WEEK 6 Flashcards
What layers encapsulate and protect the kidneys?
Firm (perirenal/nephric) fat
then renal fascia, derived from extra-peritoneal fascia (incl suprarenal gland)
then pararenal/nephric fat
Where are the kidneys located within the body? Which sits higher? Which is longer?
Extend from T12-L3
- the right is lower than the left
- left kidney is longer
- retroperitoneal
The functional unit within the kidney is the nephron, what does it consist of?
- Renal corpuscle (glomerulus)
- PCT
- Loop of Henle
- DCT
- Collecting duct
What is the functions of the nephron?
ULTRAFILTRATION 180 litres filtrate/24hr
REABSORPTION 1.5 litres urine/24h
- note that the blood flow which parallels the tubules is of equal functional importance
What posterior abdominal wall muscles is the kidneys related to?
diaphragm
quadratus lumborum
transversus abdominis
psoas major
Describe the anatomical makeup of the kidney
Has cortex and medulla, with the renal pyramids (housing the nephrons with their function of filtration and reabsorption) projecting as renal papillae into the calyces of the collecting system
Minor calyces converge on major calyces, which themselves form the renal pelvis that tucks in to the sinus of the kidney
At the hilum, the pelvis becomes the ureter that transports urine to the bladder
What is the blood supply of the kidneys?
Renal arteries, from aorta at L1/2 (L. higher than R)
- pass behind renal veins and divide at hilum into ant and post, often additional accessory extrahilar arteries from Ao
What is the lymph drainage of the kidneys?
Lymph to lumbar nodes, lateral to aorta
What structures are found in the kidneys hilum, from ant to post?
Vein
Artery
Pelvis of ureter
What 2 things does the left renal vein also receive?
Suprarenal and gonadal veins
Where is the IVC located? What does this result in in renal arteries? Why is this significant?
The IVC is to the right of the midline, so the right renal vein is short, making surgery difficult
Describe the various branching that occurs to the renal vein as it enters the hilum of the kidney.
Each renal artery divides into 5 segmental arteries
- lobar arteries arise from each segmental artery (one for each pyramid)
- before entering renal substance each lobar gives 2/3 interlobar arteries
What is the pathway of the interlobar arteries?
run toward the cortex on each side of the
renal pyramid
- At the junction of the cortex and the medulla the interlobar arteries give off the arcuate arteries, which arch over the bases of the pyramids
- The arcuate arteries give off several interlobular arteries that
ascend in the cortex
What are the afferent glomerular arterioles?
Arise as branches of the interlobular arteries
- give blood directly into the renal corpuscle
What is the nerve supply of the kidney?
Derived from T 12 and L 1, referring pain to back and lumbar region, as well as loin to groin.
- Afferents in the vagus may cause the nausea and vomiting associated with such pain
What is the ureters?
Muscular tubes that transport urine to the bladder
Where are the 3 places that the ureters narrow? This is where stones are most likely to stick.
Pelvic ureteric junction
Crossing the pelvic brim
Passing through the bladder wall
What structures does the ureters lie anterior to?
Psoas major
Branches of lumbar plexus
- cross the bifurcation of the common iliac artery
Normally (according to anatomy books) where do the ureters lie? Why is this not always the case?
Overlie the lumbar TPs
- due to normal human variation
Describe the position of the ureters in the pelvis, in both males and females. What structures do they need to pass between?
Enters pelvis from posterior abdominal wall - but much reach bladder which is anterior
- in males it passes between vas and seminal vesicle
- in females it passes posterior to ovary, inferior to uterine artery, passing the cervix and lateral fornix of the vagina
What is the blood supply of the ureters?
Aorta Renal Gonadal Common and int iliac Uterine, vaginal (females) Vesical (males)
Why is the lymphatic drainage of the ureters?
Para-aortic and iliac nodes
Describe the entrance of the ureters into the bladder wall, why is this significant?
Pass through the bladder wall obliquely
- creating a flap valve that prevents urine in the bladder from backing up and returning into the ureter (ureteric reflux)
What is the nerve supply of the ureters?
Complex, autonomic supply, more at lower end
- nerves aren’t required for peristalsis as there are many ‘pacemakers’ in calyces - muscle cell to muscle cell propagation of conduction, contraction - modulated by autonomic
D
- derived segmetally T10-12, L1, S2-4 from aortic, renal and pelvic pelvises
- referred pain mainlt T11 - L2 = loin to groin and scrotum OR labia
Where is the bladder located? What control is detrusor under?
Muscular sac resting on the pelvic floor anterior, behind the pubic bones, in the midline
- control of PS nerves derived from S2-4
How do males prevent semen backflowing into the bladder?
A preprostatic, internal sphincter (sympathetic)
Why do females not need a sphincter in the bladder?
