What are some medical resources used less by Indigenous than nonI
- PBS (pharm) - MBS (medical) - dental
Why preventative health?
- improves health care - IAs are high users of publicy funded systems - majority of IA health burden is in preventable chronic disease (cause large proportion of excess death) - bigger 'return' on investments - decrease later costs
prevent onset of disease
Detect preclinical disease for cure/prevention progression
Accessing health care for indigenous people is tainted by...
experience/memory of discrimination and insensitivity in accessing healthcare
Example of commonly used clinical history tool that is inappropriate with indigenous people?
Pain rating (1-10) - aboriginal men avoid expressing pain
5 reasons found by Aboriginal & TSI health survey for why they don't seek healthcare?
1. access difficulties2. cost 3. transport/distance 4. lack of available services 5. cultural barriers
Definte institutional racism
Societal systems or patterns that have the net effect of imposing oppressive or negative conditions against identifiable groups based on race/ethnicity
The increasing shift to shorten hospitalisation visits impedes...
1. opportunities for education 2. links to primary care
Importance of communication skills in I healthcare
- history & language- building trust with pt - giving adequate time for effective communication - including Aboriginal health workers as members of health care team
when healthcare providers disregard social and cultural context - mismanage patient or exacerbate stress/pain
Overall discrimination in health care
System established according to western model is perceived as benign/fair but in fact is inappropriate & discriminatory for aboriginal health care issues
Ways to combat this lack of integrative healthcare?
- encourage physicians to engage with community- establish contact with elders - change the system (doesn't offer holisitic sociocultural context of patient's problem)
Captain Cook claims Eastern Australia
Wars and attacks throughout
begin moving indigenous people into missions and have protection and control policies
Federation, Aboriginal people not recognised
When did the assimilation policuy begin (roughly)?
Right to vote in federal elections
first half 20th century - belief that In genetically inferior - 'dying out' (segregation)
Health strategies of 70-90s
based on increasing access to mainstream health services
Who governs aboriginal health services management?
local Aboriginal community - to deliver culturally appropriate compreghensive primary healthcare
Staffing of aboriginal health services
64% are A and TSI
Why is the funding to indigenous health inadequate (despite beliefs to contrary)
- is 18% more per person BUT there is 3x higher disease and death rates - is only 2.8% of total health expenditure - inadequate access to mainstream health funds ( medicare, PBS) - increasingly relient on short-term or specific program funds to prop up core capacity
Shared responsibility agreements (SRAs)
trade of service provisions for adoption of prescribed behaviours (e.g. welfare for work policies) - perceivecd by Aboriginal leaders as coercive and paternalistic - no health care improvements as a result
3 reasons for why there has been little improvement in A healthcare over last 30 years
1. denial of history2. jockeying over state & federal govt responsibilities 3. huge turn-abouts in policy (centralisation v regionalisation)
Caring for country promotes
ecological, spiritual and human health
6 activites that involve 'caring for country'1
1. time on country2. burning annual grasses 3. fathering food & medicinal resources 4. protecting sacred areas 5. ceremony 6. producing artwork
Give some examples of how Caring for country activities are associated with better healthcare outcomes
social determinants of healtyh and looks beyond traditional biochemical model
Holistic health encompasses (4)
1. mental2. physical 3. spiritual 4. cultural Requires harmony of these factors and land.
3 modes of 'connection to land'
1. localised knowledge of region's natural history2. past personal / family experiences 3. deeper connection: traditional stories/beliefs (ongoing through hunting/gathering and being 'on country')
Quality time 'on country' reduces risk of disease - T/F?
true, impacts on mental health, DM, CV risk
What is 'historical trauma'
subjective experiencing and remembering of events in the mind of an individual or the life of a community, passed from adults to children - collective emotional injury over lifespans and across generations
'soreness of spirit'
mental illness, caused by loss of social networks, destruction of kinship and dislocation from ancestral lands
Rates of psychological distress in A's is ___x higher
2x - 27% reported high/v. high distress
Common life stressors:
- death of family member/friend in last year- serious illness/disability - alcohol problems
T/F mental health is only a component of social & emotional wellbeing
True, other components are connection to land, culture, spirituality, ancestry, family and community
NATSIHS looks at 8 domains, name them
1. psychological distress (hopelessness?) 2. impact of psyc distress (activites affected) 3. positive wellbeing (balance?) 4. anger ((useful indicator of distress) 5. life stressors 6. discrimination (rejection, persecution) 7. cultural identification (if broken, detrimental effects to health) 8. removal from natural family (core unit, threatened throughout history)
Positive wellbeing was higher/lower in remote areas?
Psychological distress is more common in people who use...
1. dreamtime stories 2. sense of belonging to sea, land, other people and one's culture
In aboriginal spirituality there is no ______ of past and present or dichotomy of objects and ____.
In aboriginal spirituality there is no demarcation of past and present or dichotomy of objects and persons
3 mental illness conditions linked to spirituality:
1. depression2. anxiety 3. aggression (sick in spirit)
Where Aboriginals nomadic?
NO - needed permission to travel to another tribe's land or 'country'
What is 'Closing the Gap'
CTG is formal commitment by Aust. Govt. in 2008 to work togetehr to achieve equality in health status amd life expectancy between A & TSI and nonInd by 2030.
2 things brought about CTG
1. Social Justice Report (2005)2. CTG campaign 2006-7
5 Major Aims of CTG
1. life expectancy 2. child mortality 3. early childhood education 4. educatinal achievement 5. employment outcomes (halve)
2 goals of economic participation
1. enhance employment opportunities 2. policies on barriers to participation
4 things to improve in current poor living conditions:
1. water 2. waste collection 3. electricity 4. housing infrastructure
Children are a priority group because they are especially vulnerable to?
