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649 Cards in this Set

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What makes up the the abdominopelvic cavity?

Peritoneal cavity and retroperitoneal cavity

What is the retroperitoneal space?


Give an example.

-Several small spaces

-pararenal space

What does retroperitoneal space mean?

The space behind the peritoneal cavity.

Name 3 organs that are intraperitoneal. What do they have?

Liver, Stomach, Spleen


They are covered by peritoneal in the front and the back.

Name 4 retroperitoneal organs.


What part of the organs is covered by peritoneum?

aorta, IVC, kidneys and suprarenal glands


Anterior surface only

What does secondary retroperitoneal mean?

Starts inside the peritoneal cavity but in the development it moves out of the peritoneal cavity and into the retroperitoneal space.

Give 4 examples of organs that are secondary retroperitoneal.

pancreas, duodenum, asc + desc colon

What are the kidneys associated with?

The blood

Name the 4 urinary organs.

•kidneys

•ureters


•urinary bladder


•urethra

What does the kidneys produce?
- produce urine
What is the job of the ureters?
– conveys urine to bladder
What is the job of the urinary bladder?
– temporary reservoir
What is the job of the urethra?
– empties bladder to outside the body

What organ of the urinary system is not retroperitoneal?

urethra

Describe the location of the kidneys.

•Posterior abdominal wall

•Superior pole T12


•Inferior pole L3


•Right slightly lower

Describe the relation of the kidneys to abdominal wall muscles.

-Diaphragm is superior

-Psoas major is medial


-Quadratus lumborum is posterior and lateral

What does this show?

What does this show?

A kidney stone

What does calculus mean?

Kidney Stone

How many cm are the kidneys away from the mid-dorsal line?

5cm

What is the size of the kidney?

11 x 6 x 3 cms

What is the shape of the kidney?

Bean shaped

What 4 organs are around and near the right kidney?

1.right suprarenal gland

2.liver


3.rightcolic flexure


4.duodenum

What 6 organs are around and near the left kidney?

1.left suprarenal gland

2.stomach


3.spleen


4.pancreas


5.leftcolic flexure


6.jejunum

What is under the box?

What is under the box?

Cortex

Renal pyramid

Renal column

Renal capsule

Renal sinus

Medulla

renal hilum

ureter

renal pelvis

minor calyx

What contains the glomerulus in the kidney?

cortex

What does the medulla contain in the kidney?

renal pyramids (collecting ducts for urea)

What 2 things make up the parenchima in the kidney?


What are they?

cortex and renal pyramids




functional kidney

What part of the kidney do structures exit and enter?

Renal hilum

What artery supplies the kidney?


What is the cause from the aorta?

-Renal artery

- straight off the aorta just below SMA

What vein drains the kidney?


What is the cause when it drained?

•Renal vein

• IVC that is anterior to artery

Why are the arteries and veins to the kidneys different?

As the aorta and IVC are side by side so one side will be longer than the other.

What is the lympathics of the kidney?

drainto lateral aortic nodes

What are the 5 main functions of the kidney regulationof blood?

1.ionic composition (e.g. Na)

2.pH (excrete H+)


3.volume (water)


4.pressure (renin)


5.osmolarity

What hormone does the kidney release that helps with Ca2+?

calcitriol

What is the other name for the suprarenal gland?

adrenal gland

Where are the suprarenal glands situated?

•Locatedover kidneys (coordinates same as upper pole)

- T12


-Separatefrom kidneys in own fascial compartment

What are the shapes of the suprarenal glands on both sides?

pyramidal(right)

semilunar (left)

What are the vessels of suprarenal glands?


What are the nerves?

Vessels: Suprarenal arteries and veins Nerves: abdominopelvic n. (greater, less and least sp)

What hormones does the cortex of the suprarenal produce?

1.corticosteroids (e.g. cortisol)

2.sex hormones (e.g. progesterone)

What hormone does the medulla of the suprarenal produce?

adrenaline

Describe the ureter and its blood supply.

•Verymuscular ducts

•25-30 cms, from renal pelvis to bladder(posterior wall)


•Blood supply from several sources (renal, aorta, iliac)

What are the 3 constrictions for kidney stones in the urinary system?

1. ureteropelvic junction    2. crossing iliac vessels (pelvic brim)
3. entering bladder
1. ureteropelvic junction

2. crossing iliac vessels (pelvic brim)


3. entering bladder

What happens at the crossing of the ureter with the iliac?

The ureter kinks and goes backwards after crossing the iliac vessels therefore kidney stones can get stuck here.

Where are the bladder and urethra located?

thetrue pelvis

What is the bladder's gross anatomy?

invertedpyramid with urethra at apex

What is the length of the urethra in females?

4cm

What is the length of the urethra in males?

20 cm

What is the route of the urethra?

Passesunder pubic symphysis; crosses pelvic floor muscles toreach genitals

What 3 things protect the kidneys?

perirenal fat, ribs and the vertebral column

What 3 things happen in kidney injury?

•Crushagainst ribs or column

•Bruising to laceration


•Rapid blood loss

Why is there rapid blood loss if there is kidney injury?

As the kidneys get 20% of the cardiac output.

What 2 things can cause renal pain?


What can cause these?

1.Stretchingcapsule

2.spasm smooth muscleof renal pelvis




Infection or inflammation

What are the afferent fibres in renal plexus?

leastsplanchnic nerve

Where is renal pain referred to?

•cutaneousarea of T12 -territory of subcostal nerve

What can cause renal colic?

Peristalticwaves of ureter in attempting to pass a stone

What is colic pain?

Pain caused by something inside the lumen causing the lumen to be stretched.

Where does severe renal pain spread to?

CNS and causes nausea.

Describe a renal transplantation.

•Transplantis inserted into iliac fossa

•Incision done just over inguinal ligament (parallel)


•Vessel anastomosis


- renal artery to external iliac artery and renal vein to external iliac vein


•Ureterocystostomy – straight into bladder

What are the 5 most common kidney malformations?

•Bilateral/Unilateralrenal agenesis

•Supernumerary kidneys


•Renal fusion


•Ectopic kidney


•Simple/polycystic kidney

What % of people have kidney malformations?

7%

What does agenesis mean?

Didn't develop.

Renal fusion

Renal rotation

Duplication of ureter

Anomalies of renal pelvis and calyces

What occurs in the excretion function of the kidney?

Theremoval of organic waste productsfrom body fluids

What occurs in the elimination function of the kidney?

Thedischarge of waste products intothe environment

What 2 excretion patterns occur in the kidneys?

-Excretionof endogenous waste products -Excretionof drugs and their metabolites

What 2 functions are controlled by the homeostasis function of the kidneys?

-Waterand electrolyte balance

-Acid-basebalance

What is the optimum pH of the blood?

7.4

What 2 hormones does the kidney release?

erythropoietin and renin

What does erythropoietin promote?

The bone marrow to produce RBC.

What 5 things can go wrong with the kidney?

1.Reductionin renal excretory function 2.Reductionin renal excretory function

3. Inabilityto maintain salt and water balance


4.acid-base balance


5. Compromisedhormone function

What causes uraemia and azotaemia?

Build up of waste products in the blood.

What happens when you cannot maintain salt and waterbalance?

Swelling of arms and legs

What happens when acid-base balance is not sustained?

Acidosis occurs and this causes them the breath fast.

What is it called when there is rapid failure of the kidneys?

acutekidney injury (AKI)

What % of renal failure is acute kidney injury?

10%

What is it called when it takes many months or, more typically, years to develop kidney disease?

chronickidney disease (CKD)

What % of chronic kidney disease is caused by diabetic related chronic kidney disease?

20 to 40%

What 2 things have to happen to make a chronic kidney disease patient better?

dialysis or transplanted kidney.

What % of renal function can you lose without seeing any symptoms?

60%

What is paraquat and what can it cause?

Weedkiller and acute kidney injury

What does diabetic kidney disease increase the risk of?

cardiovascular event (eg MI or Stroke)

Name 2 types of chronic kidney disease?

nephrotic syndrome and interstitial nephritis.

What is a nephron?

is the “functional unit”of the kidney responsibleforurine formation and composition

What is the route of urine from the medulla?

pyramidsdrain into pelvis whichdrain into ureters

How many nephrons are there in a kidney?

1 million +

What are the 5 distinct sections of the nephron?

•Glomerulus(Renalcorpuscle)

•Proximaltubule(PT)


•Loopof Henle (LOH)


•Distal tubule (DT)


•Collectingduct (CD)

What happens to the nephrons has you get older?

numbers decline with age therefore you have to be careful with older patients and drugs.

What are the 2 types of nephrons?

1.CORTICAL NEPHRONS

2.JUXTAMEDULLARY NEPHRONS

Describe the cortical nephrons.

Describe the cortical nephrons.

~85% of all nephrons in human kidneys

-Locatedin the cortex


-Shortloop of Henleinto medulla

Describe the juxtamedullary nephrons.

Describe the juxtamedullary nephrons.

-20-30% of all nephrons in humankidneys

-Situatedcloser to medulla


-Loopof Henleextends deep into renalpyramids ( so more reabsorption can occur)

Describe the blood supply to the kidney?



cortical nephron

juxtamedullary nephron

What do juxtamedullary nephrons have instead of peritubular capillaries?

Vasa recta - these are longer than peritubular capillaries

What is the sympathetic nerve supply to the kidney?

postganglionicfibres from sympathetic chain and fibres from coeliac ganglion

What nerve reduces blood supply to the kidney during stress (fightor flight response)?

Sympathetic

What is the parasympathetic nerve supply to the kidney? What may this do?

efferentsupply from vagus -ganglion in hilum

- maycontrol tone of efferent arterioles- Maymodify glomerular filtration rate (GFR) and renal blood flow (RBF)

What are the 3 main functions of the nephron?

FILTRATION

REABSORPTION


SECRETION

Describe the FILTRATION part in the nephron.
FILTRATIONof blood toproducea filtrate
Describe the REABSORPTION part in the nephron.
REABSORPTIONof water, ionsand organic nutrients fromfiltrate
Describe the SECRETION part in the nephron.
SECRETIONof waste productsinto tubular fluid

What are the 2 types of reabsorption in the nephron?

1. Transcellular transport:-movement throughcells

2. Paracellular transport:-movement betweencells

Where does the filtration occur in the nephron?

glomerulus

What 5 small molecules are filtered in the glomerular filtration?

•Electrolytes

•Aminoacids


•Glucose


•Metabolicwaste


•Mostdrugs

What 4 cells and molecules remain in the blood during the filtration phase?

•Redblood cells

•Lipids


•Proteins


•Somedrugs

What patients have typical protein in the urine?

diabetics (albumin is present)

What % of filtered water, electrolytes and nutrients are reabsorbed in the tubular reabsorption?

99%

What happens to some of the solutes like Na+ in the tubular reabsorption phase?

are reabsorbed down concentrationand/or electrochemical gradients

What happens to glucose in the tubular reabsorption phase?

undergoactive transport

What happens to the water in the reabsorption phase?

Waterfollows passively along the osmotic gradient created by solute (Na+)reuptake

What is required in the tubular reabsorption phase?

