer of retina
lies closest to vitreous chamber and contains rods and cones
What is non-proliferative diabetic retinopathy associated with?
exudate = yellow spots on retina
exudate precipitates out due to macular edema
macular edema! sign of non-proliferative!
What is proliferative retinopathy associated with?
blood in vitreous chamber
Steps of proliferative DM retinopathy (4)
Leukocytes attach to small capillaries and capillaries close
Swelling of nerve layer causes the retina to not get enough blood
Retina produces VGEF in attempt to get new capillaries which leads to neovascularization
Neovascularization is not strong and these new vessels break and spill blood into the vitreous chamber
Overall formula of aerobic glycolysis
1 glucose => 2 pyruvate + 2 ATP + 2 NADH
Overall formula of anaerobic glycolysis
1 glucose => 2 lactate + 2 ATP
What activates PFK-1 in the muscles?
ATP/AMP ratio
more AMP stimulates glycolysis
3 starting products of gluconeogenesis
Glycerol from fatty acid oxidation
Pyruvate
Amino acids (alanine and glutamine)
Why is glycolysis considered anabolic in the liver?
2 pyruvate molecules are converted to acetyl-CoA which then leads to fatty acid synthesis
Which receptor has a lower affinity for glucose? Why?
GLUT2
only want to uptake glucose when there is a surplus in liver (storage), pancreatic B-cell (insulin secretion), and intestines (after eating)
General steps of insulin release
Glucose enters B-cell through GLUT2
Goes through glycolysis and ATP levels rise
K+ channels close and membrane depolarizes
Ca2+ channels open and insulin is released
Citric Acid Cycle
oxidizes acetyl-CoA to FADH2 and NADH to be used by the ETC
Cori Cycle
connects anaerobic glycolysis (muscle) and gluconeogenesis (liver)
pyruvate is the intermediate
lactate from anaerobic glycolysis is used as the starting product for gluconeogenesis which then make more glucose for glycolysis
4 hallmarks of metabolic syndrome
Obesity, insulin resistance, dyslipidemia, and HTN
Sulfonylurea + meglitinides
cause K+ channels to close and trigger insulin release
DPP-4
inhibit the breakdown of incretins (GIP / GLP-1)
incretins trigger insulin release
having incretins longer = more insulin release
alpha-glucosidase
prevent glucose reuptake from the GI tract
can lead to GI side effects
SGLT2 inhibitors
prevents renal recovery of glucose from filtrate
SGLT2 is a synporter for glucose with Na+
Thiazolidinedoines
increase insulin sensitivity
associated with transcription via PPAR-y
If dietary adjustments correct a problem with excess triglycerides, what does this indicate?
there was a problem with chylomicrons
lipoprotein lipase
breaks down triglycerides in VLDL / chylomicron to deliver FA to tissues
cofactor is C-11
What is required for maturation of VLDL into IDL / LDL?
offloading of triglycerides
need LPL to accomplish this (break down triglycerides)
What 3 enzymes are used in reverse transport?
LCAT
CETP
SR-B1
LCAT
makes cholesterol ester
allows cholesterol to be transported by HDL
CETP
moves cholesterol ester from HDL to other lipoproteins
SR-B1
directly transports cholesterol ester to tissue/ liver
see a lot in adrenal gland / sex organs where cholesterol is needed to make hormones
What is mutated in familial hypercholesterolemia?
LDL receptor
Incomplete dominance in familial hypercholesterolemia
heterzygotes have milder disease than heterozygotes
autosomal dominant disease
Which type of muscle has peripheral nuclei?
skeletal muscle
Which type of muscle does not have striations?
smooth muscle
What does collagen often look like?
often looks wavy
What is an irreversible change in cell damage?
mitochondrial fragmentation
If someone has jaundice, what labs should you check? Why not AST?
check bilirubin
AST is not as specific
Why are both PTT and closure time affected by vWD?
closure time is affected due to lack of vWF / low platelet aggregation
PTT is affected by vWF’s dual activity to stabilize Factor VIII in the intrinsic pathway
Where do thrombus exclusively occur?
they exclusively occur in the vascular system
this is different from blood clots which can occur anywhere
Where are lines of Zahn?
only found in thrombi
not seen in blood clots
List all the Vitamin K dependent factors
Protein C + S
II, VII, IX and X
What type of necrosis forms pus?
liquefactive necrosis
After an MI, what type of necrosis do cardiac myocytes undergo?
coagulative necrosis
After an MI, what type of necrosis do cardiac vessels undergo?
fibrinoid necrosis
What are 3 classic signs of apoptosis?
Shrunken
Fragmented nucleus
Apoptotic bodies
Bcl-2
inhibitor of the apoptotic pathway
Bcl-2 inhibits the recruitment and oligomerization of Bax
Also prevents the release of cytochrome C
Bad protein
Bad protein normally acts to inhibit the action of Bcl2, allowing more apoptosis
Which caspase is unique to intrinsic apoptosis?
caspase 9
Which caspase is unique to extrinsic apoptosis?
caspase 8
Where are death ligands found?
in the extrinsic apoptosis pathways
Where is cytochrome C found?
in the intrinsic pathway of apoptosis
What is the FAS ligand associated with?
the extrinsic pathway of apoptosis
How do plaques form?