Disease transmission from overcrowding & unhygienic houses
CTG PBS co-payment system
Improves PBS access (lower/nil cost) to A & TSI people living with or at risk of chronic disease (CTG annotated scripts)
Prescribers of CTG-annotated scripts must be:
- practitioner working in practice participating in Indigenous Health Incentive (under PIP)- working in IHS rural/urban - any specialist in any practice if patient is eligible under CTG-PBS Co-payment measure
People experience affirmitive action (school, scholarships etc.) and give back to community (act as role model, work in that community). People receive Govt. support
Issues with affirmative action:
- Doubts about deserving support (worse with mainstream hostility, system racism) - assumption of indigneous as 'victim' - doubt self-worth and identity - need to see recipients as multiple identities not just as 'indigenous' - cam be combatted by making sure that recipients are capable
Structure of Indigenous Health Services
- Aboriginal health worker is 1st point of call - Dr is not centre of health serrvice, community is - locally elected Board of management express community's wishes (respond to their social, emotional and cultural wellbeing) - improves access - deal with ALL patients issues ie. referals for counselling, mental health etc. - preventative health - family wellbeing, nutrition, immunisations - holistic healthcare model, has trust of community members
What do Aboriginal Health Services offer? list 5
1. social welfare 2. health education and promotion 3. mental health 4. environmental health 5. clinical services
National Aboriginal Community Control Health Organisation(NACCHO)
national body (network) - represents >150 ACCHSs, represents, and liases, fosters cooperation with govt.
Other diverse roles of ACCHs:
Community development - employment - education - empowerment -social action
Barriers of previous interventions (before early years)
- negative stigma (interference, control) - based on premise that parents are imcompetent (stereotypes of neglect, abuse, assault)
- assume all parents love their children - social mapping (focus on existing strengths, energies & skills of comunity) - 'yarning' - consultation, listen and learn from community (what can be done better?)
Intervention engaged Indigenous parents becuase it stemmed from community strenghts
V/Q > 1
area being adequately ventilated but not perfused well enough
V/Q < 1
area not being well ventilated but well perfused
Yuendumu Old People's Programme
- maintains 'high care' for elderly in Alice Springs - Cultural comfort (family care) - designed to accommodate traditional organisation of domestic camps, gender relationships and avoidance relationships - services provided by local people (speak language, known to client group) - connected to wider community
Benefits of a cultural comfort home
- high compliance therefor more effective- promotes self-relience & community ownership - feasible model for delivery of aged care in indigenous communities - 'family model'
Rate of renal disease in indigenous v. nonInd
10x higher in In
Why is kidney donation not an acceptable option for In?
akin to 'giving spirit away'
T/F there is a strong link between early asymptomatic phases of renal adn CVS disease
S: surgery for trichiasis A: antibiotics F: facial cleanliness E: environmental improvement
What causes Acute Rheumatic Heart Disease (ARF)
- immunological reaction to infection with group A strep
What is ARF
causes acute, generalised inflammation affecting heart, joints, brain and skin
Who are the victims of ARF and RHD?
children and adolescents of indigen ous communities
Transmission of group A strep by:
- poor living conditions- hygiene standards - poor health services - acess to penicillin
rheumatic heart disease, resulting from damage to mitral/aortic valves frorm ARF
Treatment of ARF
- suspected ARF patients should be hospitalised- 2ndary prophylaxis with 4-weekly BPG (min. 10 years/until 21 yo) - moderate - severe RHD - continue until age 35-40 -there is very poor adherence to ARF tx (scheduled injections are difficult)
What is the disparity between ind. and nonind. hospital care of acute coronary syndrome?
3x rate of events, 2x in hospital death rate BUT much lower rate of angiography, angioplasty, stent/bypass procedures
Issues with women's sexual health
- care must be culturally appropriate - aborigine's lack of conidence in healthcare (contributes to lower health status) - Protection era: women targeted, removed from homes and forced medical sexual health examinations/tx (power, distrust) - need to be able to trust nurses (need Aboriginal health care workers)
nurse and client both have own cultures -all interactions are bicultural - need focus on being regardful of differences and recognise them
3 key findings of the sexual health nurses report?
-need trustworthy relationships with nurses, AHCWs and pts (more difficult in urban areas where unsure of community structure, elders etc.)- recognition of aboriginal culture - also important in urban areas (nurses need to trained for cultural skills) - women's health business requires gender considerations (cannot mix with men on these issues)
Smoking in indigenous communities
Rates have NOT declined (unlike rest of Australia) - mainstream anti-smoking campaigns not working
Effective anti-smoking ideals for Ind:
- focus on wellness (not illness), support, empower, trust & resilience - changing person's life, identity & autonomy over the process - positive factors: significant life event and supportive relationships - broader initiatives - imrpoved standard of living, education, employment etc.
What percentage of life expectancy gap does tobacco account for?
Smoking during pregnancy is a major risk factor for...
- culture 'bush' tobacco- colonisation - paid in tobacco - addiction & other priorities (alcohol) - normalisation - part of social life, reinforces family relationship - less preventitive services (none for Ind til 2000) - lower SES Protective factors: finishing grade 12, higher income, employment all less likely to smoke
Aboriginal Health Workers roles
- first point of contact (screening)- collect culturally appropriate info - normally good trusting relationship - check understanding, help will follow-up - can accompany them to other health professionals if needed - coordinate other appts and services - bring understanding of cultural safety
Are Aboriginal health workers registered?