Reabsorptionof solutes requires energy in the form of adenosine triphosphate (ATP)

What is present in the tubular secretion area to filter larger substances that cannot go through the glomerulus?

Specialisedpumps in the Peritubular Capillary can transport compounds from the plasma into the nephron forexcretion

What are the 2 kinds of pumps in the tubular secretion in the peritubular capillaries?

1. For organic acids(e.g.uric acid, diuretics, antibiotics– e.g. penicillin)

2. For organic bases(e.g.creatinine,procainamide)

What is transported by the organic acids pump?

uric acid, diuretics, antibiotics– e.g. penicillin

What is transported by the organic base pump?

e.g.creatinine,procainamide

What is the route of formation of urine? 5 steps

1. Glomerulus:-Filtration of blood 2. Proximal tubule: Reabsorption of filtrate and Secretion into tubule 3. Loop of Henle:-Concentration of urine 4. Distal tubule/Collecting duct:-Final modification of urine 5. Urineleaves kidney

Define Obesity.

Obesity is a disorder in whichexcess body fat has accumulated to an extent that health may be adverselyaffected

What is the most widely used measurement for obesity?

Body Mass Index

How do you calculate the BMI?

•BMI=person’s weight in kilograms divided by the square of theirheight in metres

What BMI or above classes a patient as obese?

•Obesity is BMI of 30 kg/m2

When is BMI not a good indicator of body fat mass? (4 groups)

•Athletes

•People at the extremes of the heightdistribution


•Non-Caucasian populations


-For child

What 5 other ways can you assess obesity?

•Self assessment

•Appearance- on ward rounds


•% of ideal body weight


•Waist to hip ratios


•Skinfold measurements(hard to do)

What obesity type does this occur? 

What obesity type does this occur?

Central

What obesity type does this occur? 
What obesity type does this occur?

General

Why is obesity seen as an epidemic?

•Worldwide increase in prevalence

•Effect dramatic, and accelerated inlast decade

What has Obesity overtake as cause of preventable death?

smoking and malnutrition

What is the increase of UK patients treated for or with obesity?

10 xno of people treated with or for obesity

What do women have that increase their chance of obesity?

1`•Women have higher % body-fat and somore prone to weight gain

What type of obesity are middle-age men prone?

abdominal obesity

What do we know about the relationship between race, socioeconomic and obesity?

Relationship complex and depends onrace and socioeconomic status
In Western society what socioeconomic group has the highest amount of obesity?
In Western society, incidence is higher in low socioeconomic groups

Why is ethnic backgrounds and obesity are hard topic?

As different ethnic groups have different susceptibilities for obesity therefore it is a complex problem.

What is the Brighton obesity rate like?

InBrighton generally we have less obese andoverweight people that the average of the UK
What are the health consequences of obesity?
•Early death•Diabetes•Cardiac disease•Breathing abnormalities•Reproductive function•Gallstones•Cancer•Osteoarthritis •Gastro-oesophageal reflux•Lower limb swelling•Varicose veins•Excessive sweating•Impaired liver function•Low self esteem•Depression
What is Type 2 diabetes is characterised by?
bythe resistance to the action of insulin, rather than a deficiency of insulin(Type 1)
It what population is Type 2 diabetes is now being diagnosed?
in children and young adults

What four medical problems can obesity act on?

•Heart failure

•Coronary heart disease


- early death


- breathing problems



At what age does the BMI of a person predict their mortality at 70?

BMI at 30-49 years predicts mortality at 70
What does fat alter in obese patient in breathing problems?
the mechanical propertiesof the chest wall & diaphragm

What does sleep apnoea increase the risks of?

MI and stroke

Describe the effects on men's reproductive function when they have obesity.

–decreasedlibido

–impotence

Describe the effects on women's reproductive function when they have obesity.
–alteredperiods

–infertility


–complicationsof pregnancy


–weight loss often reverses the changes in females

What cancer is most common in men with obesity?

•In men – colorectal and prostate

What cancer is most common in women with obesity?

•In women – gall bladder, breast and endometrium
What cancer is most common in people with obesity?
•In both sexes – oesophageal, kidney& pancreatic
What are the Psychological consequences frequently of obesity and what occurs with them?
•Through depression

•Stigmatisation


•Work-related limitations




They ignored & may play role in maintenance.

What is the link between obesity and depression?

significantco-morbidity between obesity & depression

What is a better predictor for being overweight than actual weight?

Perception ofbeing overweight (orunderweight) is a better predictor of psychological distress than is actualbody weight

Decrease the stigma of obesity.

•Widespread belief that obese peopleare “lazy”

•Even doctors hold these beliefs


•Stigma of obesity correlates withbody-size and body-shape dissatisfaction


-Stigma-experiences increase desireto avoidexercise

Describe the weightdiscrimination.

•Women’s wages inversely correlatewith BMI

•Discrimination for educational access (USA)


-Discrimination at job interview

What improves afterobesitysurgery?
–improvedmental health (except anxiety)–improvement declines over time

–relatedto long-term wt loss


–Removalof “shame”

What can 10%wt loss over 13 weeks in mild obesity improve?
–improvedmental health

–largerbenefits in physical health

What are the threemain classes of treatments for Obesity?
1.Drug-based

2. Surgical interventions


3. Behavioural change

What is the current UK option for obesity drug?
•Orlistat - a pancreatic lipase inhibitor•Reduces fat absorption from smallintestine

•From April 2009: available over thecounter without prescription


Effect is to generate adverseside-effects iffat is consumed: indirectly promotes selection of low-fat diet

What type of drug for Orlistat?

Obesity and a pancreatic lipase inhibitor.

What are the ineffective surgical procedures for weight lose?

jaw wiring and liposuction
What are the effective surgical procedures for weight lose?
stomach stapling andIntestinal bypass

When are surgical options available for obesity?

•patient is morbidly obese (BMI>40, orBMI >37 if complications)

•All other therapies have been triedand failed


•Patient is medically fit

Describe the Roux-en-Y bypass for obesity.

Describe the Roux-en-Y bypass for obesity.

•Stomach stapling combined withbypass of upper intestine

•Effective sustained weight loss andfewer complications


•Surprisingly enhancessatiety& reduces hunger hormone ghrelin

What are the 3 therapies of behavioural treatments for obesity?

1.reduceenergy intake and/or

2.promoteenergy loss and/or 3.strengthenpersonal resources needed to achieve these behavioural changes.

Name 2 targetbehaviours for behaviour therapy for obesity.

•Behavioural skills training tomodify eating;–Eatslower, healthy choices, etc•Behaviour skills training to modifyphysical activity habits to prevent weight regain: –Goal-basedexercise plans, diaries, etc

When can family-based counselling sessions be used in obesity?

When the children are obese.

What are the 3 Es for lifestyle changing in obesity?

•Encouragement

•Empowerment


•Environment

Describe the Encouragement stage of the three Es.

•Simple advice and information



•Useful trigger, but unlikely to beeffective or sustainable across whole population

Describe the Empowerment stage of the three Es.

•The development of knowledge, life skills andconfidence to enable people to make healthy choices

•For example–Foodshopping & cooking skills(in the family)–Nutritionalprinciples–Buildingconfidence & self esteem

Describe the Environmental stage of the three Es.

•Environmental change can be physical, social, economic andcultural

•‘Healthier choices become easier choices’

Why are the lifestyle changes in obesity difficult?

-geneticsusceptibilities


-environmentaldeterminants


-lackof investment

Why is obesity so hard to treat?

It is a complex disease

What is the best predictor of body-size?

Genetics

What are some forms of obesity associated with?

specific genetic deficiencies

What is reducing energy expenditure in the Western world?

–lowlevels of physical activity

–appealof sedentary behaviours


–Optionsto change not yet attractive enough

What are the nutritionalenvironment changes in the UK that effect Obesity?

–increasein energy intake

–increasedaccess & availability of energy dense food


–Portionsize (increasing) andmeal training


healthy food is more expensive &time-consuming

Describe TVwatching and obesity.
•prevalence lowest in childrenviewing <1 hr/day

•highest in those watching 4+ hrs/day•higher energy intake in high viewers

Why is information not motivation when it comes to obesity?

•Health psychologists have shownthat information alone isineffective in changing behaviour

•Health behaviour change requires increasedmotivation, self-esteem etc. as well as information

Why are some patient who are not obese just left?

Changingbehavior is a slow process and takes along time to talk about in the GPsurgery therefore is often not discussed.

What psycho treatment has been shown to increase self efficacy in obese patients?

Self-affirmation treatment enhancesself-efficacy, facilitating behavioural change



Several recent studies show simple self-affirmation manipulationsenhance weight loss

Define Self affirmation.

the recognition and assertion of the existence and value of one's individual self.
Describe thedanger of forbiddenfood.
•Labeling a food as forbidden increases its attractiveness–“avoidthe red food”


•Labeling a food as “healthy” produces counter-productiveexpectations:


–That it won’t taste good


–Or won’t satisfy appetite

What does this graph show about diets?

What does this graph show about diets?

Harsh= no history of dieting

Plain = history of dieting


This shows that the women who had tocarry the choc and who had dieted previously ate more chocolates in thelab.

What are the major dietary changes in modern times?

•choice, availability &purchasing power•promotion of foods to children

•larger food portions


•increases in:–confectionery,savoury snacks, soft drinks–foodaway from home

Why are soft drinks important to count in the diet?

containcalories that still get taken as carbs and converted to fats

What are the 3 politics of obesity?

1. improvedprosperity

2. food overproduction


3. majorindustries benefit from overeating

What are the 5 main stages of urine production?

1: Glomerulus:Filtrationof blood

2: Proximal tubule:Reabsorptionof filtrateSecretioninto tubule


3: Loop of Henle:Concentrationof urine4: Distal tubuleModificationof urine


5: Collecting duct:Finalmodification of urine

What are the 3 major functions of the nephron?

1.FILTRATION of blood toproduce a filtrate

2. REABSORPTION of water, ions and organic nutrients from filtrate


3.SECRETION of waste products into tubular fluid

What is the glomerulus?

A sac containing capillaries with an afferent and efferent arterioles.

What are the 2 forces that are involved in renal filtration?

–Blood pressure

–Differing diameter of afferent and efferent arterioles

What is glomerular filtration rate (GFR) and what can it be measured for?

=125 mL/min or 180 L/day

= Rate at which glomerular filtrate is produced


- GFR can be measured clinically and used as an indicator of renal function

What is the first stage of urine formation?

Glomerular Filtration

What is ultrafiltration? Where does it occur?

filtration on a molecularscale



the kidney

What small molecules are filtered in the glomerular?

-Electrolytes

-Amino acids


-Glucose,


-Metabolic waste


-Drug metabolites, some drugs

What cells and large molecules remain in the blood during glomerular filtration?

-Red blood cells

-Lipids


-Proteins,


-Many drugs

Describe the 3 stages of glomerular filtration.

1:Pores in glomerular capillary epithelium2:The basement membrane of Bowman’scapsule (includescontractile mesangialcells)

3:Epithelial cells of Bowman’s capsule(Podocytes)via filtration slitsintocapsular space

What 2 factors does filtration in glomerular filtration?

blood pressure

renal blood flow

What are podocytes?

