Urinary System Week 1-9

What is the prognosis for those with IgA nephropathy?

(Put in lecture but may be wrong due to difference in geeky medics and LUSUMA notes) - 1/3rd resolve - 1.3rd haematuria continues but with no progression to end stage renal disease - 1/3rd progression to ERSD

What happens in the glomerulus?

- 125ml / min GFR - Relatively small molecules go through

What pumps are present on the basolateral membrane of the S1 proximal convoluted tubule?

- 3NA-2K-ATPase - Na+-HCO3- co-transporter, which brings back carbonate to the rest of the body

Describe the epidemiology of bladder cancer in the UK

- 4th most common cancer in men - 11th most common cancer in women - Incidence is decreasing in the UK - Male to female ratio is 2.5:1 - But presentation is often more advanced in women - 90% of bladder cancers are transitional cell carcinomas (TCC)

What happens in the proximal convoluted tubule?

- 67% Na+ with Cl- - HCO3- - Ca2+ - 70% water - Secretes H+ - Secretes ammonium ions - Secretes creatinine - Drugs - Toxins

Where are potassium ions reabsorbed in the kidneys?

- 67% passively in the proximal tubule - 20% actively in the Loop of Henle

What does the proximal convoluted tubule reabsorb?

- 67% water - 67% Na+ - 100% glucose - 100% amino acids - 90% HCO3-

Discuss the staging of bladder cancer?

- 75% of cancers are superficial (Ta/T1) - 5% are Tis (in situ, small group and very aggressive) - 20% are muscle invasive - T2 / T3 / T4

Which parts of the nephron is hydrogen carbonate recovered?

- 80%-90% recovered in the proximal convoluted tubule - Remainder is recovered in the thick ascending limb of the loop of Henle

Describe the epidemiology of renal cell carcinoma

- 8th most common cancer in the UK - 95% of all upper urinary tract tumours - Incidence and mortality are increasing - Male to female ratio is 3:2 - 30% of renal cell carcinomas have metastases on presentation

What are the two mechanisms in which plasma osmolarity is controlled?

- ADH - Thirst: putting more liquid into the body

Describe metabolic acidosis and how it is corrected

- Acids are produced metabolically - Produce more H+ and an anion (e.g. lactate, ketones etc) - H+ reacts with HCO3-, producing carbon dioxide which is breathed out

Describe what makes up the haematuria?

- Aconthocytes: A form of red blood cell that has a spiked cell membrane, due to abnormal thorny projections (see picture on left) - Red cell casts, which is a urinary cast composed of red blood cells in various stages of degeneration and visibility, which is characteristic of glomerular disease or renal parenchymal bleeding (picture on right)

Hence overall, what are the actions of sympathetic stimulation on the nephron?

- Acts on arterioles to reduce the renal blood flow - Stimulates granule cells of the afferent arteriole to release renin - Stimulates sodium ion reabsorption in the proximal convoluted tubue

What organs lie in relation to the right kidney?

- Adrenal - Liver - Duodenum - Colon - ascending - Ileum

What does hypokalaemia affect?

- Affects excitable cells - Affects the heart most where it causes arrhythmia - Effects on acid base balance

What arteries arrive at the vascular pole of the nephron?

- Afferent arterioles - Efferent arterioles - Glomerulus

Describe the factors that influence treatment decisions of prostate cancer

- Age - Digital rectal examination if it is found that: - Localised (T1/T2) - Locally advanced (T3) - Advanced (T4) - Prostate specific antigen serum levels if high - Biopsies - Gleason Grade - MRI and bone scan - Nodal metastases (metastasis to lymph nodes) - Visceral metastases (metastasis to internal organs)

Give two examples of K_ sparing diuretics

- Amiloride - Triameterene

What treatment is given to women with aysmptomatic bacteruira in pregnancy?

- Amoxicillin 250mg three times daily for 7 days - Nitrofurantoin 50mg four times daily for 100mg twice daily for seven days - Trimethoprim 200mg twice daily for 7 days - Cefalexin 500mg twice daily or 250mg 6-hourly for 7 days (less preferred)

What does bilateral lesions of the pontine storage centre (lateral pons) leads to?