Yes - recognised as part of health care delivery in Australia (growing importance)
rate of end-stage renal disease changes from 1996 to 2006
Percentage of australian population that is ATIS
proportion of ATIS who smoke
How many indigenous people had reported recent discrimination?
What proportion of indigenous adults have reported being a victim of violence (last 12 months)
Rate of hospitalisations for indg v non-ind
What condition accounts for the majority of the mortality gap?
Chronic disease *80%
Leading cause of death in children (5-14)
external causes (3x nonIN)
Ratio of Govt. health care expenditure ind:nonInd
List 6 indicators for cholesterol and CKD screening
1. family hx2. overweight, obesity 3. smoking 4. DM 5. elevated BP 6. all people >30yo
'twin towers' in poor aboriginal healthcare
1. institutionalised racism 2. misunderstaind in communication
Define aboriginal concept of 'country'
interdependent relationship between Indigenous peoples and their ancestral lands and seas
Hospitalisations for self-harm are more than ___ x as likely in Ind
Social and emotional wellbeing encompasses
1. mental2. social 3. spiritual 4. cultural wellbeing (includes family and community)
Is spirituality static or dynamic?
Dynamic: evolves, is a contemporary expression, transformed by engaging cultures, technologies and religion
List 5 'building blocks' of CTG
1. early childhood2. economic participation 3. healthy homes 4. safe communities 5. governance and leadership
Eligibility criteria for CTG-PBS co-payment measure
1. have or at risk of chronic disease2. ATSI 3. would experience setbacks if not given medication 4. unlikely tro adhere to medications without assitance through the Measure
(all age eligible)
Markers of early renal disease1
1. albuminuria2. urine albumin:creatinine ratio (ACR) 3. GFR (+CVS risks)
Prevalence of OM in indigenous children?
12% (3x rate that WHO classes as a 'massive health problem'
Risk factors for DM
MOST ARE IDENTIFIABLE (potential for earlier prevention)- diet & obesity - physical activity - poor living conditions - low SES
What does cultural competence involve?
1. being aware that peron's culture shapes understanding health & illness2. learning about specific cultural beliefs that surroundmental illness 3. learning how mental illness is described in a person's community 4. being aware of waht concepts, behaviours or language are taboo
what is the difference between ischema and hypoxia?
ischema includes the lack of oxygen but also other substrates in the blood which causes more damage.
what is the hallmark sign of reversible injury?
why do cells swell in response to ischema?
ATP depletion which alters the ion concentrations.
contaminated with bacteria ; undergo coagulation necrosis followed by liquefaction to produce an abscess
what is a bland infarct?
an infarct w/o infection
no infection of the infarct site
what is specific to brain infarcts?
1. the nature of the blood supply
2.rate of occlusion developments
3.type of affected tissue
these are all influences on _______.
what are the two types of infarcts?
transmural and endocardial.
What separates the tunica media from the tunica adventicia?
the external elastic lamina
what is the response to retention hypothesis?
1. lipoprotein retention is the enacting event of atherosclerosis.
2.MIgration of lipoproteins forms LDL
3. LDL is then taken up by macrophages to become foam cells
what is the oxidative modification hypothesis of atherosclerosis?
LDL on its own is not atherogenic, but when it migrates to prone sites it gets oxidized. OX-LDL signals for macrophage uptake--> foam cells. The Ox LDL then signals for lymphocytes and monocytes and stimulates dmc proliferation. this is a cycle that keeps expanding causing a plaque formation
Oxidative Modification Hypothesis of Atherosclerosis
LDL itself isn't the problem but rather the oxidation of LDL that causes atherosclerosis
what is endothelial dysfunctions role in plaque formation ?
Atherosclerosis begins with endothelial injury or dysfunction characterized by enhanced endothelial permeability and low-density lipoprotein (LDL) deposition in the subendothelial space.
what is hypercholestrolemia and whats its importance in atherosclerosis?
it is the build up of extracellular lipids. This makes them available to be reactive and migrate into the epithelial
what is step 2 in the initiation of atherosclerosis?
leukocyte recruitment and accumulation. This is done by increasing adhesion molecule expression and chemoattractants directing the migration of leukocytes.
Step 3. intracellular lipid accumulation
lipids are taken up via scavenger receptors. then the cytokines stimulate macrophages to proliferate
what is step 4 in atheroma progression?
smc proliferation and migration. SMC's change phenotype so they can sense chemoattractants and migrate around.
What are the risk factors for acute MI?
in order of most common to least common, what are the three main sites for coronary blockage?
LAD > RCA > Circumflex
______ presents as a lateral wall infarction of the L. Ventricle?
circumflex artery occlusion
_______presentas a anterior and septal death.
_______presentas a posterior wall infarcts?
why is the endocardium most prone to ischemia?
because it is the last part of the tissue to get supplied by blood, which means its the first to lose blood flow.
in response to myocardial ischemia what happens in the first few seconds to the tissue?
the tissue converted from aerobic to anaerobic glycolysis
what is the morphology of an MI at 3-7 days?
1. red granulation tissue moves in
2. macrophages start cleaning up
3. maximum sofness --> prone to injury
what are the signs in MI at 7-10 days?
area is bright yellow and granulation tissue/collagen are well formed.
what are the signs of MI 2 months out?
white non contractile fibrous tissue ( scar) has replaced the myocardium
what are the two dangers associated with repercussion of ischemic tissue?
