phase 1 week 10 Flashcards
Describe the blood supply to the kidney
renal artery divides into segmental arteries, which then divide to become lobar arteries. Between the medullary pyramids they branch to become interlobular arteries. These extend towards the cortex then arch round the bases of the medullary pyramids to form the arcuate arteries. From the arcuate arteries, interlobular arteries penetrate the cortex. Branches of the interlobular arteries called afferent arterioles carry blood directly into nephrons
What is the normal intake of fluids in an adult?
about 1200ml water
1000ml food
metabolic 300ml
total about 2.5 litres
What is the normal fluid output for adults?
urine about 1500ml sweat about 100ml faeces about 200ml insensible loss about 700ml total about 2.5 litres
describe the sequence of blood vessels in the kidney
afferent arteriole glomerular capillary efferent arteriole tubular capillary venule
How many nephrons are there?
10 to the power of 6
what are the 2 types of nephron ?
junta-meduallry
superficial
Describe a nephron
each nephron is a tube
the nephron wall is a continuous layer of epithelium
the cell shapes in the wall are very different
this reflects activity; surface area, ion pumping etc
What is meant by ultrafiltration?
driven by blood pressure
high renal blood flow
high filtration rate
what is meant by reabsorption?
active pumping from filtrate into tubules
water, glucose, amino acids, electrolytes etc
What is meant by secretion?
active pumping into tubules
for substances to be eliminated faster than filtration alone allows
what are pumping rates controlled by?
hormones
Describe glomerulus ultrafiltration
high glomerular capillary pressure
filtration of small molecules through slits between podocytes (ions, water, glucose, amino acids etc)
limit is space between posocyte processes
filtration rate 90-140ml/min
Describe what happens at the proximal convoluted tubule
active reabsorption
brush border
active reabsorption of glucose, Na+, K+ ions
Co transporters, aqueous channels, membrane pumps
Substantial water reabsorption
What has occurred by the end of the PCT?
complete reabsorption of glucose, amino acids
Substantial reabsorption of Na+, water
volume filtrate reduced by 2/3
Describe what happens at the loop of Henle
counter-current concentration
thinner wall during descent into medulla
thicker wall during ascent -active pumping out of tubule
solute diffuses into descending tubule;
countercurrent mechanism “recycles” solutes
ion pumping develops high osmotic pressures at the tip of the loop
no net reabsorption here
Describe what happens at the distal convoluted tubule
more solute reabsorption and secretion
similar structure and function to proximal tubule
no need for glucose transported
less intense electrolyte and water reabsorption
DCT ion pumping can be controlled by hormones like aldosterone to “fine tune” Na+ and K+ exchange
describe what happens at the collecting duct
concentration of urine
if CDs are permeable to water it may be drawn out by the high osmotic pressure present at the tip of the loop of Henle
Duct permeability set by ADH
if ADH is present aquaporins are inserted into the luminal membrane to allow water movement
Describe the kidneys control of the blood pressure
hypofiltration and sympathetic stimulation initiates secretion of renin by the juxtaglomerular apparatus
renin converts angiotensinogen to angiotensin II which is a powerful vasoconstrictor
Describe the kidneys control of salt balance
When electrolyte concentrations fall aldosterone is produced by the glomerulosa cells of the adrenal cortex
This increases the reabsorption of Na+, CL- and therefore water
It increases the secretion of K+ ions
Describe the pathophysiology of benign prostate hyperplasia
BPH is a benign increase in the size of the prostate
hyperplasia of prostate stromal and epithelial cells in the transition zone of the prostate
may impinge on the urethra and increase resistance in the flow of urine from the bladder
increased likelihood of urinary tract infections
What is the pathophysiology of BPH?
benign prostatic hyperplasia
BPH is a benign increase in size of prostate stromal and epithelial cells in the transition zone of the prostate
May impinge on the urethra and increase resistance in flow of urine from the bladder
Describe PSA screening and why it is not used in the UK
prostate specific antigen screening
PSA tests are unreliable and can suggest prostate cancer where there is none
20% of men with prostate cancer don’t have elevated PSA
PSA testing alone can’t determine whether symptoms are due to BPH or prostate cancer because both conditions can elevate PSA levels
What is screening?
a strategy used in a population to identify unrecognised disease in individuals without signs or symptoms
performed on individuals in apparently good health
What are the conditions of screening?