Epithelial cells of the Bowman's capsule and they act as an effective barrier to stop large molecules. They have feet like projections that interwine with each other meaning they can make the space between them larger or smaller.

What are destroyed in the glomerular filtration in diabetes?

The podocytes are poisoned by the high glucose and this means that blood and proteins can move through into the glomerular capsule.

What are the spaces between the pores called?

Fenestration

What forces does the diagram shows? 

What forces does the diagram shows?

Pgc = Glomerular capillary hydrostatic pressure


bs= Bowman's space oncotic pressure


Pbs= Bowman's space hydrostatic pressure


gc= Glomerular capillary oncotic pressure

What pressures are out of the capillary into the bowman's?

Pgc = Glomerular capillary hydrostatic pressure

bs= Bowman's space oncotic pressure

What pressures are out of the bowman's capillary into the capillary?

Pbs= Bowman's space hydrostatic pressure

gc= Glomerular capillary oncotic pressure

What is the equation for the filtration rate and which pressure can normally be classed as zero?

Filtrationpressure = (PGC+ BS)– (PBS+ GC)…butBSalmost 0 so...



Filtrationpressure = (PGC)– (PBS+ GC)

What is the net filtration pressure?

=10 mmHg

What happens to the osmotic pressure?

Osmotic pressure increases as you take water out of the capillaries and this means a blood moves through capillaries the net filtration pressure is lost.

What generally remains constant even when BP changes?

Glomerular Filtration Rate

What regulates the GFR in the kidney so it can withstand BP changes?

regulatory mechanisms known as autoregulation of renal blood flow

It involves adjustments of the diameterof the afferent arteriole

What does the autoregulation in denervated and isolated kidneys show?

so it is not a neuronal or hormonalresponse but instead, a local effect
What does this graph show?

What does this graph show?

Renalblood flow (RBF) and GFRaremaintained evenif systemic BP changes

What are the 2 hypotheses involved in Renal Blood Flow? What do many people think about these hypotheses?

Myogenic and Metabolic



That they both play some part in the renal blood flow regulation

What is the myogenic hypothesis for Renal Blood Flow?

- autoregulation isdue to response of renal arterioles to stretch (re:Starling’s Law):e.g. if BP increases, thearterioles automatically constrict to reduce RBF

What is the metabolic hypothesis for Renal Blood Flow?

-renal metabolites maintain a degree of vasodilation – these are modulated tocontrol RBF

What occurs to the GFR when the BP decreases and how does the body compensate?

GFR decreases and this means that the afferent artery dilates and the efferent artery constricts and the GFR returns to normal.

What 4 local effectors dilate the afferent artery?

Prostaglandins,ANP, dopamine, NO, kinins

What constricts the efferent artery?

Ang II

What happens to the GFR when the BP increases?

GFR increases and this means that the afferent artery constricts and the efferent artery dilates and the GFR returns to normal.

What 4 local effectors constrict the afferent artery?

Noradrenaline(fromsympnerves), endothelin,adenosine, ADH

What dilates the efferent artery?

adenosine

Describe the changes in GFR that effect the systemic blood pressure.

1.Adrop in filtration pressure (e.g. due to declining BP) causes a drop in GFR

2: Lower GFR means less Na+enters the proximal tubule


3: The maculadensasenses a change in tubular Na+levels


4: This stimulates juxtaglomerular cellsto release renin into the blood


5: Renin release leads to generation ofangiotensin II


6: AngII is a vasocontrictorwhich causes BP to increase


7: Increased BP causes filtration pressure to increase and GFRreturns to normal

What are the juxtaglomerular cells and macula densa?

What are the juxtaglomerular cells and macula densa?

The maculadensasenses a change in tubular Na+levels. This stimulates juxtaglomerular cellsto release renin into the blood

What are reabsorbed in the proximal tubule? What are they driven by? What are the 2 routes of reabsorption?

–Glucose–Amino acids–Small amount of filtered proteins

Thedriving force for this reabsorption is Na+K+ATPase




Transcellular and paracellular reabsorption

What does this show about Na/K ATPase in the proximal tubule cell?

What does this show about Na/K ATPase in the proximal tubule cell?

Na+-K+-ATPasepumps out Na+ from cells into the blood againstchemical and electrical gradients.

This process requires ATP. (lots of mitochondria and need a lot of o2)


Accompanied by entry of K+ ions which rapidly diffuses out ofcell.

What does the Na/K ATPase on the basolateral membrane of the proximal tubule cell produce and what does it allow?

It produces a conc gradient and there is a lower Na+ in the cell and this allows the Na+ into the cells from the proximal tubule.

What follows Na+ into the proximal tubule cells?

Cl-follows Na+ by facilitateddiffusionPhosphate(PO42-)and sulphate (SO42-)are also co-transportedwith Na+.


What charge are there in the proximal tubule cells and what does this lead to?
Inside the cells have a lot of protein therefore an overall - change and this attracts Na+ into the cell and this means Na+ moves from a electrical gradient.

What % of water is reabsorbed in the PT?




What routes of water movement are there?

60-70%




Transcellular and paracellular

What are required for water to move transcellular?

Transcellularroutes involve aquaporin (AP) channels located on apical and basolateralsurfaces.


There is no activewater reabsorption along nephron - it occurs by osmosis andit follows sodium.

Where are Aquaporin-1(AP-1) found?

Abundant distribution in proximaltubule.Wide distribution (e.g. lung, brain)
Where are Aquaporin-2(AP-2) found?
Present in collectingducton apical surface AP-2 channel expression controlledby antidiuretic hormone (ADH)
Where are Aquaporins-3& 4 (AP-3 & AP-4) found?
Present on basolateralsurface of collecting duct cells

What is glucose co-transported with into the PT cells? What is moved down?

with sodium and it moves down a conc gradient.

What SGLT is found in the curly apical part of the PT? What Glut is found on the basolateral membrane? What % of water do they reabsorbed?



SGLT 2


GLUT 2


90%

What SGLT is found in the straight apical part of the PT? What Glut is found on the basolateral membrane? What % of water do they reabsorbed?

SGLT 1


GLUT 1


10%

What does this show about the reabsorption of glucose?

What does this show about the reabsorption of glucose?

This shows that the transporters can be saturated and this is why diabetics can have glucose in their urine.

Name some SGLT2 inhibitors.


What can they be used for?

DapagliflozinCanagliflozinEmpagliflozin(BI-10773)Ipragliflozin(ASP-1941)TopogliflozinErtugliflozin(PF-4971729/MK-8835)RemogliflozinSergliflozin



Ideahere is to make diabetic patients excrete more Glucoseleading to an overall hypoglycaemic effect

How is K+ reabsorbed? What % in the PT?

70 % of filtered K+ is reabsorbed in the PT, mostlypassively via tight junctions (i.e. paracellularly)

How is Urea reabsorbed? What % in the PT?

40–50 % filtered urea is reabsorbedpassively in the PT down its concentration gradient

How is Amino Acids? What % in the PT?

7 independent transport processesfor reabsorbtion of AAs from the PT – depends ontype of AA



High Tm for transport so that as much aspossible is reabsorbed from PT

How is Proteins reabsorbed in PT?

Reabsorbedfrom the PT via receptor-mediated endocytosis
Describe Protein Reabsorption from the PT.

Describe Protein Reabsorption from the PT.

•Smallamounts of protein pass into filtrate via the glomerulus

•Theseare reabsorbed by pinocytosis vesiclestransported into cell, degraded by lysosomes and amino acids returned to blood


•Onlylimited transport capacity (low Tm) proteinuriais a sign of glomerular damage and impending renal failure

Describe the secretion from the PT and the two kinds of pump?

Specialisedpumps in the PT can transport compounds from the plasma into the nephron–

Two kinds of “pumps”(includes OAT, URAT):


•For organicacids(e.g. uric acid, diuretics,antibiotics - penicillin)


•For organicbases(e.g. creatinine,procainamide)

What do the secretory pumps in the PT allow?

They allow the filtrations that cannot be filtered at the glomerulus to be moved into the urine and these molecules are normally protein bound.

Describe the PAH into the PT.

Describe the PAH into the PT.

•Para-amino hippurate (PAH)is secretedinto PT from blood

•Notan endogenous compound (from plants) so PAH can be used as a tool to measure tubularsecretion


•TransportedintoPT cells from blood with a-ketoglutarateor other di/tri carboxylates


•Transportedout of PT cells in exchange for another anion present in the PT lumen

Name some organic acids in endogenous acids.

cAMP

Bile salts


Hippurates


Oxalate


Prostaglandins


Urate (Uric acid)

Name some organic acid drugs.

Acetozolamide

Chlorothiazide


Furosemide


Penicillin


Probencid


Salicylate (Aspirin)


Hydrochlorothiazide


Bumetanide


PAH – useful for measuring PT secretion

Name some organic bases secreted into urine by the PT Endogenous bases.




Creatinine Dopamine Adrenaline (Epinephrine) Noradrenaline (Norepinephrine) Histamine Choline

Thiamine and Guanidine

Name some organic bases secreted into urine by PT Drugs.

Atropine Isoproterenol Cimetidine Morphine Quinine Amiloride Procainamide

What order do the renal vessels normally run in when you are looking from the front?

The vein runs in front of the arteries meaning that the left renal vein runs over the aorta

What order do the renal vessels normally run in when you are looking from the front?

The vein runs in front of the arteries meaning that the left renal vein runs over the aorta

What vein joins the left renal vein before it reaches the IVC?

The Gonodal and ovarian vein in males and females

Where does the filtrate go when it leaves the proximal tubule?

Loop of Henle

What is the aim in the loop of henle?

Theaim here is to recover fluid and solutes from the glomerular filtrate

What are the 2 stages of reabsorption in the loop of henle?

(1)Extractionof water in the descendinglimb

(2)Extractionof Na+and Cl- inthe ascendinglimb

What type of nephron can perform reabsorption better and why?

Thisprocess is of more importance for juxtamedullarynephronswhich have longer loops of Henle

Describe the reabsorption of water in the descending limb of the loop of henle.

-Thin descending limb

- Cellsare flat, no active transport of salts (e.g. Na+, Cl-)


-But freely permeable to water via Aquaporin-1 channels


-Also some passive movement of water via tight junctions

Describe the reabsorption of electrolyse in the ascending limb of the loop of henle.

- Thickascending limb

-Tubular wall is impermeable to water -But has specialisedNa+/K+/2Cl-(NKCC2) co-transporters



What does show in the loop of henle?

What does show in the loop of henle?

This shows the nkcc2 in the ascending limb of the loop of henle and that it is driven by the na/k ATPase on the basolateral side it alose shows that the inside of the cells are -ve changed due to proteins and therefore positive ions Ca2+ and Mg+ are moved paracellularly.

What is the water that enters the loop of henle? What happens to it in the descending LOH?