1. Contraction band necrosis: caused by a flood of calcium contracting the muscle which is currently weak and tearing apart the sarcolemma.
2. Free Radical Damage.
What are the 5 major steps to heart formation? and what weeks do they occur at?
1. Tube formation : Wk3
2.Looping wk 4 ( heart beat on day 22)
3. Septation wk 4-5
4. outflow tract septation 4-8
5. valve formation 6-9
IN the heart tube, what is the organization of structures superiorly to inferiorly?
1. Blood outflow arterial
2. Trucus arteriosus
3. Bulbus cordis
5. primitive atria
6. sinus venosus
7. inflow tract : venous.
what cells give rise to septation of the outflow tract?
neural crest cells.
- out-pouchings of the cardiac jelly that will eventually form the atrial-ventricular septum- septum intermedium
- cushions will also remodel to form valves
what do the cardiac cushions give rise to?
1. L/R auricles
2. carne trabeculae
3. Valves and septa
4. outflow tract septation.
where is fetal blood flow the highest concetration of O2 ( 80%)
the coronary arteries. this is because all the rest of the blood in the arteries has some deoxygenated blood flowing in.
ductus arteriosus, IVC, SVC, pulmonary trunk, decending aorta, umbilical artery. where would we find the highest O2
IVC: this has the ductus venosus which comes from the umbilical vein ( oxygenated)
what are the remnant structures of the ductus arteriosus and the ductus venosus?
the ligamentum arteriosum and the ligamentum venosum
microdeletion at chromosome 22q11
thymic, parathyroic, cardiac defects; cleft palate, abnormal face
* issue with the neural crest cell migration.
what are the origins of melanocytes?
they are neural crest cell in origin. so any kind of melanoma is a prexisting neural crest cell issue.
what is the resting potential for autorhythmic cells?
describe the autorhythmic depolarization?
1. Funny current causes Na to come in and depolarize.
2. Calcium T-type calcium channels open.
3. L-type calcium channels open. ( depolarization
4. Potassium efflux ( repolarization
describe the action potential of a cardiac contractile cell.
1. -90 depolarization by Fast Na channels
2. Inactivatino of Na channels and activation of Fast Potassium.
3. Fast potassium out and slow Calcium in ( plateu)
4. K out fast - repolarization
how does Ach affect heart rate?
It is the parasympathetic respons at the muscarinic receptors. Opens up K channels and hyperpolarizes the cells taking longer to reach depolarization = slower HR
how do catecholamines affect heart rate?
B1 adrenoreceptors facilitate the opening of Calcium into the cell for depolarization quicker ( increase the slope) and increase HR.
what is the difference between HB and MB?
HB is tetrameric and MB is monomeric. it has a much higher affinity for O2 than HB>
what are the three ways that Co2 is carried in the body?
1. Bicarb -70%
2. Carbamino HB- 23%
3. dissolved in plasma - 7%
how does hemaglobin's conformation change in the presence of O2 ?
in high O2 regions, it is more stable in the oxyhb, so it binds easy. In the low o2 regions ( tissues) it has less affinity for O2 which means that it drops it off.
what conditions shift the HB affinity curve to the right?
1. High CO2
2. decreased PH
3. High 2,3 BPG ( stabilizes Deoxy form)
* this means that O2 wants to fall off into the tissues.
Why is the O2 change in Partial pressure so large(104 to 40) but the change in Co2 pressure is only about 5mmhg ( 40-45)
Co2 diffuses 20 times easier than O2. doesnt need a massive conc gradient to follow.
describe the steps to the pathogenesis of atherosclerosis. 7 steps.
1. Endothelial tissue injury
2.lipids bind in subendothelial space
3. lipids get oxidized
4. foam cell formation from macrophages.
5. formation of fatty streaks
6. smc proliferation and migration in intima
7. ECM synthesis and fibrous cap formation.
What is warfarin's mechanism of action?
Warfarin inhibits the synthesis of vitamin K dependent coagulation factors, such as VII, IX, X and II.
Note that warfarin does not dissolve the clot, natural proteases will do that instead. However, it stops the progression of clot formation.
what is the sign of a previous myocardial infarction?
pathological q wave.
what are some signs of air way remodelling?
1. goblet cell metaplasia
2.thickened basment membrane
3.thickened airway smooth muscle
4.inflammatory cells in submucosa.
V/Q of greater than one = ?
a physiological dead space.
V/Q of less than 1 = ?
ventilation deficit. Asthma or acute pulmonary edema.
what is the lungs response to high amounts of oxygen during hyperventilation?
relax arteriolar smooth muscle and increase blood flow ( Q)
what happens if we have low blood flow to a certain area?
decrease the flow of air to the tissue. ( decreased V)
how does the lung respond to low air flow?
by vaso constricting the blood to that site.
how does the lung respond to high blood fow?
dilation of air ways to increase Ventilation
What are the signs of type one respiratory failure?
lung tissue damage causing a V/Q mismatch. This causes hypoxia without hypercapnia ( can blow off Co2 but cant get O2 in. )
what is characterized by type 2 resp failure?
pump malfunction. hypoxia with hypercapnia : cant clear Co2. COPD/ resp center depression.
how do we compensate with metabolic acidosis?
by increasing RR.
how do we compensate with respiratory acidosis?
Increase bicarb from kidneys.
what is atopy?
the allergic hyper insensitivity, producing IgE to inoccuous bodies.
allergic hypersensitivity that form IgE against foreign proteins
what do Th2 cells release in response to apc bring them something?
what are azithromyacin, clarithromyacin, erythromyacin and how do they function? Also what type of bacteria do they work best on?