- An inability to store urine - Reduction in bladder activity - Excessive Detrusor muscle activity - Relaxation of the urethra - Premature voiding - Leaky bladder (incontinence)

What organs does the left adrenal gland lie in relation to?

- Anteromedial to the kidney - Posterior to the stomach - Pancreas and splenic vessels - Medial to the spleen

Discuss the classification of haematuria

- As visible or non-visible

What is the state of most patients diagnosed with prostate cancer?

- Asymptomatic - Have a localised disease - Unlikely to die of prostate cancer

Give two examples of thiazide diuretics

- Bendroflumethiazide - Metolazone

Describe the histological appearance of the thick ascending limb

- Best seen in the medulla - Interspersed with thin limbs, vasa recta and the collecting duct - Simple cuboidal epithelium - No brush border

What would you aim to find out when through examination of someone with haematuria?

- Blood pressure - If an abdominal mass is present - Varicocele - which are a collection of veins in the scrotum, typically described as a bag of worms - Leg swelling - Assess prostate by DRE to see the size and texture of the prostate

What are the clinical features of rickets / osteomalacia?

- Bone pain, tenderness - Muscle weakness - Short stature - Multiple bone deformities - Fractures

What would you look for in bloods in a metabolic screen?

- Bone profile - Urea and electrolytes - PTH - Vitamin D - Urate - Bicarbonate

What are the various compositions of renal calculi?

- Calcium oxolate (monohydrate or dihydrate) - Uric acid - Struvite (magnesium ammonium phosphate) - Calcium phosphate - Cysteinw Less common: - Xanthine - Drug-related stones

Where are the baroreceptors found?

- Carotid sinus - Aortic arch

How does cirrhosis of the liver cause extracellular expansion and oedema?

- Causes less albumin production in the liver - Leads to low plasma albumin - Causes a low oncotic pressure - Leads to oedema - Leads to a reduced circulatory volume - RAAS activated - Sodium ion and water retention - Expansion of the extracelullar fluid and worsengin oedema

What does hyperkalaemia affect?

- Changes the resting membrane potential of cells - The more excitable the cell, the more it is affected - Affects the heart most where it causes arrhythmia and cessation of beating - Effects on acid base balance

How do we treat high risk non-muscle invasive transitional cell carcinoma?

- Check cytoscopies (a camera that is used to look inside the bladder) - Intravesicular chemotheray / immunotherapy. The drug is inserted directly into the bladder via catheter

What are other examples of infection that can trigger glomerulonephritis?

- Classically group A beta haemolytic strep - Nephrotic syndrome: - Macroscopic haematuria - Proteinuria - Low C3 - Elevated anti-streptolysin titre

What happens in the loop of Henle descending?

- Concentrates filtrate due water reabsorption - 25%

What are the functional abnormalities that are risk factors of developing UTIs in children?

- Constipation - Dysfunctional elimination syndrome is voluntary, prolonged and inappropriate withholding of the urine or faeces - Recent infection / irritation of the genital area that prevents regular voiding e.g. chickenpox, vulvitis and sexual abuse

What happens in the DCT?

- Controlled reabsorption of water - Concentrates urine action under ADH - Reabsorbs water and sodium ions due to aldosterone in principle cells - Variable amounts of bicarbonate reabsorption in the inetercalated cells - Secretes potassium ions as a result of aldosterone

What are the two layers of the kidney?

- Cortex - Medulla

Describe the histological appearance of the distal convoluted tubule

- Cortical (in the cortex) - Makes contact with its parent glomerulus - No brush border - Larger lumen than the PCT

What would you look for in the urine in a metabolic screen?

- Creatinine - Caclium - Oxalate - Citrate - pH - Magnesium - Phosphate - Uric acid - Sodium - Urea (- Amino acid cystine)

Explain the pathogenesis to why infections can trigger IgA nephropathy?

- Deposition of immune complexes (microbial antigen, IgG and complement), circulating or planted - Glomerular hyper cellularity (neutrophils) - May lead to crescents - IF capillary wall deposits

What glomerulopathies occur in systemic disease?

- Diabetes - Vaculities - Goodpasture syndrome - Sytemic lupus

What are the common secondary causes of proteinuria / nephrotic syndrome?

