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Week 11 - Diseases
w11
116
Pharmacology
Undergraduate 1
01/18/2016

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Cards

Term
What movements does the knee joint articulate
Definition
-flexion and extension
-internal and external rotation
-6 total degrees of freedom
Term
what are the two articulating joints within the knee
Definition
patella-femoral
tibiofemoral
Term
What are the ligaments in the knee joint
Definition
-medial and lateral collateral ligaments
-anterior and posterior cruciate ligaments
-patella ligament
Term
What are proteoglycans
Definition
-protein polysaccharides synthesised by chondrocytes
-negatively charged
-protein core with GAGs attached

MAIN ONE IN CARTILAGE IS AGGRECAN
Term
what is the main role of chondrocytes
Definition
breakdown/remake/maintain matrix
Term
What is osteoarthritis?
Definition
cartilage degeneration
Term
what happens in early osteoarthritis?
Definition
1.cartilage fibrilation and decreased proteoglycans = ;pad bearing capactiy and lubrication deteriarates
2.cartilage decolours/softens and surface irregulates
3.more susceptable to mechanical damage
4.collagen network deteriorates and allows increased water retention = stiffness of tissue
5.chondrocytes attempt repair
6.collagen breaks down = production of collagenases
Term
what happens in advanced osteoarthritis?
Definition
1.full thickness defects develop done to the bone
2.osteochondral fractures
3.deformation of bone and loss of PGs
4.wound healing response (cells from bone marrow)
5.fibrocartilage is formed (worse than hyaline)
Term
What role do chondrocytes have in OA?
Definition
source of destructive enzymes
matrix remodelling
synthesise cytokines:
-inflammatory
-catabolic
-inhibitory
-anabolic
Term
what are matrix metalloproteases (MMP)
Definition
produced by chondrocytes and are involved in matrix turnover, tissue remodelling and resorption.
tightly regulated by cytokines
they act on collagens, proteoglycans and other non-collagenous proteins of cartilage
Term
what do MMP degrade?
Definition
collagenous
gelatinous
GAGs
others
Term
What is the initiator of OA?
Definition
disease of whole joint not just cartilage
abnormal mechanical loading
biochemical factors
Term
How is OA and the immune system related?
Definition
-increased amount of complement proteins in the synovial fluid of patients with OA than healthy ones
Term
what is the drug target for drugs that may prevent OA
Definition
complement systems
Term
What is current treatment for OA
Definition
drugs target symptoms rather than causes
moderate pain relief
concerning side effects
Term
What is Rheumatoid arthritis
Definition
systematic inflammatory autoimmune disease
synovial joint
inflammatory response of synovium
proliferation of synovial cells = excessive synovial fluid
=destruction of cartilage and stiffness of joints
Term
What are the causes of RA
Definition
genes
environmental factors
chance
SMOKING IS MOST SIGNIFICANT
Term
Describe the pathogenesis of RA
Definition
1.lungs encounter smoke
2.macrophages are activated
3.cells undergo apoptosis/necrosis/both
4.increased synthesis of peptidylarginine deiminases
5.causes citrullination of proteins in lungs
6.these bind to HLA-DR molecules on APC
7.smoking further contributes to t-cell and b-cell activation by triggering APCs in lung leading to increased antibody production
8.this occurs years before onset of RA and leads to immune complex formation
Term
What are the treatments for RA
Definition
1.pharmaceuticals
2.antiinflammatories
3.analgesics.
Term
What is the difference between autosomal and sex-linked inheritance?
Definition
A=trait/disorder on autosomal gene
S=on sex gene
Term
define genome
Definition
all dna coding for an organism
Term
define somatic cell mutation
Definition
cannot be transmitted to offspring
Term
define gonodal mutations
Definition
can be passed on to offspring
Term
what are chromosomal mutations
Definition
extra/lost chromosomes
damage to chromosomes
Term
what are submicroscopic muations
Definition
changes to more nucleotides
Term
what are SNPs
Definition
involves the replacement of a single nucleotide by another
Term
Describe the 4
Definition
transition
transversion
deletions
insertions
Term
define a synonymous mutation
Definition
no change (produces the same amino acid)
Term
define a non-synonymous mutation
Definition
alteration in the encoded polypeptide which results in disease. There are 3 things: missense, nonsense, frameshift
Term
what happens in a missense mutation?