As the neck of the bladder is above the pelvic floor, so that pressure of the pelvic organs, as well as levator ani contribute to urinary continence
What happens as the bladder distends? Why is this useful?
Pushes peritoneum up, above and behind it so that bladder lies directly behind anterior abdominal wall
- useful for when inserting a suprapubic catheter
Describe the urethra in females.
Passes through ext sphincter of striated muscle just inf to bladder neck
- embedded in the anterior vaginal wall and opens in the vulva as an AP slit immediately anterior to the vagina
Describe the urethra in males, remember there is 4 parts.
- Preprostatic at bladder neck (position of smooth int sphincter)
- Prostatic
- Membranous surrounded by striated ext sphincter
- spongy or penile urethra
What is the vascular supply of the bladder and urethra?
ARTERIES: branches of int iliac - superior and inferior vesical; internal pudendal; also branches from arteries to adj structures (vaginal, uterine)
VEINS: vesical (and prostatic) plexuses converge on internal pudendal and internal iliac
What is the lymph of the bladder and urethra?
To int and ext iliac nodes
What facilitates tumour spread in the prostate?
There are communications of the rpstate with the vaveless veins of the vertebral plexuses (Batson)
What is the nerve supply of the bladder and urethra?
REQUIRE:
- somatic motor for control of striated muscle (ext sphincter)
- autonomic (motor) both S and PS (male pre-prostatic sphincter, detrusor)
DERIVED FROM:
S2-3
- pudendal nerve and its branches
- S and PS in pelvic plexus
How does the bladder fill? How much can the bladder hold?
PS to detrusor ‘switched off’
- usual volume (male) = 400ml, if you reach 500ml then pain in lower abdomen and perineum
What happens when the bladder is full?
Causes desire to micturate
- afferents to SC, then ‘M’ centre in pons stimulates preganglionic PS neurones at S2-4
- 1y neurones stimulate 2y neurones in bladder wall ganglia, causing detrusor contraction
- simultaneous relaxation of the external urethral sphincter, pudendal nerve (S2-4) and contraction of abdo. wall; sensation of urine in urethra maintains the relfex
How are substance use disorders measured?
The DSM-V specifies criteria for ‘substance-related and addictive disorders’
What is the criteria for a substance use disorder? (HINT: there’s 11 points)
- Taking the substance in larger amounts or for longer than you meant to
- Wanting to cut down/stop using but not managing to
- Spending alot of time getting, using, or recovering from the use of substance
- Cravings and urges to use
- Not managing to do what you should at work, home or school because of substance use
- Continuing to use, even when relationship problems caused
- Giving up social, occupational or recreational activities because of substance use
- Using again and again, even when puts you in danger
- Continuing to use, even when you know you have a physical or psychological problem that could have been caused/made worse by substance
- Needing more of substance to get effect you want (tolerance)
- Development of withdrawal symptoms which may be relieved by taking more of substance
What are (i) depressants (ii) stimulants? Give examples of substances for each.
(i) Drugs that dampen down CNS e.g. alcohol, opioids, benzodiazepines
(ii) Have excitatory effects on CNS e.g. cocaine, amphetamine, nicotine caffiene, ecstasy
Give 4 examples of hallucinogens.
Cannabis
LSD
Mushrooms
Solvents
What are the acute signs of use of (i) alcohol (ii) cannabis (iii) stimulants (iv) opiates (v) sedatives e.g. benzos?
(i) smell, slurred speech, flushing skin, disinhibition, tremor, agitation, mints/perfume
(ii) Bloodshot eyes, brown fingers, drowsiness/slowed down, smell, lack of focus/concentration
(iii) agitation, pressure of speech, lack of focus/concentration, mood fluctuation
(iv) Gauching, ‘pinned’ pupils, signs of injecting, brown fingers, flu like symptoms (withdrawal)
(v) Drowsiness, slurred speech, poor memory/recollection
State the various addiction potentials for certain substances.
HIGH >20% - heroin, methadone, nicotine
MODERATE 10-20% - amphetamines, ecstasy, cocaine, alcohol, cannabis, benzodiazepines
LOW 5-10% - inhalants, steroids
What are the 6 models of addiction?
- Moral models
- Disease models
- Biological/Medical models
- Personality models
- Behavioural models
- Biopsychosocial model
What are the moral models? What is the primary causal factor? What can treatment include? Who should provide the treatment?
Term ‘alcoholic’ introduced in 1849
- addictions are seen as wilful violations of societal rules and norms, a result of human weakness
- individual is the primary causal factor; no biological basis for addiction but instead something morally wrong with addicted individual
- treatment may include moral persuasion, imprisonment or spiritual guidance
- church, law enforcement and courts are ‘agents of change’ who should provide ‘treatment’
What is the dispositional disease model? What is the primary causal factor?