Fluidentering LOH from proximaltubule is isotonic(300mOsm)

Waterreabsorbed out of descendingLOHBythe tip of the LOH, the filtrateishypertonic(i.e. veryconcentrated,1,200 mOsm)

What happens to the hypertonic solution at the tip when it moves through the ascending loop of henle?

Solutes(e.g. Na+,Cl-)are thenpumpedout of the ascending LOHBythe end of the LOH, the filtrateentering the distal tubuleis hypotonic (150 mOsm)

Describe the countercurrent multiplication in the loop of henle.

Createslarge osmotic gradient withinmedulla facilitatedby Na+/K+/2Cl- transportin ascending limb of LOHPermitspassive reabsorption ofwaterfrom tubular fluid indescendingLOH…
What ion transporters does this show?

What ion transporters does this show?

This shows a very powerful salt pump to allow the H2O to be taken out of the descending limb.

What helps the Na/K/Cl pump with the osmotic pressure when you are dehydrated?

Ureafreely filtered at glomerulus some is reabsorption in the proximal tubule,but LOH and distal tubulerelatively impermeable tourea


Ureacan diffuse out ofcollectingduct into medulladownits concentrationgradient



What occurs in the distal tubule?

-furtheradjustment of urine

–Sodium(Na+)and chloride (Cl-) ions are actively reabsorbed fromthe tubular fluid –This is in exchange for potassium(K+)or hydrogen (H+) ions which are secreted into the tubular fluid

What exchange in the distal tubule is controlled by aldosterone?

Na+ and Cl- in exchange for potassium(K+)or hydrogen (H+) ions which are secreted into the tubular fluid–

What exchanges occurs through the whole length of the distal tubule?

Na+ and Cl- exchanged for K+throughout the DT

What exchanges only occur in the later distal tubule and early collecting duct?

Na+ exchanged for K+in late DT and early collecting duct
Where are PRINCIPALCELLS in the kidney and what do they do and what are the sensitive to?
Na+ exchanged for K+in late DT and early collecting duct

- These cells are sensitive to aldosterone

What does this show?

What does this show?

This shows the reabsorption of sodium and chloride throughout the distal tubule.

What does this show?

What does this show?

This shows the principle cells and the aldosterone secretive cell in the later distal tubule and the collecting duct.

Describe the principle cells and what form part of?

•Exchange Na+ for K+ in the late DT and early collecting duct

-sensitive to aldosterone


-This exchange forms part of the renin-angiotensin-aldosterone system (RAAS):

What detects the decrease in BP in the kidneys and what system does it involve?

What cells in the distal tubule detect low Na+?

Marcula densa

What cells release aldosterone in the kidney?

Juxtoglomerular cells

What does aldosterone do in the kidney to when the BP is low?

It up regulates Na+/K+ reabsorption by increasing the expression of channels and this means moreNa+reabsorbed so more water moves into plasma so BP increases.

What cells are required for the exchange of Na+ and H+ in the distal tubule and early collecting duct? What types are there?

INTERCALATEDCELLS

- Subtypes exist called a and b intercalated cells

Describe a-Intercalated Cells.

Secretesacid (H+)viaH+/Na+or H+/K+exchange,involvingATPase or H+ATPase



Reabsorbsbicarbonate (HCO3-)




What cells in the kidney are involved in the acid/base balance?

a-Intercalated Cells if they secrete H+ into the urine the pH in the blood will rise.

What hormone allows the collecting duct to become more permeable to water?

Antidiuretic hormone (ADH)

What is ADH also know as?

Also known as ‘vasopressin’ or8-arginine-vasopressin (to distinguish it from ADH of some other species, e.g. ADH is 8-lysine-vasopressin in pigs)

Where in the body is ADH produced?

Releasedfrom the posterior pituitary but produced in the hypothalamus

What is the half life of ADH?

-Plasmahalf life is 10-15 min (liver and renal metabolism)

Where does ADH act on the kidney?

ADHacts on vasopressin V2 receptors on basal membrane ofprincipal cells in DT and collecting duct cells leading to activation ofintracellular (aquaporin-2 or AP-2) water channels so that water can be taken back into the blood.

Describe what happens when you are severely dehydrated and maximal circulating ADH occurs.

-Collectingduct becomes permeable to water sowater reabsorption occurs

-Reabsorbsup to 66 % of the water entering the collecting duct


–Deliveryof fluid to the collecting duct is low (~ 8 L/day)


–Urinevolume can be reduced to 300mL/day

Describe what happens when there is no circulating ADH.

•Reabsorptionof water occurs at various sites in the nephron as described previously

•Collecting duct wall becomes impermeableto water so alarge volume of water is excreted (up to 30 L/day !!!)

What is the Lack of ADH called?

Diabetes insipidus – can be treated using synthetic ADH

What are the 2 types ofDiabetesInsipidus?

Nephrogenic and neurogenic

Describe Nephrogenic Diabetes Insipidus.

Dueto inability of kidneytorespond normally to ADH

Treatment:Hydrochlorothiazide(diuretic)Indometacin(anti-inflammatory)

Describe Neurogenic Diabetes Insipidus.

Dueto lack of ADH production bythe brain

Treatment:Desmopressin (ADHanalogue)Carbamezapine(anti-convulsive)

What is SIADH?

SIADH= Syndromeof InappropriateADH Excessive release of ADH, e.g. due to head injury, unwanted effects of drugs (ecstasy)


SIADHcan cause hyponatraemia andpossibly fluid overload


Treatment:V2receptor blockers (ADH inhibitors), e.g. demeclocycline

Name some agents that INCREASES ADH release. What do they lead to?

–Nicotine–Ether–Morphine–Barbiturates



Anti-Diureticaction(urineexcretion decreases)

Name an agent that DECREASES ADH release. What does it lead to?

–Alcohol



Diureticaction(urineexcretion increases)

What happens to all that water andsolutes reabsorbed from the tubule?

It is all taken back into the peritubular vessels and vasa recta surroundingthe tubule.

What are the 4 sets of bones that outline the PAW?

1. Lumbar vertebrae (l1-5)


2. Sacrum


3. Ilia


4. Ribs T11/12

What are the 4 muscles that make up the PAW?

1. Diaphragm


2. Quadratus Lumborum


3. Iliacus


4. Psoas

Describe the diaphragm.

Anchored by crura


Central Tendon


Hilatus for vessels

What are the 3 main hilatus in the diaphragm and what vertebral level to the occur?

T8- IVC

T10 – oesophagus


T12 – aorta

Why does the diaphragm have a tendon in the middle?

This is so the tendon doesn't contract and the space stays the same therefore the liver can be anchored to the diaphragm.

Describe the quadratus lumborum.

-post to kidneys

- Rib 12 to iliac crest


- Abd stability/lateral flexion


- Works in the opposite way to Obliques

Describe the iliacus and psoas muscles.

-Iliacus: iliac blade

- Psoas: Lumbar vertebrae


- Lesser trochanter femur


- Hip flexors


- run under the inguinal ligament.

What is the VAN of the diaphragm?

Vein/Artery: Sup and inf phrenic




Nerves: Phrenic, Intercostal and subcostal

What is the VAN of the Q lumborum?

Vein/Artery: Lumbar




Nerves: T12-14

What is the VAN of the Iliopsoas?

Vein/Artery: Lumbar




Nerves: L2-4

Name the branches of the aorta from the diaphragm down.

T12- Celiac trunk


L1- Sup Mes


L2- Renal vessels


L2- Gonadal


L3- Inf Mes


L4/5- Aorta bifurcation into common iliac

Where do the femoral vessels run?

The inguinal ligament.

Describe the vessels in the aorta.

• 3midline vessels (e.g. coeliac)

•Paired parietal (e.g. lumbar)


•Paired visceral (e.g. renal, gonadal)

Where on the abd aorta are aneurysm more likely?

Below renal arteries

What can aneurysms lead to?

atherosclerosis (weakens walls)


This can lead to occlusion of the aortic bifurcation called claudication and this can lead to Impotence

What is claudication?

Pain in lower limb as blood is not flowing optimally down the leg.

What can the kinks in the abd aorta lead to?

Increase chance of clotting.

What is somatic innervation?

voluntary muscle control and sensation (e.g. touch, temperature, etc)



(larger than autonomic)

What is autonomic innervation?

outsideour control (e.g. sweating, vasodilation, etc)

What are the 2 types of autonomic system?

-insegmented structures (muscle, skin etc) (derma tons)

-in viscera (stomach, lungs, heart, brain etc)

Where are the somatic nerves in the abd?

-muscles of anterior/posterior abdominal wall, joints (e.g. intervertebral) ,skin etc

Where are the autonomic nerves in the abd?

-in segmented structures (blood vessels in muscle, sweat glands in skin etc)

-in viscera, aka splanchnic (Greek: ‘entrails’) (peristalsis of stomach, heartrate etc)

Where do the somatic nerves come from in the spine?

Lumbarplexus (L1-L4) – motor andsensory

Where do the autonomic sympathetic nerves come from in the spine?

-Segmented => sympathetic chain (paravertebral)

-Viscera => celiac, sup and inf mesenteric (prevertebral- sitting in front of the aorta)

Where do the autonomic parasympathetic nerves come from in the spine?

vagus and pelvic splanchnic

Describe the pre vertebral ganglia.

nervesoriginate in spinal cord and project to these ganglia bypassing the symp chain and from these to theviscera => splanchnic nerves
What is the arrow pointing at? 

What is the arrow pointing at?

Where do the splanchnic nerves originate from?

the thoracic region and move through the diaphragm.

What is weird about the greater splanchnic nerve?

It is very thin and hard to dissect

What are the arrows pointing at? 

What are the arrows pointing at?

What is a plexus?

Plexus is when nerves join together and split again forming a network of nerves.

What is the innervation of the suprarenal glands?

by greater, lesserand least splanchnic nerves that lead to the Celiacand aorticorenal ganglia

What is the innervation of the kidney?

Kidneys innervated mostly by fibres from the least splanchnic nerve

What does the suprarenals not have?

a parasympathetic supply

Where does somatic abd pain arise from?

skin

fascia


muscle


parietal peritoneum

What is somatic abd pain like?

Preciselylocalised, severe and sharp

What is called when somatic abd pain occurs only on one side?

Whenoccurring on one side from midline => lateralised

Where does visceral abd pain arise from?

abdominalorgans

mesenteries


visceral peritoneum

What are the causes of visceral abd pain?

1. stretching viscus or mesentery

2. impaired blood supply to viscus (ischaemia)


3. chemical damage to viscus (ulcers in the stomach leak and damage other organs)



What is visceral abd pain like?

1. Dull and poorly localised

2. pain is referred to midline (embryology)

What is a special type of visceral abd pain and what causes it?

Colic pain is a form of visceral pain and is caused by something obstructing the lumen.

What is referred pain?

Describespain at a location other than site of origin stimulus but supplied by same oradjacent segments of the spinal cord

What can cause referred pain?

bothsomatic and visceral structures may produce referred pain

Where does visceral pain from the stomach refer to?

T5-9

Where does visceral pain from the appendix refer to?

T10

Where does visceral pain from the gall bladder refer to?

T7-9

Where does visceral pain from the gall bladder with parietal peritoneum involvement refer to?