They are Macrolides , protein synthesis inhibitors. They attack the 50s subunit. They work well against gram positive cocci cells so we should use them against infections if we are allergic to pennicillin.
competitive antagonist at CysLT-receptors that block effects of LTC4, LTD4, LTE4 thus decrease bronchoconstriction
AE's: headache, GI
block airway M3-receptors preventing bronchoconstriction and bronchial mucus secretions
Blocks muscarinic acetylcholine receptors M3R, without specificity for subtypes, and promotes the degradation of cyclic guanosine monophosphate (cGMP), resulting in a decreased intracellular concentration of cGMP. NOT to be used as a short-acting bronchodilator
(Theophylline & Aminophylline)
bronchodilators by inhibiting PDE which increases c-AMP and c-GMP causing smooth muscle relaxation
AE's: stimulate heart & mild diuretic
Cromoglycate & nedocromil
prophylactic help decrease bronchospasms & inflammation present in resp. illnesses by reducing release of mast cells thus reducing activation of eosinophils and reducing leukocyte trafficking
AE's: upper respiratory tract irritation
Cromoglycate and Nedocromil
Prophylactic that decrease immediate late phase though mechanism unknown: decrease release of mediators from mast cells so decrease eosinophils and leukocytes
kidney pelvis meeting ureter, bend in the ureter, and where the ureter meets the bladder
*thinnest parts of the kidney*
Embryological Kidney is...
lobulated and then later fuses together into one structure
Where do the kidneys initially develop?
at the bladder and then ascend
What is a horseshoe kidney?
Congenital abnormality where kidneys are attached as they ascend
Is the aorta or the IVC furthest back
Kidney and ureter derived from the ____ mesoderm
at week 4
Ureteric bud give rise to:
collecting tubules, minor and major calyces, ureter, and kidney pelvis
mesonephric duct gives rise to the male or female gential system
male - wolfian ducts
Metanephric blastema gives rise to:
everything from the bowman's capsule to the collecting duct
Where does the glomerulus arise from?
Is the pronephros functional?
Renin regulates ____ which secretes aldosterone
What is the rate limiting step on angiotension II
3 major regulators of RAAS system
1. activation of the sympathetic nerves (beta 1-adrenoceptors)
2. reduced MAP
3. decreased Na conc in the distal tubues
kidney is a ____ driven filter
Macula densa cells
in distal tubules
cause release renin by communicating with the juxtaglomerular cells after they sense a decrease in sodium
70% of absorption should occur in the?
proximal convulated tubule
Where are brush borders located?
proximal convoluted tubule
they increase surface area for absorption
20% of absorption in the?
Loop of Henle
9% of absorption occurs in the?
1% of the absorption occurs in the?
collecting duct via the Enac channels
what secretes renin?
Angiotensinogen is converted to angiotension I by?
angiotension I is converted into angiotension II by?
ACE in the lungs
Angiotension II main effects in the body
1. cardiac hypertrophy
2. systemic vasoconstriction via AT1 receptors
3. brain - thirst - increased blood volume
4. renal sodium and fluid retention
5. pituitary - ADH - Na and fluid retention
6. adrenal cortex - aldosterone - Na and fluid retention
7. peripheral and central nervous system by amplifying SNA increasing vasoconstriction and increases CO
Angiotension II main function:
Which kidney feels it the most when there is an obstruction in one of them and HT occurs in the body?
the healthy one because nephrons knocking out the glomeruli so lower GFR rate thus destroying the kidney
AT1 receptor antagonists
Losartan, Valsartan, Candesartan
non-peptide competitive inhibitors of AT1 receptors thus blocking action of angiotensin II
AE's: anti-HT, cell growth effects
What 3 drugs should you never give a patient?
NSAIDs, ACE inhibitors, and diuretics
What will increase GFR rate?
Afferent arteriole dilation - prostaglandins, low dose dopamine, ANP, and NO
Efferent arteriole constriction - low dose angiotensin II
What will decrease GFR?
Afferent arteriole constriction - high dose angiotensin II, noradrenaline, NSAIDS
Efferent arteriole dilation - ACE inhibitors and all antagonists
post renal obstruction will increase Bowman's hydrostatic pressure, increase albumin
What are the gram positives?
All the Staph and Streps
What are gram negatives?
E. coli, Pseudomonas aeruginosa, Bordetella pertusis
Most important enzyme in drug metabolism
Which is the hepatic cytochrome?
Nitrates + Sildenafil
synergy since nitrates create more cGMP while Sildenafil inhibits phosphodiesterase which would convert to cGMP to GMP = so together they cause more smooth muscle relaxation and vasodilation
5 types of drug interactions
Drugs are primarily excreted by the ____
Drugs are primarily secreted in the ____ _____
agonist + antagonist
3 ways diets can affect drugs
1. drug absorption
2. urinary pH
What food will interact with about 50% of drugs?
What are a few important factors when giving neonates/infants drugs
1. they have a lower GFR
2. more total body water so volume of distribution can increase
3. they have low metabolizing capability
4. pharmacological variation high
What are a few important factors when giving drugs to geriatrics?
1. reduced hepatic and renal function
2. altered circulating plasma proteins
3. less receptors & reduced body water
Gray baby syndrome
due to chloramphenicol - would get large build ups of it
gray skin, cyanosis, abdominal swelling, hypothermia, HT, death
2 major drug-disease interactions
1. disease may affect efficacy of drug
2. drug may make the disease worse
where is the primary site for drug metabolism?
liver - first pass metabolism
2 reasons for metabolism of xenobiotics
1. increase rate of elimination - more water soluble
2. decrease toxicity
3. termination of effect
Phase I enzymatic reactions
try to detoxify the drug by introducing or exposing a certain functional group on the drug
oxidation, reduction, hydrolysis
Phase II enzymatic metabolism
try to make drugs more water soluble
sulfation, acetylation, glucuronidation
What is the most important hepatic cytochrome system?