LDL particles are transcytosed acrossed the endothelium and accumulate in the subendothelium
in the subendothelium, the LDL particles are converted into cholesterol crystals
cholesterol crystals (form within the intima) are phagocytosed by macrophages
macrophages stimulate recruitment of T-cells and IFN-y
What is characteristic of unstable plaque? What are the 2 parts of a plaque?
2 parts: fibrous cap + necrotic center
Unstable: thin fibrous cap
Apo A-1
found on HDL
activates LCAT
Apo B-48
found on chylomicrons
What binds to the LDL receptor?
C-terminal of Apo B-100
What binds to the remnant receptor?
Apo E
Xanthuma
cutaneous deposit of cholesterol that can be seen in familial HLD
PCSK-9 inhibitors
prevent degradation of LDL receptors
more LDL receptors are expressed which lowers serum cholesterol levels
List the order that cardiac markers peak after an MI
CK-MB
Troponin I (24 hours)
AST (2 days)
LDH (3 days)
List the 3 receptors platelets express and what they bind to:
Fibrinogen - GpIIb/a
vWF - Gp1B
collagen - a2B1
What do activated platelets express?
phosphatidylserine
Dense granules of platelets contain …
ADP and Ca2+
Alpha granules of platelets contain:
vWF
What factors does thrombin activate (positive feedback)?
8, 5 , 11, and 13
t-Pa
converts plasminogen to plasmin to activate fibrinolysis
Virchow triad
endothelial injury, stasis in blood flow, hypercoagulable state
Aspirin
NSAID
binds COX1 to prevent Thromboxane A
Thromboxane A
vasoconstrictor that promotes clotting
Heparin
combines with antithrombin to inhibit activity of thrombin and factor X
Clopidigrel
antiplatelet that blocks ADP receptors to inhibit platelet activation
Rivaroxaban
anticoagulation that directly inhibits factor X (x is in name)
Warfarin
anticoagulation that inhibits vitamin K-dependent clotting factor synthesis
What type of necrosis creates abscesses? How about granulomas?
abscesses: liquefactive necrosis
granulomas: caseous necrosis
How does necrosis stain?
basophilic due to accumulation of calcium lipid salts due to saponification
Does atherosclerosis occur in veins?
No, only in arteries
What are some signals of apoptosis?
phosphatidylserine
ADP/UTP
Difference between scar tissue and granulation tissue
Scar tissue is rich in collagen with little capillaries
granulation tissue has many capillaries
When does coagulative necrosis turn into scarring following MI?
coagulative necrosis comes first 1-3 days post MI
granulation tissue occurs 10+ days later
What is scar tissue abundunant in?
myofibroblasts and TGF-beta
What does TGF-beta inhibit?
inflammation
also inhibits keratinocytes
What is hypertrophic scar mostly composed of?
type III collagen
What is keloid scar mostly composed of?
type I and type III collagens
How long are platelets stable for?
5 days at room temperature
they have the highest rate of infection since they have to be kept at room temp
Who is RhoGam given to?
all Rh- moms when pregnant
Histamine
amine that is an early mediator of acute inflammation
leads to vasodilation
Serotonin
amine that is an early mediator of acute inflammation
vasoconstrictor
List the 3 basic steps of leukocyte recruitment and the proteins associated with them
Rolling - selectins
Firm adhesion - integrins
Migration - PECAM
What leads to formation of an exudate?
contraction of endothelial cells which leads to increased vascular permeability
What leads to formation of transudate?
changes in hydrostatic or oncotic pressure
How does Factor V leiden prolong the bleeding time?
It only has 2 binding sites so it is activated for longer
If you have an arterial clot, what type of clot is it?
a white clot
If both PT and PTT are prolonged, what are you thinking about?
problem with fibrinogen or vitamin K production
Difference between ITP and vWD?
vWD has normal platelet count
If you have pancytopenia, what should you be worried about / what do you need to do?
worried about leukemia
need to check a bone marrow biopsy
What 3 organs does GvHD affect?
skin, intestine and liver
What risk is increased and which risk is decreased with syngeneic transplant?
risk of GvHD is decreased
risk of relapse is increased
How can you tell the difference in symptoms between extravascular and intravascular hemolysis?
in extravascular hemolysis, there will be no mention of dark urine
in extravascular hemolysis, there is also hepatosplenomegaly that you do not see in intravascular
Hypersegmented neutrophils indicate ….
vitamin B12 or folate deficiency
can differentiate by checking neuro symptoms
Laminin
component of basement membrane that you want to dowregulate during epidermis migration under eschar
When does fibrosis vs. scarring occur
Fibrosis = chronic inflammation
Scarring = acute injury
Primary vs. secondary provisional matrix
primary = formation of fibrin clot
secondary = granulation tissue
Which layer of skin has tight junctions?
stratum granulosum
What type of tissue makes up dermis?