C3 and 4

What nerves carries painsignals from pleuraor peritoneum of the central part of the diaphragm?
phrenic C3-5
What nerves carries painsignals from pleuraor peritoneum of the peripheral diaphragm?
intercostals T7-11
What nerves carries painsignals from the ant abd wall to the reach CNS by following nerves
T7-12 and L1

Who is more likely to get UTI?

1.Up to 20% of women in lifetime,many recurrent, most not severe

2.1 to 2% of infants, boys < 3months old 3. Men rare until old age (prostaticenlargement)


4. 20% asymptomatic bacteriuria inelderly


5. 10% of hospital catheterisedpatients

Why are women more likely to get UTI?

shorter urethra

Why do infants get UTI?

As they do not have a full immunity.

What are the 2 types of UTIs?

1. Uncomplicated “Upper” UTI

2. Uncomplicated “Lower” UTI

What is the other name for Uncomplicated “Upper” UTI ?
Acutepyelonephritis
What are the other names for Uncomplicated “Lower” UTI?
Cystitis

Urethritis,Prostatitis, Epididymo-orchitis

What is involved in acute pyelonephritis?

Kidneys and urether

What is involved in cystitis?

bladder, uretha and postate

What should urine in the ureters and bladder be?

sterile

Where do most UTIs occur?

gutbacteria ascending urethra

What is the most common community organism causing UTIs?

(Gramnegrods)Escherichia coli80% (uropathogenic strain)

What are the most common hospital organisms that cause UTIs?

pseudomonas,MRSA and (staph causes a very small amount)

What host factors contribute to lower UTIs?

1.Obstruction

2.Poorbladder emptying


3. Catheterisation/instrumentation 4.Vesico-entericfistula


5.Sexualintercourse


6. Diabetes (glucose in the urine)


7. Dehydration

What host factors contribute to upper UTIs?

1. Vesico-uretericreflux

2. Obstruction

What are the bacterial virulence for UTIs?

1. abilityto colonise periurethral area (colon, vaginal tract)

2. abilityto invade uroepithelium


3. pili/fimbriae/othersurface antigens


4. toxins (products)


5. capsularpolysaccharide inhibits phagocytosis by neutrophils

What are the clinical diagnosis's for Lower UTIs?

1. bladderand urethral symptoms

2. overlapwith urethritisdysuria,frequency, urgency, suprapubicpain, nocturia, smelly/cloudyurine/visible, bloodchildren,elderly and catheterised can be non-specific

What are the clinical diagnosis's for Higher UTIs?
fever,rigors, loin pain (above kidneys), renalangle tenderness

oftenlower UTI symptoms in additionifpain radiation to groin - stone?


riskof bacteraemia


malaise, high HR and Resp rate as well as hypotensive and lower Urine output.

What test is done first for UTIs?

Dipstick

Describe UTIs diagnosis.

Controversial

Notdiagnostic


Mainuse to determine treatment if symptoms vague


Lookfor nitrites +/- leucocytes


treatdon’tneed to send urine for culture in simple cystitis in a non-pregnant adultfemale

What does a negative UTI dipstick show?

If negative, excludes UTI

What happens it nitrites are present in UTI dipstick?

if nitrites positive with symptoms suggestive of cystitis,

What are nitrites +/- leucocytes a sign off in UTIs?

Indicators of organisms present

What do microscopy show in UTIs?

redcells, white cells, epithelial cells and organisms

What do epithelial cells show in UTIs?

contamination of sample of urine

What do white cells show in UTIs?

infection

What is shown in culture and antibiotic sensitivity?

quantitative

>10^5 organismsper ml is “significant bacteriuria”(in MSU only)


ie,probably not contaminants (90% specific)UTIcan be < 10^5


Have to have more than 100 white cells to be cultured.

What are used to culture UTI samples?

Agar plates

What does this show?

What does this show?

antibiotic sensitivity testing for UTIs.

What empiric antibiotics cover?

mustcover likely organisms eg Ecoli

How should antibotics for UTIs be taken and what is the exception?

Orally but upper can be given 24hrs IV treatment

What antibiotics should be given for cystitis?

trimethoprimor nitrofurantoin
What antibiotics should be given for pyelonephritis?

co-amoxiclav

What do you need to consider before treating UTIs with antibiotics?

cover, route, target and side effects

What should you consider with a upper UTI?

the systemic amount of antibiotics in the blood should remain high.

What is happening to antibiotic resistance?

Increasing

What are diuretic agents?

Any compound that causes the excretion of an increased volume of urine

More accurate: a drug that increases the excretion of both fluids and solutes

What do Natriuretic do?
increases Na+ excretion

Can occur naturally in blood as they are produced by the heart.

What do Kaliuretic do?

increases K+ excretion

What do most diuretics increase?

increase excretion of Na+ andwater by the kidneys

1) They reduce reabsorption of Na+ from the filtrate


2) Increased water loss issecondary to Na+excretion

What are the 2 modes of action of diuretics?

1) Direct action on the cells ofthe nephron (more common)

2) Modification of content of thefiltrate

What are the 2 major applications of diuretic agents?

1)Reduce circulating fluid volume

2)Removal of excess body fluid (oedema)

What things are helped by diuretics?

-hypertension

- chronic heart failure


- liver cirrhosis


- renal disease


- premenstrual oedema


- toxic oedema


- increaseelimination of drugs


-rapid weight loss (abuse)



What 2 other actions do diuretics have?

-glaucoma (reduces intra-ocular pressure)

- epilepsy (reduces pressure of CSF?)

Where do most diuretics have effect?

the thick ascending limb

Name the main site of action of Carbonicanhydrase inhibitors.

Proximal tubule
Where do Osmoticdiuretics work?
Proximal tubule

Descending Loop of Henle (i.e. water permeable parts of the nephron where Aqup1 are seen)

Where do Loop diuretics work?
Ascending Loop of Henle
Where do Thiazides diuretics work?
Early Distal tubule

Where do Potassium-sparing diuretics work?

Late distal tubule

Early collecting tubule

What are the 2 types of Potassium- sparing diuretics?

-Aldosterone antagonists


- Non-aldosterone antagonists

Where are most diuretic agents secreted and why?

Most(not all) are secreted (pumped) into the proximal tubule from blood as they are protein bound and then they produce their actions from the luminal(urine) side of the tubule.

Describe loop diuretics.

•Mosteffective diuretics available

•Inhibitthe Na+/K+/2Cl-transporters(NKCC2) in the thick ascending limb of loop of Henle:this reduces reabsorption of Na+, K+ and Cl-


•ReducedNa+ reabsorption leads to rapid andprofound diuresis.

What does Furosemide do to urine Na+ and volume?

Increase Na+ in the urine as well as the urine volume.

How do oral absorption of loop diuretics work?

diuresis in 60 minutes and persists for 4-6hours (called Lasix as it lasts6h)

How do IV administration loop diuretics work?

diuresis begins within 5 minutes and persistsfor 2 hours

How do IM administration loop diuretics work?

diuresis begins in 30 minutes

What are the clinical uses of loop diuretics?

•Acutepulmonary oedema

•Chronicheart failure


•Cirrhosisof the liver


•Resistanthypertension


•Nephroticsyndrome


•Acuterenal failure

What are the unwanted effects of loop diuretics?

•Dehydration

•K+loss leading to low plasma K+(hypokalaemia)


•Metabolicalkalosis (due to H+loss in urine)


•Hypokalaemiacan potentiate effects of cardiac glycosides (heart drugs)


•Deafness(when used with aminoglycoside antibiotics)

What does frusemide do to K+ secrete?

K+ increases in the urine.

What do loop diuretics cause in the DT?

Loopdiuretics cause increased Na+delivery to the DT and thisis exchanged for K+in the DT which is excreted in the urine.

ThisK+ loss contributes to the hypokalaemia associated with loop diuretics

Describe the Thiazide diuretics.

•Actin the distal tubule toinhibit the apical Na+/Cl-co-transporter

•Causemoderate but sustained Na+excretion with increased water excretion •Wellabsorbed from GI tract and long duration of action: up to 24 h


- Good for elderly patients

Compare Thiazide and Loop diuretics.

Thiazide is a moderately powerful diuresis: but maximum diuresis produced is considerably lower than that produced by loop diuretics.

What is the main thiazide diuretic?

bendroflumethiazide

What are the clinical uses for Thiazide diuretics?

•Hypertension

•Oedema


•Mildheart failure

What are the unwanted effects of Thiazide diuretics?

•PlasmaK+depletion (due to urinary K+loss)

•Metabolicalkalosis (due to urinary H+loss)


•Increasedplasma uric acid – gout


•Hyperglycaemia(increased blood glucose – linked to K+)


•Increasedplasma cholesterol (with long-term use)


•Maleimpotence (reversible)

What diuretics can cause hypokalaemia?

Due to increased loss of K+ in the urine, loop diuretics andthiazides can cause hypokalaemia (decreased plasma K+)



thisis an unwanted effect

What are the symptoms of mild hypokalaemia?

fatigue, drowsiness, dizziness, muscle weakness
What are the symptoms of Severe hypokalaemia?
abnormal heart rhythm, muscle paralysis, death

What type of diuretic can avoid hypokalaemia?

Potassium-sparing diuretics can avoid this problem

How do potassium- sparing diuretics work?

- Act on distal tubules to inhibit Na+ reabsorption

- However, K+ is not secreted into the distal tubule

What are the 2 types of potassium sparing diuretics?

–Aldosterone antagonists (e.g. eplerenone, spironolactone)

–Non-Aldosterone antagonists (e.g. amiloride, triamterene)

Describe potassium- sparing diuretics.

Competitive antagonists ofaldosterone - reduce Na+channel formation

•Reduces Na+ absorption from distal tubule


•Limited diuretic action (not as potent as loop diuretics orthiazides)


•Mechanism depends on reduction ofprotein expression in distal tubular cells so effects may take several days todevelop

What are the clinical uses of spironolactone?

•Heartfailure

•OedemaEplerenone


–Can also be used for resistanthypertension but some concerns over long-term use due to possibleincidence of cancer (note: reported in rat studies only)

What type of diuretics are spironolactone?

Potassium sparing

What are the unwanted effects of spironolactone?

•Hyperkalaemia(increased plasma K+ levels)– needs to be monitored regularly •Metabolicacidosis (due to increased plasma H+)

•GIupsets (peptic ulceration reported) •Gynaecomastia (breasts in males),menstrual disorders, testicular atrophy

Describe Triamterene and Amiloride.

•Weak diuretics - act on distaltubule to inhibit Na+reabsorption and decrease K+ excretion

•Blocks luminal Na+ channel by which aldosteroneproduces its main effects


What are the unwanted effects of Triamterene and Amiloride?

Hyperkalaemia, but also metabolic acidosis, GI disturbances, skin rashes

What are the 2 reasons diuretics are used in combination?

(1)To increase diuretic effect

(2) To avoid the unwanted effects of hypokalaemia

Describe the use of diuretics in combination to increase diuretic effect.