Definition
SNPs lead to coding for a different aa and hence altered protein.
reduces activity or altered characteristics
Term
what happens in a nonsense mutation?
Definition
substitution that leads to generation of a stop codon therefore premature termination of translation.
unlikely to retain biological function.
Term
what happens in a frameshift mutation?
Definition
when a non multiple of 3 is inserted the reading frame is disrupted.
abnormal protein function.
may also result in a subsequent stop codon
Term
how can a mutation cause loss of function to a protein
Definition
reduced activity (hypomorph)
decreased stability (null allele)
loss of gene product
inherited enzyme function reduction
Term
how can a mutation cause gain of function to a protein
Definition
increased level of gene receptors
development of new functions of gene product
Term
What is huntingtons disease caused by
Definition
expanded triplet repeat mutations of the huntington gene cause aggregations in the CNS
single gene, autosomal dominant inheritance
slow selected cell death in CNS
movement disorder and intellectual impairments
Term
What are LDL receptors
Definition
cell surface receptors allowing for endocytosis of LDLs
present on all nucleated cells, important in liver
Term
What are LDLs
Definition
transport mechanism for fats in an aqueous environment
transport cholesterol and triglycerides
Term
Describe the mechanism
Definition
1. ldl binds to receptor in clathrin coated pit
2.forms vesicle which fuses with endosome containing H+
3. protons cause receptor and ldl to go to opposite ends
4.vesicle splits, receptor goes back to surface
5.acid hydrolase degrades ldl's into amino acids and cholesterol
Term
What are the effects of LDL receptor mutations?
Definition
1. ER ->receptor synthesis
2.Goldi -> receptor modification
3.Cholesterol cannot bind to receptors
4.cannot endocytose into clathrin pits
5.receptors cannot traffic back
Term
what do all ldl receptor mutations cause
Definition
high levels of cholesterol in the blood
Term
What is familial hypercholesterolemia FH?
Definition
inability to internalise LDLs at the normal rate and high blood LDL levels. LDL's circulate for twice as long.
Term
What accelerated atherosclerosis lead to
Definition
cardiovascular disease
Term
which is more common hetero or homo?
Definition
hetero
Term
Define atherosclerosis
Definition
disease of the arterial characterised by the deposition of fatty material on inner walls. no symptoms at first
Term
What are the 3 fatty deposit types and where do they appear?
Definition
Xarithoma -> tendons (hands, elbow, knees and feet)
Xarithelamas -> eyelids
Corneal arcus -> iris and cornea
Term
What cholesterol levels fo FH patients have?
Definition
>200mg/dL
Term
What are the effects of atherosclerosis
Definition
-cholesterol deposited in artery wall
-chronic inflammatory response
-weakening/hardening/narrowing of arteries
Term
What does atherosclerosis increase your risk of
Definition
angina pectoris
coronary thrombosis
myocardial infarction
Term
How is hetereozygous FH treated?
Definition
-prevention of CVD:lifestyle, diet, exercise
-pharmaceuticals: statins, bile acid sequestrants, fenofibrate
Term
How is homozygous FH treated?
Definition
-drug therapy
-xanthoma removal
-invasive treatments
Term
What does CVD include
Definition
all diseases of the heart and circulation:
-coronary heart disease
-angina
-heart attack
-congenital heart disease
-stroke
Term
Describe the mechanism of atherosclerosis
Definition
1.increased blood plasma lipids
2.circulatin monocytes begin removing excess cholesterol rich lipoproteins
3.monocytes filled with lipid droplets become foam cells and attach to endothelial lining of blood vessel walls
4.they release cytokines causing SMC to divide
5.other monocytes invade area
6.endothelial cells start phagocytising lipids
7.plaque formation
Term
How can atherosclerosis lead to clot formation
Definition
1.when conditions persits, endothelial cells become swollen with lipids and gaps appear in the lining
2. rbc attach to exposed collagen and clot forms
Term
What causes atherosclerosis
Definition
smoking
diabetes
high fat diet
sedentary lifestyle
overweight
high blood pressure/cholesterol
Term
What 3 parallel circuits is the cardiovascular system divided into
Definition
pulmonary
coronary
systematic
Term
Define angiography
Definition
medical imagining technique used to visualise blood vessels and organs.
injection of radio-opaque dye into the coronary circulation and detects blockages using xrays.
Term
What events lead to angina pectoris/heart attack?
Definition
accumulation of atherosclerotic plaques in coronary arteries
blood flow to the myocardium is restricted
Term
How is CAD detected?