1935
Primary causal factor is individual, however, loss of control and restraint is a central premise
- the disease of addiction is irreversible, no cure but can be arrested via total abstinence
- benevolent model for individual and corporate organisations
- move from legal domain to medicine
- AA and NA subscribe in part to this model “addiction is my disease”
What is the biological/medical models? What does it have emphasis on? What is the agent of change?
1970s
- similar to dispositional disease models
- emphasis on genetic and physiological processes in determining addiction, therefore primary causal factor is the individual
- tries to identify unique biological conditions which contribute to addiction (i.e. disorder of brain function)
- considers pharmacology of substance
- agent of change = medical establishment as can use expert knowledge to look at interaction between individual and substance
What evidence supports the medical model?
Addiction is 50% heritable
Physiological processes influence vulnerability and behaviour (e.g. oriental ‘flushing response’, tolerance)
There are discrete neural circuits involved in different stages of addiction (binge intoxication, withdrawal/negative effect, preoccupation/anticipation)
What are the problems with the medical model?
Medical treatments effectively reduce harm but less effective in promoting abstinence
- they don’t exist for many addictive behaviours yet people still recover
- addiction is primarily a disorder of behaviour (compulsivity and impulsivity)
- not nature vs nurture but nature via nurture
What are personality models? What is the primary causal factor? What personality traits contribute to addiction? How is addiction resolved? What are the agents of change?
Late 1950s
- primary causal factor = individual as the roots of their addiction lie in their abnormal personality
- personality traits such as poor impulse control, low self-esteem, inability to cope with stress, egocentricity, manipulative traits, and a need for control and power plus a feeling of powerlessness all contribute to addiction
- resolution requires restructuring of personality therefore agents of change = psychiatry
What are the behavioural models? What is conditioning? What is substance misuse?
Conditioning is the process of behaviour modification whereby an individual comes to associate a dsired behaviour with a prev unrelated stimuli
- takign substances is pleasurable and likely to lead to rewarding consequences resulting in continued/increased use
- substance misuse = learned behaviour therefore treatment must involve ‘relearning new behaviours’
Describe the difference between the Classical (pavlovian) conditioning and the operant (skinnerian) conditioning.
CLASSICAL = Associative learning
- learning by connecting 2 cues. One already elicits a response and the other comes to
OPERANT = Instrumental learning
- learning by connecting the consequences of actions with preceding behaviour
What is the difference between punishment and reinforcement?
Reinforcement increases the frequency of behaviour
Punishment decreases frequency of behaviour
What is the cognitive behavioural model? What is the central premise? What is the assumption?
Central premise = in addition to unconscious processes, perception and thought influences emotion and behaviour
- ‘addictive thinking’ maintains drug use
- changes in addictive behaviour occur due to changes in motivation, cognition and appraisal
- assumption = changing content of cognition and motivation can influence behaviour
What are the various cognitive theories with regards to substance overuse?
- Addiction recruits and influences cognitive processes - memory and attention bias
- Pay greater attention to addiction related cues
- Selectively recall particular addiction related information
- Lack of cognitive control
- Implicit bias towards detection of addiction related cues (increases craving)
- Leads to involuntary responses such as addictive behaviour
Name and give phrase examples for the 5 types of thinking errors.
- PERMISSION-GIVING = ‘it’s just a treat’
- MINIMISATION = ‘it’s only one’
- RATIONALISATION = ‘ I haven’t had it for a whole week so why not?’
- DENIAL = ‘I can use and stay in control’
- BLAMING = ‘She made me angry so I had to use’
What is the biopsychosocial model? What is it concerned with?
Prevailing psychological model that is concerned with the interaction of biological factors (e.g. physical health, genetics), psychological factors (mental health) and social factors (finances, social support etc.)
- holistic approach, no factors are dominant
- interaction of biological, psychological, and social factors help to inform a psychological formulation of an individual’s substance misuse
What is a basic physical formulation model?
Predisposing factors
Precipitating factors (triggers)
Protective factors
Maintaining factors
in the middle = the presenting problem
What are the 3 methods of assessment?
- Self report
- Corroboration from other sources (partners, family, friend, other professionals, case notes etc)
- Objective assessment methods
Describe the self report used as a method of assessment of addiction.
A) Structured clinical interview
- used to structure initial client assessment
- this can be followed up with a more detailed, formal assessment of identified/suspected problem
B) Standard assessment measures
- include measures of drug use, alcohol use, cognitive assessment, mental health etc
Describe the objective assessment methods used as a method of assessment of addiction.
DRUG USE = analysis of urine, blood, saliva etc
INJECTING BEHAVIOUR = examination of injecting sites
DEPENDENCY/WITHDRAWAL = observation while in withdrawal
BBV = blood tests
GENERAL HEALTH = full medical examination
What are the outcomes from the assessment of substance addiction?