1. Some patients do not respond well to justone type of diuretic (e.g. loop diuretics) – reasons unknown,probably genetic

2. Combinations of diuretics with differentsites of action can sometimes provide a synergistic action…this can becomecomplicated.

Describe the use of diuretics in combination to avoid hypokalaemia.

- Combinations of loop diureticsor thiazides with potassium-sparing diuretics

- Diuretic preparationscontaining K+…….

How can hypoklaemia be avoided?

Having K+ supplements added to the drugs.

What is the main type of CarbonicAnhydrase Inhibitors?

azetozolamide

How do Carbonic Anhydrase Inhibitors work ?

•Blockssodium bicarbonate (NaHCO3)reabsorption in the PT

•Thesewere the earliest diuretic agents developed


•Causesonly weak diuresis so not now commonly used as diuretic agent

What are Carbonic Anhydrase Inhibitors used to treat?

-glaucoma(reduces intraoccularpressure)- epilepsy(reduces volume and pressure of CSF)
What are the unwanted effects of Carbonic Anhydrase Inhibitors?
- metabolic acidosis (due to excretion of HCO3-)

-enhancesrenal stone formation (due to alkaline urine)

What is the main example of Osmotic diuretics?

mannitol

Describe mannitol.

•Non-reabsorbablesolute which undergoes glomerular filtration

•Excretedwithin 30-60 min


•Diuresisbegins in 30-60 min and persists for 6-8 h

What are the clinical uses for osmotic diuretics?

•Treatmentof raised intercranialpressure (cerebral oedema)

•Treatmentof intraoccularpressure (glaucoma)


•Ifgiven orally, can cause ‘osmotic diarrhoea’ – eliminates toxins


•Maybe useful for treatment of acute renal failure

What are the unwanted effects of osmotic diuretics?

•Presence in blood also exerts osmotic pressure leading to increased plasma volume

What patients cannot be used for osmotic diuretics?

so they can’t be used in patients with hypertension

What is the most simple diuretic?

water

Describe water as a diuretic.

Undernormal conditions, increased water intake leads to increase in volume of urineexcreted
What is the Mostimportant hormone in regulating water balance?
•Processis controlled by a hormone: antidiuretichormone(ADH)

•Normallysome ADH is present in the circulation, maintaining urine volume at approximately 1.5 L/day

Describe the action of water as a diuretic?

1. Increasedfluid intake leads to reduced secretion of ADH from the posterior pituitary dueto reduced in plasma osmolality.

2. Reducedexpression of AP-2 receptors onapical surface of DT and collecting duct cellsmeans more water excretion

What do AP-2 move and not move?

Water and they don't move Na+

Name the Agent which inhibitADH releaseand therefore, increaseurine excretion.
–Alcohol (althoughtolerance develops rapidly so diuresis not sustained)
Name the Agents which increaseADH releaseand therefore, reduceurine excretion?
–Nicotine(anecdotalevidence)

–Ether


–Morphine


–Barbiturates

Name some examples of Xanthines.

caffeine, theophylline, theobromine



Commonly found in tea and coffee

How do Xanthines produce diuretic effect?

-Produce their weak diuretic effect byincreasing cardiac output

-Possibly also some vasodilatation of theglomerular afferent arteriole


-Results in increased renal and glomerularblood flow which increases glomerular filtration rate and urine output

Name the order of power of the diuretics.

loop diuretics > thiazides >potassium sparing diuretics
Why measure renal function?
1: Identificationof renal impairment in your patient

2: Modificationof dosages of drugs which are cleared bythe kidneys

What Patients are at Risk of DevelopingRenal Failure?
1: Extremesof age

2. Polypharmacy


3. Specificdisease states


4.Patientsreceiving large long-term analgesia


5.Transplantpatients


6. DrugTherapy


7.Patientsundergoing imaging procedures

How do you monitor a patient's renal function? What does monitoring allow?

1: Patient’sclinical condition

2: Modernimaging techniques


3: Biochemicaldata




Allows evaluation of the ability of the kidneys to handle water and solutes

Describe the monitoring of Patient's clinical conditions in renal function.

a: Clinical assessment- Justlooking at the patient, and listening to what they tell you abouttheir symptoms, can often give clues about their renal function


b:Use of bedside clinical data- weight charts, fluid balance charts, degree of oedema, results of urine dipstick testing.

Describe the monitoring of Modern Imaging Techniques in renal function.

Include macroscopic views of renal bloodflow, filtration and excretory function.


Some of these are used clinically butsome can only be currently used experimentally inthe lab

Name the 3 types of renography.

· Gammacamera planar scintigraphy

· Positronemission tomography (PET)


·Single photon emission computerised tomography (SPECT)

What is biochemical data useful for?

- Identifying renal impairment

What are the 2 types of blood markers of renal function that are used in biochemical data?

·Plasmaor serum creatinine (sCr)

● Plasma orserum urea or blood urea nitrogen (BUN)

What does plasma include?
plasma = serum + clotting proteins (e.g. fibrinogen)

Describe creatine as a indictor of renal function.

-Breakdown product of creatinephosphate in muscle

· Generallyproduced at a constant rate


· Filteredat the glomerulus with some secretion into the proximaltubule


· Normalrange in plasma: 40-120mmol/L

How is plasma creatinine increased artificially?

•Largemuscle mass, dietary intake•Drugs which interfere with analysis (Jaffereaction)

• Drugswhich inhibit tubular secretion •Ketoacidosis(affects analysis)


•Ethnicity(higher creatinekinase activity in black population)

How is plasma creatinine decreased artificially?

•Reducedmuscle mass (e.g. the elderly)•Cachexia/ starvation

•Immobility


•Pregnancy(due to increased plasma volume in the mother)


•Severeliver disease (as liver is also a source of creatinine)

Describe urea as a indicator of renal function.

·Liver produces urea in the ureacycle as a waste product of protein digestion

·Filtered at the glomerulus,secreted and reabsorbed in the tubule


· Plasma urea (BUN – Blood urea nitrogen) Normal range: 2.5-7.5 mmol/L >20mmol/Lindicates moderate to severe renal failure

How is plasma urea decreased artificially?

•Malnutrition

•Liverdisease


•Sicklecell anaemia (due to ­GFR)


•SIADH

How is plasma urea increased artificially?
•Highprotein diet

•Hypercatabolicconditions •Gastrointestinalbleeding (digested blood is a source of urea)


•Muscleinjury


•Drugse.g. Glucocorticoids, Tetracycline•Hypovolaemia

What makes biochemical data useful?

- Identifying renal impairment

-Evaluationof the ability of the kidneys tohandle water and solutes


-Modifyingdosages of drugs which are cleared by the kidneys

What do some methods of biochemical data measure?

“renal clearance” ofvarious substances
What would an ideal marker of kidney function be able to do?
- A naturally occurring molecule

- Not metabolised


- Only excreted by the kidney


- Filtered but not secreted or reabsorbed by the kidney

Describe the path of INULIN in renal clearance.

freelyfiltered but not reabsorbed or secreted



Excretion rate = rate it wasfiltered

Describe the path of electrolytes in renal clearance.

freelyfiltered and partly or mostly reabsorbed

Excretion rate = filtration rate – reabsorbed

Describe the path of glucose and amino acids in renal clearance.

freelyfiltered but fully reabsorbed



No excretion (normally)

Describe the path of PAH in renal clearance.

freelyfiltered, not reabsorbed, fully secreted



Substance therefore rapidly andeffectively cleared

Define renal clearance.

the volume of plasma completely cleared of a given substance in unit time



Comparesrate at which glomeruli filter asubstance withthe rate at which the kidneys excrete it viathe urine

What is renal clearance a measure of?

Measurementof difference in amount filtered and excreted allows estimation of the netamount reabsorbed or secreted by the renal tubules

What does renal clearance provide information on?

-Glomerularfiltration (F)

-Tubularreabsorption (R)


-Tubularsecretion (S)

What is the clearance of a solute?

Is thevirtual volume of blood that would be totally cleared of a solute in a giventime (so measured in ml/min)
What does the Rate at which kidneys excrete solute into urine =?
rate at which solute disappears from blood plasma

What is the equation for renal clearance?

What are the drawbacks of the renal clearance equation?

•Measuring clearance meansmeasurement of OVERALL nephron function i.e. all ~2 million nephrons in both kidneys

•This gives the SUM of ALL transportprocesses occurring along nephrons…


•…but no information about precisetubular sites or mechanisms of transport

What can be used to estimate GFR? Which one is better?

-GFR can be estimated by measurementof the clearance of CREATININE i.e.CREATININE CLEARANCE but creatinineis filtered AND secreted into tubule


-Amore accurate estimation is provided by measurement of INULINclearance – itis filtered but NOT secreted into tubule

What is INULIN?

is a plant polysaccharide Mw 5200Da

What happens to INULIN in the kidney?

It isfreely filtered - i.e. plasma and tubular concentration is same but it is NOT secreted and is NOTreabsorbed

What does inulin clearance =?

= GFR

•e.g.when inulin concentration is 1mg/mL in plasma and 125mg/mL in urine and urineflow rate is 1 mL/min… …thenGFR = 125 mL/min

What if a substance has clearance greater than inulin?

Then it must also be being secreted;

What if a substance has clearance less than inulin?

less means that it must be being reabsorbed or not filtered freely at the glomerulus

What is the most reliable method of measuring GFR?

Inulin Clearance

Why is Inulin clearance not useful clinically?

•Inulinmust be administered by IV to get relatively constant plasma levels

•Chemicalanalysis of inulin in plasma and urine is technically demanding


•Coulduse radiolabelled compounds instead, e.g. radioactive Vit B orEDTA •However,these may also bind to proteins and distort results


-Problemsof IV infusion of GFR marker are avoided by using an endogenous substance withinulin-like properties

What is creatinine filtered by and secreted by?

•Creatinine is filtered atthe glomerulus…•…butsome of it is also secreted intothe proximal tubule

What does the equation of creatinine actually show?

over-estimate GFRby about 20% in humans i.e.it would produce a GFR value of about 150 mL/min

How is the error in GFR overcome?

Over-estimate GFRby about 20%.

•However,the colourimetrymethods used to measure creatinine(e.g. the Jaffe method) under-estimates creatinineconcentrations by about 20 %


•Luckily,these 2 errors cancel each other out, and calculated creatinineclearance ≈ inulin clearance (i.e. 125 mL/min)

Why is creatinine clearance used to measure GFR?

•Cheap,easy, reliable, used clinically•AvoidsIV infusion, just requires venous blood and urine samples

•Creatinineusually produced by creatininephosphate metabolism in muscle


•Mustremember to take into account if person has muscle disease/damage or has hadlarge quantities of meat to eat•Usuallymeasure over a 24 hrperiod to get reliable results and take samples before breakfast

How can creatinine clearance be adjusted to take into account different people?

totake account of body surface area





CorrectedCreatinineclearance = (Measured CrCl x1.73)/Body Surface area (m2)

What equation can be used to estimate GFR with collecting urine? In the world and the UK?

Cockcroft-Gault Formula





MDRD(Modification of Diet in Renal Disease) Formula

PAH clearance to measure renal blood flow.