- Diabetes Mellitus - microvascular complication - Amyloidosis (group of diseases in which abnormal protein, known as amyloid fibrils, builds up in tissue)

Describe the histological appearance of the thin descending and ascending limb

- Dips down into the medulla - Lined with simple squamous epithelium - No active transport - No brush border - Looks a lot like small capilliaries but with no RBCs

What is the triad of basic treatment of nephrotic syndrome?

- Diuretics in order to reduce blood volume, to get rid of the water and oedema - Fluid / salt restriction. People on diuretics get thirsty, and therefore if they drink an increased amount they will receive no benefit from the diuretics. -ACE inhibitors / angiotensin receptor blockers. These change the regulation of the glomeruli to reduce the amount of proteins lost.

What drugs are used to treat patients with urinary incontinence?

- Duloxetine - Anticholinergics - Botulinum toxin

When during catheterisation may bacteria gain entry into the bladder?

- During insertion of the catheter - During manipulation of the catheter or drainage system - Around the catheter

What are the symptoms of pyelonephritis?

- Dysuria and frequency - BACK AND LOIN PAIN - Rigors (intermittent shaking) - FEVER - High pulse rate - Looking pale, unwell and sweaty

How do we prevent UTIs caused by catheters?

- Ensure an indwelling urinary catheter is appropriate - Ensure measures are in place to prevent the introduction of infection

What are the most common bacteria to cause UTIs

- Enteric pathogens e.g. E.coli - Second is candida

What are non-pharmacological approaches to treating hypertension?

- Exercise - Diet - Reduced Na+ intake

What are the secondary causes of FSGS?

- Familial / genetic - Virus associated - HIV-1 (HIV-assocaited nephropathy) - Drug induced - Heroin (heroin-nephropathy), interferon, lithium - Pamidronate, Sirolimus - An adaptive response to: - Obesity - arterial hypertension - Reduced nephronmass

Describe the characteristics of the thick ascending limb and the distal convoluted tubule

- Few microvilli - Many mitochondria for active transport

Name five functions of the kidneys

- Filters small waste molecules and do not reabsorb them, so they are lost in the urine - Recovers the completely filtered molecules that are essential e.g. glucose - Controls the plasma volume by filtering and variably recovering salts - Controls plasma osmolarity by filtering and variably recovering water - Controls the plasma pH by filtering and variably recovering hydrogen carbonate and active secretion of hydrogen ions

When does the clearance of X = the GFR?

- Freely filterable at the glomerulus - Not reabsorbed by tubules - Not secreted by tubules - Not synthesised by tubules - Not broken down by tubules

Describe the symptoms that come under storage in LUTS

- Frequency - Urgency - Nocturia - Incontinence

Give two examples of loop diuretics

- Furosemide - Bumetanide

Give examples of other substances that are reabsorbed with sodium ions in this wat

- Glucose - Amino acids - Water soluble vitamins B and C - Lactate - Acetate - Ketones - Kreb cycle intermediates

What are the metabolic adverse effects of diuretics?

- Glucose intolerance - Increase in LDL levels

How do uric acid stones arise?

- Gout - Role of allopurinol which treats gout - Citrate (alkalinisation)

Describe the musuclature of the bladder

- Has three layers of muscle like the ureter - Internal epithelium is transitional - Surrounded by an outer adventitia

In both males and females, how would you examine the patient you suspect had urinary incontinence?

- Height - Weight - Abdominal examination to exclude palpable bladder - Do a limited neurological examination, where a loss of sensation in the peritoneal area can cause sphincter damage

What stimulates the increase in sodium ion reabsorption, to therefore increase potassium ion secretion, in the principal cells of the DCT?

- High extracellular fluid concentration of potassium ions - Aldosterone - High extracellular fluid pH

What alternative treatments are being developed for those with localised prostate cancer?

- High intensity focused ultrasound - Primary cyrotherapy, which freezes the prostate - High dose brachytherapy

How can we prevent the formation of renal stones?

- Hydration - Diet and lifestyle - Stone inhibitors - Urine pH Specific treatment of the type of stone: - Oxalate stone - Urate stones - Staghorn / struvite - Cystine

In what circumstances is there hypercalcaemia, which causes the negative feedback of PTH, to result in decreased PTH levels?