Beginnings of therapeutic relationship
- as much of the info mentioned as we can get
- an initial treatment plan: informed by formulation of current difficulties
- an initial sense of how the client might get there (treatment process)
How are the following terms defined; (i) Stage 1 HT (ii) Stage 2 HT (iii) Stage 3 HT?
(i) CBP 140/90 mmHg or higher ABPM or HBPM 135/85mmHg or higher (ii) CBP 160/11mmHg or higher ABPM or HBPM 150/95 mmHg (iii) Clinic BP 180/110 mmHg or higher
What should you do if the clinic BP is 140/90 mmHg or higher?
Offer ambulatory blood pressure monitoring (ABPM) to confirm diagnosis of BP
How do you use (i) ABPM (ii) HBPM to confirm diagnosis of HT?
(i) 2 measurements per hour during persons usual waking hours, average of at least 14 measurements to confirm diagnosis
(ii) 2 consecutive seated measurements, at least 1 min apart
- BP recorded twice a day for 4 days min (preferably 1 week)
- measurements on 1st day discarded and an average value of all remaining is used
Who do you offer antihypertensive drug treatment to?
- who have stage 1 HT, aged under 80 and meet identified criteria
- who have stage 2 HT at any age
What happens in the DCT and collecting ducts in the absence of ADH?
This portion of the tubule is also impermeable to water and the tubular fluid becomes even more dilute to as low as 50 mOsm/L
What is the target CBP for people (i) aged under 80 (ii) 80 and over?
(i) 140/90 mmHg
(ii) 150/90 mmHg
What is a ‘white-coat effect’?
Discrepancy of more than 20/10 mmHg between clinic and average daytime ABPM or average HBPM measurements at time of diagnosis
What needs to happen for the kidneys to produce a highly concentrated urine?
High level of ADH that allows the distal tubules and collecting ducts to become permeable to water and so reabsorbed
- also needs a gradient to pull this water out so there needs to be a high osmolarity of the renal medullary interstitial fluid
What are the factors that contribute to the build up of osmolarity in the medulla? (HINT: there’s 5 factors)
- passive absorption of ions across epithelial of thin ascending limb of loop of Henle
- active transport of Na ions and co-transport of potassium, chloride and other ions out of thick portion of ascending limb of loop of Henle
- active transport of ions from collecting duct
- facilitate diffusion of urea from medullary portion of collection ducts into medullary interstitium
- diffusion of only small amounts of water from medullary tubules into the medullary interstitium and far less than the reabsorption of ions that occurs there, this sets up an osmotic imbalance and gradient
What are the lifestyle interventions for HT patients?
Offer guidance and advice about
- diet and exercise
- alcohol consumption and smoking
What are the 6 steps of the counter current mechanism?
- fluid enters loop of Henle fromPCT at 300 mOsm/L - the same as plasma
- active transport of ions from thick ascending limb establishes a 200 mOsm/L gradient between tubular fluid and interstitial fluid. 400 mOsm/L occurs in medullary interstitium compared to 200 mOsm/L in ascending tubule fluid
- tubular fluid in descending limb now equilibrates with the interstitial fluid as water moves out of the descending limb into medullary interstitial fluid. Continued transport of ions but not water in ascending limb maintains gradient
- flow of fluid into loop of Henle from PCT moves fluid in limbs on. Hyper-osmotic fluid in descending limb moves on into ascending limb
- additional ions pumped out of fluid from ascending limb till 200mOsm/L gradient established between asc limb tubule fluid and medullary interstitium. Interstitial osmolarity rises to 500mOsm/L and asc tubule falls to 300mOsm/L
- movement of water out desc limb of loop of Henle to reach osmotic equilibrium with medullary interstitial fluid. Increases osmolarity of tubule fluid in desc limb up to 500mOsm/L which moves onto asc limb for processes of sodium and other ion movement to continue
How many times are the counter current mechanism steps repeated?
Over and over until the net effect is that osmolarity of the deepest part of the medulla rises to 1200 to 1400 mOsm/L
How does blood volume control BP?
OSMOLARITY
- monitored by osmoreceptors in hypothalamus and mediated by solutes, mainly NaCl
What helps preserve the osmotic gradient in the medulla?
Water absorption in the kidney cortex rather than the medulla
How does renin release help to control BP?
Juxtaglomerular apparatus
- macular densa cels of DCT monitor BP
- granular cells of afferent arteriole monitor stretch
- sympathetic
RENIN = enzyme that converts angiotensinogen to angiotensin 1, which is converted to angiotensin II by ACE
- angiotensin II = hormone that raises BP
What happens to the collecting ducts if high levels of ADH are present?
They become permeable to water and the fluid at the end of the collecting ducts is the same osmolarity as the renal medulla - about 1200 mOsm/L
- therefore b reabsorbing as much water as poss the kidneys can produce a concentrated urine
What is the function and MoA of ACE inhibitors? What are the side effects?