dense irregular connective tissue
Dystrophic vs. metastatic calcification
Dystrophic is fairly normal Ca2+ deposition on vessel (stains basophilic)
Metastatic is Ca2+ deposition with abnormal growth
Sclerosis
excess deposit of extracellular matrix
Forward typing / direct Coombs
patient’s RBCs are tested against commercial antibody
Reverse typing / indirect Coombs
patient’s serum are tested against known antigens
Why does acute hemolytic transfusion reaction occur?
mismatched blood triggers IgG antibody response
incorrect blood type given
2 forms of prep for stem cell transplant
myeloablative
immunosuppresants
2 general causes of aplastic anemia
DNA damage (treat with transplant)
autoimmune disease (treat with immunosuppresion)
GvHD vs. Graft Failure
GvHD is when donor-derived cells attack the patient’s self-cells
Graft failure is when body attacks the donor cells
What is the cause of acute spherocytes?
autoimmune hemolytic anemia (can be intracellular or extracellular)
5 hypoproliferative anemias
anemia of inflammation, B12+folate deficiency, lead toxicity, aplastic anemia, iron deficiency anemia
these will all have a low retic
Anemia of inflammation vs. iron def. anemia
anemia of inflammation will have low TIBC in addition to low iron
When does megaloblastic anemia occur?
during vitamin B12 def.
Aplastic anemia vs. ITP
ITP only platelet count is low
aplastic anemia there is pancytopenia
What does the suffix -cytosis mean?
high count
ex: leukocytosis = high WBC
Can you do a platelet transfusion to cure ITP?
No, the antibodies will continue to degrade the new platelets
need to do immunosuppresion or splenectomy to treat ITP
How to tell the difference between primary and secondary hemostasis?
primary: mucosal bleeding
secondary: deep / joint bleeding
What should you check in secondary hemostasis?
PT / PTT and mixing studies
What should you check in primary hemostasis?
vWF and ITP
(platelets normal in vWF)
What type of cells are seen in G6PD?
Heinz bodies and bite cells
When are schistocytes seen?
HUS
When is basophilic stipling seen?
iron and lead toxicity
What type of cell has bilobed nucleus?
eosinophil
What type of cell has a large, sometimes odd-shaped nucleus?
monocyte
How do neutrophils appear on smear?
multilobed
When is agglutination seen?
autoimmune hemolytic anemia
C. diff route of transmission
fecal oral transmission
hand washing prevents transmission
What types of organisms does endogenous acquisition normally occur with?
gram negative bacteria
C. Diff
What can the non-treponemal syphilis screen show?
can distinguish active (high titer) from old/cured infection
RPR is non-treponemal syphilis screen
What is an example of a treponemal syphilis screen? What can this tell you?
IgM/IgG screen
Tells you that the patient was infected at some point. Cannot distinguish between active and cured infection
Can non-treponemal (RPR) testing tell you primary vs. secondary syphilis?
no!
What is the preferred first line treatment for HIV?
integrase inhibitor
nucleoside reverse transcriptase inhibitor (NRTI)
What leads to chronic inflammation in HIV?
dysbiosis (imbalance in gut) and microbial translocation due to permanent loss of Gut Associated Lymphoid Tissue
Signs of candida
yeast cells with pseudohyphae
budding yeast
white patches in mouth (if oral thrush)
What do you use to treat HCV?
NS5B polymerase ingibitors
What do you use to treat influenza?
neuraminidase inhibitors
What is the only mold we have learned?
aspergillus
What do we use to treat cryptococcus?
amphotericin + flucytosine
Patients on anti-TNF inhibitors / immunosuppressants are at risk for what infection?
TB
need TNF-a to form granuloma in order to control the infection
How does TB transmission normally occur?
airborne
aerosol droplet typically by cough from someone with active TV
What is more specific TST or IGRA?
IGRA since this can tell the difference between old infection and BCG vaccine which the TST (PPD) test cannot
Rifampin MOA
inhibition of DNA-dependent RNA polymerase
Ethambutol MOA
interferes with arabinosyl transferase to prevent polymerization of cell wall
Isoniazid MOA
inhibits mycolic acid synthesis pathways
Why do plasma cells have large cytoplasm?
need lots of ER to generate antibodies
How can you describe N. gonorrhea ?
gram negative diplococci
Cervical lymphadenopathy in toddlers indicates …
MAC
3 genes of HIV and what each encodes
Env gene: gp120 and gp41
Gag gene: p24 core antigen and p17
Pol gene: reverse transcriptase, integrase and protease
Testing order for HIV
fourth generation screening
if positive, HIV 1/2 differentiation assay
then, NAAT testing
Difference between NNRTI and NRTI
NRTI = DNA analog that competes with the host DNA to block reverse transcriptase (actually DNA)
NNRTI = non-competitive inhibitor of reverse transcriptase that binds directly to reverse transcriptase
What is another example of a budding yeast ?
cryptococcus (also candida)
Sodium potassium pump
works against concentration gradient
3 Na+ out and 2 K+ in