- Hypercalcaemia of malignancy - Thyrotoxicosis - Drugs e.g. thiazides, vitamin D - Granulomatous disease e.g. sarcoidosis, TB

What is respiratory acidaemia (acidosis)?

- Hypoventilation which leads to hypercapnia - Hypercpania causes plasma pH to fall This is respiratory acidaemia (acidosis)

What would we want to find out in a patient's history is the present in the clinic with haeaturua?

- If the smoke - Their occupation - If it is painful or painless - Other lower urinary tract symptoms (indicates UTI) - Family history (important in kidney and prostate cancer, not so much bladder)

What are the three possible causes of an overactive bladder?

- Increased afferent activity - Decreased inhibitory control in the CNS - Increased detrusor sensitivity to efferent stimulation

How does portal hypertension cause extracellular fluid expansion and oedema?

- Increased venous pressure in the spanchnic circulation in the gut - In the splanchnic circulation there is a high venous pressure and a low oncotic pressure - This leads to ascites, causing the abdominal swelling and accumulation of fluid in the peritoneal cavity - Causes a reduced circulatory volume - RAAS activated - Sodium ion and water retention - Expansion of the extracellular fluid and worsening oedema

What are the disadvantages of sacral nerve neuromodulation?

- Infection requiring removal - Device failure

What can cause abacterial cystisits?

- Infection with low counts of bacteria - Infection with fastidious organisms not detected on routine culture - Sexually transmitted infections e.g. Chlamydia - Non-infective inflammation e.g. chemical

What compartments make up the extra-cellular fluid?

- Interstitial fluid (28% of TBW) - Plasma fluid (7% of TBW)

What is the anatomy of the bladder?

- Inverted pyramidal muscular sac - Apex posterior to pubic symphysis - Base separated from rectum by seminal vesicles

What mechanisms are used in histopathology and immunopathology?

- Light microscopy - Electron microscopy - Immunofluroescence

Describe the proximal convoluted tubule

- Longest - Most convoluted - Where reabsorption begins - Lined with simple cuboidal epithelium - Pronounced brush border membrane

Which parts of the nephron are found in the medulla?

- Loop of Henle - Collecting tubule - Vase recta, which is the vascular section of a nephron

In females, what three surgical interventions take place to treat stress urinary incontinence that are done with permanent intention?

- Low-tension vaginal tapes (most common) - Open retropubic suspension procedures - Classical sling procedures

What two surgical procedures are used in males to treat stress urinary incontinence?

- Male sling procedure - Artificial urinary sphincter

What are the secondary causes of membranous nephropathy?

- Malignancies, especially lymphomas - Infections - Drugs or toxins

Why do little people come to see their doctor about urinary incontinence?

- Massive impact on the quality of life - Social exclusion - Sense of shame They just put up with it.... one of those things

What are the common causes of proteinuria / nephrotic syndrome?

- Minimal change glomerulonephritis - Focal segmental glomerulosclerosis - Membranous glomerulonephritis

What three glomerular pathologies cause nephrotic syndrome?

- Minimal change glomerulonephritis - Minimal change focal segmental glomerulosclerosis - Memranous glomerulonephritis

Describe the draining system of the kidney

- Minor calyces that drain into - Major calyces that drain into - Renal pelvis that drain into - Ureter

How do we treat low risk non-muscle invasive TCC

- Monitor the cancer through checking sytoscopies (a camera that is used to look inside of the bladder) - This can be with or without intravesical chemotherapy

In a nephron, where does most active reabsorption take place?

- Mostly proximal convoluted tubule - Thick ascending limb - Distal convoluted tubule

When would you carry out a metabolic screen?

- Multiple calculi / Bilateral calculi present - Before the age of 30 - Renal failure - Solitary kidney - Family history of calculi (occurs in 55%) - Patient preference

What transporters are there on the apical membrane?

- Na+ - H+ exchange - Co-transport with glucose - Co-transport with amino acids or caboxylic acids - Co-transport with phosphate (dependent on PTH) - Aquaporin

What sodium transporters are present on the apical membrane on the proximal convoluted tubule?