Condition should be important health problem
there should be a treatment for the condition
facilities for diagnosis and treatment should be available
there should be a latent stage of the disease
the should be a test of examination for the condition
the test should be acceptable to the population
the natural history of the disease should be known
there should be an agreed policy on who to treat
the total cost of finding a case should be economically balanced in relation to medical expenditure as a whole
case finding should be a continuous process
Outline bowel screening
all men and women aged 50-74 every 2 years
Outline breast screening
mammography women aged 50-70 every 3 years
Outline cervical screening
women aged 25-65
3 yearly intervals to 50 then 5 years to 65
Describe cervical screening
cervical cancer proceeded by pre-invasive stage CIN
(Cervical intra-epithelial neoplasia)
Abnormal cells detected in cervical smear
CIN can be treated by directed focal treatment at colposcopy
What are some risk factors for cervical cancer?
sexually transmitted disease HPV cigarette smoking early age of first sexual intercourse type of contraceptive used social depravation immunosuppression
what are the two main types of drug?
small molecules
biologics
What is drug action mediated by?
the time course of the drug concentration at the site of action
Describe drug receptors
a macromolecular component of a cell with which a drug interacts to produce a response
Describe how drugs act of receptors
on cell surface or inside cell
form tight bonds with the receptor
drug needs to meet certain requirements (size, shape)
the drug can stimulate or inhibit the receptor action
this usually involves an effect on a signal transduction pathway / alters enzyme function
Give examples of types of drug receptor
enzyme linked (multiple actions) ion channel linked (speedy) G protein linked (amplifier) Nuclear (gene) linked (long lasting)
what is affinity?
measure of propensity go a drug to bind to a receptor
what is efficacy?
also called intrinsic activity
ability of a bound drug to change the receptor in a way that produces an effect; some drugs possess affinity but not efficacy
Describe antagonists and agonists
agonists have affinity and intrinsic activity
antagonists have affinity but no intrinsic activity
partial agonists have affinity but less intrinsic activity
competitive antagonists may be overcome
Describe competitive antagonists
competes with agonist for receptor
surmountable with increasing agonist concentration
reduces apparent affinity of agonist
Describe non-competitive antagonists
Drug binds to receptor and stays bound
Irreversible - does not let go of receptor
as more receptors are bound, the agonist becomes incapable of eliciting maximum effect.
What is meant by ED50?
median effective dose 50
the dose at which 50% of sample or population manifest a given effect
What is meant by TD50?
median toxic dose 50
the dose at which 50% of the populations manifests a given toxic effect
What is meant by LD50?
median lethal dose 50
dose which kills 50% of subjects
What is therapeutic index?
`TD50 or LD50 / ED50
the higher the therapeutic index the better
What is the minimum urine production rate?
1ml/min
what is the maximum urine production rate?
20ml/mon
Describe the bladder structure
bladder wall; smooth muscle (detrussor)
smooth muscle allows large volume changes
the activity of the depressor muscle is affected by reflexes, stretch of the wall ringers contractions
Describe the storage phase
early filling phase; low pressure in bladder, bladder wall and eternal sphincter relaxed
no flow in urethra; urethral pressure > bladder pressure
sensations develop, the sphincters contract to maintain continence
Describe the voiding phase
“urge” then voluntary voiding
bladder contracts, urethra and sphincter relax
What type of muscle is the external sphincter?
skeletal
Describe the innervation of the bladder and sphincter
Sympathetic L1, L2- bladder wall and internal sphincter
Parasympathetic S2,3,4 bladder wall
Somatic S2,3,4 sensory and motor to external sphincter
Describe the afferent innervation of bladder control
sensory fibres sense the stretch in the bladder wall
these afferents run in the hypogastric nerve and end the cord in the upper lumbar roots
Other sensors near the urethra sense flow of urine
skeletal muscle sensors in external sphincter
Describe efferent innervation of bladder control
Parasympathetic to depressor
sympathetic to internal sphincter
Somatic to external sphincter
Describe innervation during the storage phase
sympathetic effects dominate
adrenergic Bera effects - suppress contraction of detrussoe
Somatic fibres in the pudendal nerve control external sphincter
Describe the innervation during the voiding phase
parasympathetic actions dominate
parasympathetic fibres in the pelvic splanchnic nerve cause the depressor to contract
Describe reflex control of the bladder
via the centres in the sacral cord and in the pons
Pontine centre coordinates with higher centres