Prevents formation of ATII leading to vasodilation and decreased BP
- it binds to tissues and plasma proteins so slow elimination by glomerular filtration
SE = 1st dose hyptension, dry irritating cough due to acumulation of bradykinin and hyperkalaemia mediated by reduction of aldosterone
What is the function and MoA of Thiazide diuretics? What are the side effects?
Acts on proximal part of DCT which increases sodium excretion and urine volume, therefore reduction in BV but transient
Major effect = decrease peripheral resistance due to ‘subtle alteration in the contractile responses of vascular smooth muscle’
SE = hypokalaemia, hyperuricaemia (risk acute gout), hyperglycaemia (risk new onset diabetes), hypercalcaemia, erectle dysfunction
= thrombocytopaenia and rashes
What is the function and MoA of Calcium channel blockers? What are the side effects?
Acts by reducing Ca influx into vascular smooth muscle cells and promoting vasodilatation – also direct action on cardiac and gastrointestinal muscle cells
- there are 3 main groups but only dihydropyridine derivatives used commonly in HT
SE = headache and flushing, tachycardia (reflex activation of symp system), ankle swelling due to preferential pre-capillary arteriolar vasodilation and gum hypertrophy
What is the function and MoA of Beta blockers? What are the side effects?
Antagonise the effects of symp system or circulating catecholamines at beta1 receptors in heart, kidney, beta-2-lung, peripheral BVs and skeletal muscles
SE = bronchospasm, bradycardia, peripheral vasoconstriction (cold hands and feet), TATT(tired all the time) reduced cardiac output, masking hypoglycaemia in IDDM (type1DM), hyperglycaemia
What is the pH of the body proportional to?
HCO3- divided by the pCO2
What are the 4 actions of the kidney?
Bicarbonate filtration
Bicarbonate reabsorption
Bicarbonate regeneration by titratable acid excretion and ammonium excretion
What is the pH at the start of the PCT?
7.4
What is the (i) GFR (ii) normal plasma bicarb?
(i) 180 litres/day
(iI) 24 mmol/L
Where does the majority of reabsorption fo filtered bicarbonate occur?
85-90% in PCT
remaining 10-15% in DCT and collecting tubule
What is a specific feature of the PCT?
Contains carbonic acid
- speeding up reaction
Why must bicarbonate be regenerated? What will this regeneration do?
Acid is continually produced and the protons consume bicarb (buffering system) so it must be regenerated
- it will raise bicarb in the renal vein to a level higher than in the artery
Explain how titratable acid excretion causes bicarbonate regeneration.
Non-bicarb buffers (phosphate) enter the lumen by filtration
- H(+)+ HPO4(2-) -> H2PO4(-)
- at plasma pH 7.4, 80% monoprotic form
What are the 3 other buffers in urine other than phosphate?
Urate
Creatinine
Beta-hydroxybutyrate
What is the difference between titratable acid excretion and ammonium excretion?
Titratable acid excretion = relatively constant
but
ammonium excretion can increase markedly
What renal compensation occurs in respiratory acidaemia?
- Rise in pCO2
- Parallel change in renal tubule cells
- Intracellular acidaemia
- Increases uptake and use of glutamine and hence ammonium excretion
- Increasing bicarb regeneration
- Low intracellular pH increases tubular proton secretion and ensures optimum reabsorption of bicarbonate
What renal compensation occurs in respiratory alkalaemia?
- Fall in pCO2
- Parallel change inside the renal tubule cells
- Intracellular rise in pH
- Proton secretion falls
- Bicarbonate reabsorption falls
What factors increase bicarb reabsorption and regeneration? (HINT: there’s 6 factors)
- increasing PCO2
- increasing H+
- decreasing ECF volume
- increasing angiotensin II
- increasing aldosterone
- hypokalaemia
What factors decrease bicarb reabsorption and regeneration? (HINT: there’s 6 factors)
- decreasing PCO2
- decreasing H+
- increasing ECF volume
- decreasing angiotensin II
- decreasing aldosterone
- hyperkalaemia
What factors regulate renal bicarb handling?
Decreasing ECF volume/ increasing ATII
- stimulates Na reabsorption
- stimulates activity of Na/H exchange mechanism
- Ratio bicarb/H+ in tubular lumen falls
- excess H+ in tubules
- bicarb fully reabsorbed and new bicarb formed
What happens when kidney function is impaired? (HINT: there’s 4 things)
- renal failure
- damage to glomerulus and tubule
- will result in metabolic acidaemia (slowly)
- decrease in ammonium secretion by tubule
Define (i) pyelonephritis (ii) cystitis.
(i) kidney infection
(ii) infection confined to bladder
What are some of the potential complications of UTIs?
Stones, obstruction, polycystic kidneys, vesicoureteric reflux
- risk of kidney damage and septicaemia
What is a vesicouureteral reflux?
urine flows retrograde, or backward, from the bladder into the ureters/kidneys.