•If asubstance is completelycleared fromthe plasma, its clearance rate will be equal to the renalplasma flow(RPF)

•Clearanceof PAH - para-aminohippuricacidcan be used to estimate this:•

What is special about PAH?

•PAH not normally present in blood


Describe the route through the kidney taken by PAH.

•When given, almost all (~90%) cleared from kidney in one passage some is filtered in glomerulus and remainder secreted by proximal tubules

- ~10% bypasses tubule - travels from efferent arterioles into peritubular capillaries and then venous renal blood, and is not secreted

What is it called when Uncorrected value for PAH clearance are used?
known as “effective renal plasma flow” (ERPF)

How can the PAH be used to estimate the total renal blood flow?

•IfPAH extraction rate is 90% thentotal renal plasma flow =585/0.9

=650 mL/min


•Plasmais only one part of blood Blood= plasma (55%) + haematocrit(45%) …soif haematocrit =0.45…


…thentotal renal bloodflow =650 / (1 - 0.45) = 1182mL/min

What is wrong with the old biochemical data?

60% of kidney function has to be damaged to see some markers that where discovered first.

What is the future of kidney disease detection?

BIOMARKERS

What can be used as a indictor of chronic kidney disease?

Urinaryalbumin/protein excretion

What are the 2 main functions of the kidneys for homeostasis?

(1)Role of the kidney in volume regulation (2) Controlof acid-base balance by the kidneys
Describe the Role of the kidney in volume regulation
●Fluid balance:Theamount of water gained by the body each day equalsthe amount lost

•Electrolyte balance: Theion gain each day equals ion loss

Describe the Controlof acid-base balance by the kidneys
•Acid-base balance: H+ gainis offset by H+loss

•Highlight how the renal system interactswith thecardiovascular and respiratory systems

What 3 systems work together to maintain homeostasis?

Renal, cardiovascular and respiratory.

Where does ADH act?

The Collecting Duct is relativelyimpermeable to movement of water and solutes......however, the permeability of thecollecting duct can be considerably increased the action of antidiuretichormone(ADH).

What is ADH?

- Themost important hormone that regulates water balance


Describe how the ADH acts in the collecting duct.

- ADH acts on V2 receptors on the basal membrane of principal cells in the collecting duct

- This leads to insertion of aquaporin-2 (AP-2) water channels into the apical surface...

What is V2?

A receptor that is always expressed in the collecting duct to allow water to be moved into cells and it is also a G-coupled protein receptor.

What does maximal ADH lead to?

MaximalADH leads to production of low amounts of concentrated urine

Describe the pathway of the ADH.

V2 receptor activated > cAMP activated > Protein kinases > Vesicles with AP2 in it move to the apical side and are expressed.

What is ADH responsible for?

ADHreleased in response to changes in plasmaosmolalityand effective circulating volume(ECV)

What measures the changes in plasma osmolality and effective circulating volume (ECV) in the body?

These changes are detected by osmoreceptors and baroreceptors
Increased plasma osmolality (e.g. due to dehydration) stimulates....
osmoreceptors in the hypothalamus which trigger ADH release…



Result: more water reabsorbed from collecting ducts in kidney back into circulation. This leads to increased ECV

Increased osmolality also stimulates a second group of osmoreceptors which trigger
thirst…



Result: promotes water intake which enters circulation. This also ­ ECV

Baroreceptors:Detect changes in...
ECV

What are the 2 types of baroreceptors?

•‘Lowpressure’ blood volume receptors

•‘Highpressure’ arterial stretch receptors




Low pressure is the most important.

Where are the low pressure blood volume receptors?

Largesystemic veins

•Cardiacatria


-Pulmonaryvasculature



Where are the high pressure blood volume receptors?

•Carotid sinus

•Aortic arch


•Renal afferent arteriole (the renal baroreceptor)


What 4 parallel effector pathways do ECV trigger?

(1)RAAS (2)sympathetic nervous system (3)ADH release (4)ANP release
Feedbackcontrol of ECV exists…mediated by
baroreceptor stimulation

What 4 pathways together change renal haemodynamics andNa+ transport by renal tubule cells?

(1) RAAS (2)sympathetic nervous system (3)ADH release (4)ANP release

What is the Principalfactor controlling plasma Ang II levels?

is renin release from the JGA
Decreased ECV stimulates renin release via: 3 pathways
–Decreased renal perfusion pressure detected in the afferent arteriole the “renal baroreceptor”

–Decreased Na+ concentration in distal tubule detected by the macula densa cells the “renal Na+ sensor”


–Decreased systemic BP also triggers effects of the sympathetic nervous system on the JGA

What is the RAAS trying to do?

Increase Na+ reabsorption so that increased H2O reabsorption can occur to increase BP.

What causes hypotension?

Inappropriate increase in the RAAS system.

Describe the increase in ECV via the RAAS system.

Describe the increase in ECV via the ANS (nerve system) .
Describe the increase in ECV via ADH.

Describe the increase in ECV (with high osmolality) via ADH.

How does AtrialNatriuretic Peptide (ANP) act?
• Actions of ANP are all designed to lower ECV


What produces ANP?

•Atrial myocytes synthesize and store ANP.

When is ANP released?

•ANP released in response to atrial stretch (caused by ­ECV)

What does ANP promote? Where does it have the most effect?

•ANP promotes natriuresis (­ Na+ excretion)

•Major effect is renal vasodilatation so increased blood flow therefore increased GFR…so more Na+ excreted

What happens when more Na+ reaches the distal tubule?

•More Na+ reaches the macula densa so renin release by JGA is reduced

•Overall effect: inhibits actions of renin and opposes effects of Ang II

What happens in low pH?

- If plasma levels fall below 7.35 (acidaemia), acidosisresults

What happens in high pH?

- If plasma levels rise above7.45 (alkalaemia), alkalosisresults
What is the pH of normal range and what can abnormal range occur?
-Can result in coma, cardiac failure and circulatory collapse

- AtpH < 6.8 or > 8.0 death occurs

What do buffers do?

Buffers:Resist changes in pH

-When H+ added, buffer removes it


-When H+ removed, buffer replaces it

Why is the kidney important in acid-base balance?

•The kidneys are essential formaintaining acid-base balance

•This is important because allbiochemical processes must occur within an optimal pH window (pH 7.2 - 7.4)


•The kidneys do this in conjunctionwith the cardiovascular and respiratory systems

Describe the lungs and kidneys in acid/base balance.

•The lungs excrete a large amount ofCO2– this is a potential acid formed by metabolism (CO2reactswith water to form carbonic acid)

•The kidneys also secrete andexcrete non-volatileacidsproduced from normal metabolism which the lungs can’t excrete, e.g. lactic acid


•HOWEVER, to maintain acid-basebalance, the kidneys must also reabsorb virtually all filtered HCO3-



Why is HCO3-?

•This is important as HCO3- acts as a physiological buffer
What does this equation show? 

What does this equation show?

Therelationship between pH, HCO3- and CO2



Inverserelationship betweenpH and plasma concentrationof CO2

What part of the equation does the kidney regulate? 

What part of the equation does the kidney regulate?

HCO3- the physiological

What part of the equation does the lung regulate?
What part of the equation does the lung regulate?
Potentialacid (H2CO3)

What forms carbonic acid?

CO2reacts with water toform carbonic acid

What can cause a rise in pCO2?

lung conditions

What can cause a decrease in pCO2?

hyperventilation

What happens to PCO2 in hyperventilation?

as pCO2 levels decrease, pH increases
What happens to PCO2 in hypoventilation?
as pCO2 levels increase, pH decreases

What organ is the most effective regulator of body fluid pH?

kidneys
•IfpH of ECF falls(acidaemia) what happens to secretions?
•more secretion of H+ into filtrate AND reabsorption ofHCO3- back into ECF cause pH to increase

•Secretionof H+ inhibited when urine pH fallsbelow 4.5

•If pH of ECF increases (alkalaemia) what happens to secretions?
•secretion of H+ into filtrate and reabsorbtion of HCO3- declines. Extracellular pH decreases

What happens to electrolytes in the kidney?

•MostHCO3- infiltrate is reabsorbed, H+ is also secreted (pHurine ~ 6.0)
Acidosis:
pH of body fluids falls below 7.35Too much H+.
Solution: Get rid of H+
(i) Excrete it viathe lungs(as CO2) and the kidneys (as H+)

(ii) Produce more buffer (HCO3-) in the kidneys

Alkalosis:
pH of body fluids falls below 7.35
Solution: Increase levels of H+
(i)Reduce excretion of CO2 via the lungs(ii)Increase excretion of HCO3- buffer via the kidneys

(iii)Increase generation of H+ by the kidneys

What respiratory factors cause acidosis?

- Caused by inadequate ventilation

-Can be acute or chronic

What Metabolic factors cause acidosis?
- Results from all conditions other than respiratory that decrease pH

- Always chronic

What cause marked change in HCO3-?
Only chronic states
How can you gain H+?
–CO2 in blood (combines with H2O to form carbonic acid)

–Non-volatile acids from metabolism (e.g. lactic acid)


–Loss of HCO3- in diarrhoea or non-gastric GI fluids


–Loss of HCO3- in urine


What are the treatments of resp acidosis?

- Restore ventilation

-Treat underlying dysfunction or disease


- Give IV lactate solution (converted to HCO3- buffer in liver)

What are the treatments of metabolic acidosis?

-Give IV lactate solution (converted to HCO3- buffer in liver)

- Give isotonic HCO3-

What respiratory factors cause alkalosis?
- Caused by hyperventilation

- Can be acute or chronic

What metabolic factors cause alkalosis?

- Results from all conditions other than respiratory that increase pH

- Always chronic

What can cause a marked change in HCO3- ?
chronic states
How can you suffer a loss of H+?
–Use of H+ in metabolism of organic anions

–Loss of H+ in vomit


–Loss of H+ in urine Hyperventilation (blows off CO2)

What are the treatments of resp alkalosis?

-Treat underlying cause

- Breathe into paper bag (increases pCO2)


- Give IV Cl- containing soln (­HCO3- excretion)

What are the Treatment of Metabolic alkalosis?
- Give electrolytes to replace those lost

- Give IV Cl- containing soln


- Treat the underlying disorder

What connects the renal system and cardiovascular system?

Effectivecirculating volume control, ECF osmolality, blood pressure
What connects the renal system and resp system?
Acid-basebalance
What connects the resp system and cardiovascular system?
Gasexchange, ACE
•Final modification of tubular fluidoccurs in collecting duct under influence of
antidiuretic hormone (ADH)
•Tubular fluid exits collecting ductat tip of renal pyramid - also known as the
renal papilla
•Minor and major calyces lead to
renal pelvis
•Fluid deposition into renal pelvisstretches ? and Distension triggers?
• smooth muscle

•Distension triggers peristalticcontractions at hilus

What stimulates the peristaltic contractions at the hilus of the kidney?

pacemaker cells

Describe the main structure of the ureter?