Definition
1.patient will come to the doctor with chest pain
2.they will be injected with streptokinase to break up blood clots
3.once stable, angiography will be used to detect CA blockages
Term
Describe angioplasty (PTCA)
Definition
1.balloon catheter is threaded to destructed area
2.balloon is inflated and stretches arterial wall and squashes plaque
3.lumen is widened, balloon is deflated and catheter is withdrawn
Term
What are the problems associated with angioplasty
Definition
-balloon inflation induces ischaemia (inadequate blood supply in heart)
-damage to vessel could lead to closure of the artery again
Term
Describe bypass (CABG)
Definition
-surgical procedure that diverts blood around narrowed/clogged parts of the major arteries
-conduit normally harvested from the saphenous vein from the leg
-routine to have 2-4 grafts to bypass blocked arteries
Term
What are the problems associated with pypass
Definition
open chest surgery
involves stopping the heart
grafts can resterose (narrow)
Term
What is hypertension and give the figures
Definition
abnormally high blood pressure
systolic >140mmHg
diastolic >99mmHg
Term
what is hypertrophic cardiomyopathy
Definition
muscle wall becomes thickened which makes the muscle stiff and therefore blood is harder to pump around body
Term
what is dilated cardiomyopathy
Definition
thinning of the ventricular walls enlarges the interior of the ventricular chamber. there is impaired ventricular relaxation and the heart muscle becomes weak.
Term
what is left ventricular noncompaction
Definition
trabeculated ventricular walls create a spongy appearance, prominent in the left ventricular wall.
Term
what is cardiac hypertrophy
Definition
abnormal enlargement of the heart muscle, resulting from increased cardiomyocyte size
Term
How can increased SV result from heart failure
Definition
-increased ESV by reduced contractility
-decreased diastolic volume by impaired ventricular filling
Term
How is heart failure diagnosed
Definition
blood tests
breathing test
ECG
echocardiogram
Term
What is Wolk Parkinson White sydrome
Definition
pre-excitation of ventricular tissue
caused by abnormally fast conduction
Term
What are the characteristics
Definition
short p-r interval
slurred upstroke of the QRS
QRS widened
Term
what is the treatment
Definition
electrophysiology study followed by cathater ablation of accesory pathway
surgery/drug therapies
Term
What is diabetes insipidus
Definition
produces a copious volume of dilute urine due to the failure to reabsorb water in the renal collecting duct
Term
why is the collecting duct unable to reabsorb water
Definition
there is no vasopressin (central diabetes insipidus)
kidney cannot respond to it (nephrogenic diabetes insipidus)
Term
How is the collecting ducts permeability controlled?
Definition
1.vasopressin/adh binds to receptors on basolateral membrane
2.GPCR events follow...PKA phosphorylates AQP2
3.APQ2 moved to the apical membrane is inserted
4.water can now enter the tubular fluid and leave through APQ3/4
Term
What is central diabetes
Definition
failure to produce functional vasopressin
Term
how is central diabetes aquired
Definition
damage to the hypothalamus and or pituitory:
-trauma
-tumour
Term
what is nephrogenic diabetes
Definition
collecting ducts are unable to respond to vasopressin
Term
how is nephrogenic diabetes aquired
Definition
drugs (lithium)
electrolyte distrubances
kidney diseases
Term
what is dipsogenic diabetes insipidus
Definition
excessive drinking leads to water overload and hyponatraemia
Term
How is DI determined
Definition
water is restricted whilst weight, plasma and urine osmolarity and urine output are monitored
Term
what is the treatment for central DI
Definition
dDAVP a synthetic vasopressin
Term
what is the treatment for nephrogenic DI
Definition
water replacement
salt restriction
thiazide diuretics
Term
What does CVD include
Definition
all diseases of the heart and circulation:
-coronary heart disease
-angina
-heart attack
-congenital heart disease
-stroke
Term
Describe the mechanism of atherosclerosis
Definition
1.increased blood plasma lipids
2.circulatin monocytes begin removing excess cholesterol rich lipoproteins
3.monocytes filled with lipid droplets become foam cells and attach to endothelial lining of blood vessel walls
4.they release cytokines causing SMC to divide
5.other monocytes invade area
6.endothelial cells start phagocytising lipids
7.plaque formation
Term
How can atherosclerosis lead to clot formation
Definition
1.when conditions persits, endothelial cells become swollen with lipids and gaps appear in the lining
2. rbc attach to exposed collagen and clot forms
Term
What causes atherosclerosis
Definition
smoking
diabetes
high fat diet
sedentary lifestyle
overweight
high blood pressure/cholesterol
Term
What 3 parallel circuits is the cardiovascular system divided into
Definition
pulmonary
coronary
systematic
Term
Define angiography
Definition
medical imagining technique used to visualise blood vessels and organs.
injection of radio-opaque dye into the coronary circulation and detects blockages using xrays.