What are the (i) bacterial attributes (ii) host factors favouring UTIs?
(I0 capsular antigens, hemolysins, urease, adhesion to uroepithelium, intoital colonisation
(ii) renal calculi, ureteric reflux, tumours, pregnancy, incomplete bladder emptying, loss of sphincter control, prostatic hypertrophy, women short urethra and catheterisation
What are the most common bacterial causes of UTIs?
In community 80% E. coli
- in hospital 40% E. coli
What are the 5 types of gram -ve bacteria that cause UTIs?
Escherichia coli and proteus mirabilia
What are the 3 virulence factors of E. coli?
- Fimbriae (adhesion)
- K antigen
- Haemolysin
What is the bacterial response to adhesion?
Iron acquisition machinery activated via siderophores
- stimulates growth and reproduction
- once a monolayer has formed a biofilm may develop
- bacteria with type 1 fimbriae may become internalised in phagocytes and epithelial cells
What is the K antigen of E. coli?
It is a polysaccharide that forms a micro-capsule which confers resistance to phagocytosis
What is the protein Haemolysin (E. coli produces it)?
Cytotoxic exo-protein that damages tissue membranes in vivo and causes kidney damage
What is proteus mirabillus? What does it produce?
Gram -ve bacillus
- facultative anaerobe with a peritrichous flagellae
- produces urease
- swarming ability
What are the 5 gram +ve bacterias that cause UTIs?
Staphylococcus saprophyticus Staphylococcus epidermidis Enterococcus spp Corynebacteria Lactobacillus
Describe staphylococcus saprophyticus.
Part of normal microbiota of female peritoneum and vagina
- sexual activiity increases risk of UTI
- symptomatic cystitis
What are other bacterias/fungus/viruses that cause UTIs (HINT: there’s 3)
Candida albicans
Trichomonas vaginalis
Schistosoma haematobium
What is candida albicans? What is it often associated with?
A diploid fungus - commensal
- causes candidiasis and is an important opportunistic pathogen in immunocompromised
- often associated with antibiotic use
What is trichomonas vaginalis?
Protozoan pear-shaped flagellate
- trichomoniasis
- less common in males
What is schostosoma haematobium? How is it treated?
Trematode worm found in contaminated water
- causes shistosomiasis (bilharzia)
- gains access to host through skin and matures in the liver
- the eggs travel to and penetrate the bladder
- treated with praziquantal
What are the 3 points of entry for bacteria from catheterisation?
- Junction between catheter and collection tube
- Urethral meatus and around catheter
- Connection to drainage bag and reflux from bag to tubing
What are the various urine specimens taken for lab analysis?
MSU = mid stream specimen of urine
CSU = catheter specimen of urine - lower number of micro-organisms than MSU
Suprapubic aspiration of bladder urine - for schistosoma haematobium and other rare occasions
What are the host defences of the urinary tract?
- urine - osmolarity, pH
- sloughing of epithelial cells
- urine flow and micturition
- mucosal inhibs of bacterial adherence
- complement activation
- inflammatory response
What are the 6 types of oral antibiotics used for UTIs?
- co-trimoxazole
- nitrofuratoin
- nalidixic acid
- co-amoxiclav
- trimethoprim
- ciprofloxacin
What does cranberry juice contain?
Proanthrocyanidins
How much of the total blood flow travels into the long vasa recta in the medulla?
5%
How can the kidneys control water excretion?
By changing the concentration of ions in the nephron tubule
What is the normal osmolarity of ECF when entering the kidney? What is this reduced to in the DCT due to the reabsorption of ions?
300 mOsm/L
- reduced to 100 mOsm/L due to reabsorption of ions
How is the osmolarity is further reduced in the DCT and collecting ducts?
There is an additional reabsorption of sodium chloride
What happens in the DCT and collecting ducts in the absence of ADH?
This portion of the tubule is also impermeable to water and the tubular fluid becomes even more dilute to as low as 50 mOsm/L
What, with regards to urine, is essential for survival?
the ability to make and excrete urine that is more concentrated than plasma and is essential for survival
- allowing conservation of water especially when water intake is limited
What is the most concentrated that the human kidney can make urine? How much more concentrated is that than plasma?
1200-1400 mOsm/L
- 3 - 4 times that of plasma
What needs to happen for the kidneys to produce a highly concentrated urine?