•Tubes approximately 30 cm long•Mucosallayer:transitional epithelium

–3-8 cells thick, impermeable to urine

Supported by layers of smoothmuscle in the ureter.
-inner: longitudinal muscle (L)

-outer: circular/spiral muscle (C)


-extra outer layer of longitudinal muscle

What is the Function of the ureter?
•Dilation of renal pelvis generates action potential from pacemaker cells in hilum

•Peristaltic waves generated – between 1 to 6 per minute…


• …the number of contractions can be modulated by nervous system: - parasympathetic NS: enhanced - sympathetic NS: inhibited

•Peristaltic waves generated – between 1 to 6 per minute… • …the number of contractions can be modulated by
nervous system:

- parasympathetic NS: enhanced


- sympathetic NS: inhibited

Peristalticcontractions in ureter
•Consist of successive waves ofcontraction and relaxation of longitudinal and circular smooth muscle:

•Longitudinal smooth muscle contactsfirst. •Halfway through this contraction,circular muscle also begins to contract •Longitudinal muscle then starts torelax during latter half of circular muscle contraction •Pattern of contraction is repeatedresulting in slow but progressive movement of a pulse of urine along the ureter= PERISTALSIS

PERISTALSIS also known as in the ureter “vermiculation”
“vermiculation”
•Ureters attach to ? ofurinary bladder
•Ureters attach to posterior wall ofurinary bladder

•Pass through bladder wall atoblique angle for 2-3 cm into bladder…

…ureteral openings are ? rather than rounded

…ureteral openings are slit-like rather than rounded

Structure of the urinary bladder.

•A hollow muscular organ, consistingof fundus (body) and neck

•Outer “Detrusor” Muscle layer


•Inner Mucosal layer

•Outer “Detrusor” Muscle layer of bladder:
- consists of longitudinal, circular/spiral muscles
•Inner Mucosal layer of bladder:
- transitional epithelium

- folded into “rugae” when bladder empty - highly elastic – expands as bladder fills

What are rugae in the bladder?

pits that are present when the bladder is emptying and then expand as fluid enters.

Describe TheTrigone in the bladder.

•Triangular area bounded by openingsof ureters and entrance to urethra

- act as a funnel to channel urine towards neck of bladder

What is the function of the urinary bladder?

•Temporary storage of urine

•Up to 1 L capacity


•Stimulated to contract byparasympathetic NS

When does the bladder normally empty?

500/600 ml

The bladder is guarded by 2 sphincter:

Internalurethral sphincter and Externaluretheralsphincter
Internalurethral sphincter
-Loop of smooth muscle

-Convergence of detrusor muscle (from bladder)


-Underinvoluntarycontrol


-Normal tone keeps neck of bladder and urethra free of urine

Externaluretheralsphincter
-Circular band of skeletal musclewhere urethra passes through urogenital diaphragm

-Acts as a valve with resting muscletone-Undervoluntarycontrol

Females urinary tract:

-Opensvia external urethral orifice located between clitoris and vagina

-Shorterurethra in females therefore moresusceptible to UTIs


-Externalsphincter not as well developed leading to incontinence following childbirth due to injury

Females are more susceptible to ? due to a shorter urethra

UTIs

Males urinary tract:

-Urethra passes through prostrategland and through uro-genital diaphragm and penis

-Longer urethra compared to femalesprovide some protection against UTIs


-Prostate gland enlarges in 50%of males >60 yrs(al ongwith hypertrophy of detrusor muscle)

-Prostate gland enlargement may require?


Prostate cancer is

- may require surgical or hormone treatment



– one of the commonest cancers affecting older men (death rate ~ 3%)

Two stages of urination

(1)Bladderprogressively fills until pressure within bladder reaches a threshold level…

(2)…thiselicits the “micturationreflex” which produces a conscious desire to urinate or eventual emptying ofthe bladder

Themicturationreflex is an autonomic reflex which is
(i)inhibited by higher centresin the brain and

(ii)facilitated by cortical centresin the brain:

What does the higher centres in the brain due during micturition reflex?

•Higher centreskeep the micturationreflex under inhibition… …prevents micturationby stimulating continual tonic contraction of the external sphincter
What does the cortical centres in the brain due during micturition reflex?
•Cortical centresfacilitate micturationby initiating the micturationreflex and relaxing the external sphincter

What is the normal filling rate of the bladder?

•Bladder fills at 1 mL/min at normallevels of hydration
As bladder fills....
(intravesical) pressure increases

When do pressure peaks start to occur in the bladder?

pressure peaks (micturationcontractions or waves)

–these are periodic reflex contractions of short duration which occur aboveapproximately 200 mL urine volume

Pressure peaks (micturationcontractions or waves) an a Partiallyfull bladder:
contractions relax spontaneously after a few seconds
Pressure peaks (micturationcontractions or waves) in a Increasinglyfull bladder:
contractions more frequent, intense and last longer

What is the sympathetic innervation of the bladder?

hypogastric nerve

What is the parasympathetic innervation of the bladder?

pelvic nerve

What is the somatic innervation of the external urinary sphincter?

Pudendal nerve

Micturationis inhibitedby activity in the
hypogastric nerve (sympathetic)
Micturation is facilitatedby activity in the
pelvic nerves (para)
Duringbladder filling:

•Progressivebladder distension stimulates the ? viaactivation of stretch receptors in bladder wall and internal sphincter


•Activationof the ? leads to stimulation of the XX

pelvic nerve



Hypogastric nerve

•Hypogastricnerve stimulation causes:
(i) relaxation and reduced excitability of the bladder detrusormuscle

(ii) constriction of the internal sphincter

What is a guarding reflex?

•Hypogastricnerve stimulation causes: (i) relaxation and reduced excitability of the bladder detrusormuscle

(ii) constriction of the internal sphincter



•Also,the external sphincter is held closed by pudendalnerve

Asbladder continues to fill with urine…•Stretchreceptors in bladder continue to stimulate the ?
pelvic nerve
Stimulationof the pelvic nerve also causes:
(i) contraction of the detrusor muscle

(ii) relaxation of the internal sphincter

•Periodicreflex micturationcontractions are also stimulated...
ABOVE 200 mL.

These relax spontaneously after a fewseconds

•These micturation contractions continue to be stimulated and relax but at @@ bladder contractions begin to predominate
> 300 mL
•Full bladder sensation conveyed to ££ and then to >> causing an
Full bladder sensation conveyed to thalamus and then to cerebral cortex.





Desire to urinate starts to increase.

At appropriate time, voluntary relaxation of external sphincter occurs via $$.
pudendal nerve.
Micturation occurs, aided by
lowering of diaphragm, contraction of abdominal muscles and opening of internal sphincter
Micturation is facilitated by activity in the
pelvic nerve
Paraplegia:
complete severing of nerve inputs from cerebral cortex

–Micturationreflexes return, but without cortical control


–Periodicbut unannounced bladder emptying


– “Automatic bladder”

•Partialspinal cord damage with loss of inhibitory descending signals
–Frequenturination as excitatory impulses from cerebral cortex remain unopposed

–Knownas “Uninhibited bladder”

•Crushinjury of dorsal roots
–Afferentnerve destruction

- micturationreflexes lost despite complete efferent system


–Bladderfills to capacity and overflows dropwise


- “overflow incontinence”


–Knownas “Atonic bladder”

What type of bladder do infants have?

autonomic

3 problems that can occur with the micturation reflex?
(1)Controlof micturationcan be lost due to: - stroke injury, Alzheimer’s disease, problemsaffecting cerebral cortex or the hypothalamus (e.g. a brain tumour)

(2) Bladder sphincter muscles can lose tone (e.g.after pregnancy): - leading to urinary incontinence


(3)Urinary retentionmay develop in males if enlarged prostate gland compresses the urethra andrestricts urine flow

•Failureto store urine =
= incontinence
•Failureto empty bladder =
retention

What are the 3 main types of urinary incontinence?

•Loss of sensory nerves

•Involuntary bladder contractions •Heightened urge incontinence

Describe the Loss of sensory nerves in urinary incontinence.
– due toinjury

–Bladderfills to capacity


–Nosignals from stretch receptors in bladder


–Overflowincontinence occurs (Atonic bladder)

Describe Involuntary bladder contractions in urinary incontinence.
– due to injury

–Urge incontinence or increased frequency

Describe Heightened urge incontinence in urinary incontinence.
– sensitive bladder

–Spicy food (capsaicin)


–Caffeine/chocolate (xanthines)


–Citrus fruits (citric acid)


–Carbonated beverages (sugar, sweeteners)


–Excitement or even laughter :-D

Drugs used in urinary incontinence effecting the parasympathetic nerve.

These block the Ach released from parasympathetic nerves. 

These block the Ach released from parasympathetic nerves.

What are the 2 drugs used to effect the parasympathetic nerves in urinary incontinence?

(1) Anticholinergics

(2) Tricyclicantidepressants

Anticholinergics(muscarinic AChreceptor antagonists)
Actions:-inhibit bladder contractions

-facilitates involuntary contraction of internal bladder sphincter


Examples: Oxybutinin, Tolterodine, Propantheline, Propiverine, Flavoxate–Unwantedeffects: Dry mouth, blurred vision, palpitations,drowsiness, facial flushing

Tricyclic antidepressants
Low dose useful for short-term treatment for nocturnal enuresis in children > 10 yrs Mechanisms: - anticholinergic and direct muscle relaxant effects on the bladder (- increase noradrenaline and serotonin levels)

Examples: Amitriptyline, Imipramine, (less often) nortriptyline


Unwanted effects: Behavioural problems and relapse on withdrawal

Treatment of acute urinary retention.

–Catheterisation

–Surgery

Treatment of Chronic urinary retention.
–Pharmacologicalintervention

Surgery

Drugs used for urinary retention have an action side of...

the prostate and acts on the alpha 1 adenoreptor stimuated by NA

a-adrenergicblocking drugs

Actions:


Examples:

Actions: -Antagonist action at a1A adrenoceptors in bladder neck

- Relaxessmooth muscle at bladder neck andincreases urine flow rate


Examples: Alfuzosin, Doxazosin, Indoramin, Prazosin, Tamsulosin, Terazosin

a-adrenergicblocking drugs



Cautions:


Unwantedeffects:

Cautions: -Can reduce blood pressure so careful dosing required in patients alreadyreceiving antihypertensive treatments

-Should be avoided in patients with postural hypotension


Unwantedeffects: Hypotension, drowsiness, depression, headache, drymouth, GI disturbances

Parasympathomimetics

Actions:


Examples:

Actions: -Agonistaction atmuscarinic ACh receptors - Increasescontraction of the bladder detrusor muscle

-Limited role in relief of urinary retention – now superseded bycatheterisationExamples: Bethanechol

Parasympathomimetics

Cautions:


Unwantedeffects:

Cautions: -Use with care or avoid using in patients with cardiac disorders (e.g.arrhythmias)

-Avoid in cases involving GI ulceration, asthma, hypotension, epilepsy,Parkinsonism, pregnancy


Unwantedeffects: Nausea, vomiting, intestinal colic, bradycardia, blurredvision, sweating

Distigmine drug
– inhibits breakdown of acetylcholine

– promotes incontinence


- useful for “upper motor neurone neurogenic bladder”