- Na-H antiporter - Na-Glucose antiporter - Na-AA symporters

What transporters, responsible for sodium ion reabsorption, are located on the apical membrane of the proximal tubule?

- Na-H antiporter - Na-Glucose symporter

What two other pathologies can be noted when looking at light microscopy?

- Necrosis - Fibrosis

What are the problems with augmentation cytoplasty?

- Need to self catheterise - UTIs - Mucous - Stones - Metabolic abnormalities

What are the requirements of a good screening test?

- Needs to sensitive and specific to avoid false positives - Needs to be good value - Needs to have evidence of saving lives

What governs reabsorption into the capillaries from the tubules?

- Oncotic forces - Hydrostatic forces As the solutes move, the water follows

What sensations are stimulated when the bladder is filled to about 400ml?

- Pain sensation from the irritation of the bladder - Temperature sensation

What are the four parts of the loop of Henle?

- Pars recta (the straight section of the PCT) - Thin descending limb - Thin ascending limb - Thick ascending limb

What can cause sterile pyuria?

- Patient been treated already by antibiotics - Infected with bacteria that are difficult to isolate and culture - Be due to TB, appendicitis

Which component of the glomerular filtration membrane must be damaged for proteinuria to occur?

- Podocytes - Basal membrane This is because serum proteins in the kidney is caused by damage to the filtration apparatus the first layer is big enough to not let red blood cells through but the smaller 'sieves' are responsible for proteins and other macromolecules

What is the likely site of damage in nephrotic syndrome?

- Podocytes - Subepithelial damage

Describe the symptoms that come over post-micturition LUTS

- Post-micturition dribble - Feeling of incomplete emptying

What glomerulopathy can diabetes mellitus lead to?

- Progressive proteinuria - Progressive renal failure - Microvascular (damaged the glomerulus directly) - Mesangial sclerosis - leads to nodules - Basement membrane thickening to 4-5 times the normal width

Give examples of vasodilators used on the afferent arterioles to increase the RBF and GFR, and on the efferent to decrease the RBF and GFR

- Prostaglandins - Nitric Oxide - Bradykinin - ANP

How does nephrotic syndrome cause extracellular fluid expansion and oedema?

- Protein loss in the urine - Low plasma albumin - Low oncotic pressure - Leads to oedema due to water being brought in - Reduced circulatory volume - Leads to the activation of RAAS - Sodium ion and water retention - Expansion of the extracellular fluid and oedema

What are the classic triad of findings in relation to nephrotic syndrome?

- Proteinuria more than 3.5g per day - Hypoalbuminaemia - Oedema

What are the symtpoms of a stone that approaches the uretovesical junction?

- Quadrant pain - Urinary urgency - Frequency - Dysuria are common, mimicking bacterial cystitis

What happens in the loop of Henle ascending?

- Reabsorption of chloride ions - Reabsorption of sodium ions - No reabsorption of water - Causes filtrate to become dilute

What complications can arise from UTIs?

- Recurrent UTIs - Urinary retention - Haematuria - Renal insufficiency - Bladder calculi - Renal failure or uraemia (rare)

Describe the action of L-type calcium ion channel blockers in the treatment of hypertension

- Reduces calcium ion entry into the vascular smooth muscle cells - Results in the relaxation of vascular smooth muscle

What are the structural abnormalities that are risk factors of developing UTIs in children?

- Renal and urinary tract abnormalities, genital malformation, anorectal malformation, and spinal abnormalities - Vesicoureteric reflux if the most common structural abnormality and predisposes to pyelonephritic scarring

What does the nephton contain?

- Renal corpuscle (blood filtering component of the nephron) - Glomerulus - Bowman's capsule - Loop of Henle - Distal convoluted tubule

What does the cortex contain?

- Renal corpuscles (glomerulus and Bowman's capsules) - Medulla tubules

Which parts of a nephron is found in the cortex?

- Renal corpuscles: the glomerulus and the Bowman's capsule - Proximal convoluted tubule - Distal convoluted tubule

What are the three complications of acute pyelonephritis?

- Renal failure - Septicaemia - Preterm labour in pregnancy

What are the four surgical interventions, secondary to pharmacological, that are used to treat urge urinary incontinence?