High level of ADH that allows the distal tubules and collecting ducts to become permeable to water and so reabsorbed
- also needs a gradient to pull this water out so there needs to be a high osmolarity of the renal medullary interstitial fluid
What are the factors that contribute to the build up of osmolarity in the medulla? (HINT: there’s 5 factors)
- passive absorption of ions across epithelial of thin ascending limb of loop of Henle
- active transport of Na ions and co-transport of potassium, chloride and other ions out of thick portion of ascending limb of loop of Henle
- active transport of ions from collecting duct
- facilitate diffusion of urea from medullary portion of collection ducts into medullary interstitium
- diffusion of only small amounts of water from medullary tubules into the medullary interstitium and far less than the reabsorption of ions that occurs there, this sets up an osmotic imbalance and gradient
What is the counter current mechanism?
the loop of Henle tubular counter-current multiplier actively generates a concentration gradient being greater the deeper into the medulla you go
What are the 4 steps of the counter current mechanism?
- fluid enters loop of Henle fromPCT at 300 mOsm/L - the same as plasma
- active transport of ions from thick ascending limb establishes a 200 mOsm/L gradient between tubular fluid and interstitial fluid. 400 mOsm/L occurs in medullary interstitium compared to 200 mOsm/L in ascending tubule fluid
- tubular fluid in descending limb now equilibrates with the interstitial fluid as water moves out of the descending limb into medullary intersitial fluid. Continued transport of ions but not water in ascending limb maintains gradient
- flow of fluid into loop of Henle from PCT moves fluid in limbs on. Hyperosmotic fluid in descending limb moves on into ascending limb
How many times are the counter current mechanism steps repeated?
Over and over until the net effect is that osmolarity of the deepest part of the medulla rises to 1200 to 1400 mOsm/L
How is concentrated urine formed?
Tubular fluid leaving the loop of Henle into the DCT is about 100 mOsm/L
- DCT continues to move ions due to active transport of sodium chloride…osmolarity of the tubule fluid continues to fall.
- In cortical section of collecting ducts the amount of water that’s reabsorbed from this dilute urine is dependent on ADH levels
- in presence of ADH the absorbed water is rapidly transported out of kidney by the large blood flow through kidney cortical peritubular capillaries
What helps preserve the osmotic gradient in the medulla?
Water absorption in the kidney cortex rather than the medulla
As the fluid continues through the collecting duct and medulla, what occurs?
there is more water into the medullary interstitium
- not alot though compared to that in the kidney cortical region and this water is carried away by the vasa recta into venous supply
What happens to the collecting ducts if high levels of ADH are present?
They become permeable to water and the fluid at the end of the collecting ducts is the same osmolarity as the renal medulla - about 1200 mOsm/L
- therefore b reabsorbing as much water as poss the kidneys can produce a concentrated urine
What is the significance of urine in concentrating urine?
It can contribute to the osmolarity of the medullary interstitial gradient when the kidney needs to form max concentrated urine in dehydration
WHat happens to urea in the PCT?
45-50% of filtered urea absorbed in PCT
- but the concentration of urea in the tubular fluid still increases as the reabsorption is less than that of water
What happens to the urea in the desc loop of Henle?
urea conc continues to rise due to further water reabsorption into medullary interstitium and m/ment of urea from medullary interstitial fluid back to the tubule (passive and active secretion)
What happens to urea in the thick asc limb, the DCT and the cortical collecting ducts? How does ADH then alter this?
All relatively impermeable to urea so urea doesn’t move back into tubule fluid
BUT presence of ADH and further reabsorption of water from these cortical tubule sections results in further increases in urea conc of urea already in the tubule
What happens as the tubular fluid moves on into the medullary collecting ducts? What does the high urea conc cause? What is this facilitated by?
- even more water is absorbed and urea becomes even more concentrated
- high urea conc causes it to diffuse out of collecting ducts into medullary interstitial fluid
- facilitated by specific urea transporters, one of which is activated by ADH so enhancing m/ment of urea out collecting duct into medullary interstitial fluid
Where can small amounts of urea move back into the tubule? What this cause>
Can move back into tubule at inner medullary section of loop of Henle and can recirculate through tubule distal to this part of nephron several times
- recirculation can contribute to conc of urea in distal tubular fluids in times of dehydration
What is the levels of recirculation and tubular flow in times of FULL hydration?
tubular flow is greater and the recirculation of urea is less marked and contributes less
Describe the blood flow through the vasa recta.
Flow is low - about 5% of total renal blood flow
- this is enough to supply metabolic needs of tissues bu doesn’t result in loss of solute from medullary interstitium
What does the vasa recta serve as?
a counter current mechanism to prevent the washout of solutes from medullary interstitium
What happens to blood in medullary interstitium and cortical regions?
becomes more hypertonic as it descends into medullary interstitium and then becomes less hypertonic as it ascends back towards cortical regions
- solutes and water move to mirror concentrations in medulla
What factors (and drugs) increase levels of ADH?
- increased plasma osmolarity
- decreased blood volume
- decreased BP
- nausea
- hypoxia
DRUGS = morphine, nicotine and cyclophosphamide
What factors (and drugs) decrease levels of ADH?