Most important enzyme in hepatic metabolism of drugs?
3 variations in drug metabolism
1. tissue distribution
2. renal excretion
2 important effects hepatic disease has on drug metabolism
1. reduces amount of first pass metabolism
2. reduces elimination
when blood goes right about the liver so skips first pass metabolism
can be increased by diet, environment, etc.
leads to faster rates of metabolism & faster elimination
Where does most drug absorption occur?
Captopril, enalapril, etc.
prevent the conversion of angiotensin I to angiotensin II thus reducing vasoconstriction, Na retention, and aldosterone release so reduce BP
Losartan, -sartan, etc,
competitively block Ang II binding to the AT1 receptors thus decreasing vasoconstriction, Na retention, and aldosterone release so reduce BP
Act on the distal tubule at the Cl site of the Cl/Na cotransporter preventing the reabsorption of Na so increases amount of Na and H20 excreted reducing blood volume so in low dose decrease BP by vasodilation
Thiazide diuretics do what?
competitively inhibit the Na/Cl symporter in the DCT
Labetalol and carvedilol
non-specific beta adrenceptor antagonists so they block both the beta and alpha adrenoceptors making them potent HT drugs
alpha adrenoceptor anatgonist that acts on the alpha1 adrenoceptors in the vascular smooth muscles in the arterioles to reduce peripheral resistance and BP
alpha 2 agonist that reduces BP in HT by replacing Na from vesicles that leads to reduction of sympathetic NS and BP
3 pressures that make up GFR
GFR capillary pressure + 55
Plasma osmotic pressure -35
Bowman's capsule pressure -10
Total = +10
Regulation of GFR
autoregulation based on MAP
myogenic - increased renal perfusion etc.
tubuloglomerular - macula densa cells sense levels of Na and indicate to the juxtaglomerular cells to release renin
Normal urine output (?ml/min)
Sympathetic Nerve Activation affect on GFR
constricts the afferent and efferent arterioles reducing renal blood flow and GFR
Adrenaline/Noradrenaline affect on GFR
constrict both afferent and efferent arterioles
RAAS system affect on GFR
Ang II constricts mainly the efferent arteriole as well as increasing TPR and MAP thus stabilizing MAP and blood volume
mainly will dilate the afferent arteriole that can lead to lower GFR (NSAIDs)
ANP (atrial natriuretic hormone)
dilates afferent arterioles thus increasing GFR but inhibits renin and aldosterone secretion
what happens if low levels of Na are registered by the macula densa cells?
they will tell the juxtaglomerular cells to release renin which will cause efferent arteriole constriction increasing GFR back to normal level
Creatine is filtered at the glomerulus but neither absorbed or secreted by the tubules, so creatine levels = GFR
What is the gold standard for GFR clearance rate?
What makes a good GFR clearance marker?
Not absorbed or secreted by the kidney and either all filtered or not at all
What is the clinical standard for GFR clearance rate?
Why is creatinine not a great standard of GFR though?
It remains pretty normal until about GFR is reduced by more than 50% so great standard for those we already know have kidney issues
What time of transport is against the electrochemical gradient?
primary and secondary active transport
What type of transport is along the concentration gradient?
Name the places and percentage of fluid reabsorption is controlled
PCT = 70%
Loop = 20%
DCT = 9%
PCT reclaims what?
water, Na, amino acids, glucose, bicarb
PCT ion transporter
H/Na on lumen side
K/Na ATPase on the blood side
K on blood side transporting it back into the blood
How is glucose absorbed in the PCT
secondary active transport via a glucose/Na transporter on the lumen side pulling them in from the lumen
free Na absorption in the PCT due to the leaky epithelia cells allowing Na to move through them from the lumen into the blood; this allows water to move through as well pulling more Na with it
Isosomotic reabsorption is the overall effect of PCT
Is the PCT finely regulated?
Do glucose or amino acids normally reach the proximal straight tubule?
no, unless they are there in excess
What is different about the thick ascending loop of henle?
lumen is positive here which is opposite of most of the nephron allowing the reabsorption of Mg and Ca here via a paracellular path
Loop diuretic NaKCl2 symporter
loop diuretic that affects NaKCl2 symporter
How is salt absorbed in the Loop of Henle?
secondary active transport of Cl which gives the lumen a positive charge
Loop diuretics are also known as high ceiling diuretics because...?
more than 20% of sodium is absorbed in the thick ascending loop
What is the juxtaglomerular apparatus?
part of the distal convoluted tubule that touches the Bowman capsule containing the juxtaglomerular cells that regulate renin secretion
how is Na reabsorbed in the DCT?