Term
What events lead to angina pectoris/heart attack?
Definition
accumulation of atherosclerotic plaques in coronary arteries
blood flow to the myocardium is restricted
Term
How is CAD detected?
Definition
1.patient will come to the doctor with chest pain
2.they will be injected with streptokinase to break up blood clots
3.once stable, angiography will be used to detect CA blockages
Term
Describe angioplasty (PTCA)
Definition
1.balloon catheter is threaded to destructed area
2.balloon is inflated and stretches arterial wall and squashes plaque
3.lumen is widened, balloon is deflated and catheter is withdrawn
Term
What are the problems associated with angioplasty
Definition
-balloon inflation induces ischaemia (inadequate blood supply in heart)
-damage to vessel could lead to closure of the artery again
Term
Describe bypass (CABG)
Definition
-surgical procedure that diverts blood around narrowed/clogged parts of the major arteries
-conduit normally harvested from the saphenous vein from the leg
-routine to have 2-4 grafts to bypass blocked arteries
Term
What are the problems associated with pypass
Definition
open chest surgery
involves stopping the heart
grafts can resterose (narrow)
Term
What is hypertension and give the figures
Definition
abnormally high blood pressure
systolic >140mmHg
diastolic >99mmHg
Term
what is hypertrophic cardiomyopathy
Definition
muscle wall becomes thickened which makes the muscle stiff and therefore blood is harder to pump around body
Term
what is dilated cardiomyopathy
Definition
thinning of the ventricular walls enlarges the interior of the ventricular chamber. there is impaired ventricular relaxation and the heart muscle becomes weak.
Term
what is left ventricular noncompaction
Definition
trabeculated ventricular walls create a spongy appearance, prominent in the left ventricular wall.
Term
what is cardiac hypertrophy
Definition
abnormal enlargement of the heart muscle, resulting from increased cardiomyocyte size
Term
How can increased SV result from heart failure
Definition
-increased ESV by reduced contractility
-decreased diastolic volume by impaired ventricular filling
Term
How is heart failure diagnosed
Definition
blood tests
breathing test
ECG
echocardiogram
Term
What is Wolk Parkinson White sydrome
Definition
pre-excitation of ventricular tissue
caused by abnormally fast conduction
Term
What are the characteristics
Definition
short p-r interval
slurred upstroke of the QRS
QRS widened
Term
what is the treatment
Definition
electrophysiology study followed by cathater ablation of accesory pathway
surgery/drug therapies
Term
What is diabetes insipidus
Definition
produces a copious volume of dilute urine due to the failure to reabsorb water in the renal collecting duct
Term
why is the collecting duct unable to reabsorb water
Definition
there is no vasopressin (central diabetes insipidus)
kidney cannot respond to it (nephrogenic diabetes insipidus)
Term
How is the collecting ducts permeability controlled?
Definition
1.vasopressin/adh binds to receptors on basolateral membrane
2.GPCR events follow...PKA phosphorylates AQP2
3.APQ2 moved to the apical membrane is inserted
4.water can now enter the tubular fluid and leave through APQ3/4
Term
What is central diabetes
Definition
failure to produce functional vasopressin
Term
how is central diabetes aquired
Definition
damage to the hypothalamus and or pituitory:
-trauma
-tumour
Term
what is nephrogenic diabetes
Definition
collecting ducts are unable to respond to vasopressin
Term
how is nephrogenic diabetes aquired
Definition
drugs (lithium)
electrolyte distrubances
kidney diseases
Term
what is dipsogenic diabetes insipidus
Definition
excessive drinking leads to water overload and hyponatraemia
Term
How is DI determined
Definition
water is restricted whilst weight, plasma and urine osmolarity and urine output are monitored
Term
what is the treatment for central DI
Definition
dDAVP a synthetic vasopressin
Term
what is the treatment for nephrogenic DI
Definition
water replacement
salt restriction
thiazide diuretics
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