- decreased plasma osmolarity
- increased blood volume
- increased BP
DRUGS = alcohol, clonidine (anti HT), haloperidol (dopamine blocker)
What is the difference between glomerular filtration and tubular reabsorption? Describe tubular reabsorption.
Tubular reabsorption is highly selective
- glucose and amino acid reabsorption is almost complete so excretion is zero
- many ions such as sodium, chloride and bicarb are highly reabsorbed but their rates of reabsorption and excretion are highly variable and controlled
- waste products (urea and creatinine) poorly absorbed and excreted in large amounts
- therefore controlling the rate at which the tubule reabsorb diff substances independently of one another permits the control of body fluid composition
What can active transport do? What is an example of this?
Active transport can move a solute against an EC gradient and requires energy derived from metabolism - needs a pump that uses ATP
- in the kidney tubular cells an example of this is the transport of sodium through the tubular epithelia
- Na K pump transports sodium from interior of cell across basolateral membrane creating a low intracellular Na conc and -ve intracellular electrical potential causing sodium to diffuse from the tubular lumen into the epithelial cells through the brush border
What is secondary active transport? Explain how it works.
2 or more substances interact with a specific membrane protein (carrier molecule)
- as one of the substances diffuses down its EC gradient (e.g. Na) the energy released is used to drive another substance AGAINSt its (electro)chemical gradient
- therefore it doesn’t require ATP directly as it derives its energy from the simultaneous facilitated diffusion of another transported substance (Na) down its electrochemical gradient
How much sodium and water is reabsorbed in the proximal tubule? How is it reabsorbed?
65%
- sodium pump driven, a lot of co-transport
- secretion also occurs
What transport occurs in the loop of Henle?
20% of filtered water and 25% of sodium, chloride and potassium reabsorbed
- the thin desc segment is permeable to water diffusion and asc is impermeable
- the thick asc limb has active transporters and absorbs sodium, chloride and potassium (plus other ions)
What transport occurs in the early and late distal tubule?
5% of filtered sodium absorbed here
- impermeable to water (if no ADH present)
- pumps/absorbs Na, Cl and K just like the thick asc limb loop of Henle
- urine becomes dilute
- the late section has 2 cell types (principal cells for water and sodium absorption then intercalated cells absorb K and secrete H+)
What transport occurs in the medullary collecting ducts?
- absorbs less than 10% filtered water and Na
- final site for processing urine and therefore determines urine output and composition
- is vital to producing dilute or concentrated urine
- impermeable to water unless ADH present, permeable to urea and has urea transporters
- can secrete H+ ions so plays role in acid/base balance
What does precise regulation of body fluid volumes and solute concentrations require?
- the kidneys to excrete different solutes and water at variable rates and sometimes independently of each other
- several hormones in the body provide this specificity of tubular reabsorption
What are the 4(5) main hormones which provide the specificity of tubular reabsorption?
- aldosterone
- angiotensin II
- ADH
- atrial natriuretic peptide
- parathyroid hormone
Where is aldosterone released from? What is its function, and MoA?
Released from adrenal cortex
- an important regulator of sodium reabsorption and potassium excretion
- major site of action is on principal cells of cortical collecting duct
- stimulates Na-K ATPase pump on basolateral side of cortical collecting tubule membrane
- also increases Na permeability of luminal side of membrane
What is the function of angiotensin II (ATII)? How does it achieve this?
- perhaps body’s most powerful sodium retaining hormone that acts during haemorrhage and loss of salt and water. It increases body fluid and solute levels
- stimulates aldosterone release from adrenal cortex
- constricts afferent and/or efferent arterioles in kidney
- directly stimulates sodium reabsorption in PCT, loops of Henle, DCT and collecting ducts
- stimulates the Na pump on basolateral side of tubular epithelia and sodium-hydrogen exchange on luminal membrane (especially in PCT)
What is the function of ADH? How does it achieve this?
- increases water permeability of DCT, collecting tubule and collecting duct
- helps body conserve water
- in absence of ADH permeability of distal tubules and collecting ducts to water = low, ADH binds to specific V2 receptors and through signal transduction stimulates the movement of a vesicular associated intracellular water channel called AQP2 to the apical surface of epithelial cells
- reversible to allow control of water permeability of these distal sections of the tubule
Where are atrial natriuretic peptides secreted from? What is their function?
- by the cardiac atria when they are distended by increased blood volume
- they directly inhibit reabsorption of Na and H2O by the renal tubules especially the collecting ducts to increase solute and water loss to decrease blood volume
How does the sympathetic nervous system affect sodium and water excretion?
It can decrease excretion
- mainly by constricting renal arterioles and so decreasing GFR (decrease blood flow to vasa recta, increasing medullary interstitial osmolality)
- can also increase AT II formation (renin release) to increase tubular reabsorption, decreasing excretion of Na and H2O
What is the function of parathyroid hormone?
increases the tubular reabsorption of calcium in the DCTs