Na/Cl symporter on the lumen side
What else is reabsorbed in the DCT
Ca with PTH help
Principal cells are located where?
late distal and cortical collecting duct
Primary method of Na reabsorption in the LDT and cortical collecting duct?
volume of air moved in and out during quiet breathing
average = 500 mL
Residual Volume (RV)
volume of air remaining in lungs after max expiration
average = 1200 mL
Minimal Volume (MV)
volume that if falls below the lungs will collapse
Expiratory Reserve Volume (ERV)
difference between the volume of air left in lung after normal expiration and that after max expiration
Inspiratory Reserve Volume (IRV)
total lung capacity - volume in lungs after normal inspiration
volume of air inhaled above the tidal volume
Total Lung Capacity (TLC)
total volume of air that the lungs can hold
(residual + vital capacity)
Inspiratory Capacity (IC)
tidal volume + inspiratory reserve volume
Vital Capacity (VC)
total usable volume of lungs under voluntary control
Functional Residual Capacity (FRC)
total volume left after normal resting expiration
Obstructive Lung Diseases
increase in residual volume
obstructive lung disease - more residual volume - dynamic small airway closure
thickening of linings in small airways and mucus build up causes less diameter so more resistance so pressure loss is quicker so the point at which intrapleural pressure and alveolar are equal is while there is still a lot of air in the lungs
reversible airway obstruction with bronchial airway inflammation
obstructive lung disease - more residual volume - less recoil
lost recoil in lungs due to less alveoli so less surface tension so functional residual capacity is larger meaning can't breath out as well
If you lose surfactant molecules what will happen to lung recoil, functional residual capacity, and residual volume
increase lung recoil, decrease in FRC, and decrease in RV
Restrictive Lung Disease
decreased ability to develop negative alveolar pressure (decreased elasticity) needed to bring air into lungs so decreased inspiratory residual volume and decreased total lung capacity
Fibrosis and anything ending in -osis
Where is the majority of O2 and CO2 in the blood
Hb and bicarbonate
At what pressure of O2 is Hb 75% saturated?
40 mm Hg
Anemic patients have lower concentrations of what decreasing O2 capacity and content
Hb greater affinity for H+ than HbO2 so Hb gives up O2 to pick up H+ acting as a buffer since only free H+ adds to acidity
increased CO2 and H+ cause increase in release of O2 from Hb
Determinants of Lung Volume (4)
1. height - bigger thoracic cavity
2. gender - bigger thoracic cavity
3. age - loss of elasticity
4. anatomical build
Airway Dead Space
150 mL of air that is either freshly inspired that is expelled before being used or old air that wasn't expired completely and is inspired next time a breath is taken
only inspiring 350 mL of fresh air and only expiring 350 mL of old air each time
Physiological Dead Space
V/Q > 1
alveolar ventilated but not properly perfused
V/Q < 1
perfusion is fine but not well ventilated
Years of Adolescence
10 to 19
5 Common Symptoms of Asthma
3. thick mucus
5. airway remodeling
Triggers of Asthma (4)
4. respiratory infection
Immediate Phase of Asthma
IgE dependent mast cell degranulation and secretion of inflammatory mediators
Rapid onset and may persist for 2 hours
Mast Cells, LTC4, LTD4, and LTE cause bronchconstriction and vasodilation
Late Phase of Asthma
CD4 TH2 cells recruit and active eosinophils and cause morphological changes in the lung
IgG and activated macrophages
defense against intracellular pathogens
unfavorable response to autoantigens (DM, IBD)
IgE, eosinophils, mast cells, and mucus
defense against GI worms and ectoparasites
unfavorable response to allergens
relax contacted airway smooth muscle but no significant effect on airway inflammation
β2 Adrenoceptor Antagonists
bronchodilators - inhaled
good for initial phase of attack and can be used with others to control late phase
AE's - muscle tremors, restlessness, tachycardia, anxiety, and tolerance
bronchodilators that competitively antagonize CysLT receptors blocking effects of LTC4, LTD4, LTE
Oral with AE's headache and GI irritation
Montelukast and Zafirlukast
leukotriene anatognists that block CysLT receptors
montelukast - once daily
zafirlukast - twice daily
bronchodilators that are antimuscarinic
block airway M3 receptors preventing bronchoconstriction and decrease mucus in bronchioles
slower than beta 2 so often combined
anticholinergic bronchodilator that blocks M3 receptors preventing bronchoconstriction and mucus secretion
Theophylline and Aminophylline
Xanthines - Bronchodilators that inhibit PDE so increase cAMP and cGMP causing smooth muscle relaxation
AE's stimulate heart and weak diuretic
Budesonide, Fluticasone, and Ciclesonide
Glucocorticoids - most effective drug to treat asthma
inhibit inflammatory genes and upregulate anti-inflammatory (IL-10) also block IL-4, IL-5, IL-9, and IL-13
Combination Therapy for Asthma Treatment
Glucorticoid + long acting β2 adrenoceptor
Respiratory Control Centers in the Brain
Pons and Medulla
If PaO2 < 60 mmHg is detected:
1. activation of peripheral chemoreceptors
2. activate medullary respiratory center
3. increase ventilation
4. increase PaO2
If PaCO2 is increased and sensed:
1. activation of central chemoreceptors
2. medullar respiratory center activation
3. increased ventilation
4. decreased PaCO2
this occurs because the H from CO2 can cross the blood brain barrier to the central chemoreceptors
If Arterial Non-CO2 H+ is elevated then:
1. activation of peripheral chemoreceptors
2. activation of medullary respiratory center
3. increased ventilation
4. decreased PaCO2
5. decrease in arterial CO2-H+
since can't pass blood brain barrier works on peripheral chemoreceptors
T/F PaCO2 is inversely proportional to alveolar ventilation
If Hypocapnia or normal PaCO2 is evident that means what about ventilation
excessive or adequate
Causes of Increased Ventilation During Exercise (3)
1. decreased PaO2
2. increased PaCO2
3. increased arterial H+
4 Way Ventilation is Increased During Exercise
1. joint muscle receptors
2. body temperature
4. cerebral cortex
Non-Respiratory Factors that Influence Ventilation (4)
1. sneezing and coughing
3. emotions - laughing, crying, etc.
4. voluntary control - speaking, sighing, whistling, etc.
Normal pH = 7.35-7.45
If below? If above?
below - acidosis
above - alkalosis
If decreased pH and decreased PaCO2
If decreased pH and increased PaCO2
Compensation for Respiratory Acidosis/Alkalosis
Compensation for Metabolic Acidosis/Alkalosis
Anion Gap Formula for Metabolic:
(Na) - (Cl - HCO3)
childhood onset, increased IgE levels, and other atopic disorders may be associated
late onset, normal IgE levels, not associated with another atopy
chemicals, allergic or non-allergic mechanisms
Regulatory T cells
develop when inflammatory response requires dampening
inappropriate TH2 response
Steps to Airway Inflammation in Asthma (4)
1. antigen presenting cells - dendritic cells and macrophages
2. lymphocytes - TH2
3. Effector cells cause damage - eosinophils, mast cells, and neutrophils
4. structural cells of airways affected - epithelial, smooth muscle, and blood vessels
Immediate Response of Asthma
1. binding allergen to IgE on mast cells so they are activated and degranulated
2. release of histamine and TNF-α (inflammatory mediators)
3. bronchial smooth muscle contraction
Late Response to Asthma
1. eosinophils activation
2. release of eosinophils proteins and leukotrienes
Common Allergens: Respiratory (4), GIT (3), and Anaphylaxis (3)
1. dust, grass, cats, mold
2. peanuts, milk, eggs
3. peanuts, bees, drugs
Small doses over long time gradually increasing the dose to induce tolerance hoping to desensitize
4 Risk Factors for Asthma
1. family history
2. infantile eczema
3. early onset allergic sensitization
4. frequent viral infections in early childhood (rhinovirus and RSV)
increased levels of hygiene have led to development
tissue that covers body surfaces, organs, and lines body cavities
single layer so all cells touch basal lamina
More than 1 layer of cells
3 Types of Cell Shape
Squamous (flat), Cuboidal, Columnar
type of exocrine gland secretory mechanism
release via exocytosis
salivary and sweat glands
type of exocrine gland secretory mechanism
part of cell lost to form secretion
globlet cells and outer ear
type of exocrine gland secretory mechanism
cells die and regenerate to release secretion
skin and eyelid
CF gene on chromosome 7q31.2
Mutation on CFTR ΔF508
widespread disorder in exocrine gland secretion, autosomal recessive, mutation in 7q31 mostly ΔF508 resulting in the deletion of phenylalanine
6 Effects a Mutation of CFTR has
1. defective protein synthesis
2. defective protein processing and trafficking - most common
3. defective protein regulation
4. defective protein conductance
5. reduced protein expression
5. defective regulation of other ion channels
Affects of CFTR in the Lungs
decreased Cl transport so increased mucus causing difficulty breathing and decreased mucociliary clearance
increased Na reabsorption causes mucus to be more viscose as well
Affects of CF in the Pancreas
acini plugged with viscous secretions so can't secrete enzymes causing intestinal blockage, failure to thrive, autodigestion of pancreas from trapped enzymes, and inflammation and fibrosis leading to DM
Affects of CF in the Intestines
increased Cl in lumen and water leading to diarrhea
Affects of CF in the Sweat Glands
decreased Cl reabsorption causes decreased Na reabsorption leading to salty sweat
4 Main Affects of CF
1. mucus build up in respiratory tract so frequent infections
2. failure to thrive
4. salty sweat
How do most CF patients die
alternate forms of the same gene
recessive or dominant
number of sets of chromosomes
human cells - diploid
sex cells - haploid
23 (22 normal + sex)
Who discovered DNA structure
Watson and Crick
Gene Expression Steps (6)
2. RNA modification to premRNA (5' and poly A tail)
3. RNA splicing (remove introns)
4. mRNA transported to cytoplasm
5. mRNA translation
6. protein assembly
Start Codon and Stop Codons
AUG - start
UAA, UGA, UAG - stop
still codes for the same amino acid
codes for stop codon
codes for different amino acids and codons based on addition or subtraction
affects M and F equally
never skips a generation
affects M and F equally
may skip generations
Only affects M
No father to son transmission
F are carrier
affects M and F
affected M never have affected sons
F show less symptoms due to random X-inactivation
affects M and F
mother passes to all children
21 - Down
XXY - Klinefelters
2 copies of allele from one parent
important in imprinting
Hardy Weinberg Principle
p2 + 2pq + q2 = 1
p+q = 1
5 Requirements for Hardy Weinberg
1. no mutations
2. no selection for any genotype
3. mating random
4. no significant migration
5. population is large
increased frequency of gene mutation in population with small ancestor group
De Novo Mutations
no family history of mutation
T/F Imprinting can cause the mutation to be present but no disease
Gene mutation clinical expression factors (6)
1. nature of mutation
2. other genes
3. environmental factors
6. epigenetic factors
Drug Excretion in the Kidneys
1. unbound drugs filtered into urine in glomerulus
2. active secretion of drugs at proximal tubule
3. water reabsorbed and drug concentrated at Loop of Henle
4. passive drug reabsorption at distal tubule
Low urine pH causes what to happen to the reabsorption of drugs from blood
hard to control
oranges and grapefruits affect
Drugs metabolized in the liver are excreted how
Bile duct allowing them to return hepatic circulation via portal vein so decreases rate of drug elimination and potentially results in drug interaction in GIT