- Sacral nerve neuromodulation - Autoaugmentation - Augmentation cystoplasty - Urinary diversion

Why isn't screening for prostate cancer done in the UK?

- Screening may lead to over diagnosis, just because someone is shown to have a greater risk, doesn't mean that they will develop the disease, but they will undergo preventative measures anyway that may cause more harm (e.g. side effects) than good. - You would have to screen 1000 men to save 1 life, and teat 30 men to save 1 life - Not economically good - Not good enough evidence for saving lives - PSA are nor specific to prostate cancer, can indicate other things

What are the main host risk factors for developing a UTI?

- Shorter urethra (more infections in female) - Obstruction (enlarged prostate, pregnancy, stones, tumours) - Neurological (Incomplete emptying, residual urine) - In children ureteric reflux, where there is ascending infection from the bladder - Sexual activity

Describe the features of the proximal convoluted tubule

- Simple cuboidal epithelium - Pronounced brush border

What makes up the parietal layer of the bowman's capsule?

- Simple squamous epithelium

Describe the symptoms that come under voiding in LUTS

- Slow stream - Splitting or spraying - Intermittency - Hesitancy - Straining - Terminal dribble

What are the risk factors of upper tract transitional cell carcinomas?

- Smoking - Phenacetin abuse (principally used as an analgesic) - Balkan's nephropathy

What are the risk factors of renal cell carcinomas?

- Smoking doubles the risk - Obesity - Dialysis as this changes the way the kidneys function

What are the risk factors of bladder cancer?

- Smoking: Increases the risk by 4 times - Occupational exposure (20 year latent period) - Rubber or plastics manufacture (Arylamines) - Handling of carbon, crude oil, combustion (polyaromatic hydrocarbons) - Painters, mechanics, printers, hairdressers - Schistosomiasis: A disease causes by parasitic worms. Endemic in Egypt

What does it do to the thick ascending limb?

- Stimulates apical NaK2CL co-transporter

What organs does the right adrenal gland lie in relation to?

- Superior to the kidneys - Posterior to the inferior vena cava - Medial to the liver and duodenum

What three ways do we treat locally advanced prostate cancer?

- Surveillance - Hormones - Hormones and radiotherapy

What established treatment is used to treat renal cell carcinoma?

- Surveillance (if low risk) - Radical nephrectomy/ This includes the removal of: - Kidney - Adrenal - Surrounding fat - Upper ureter - Partial nephrectomy

What nine situations is microscopy culture and sensitivity to required for patients?

- Suspected pyelonephritis - In men - Catheterised patients if there are features of systemic infection - In elderly patients who have two signs of infection - During pregnanct - Suspected UTI in children - Recurrent of complicated infections - Abnormalities of the genitourinary tract - Failed antibiotic treatment or persistent symptoms

Give examples of the vasoconstrictors of the afferent arterioles that are used to reduce the RBF and GFR

- Sympathetic nerves - Angiotensin II - Endothelin - Renin - Adenosine

How does the ureteric bud help drive development of the definitive kidney

- The collecting system is derived from the ureteric bud -The excretory system is derived from intermediate mesoderm under the influence of the ureteric bud.

What does the renal artery become?

- The glomeruli - The vasa recta which are the straight vessels that run up and down the medulla

In what compartments is water in the body located?

- The intra-cellular fluid (65%) - The extra-cellular fluid (35%)

Overall, why does the acid we produce metabolically not deplete the hydrogen carbonate concentration?

- The kidneys recover all of the filtered hydrogen carbonate concentration - The proximal tubule makes hydrogen carbonate from amino acids, putting ammonium into the urine - The distal tubule makes hydrogen carbonate and hydrogen ions from carbon dioxide. The protons are then buffered in urine by phosphate and ammonia

What happens is a hyotonic solution is administered?

- The osmolarity of the extracellular fluid decreases - Osmosis pushed water into the cell and out of the extracellular space - The effect is an increase in extracellular fluid volume and a larger increase in intracellular fluid volume

What happens is an iosotonic saline solution is administered?

- The osmolarity of the extracellular fluid does not change - No osmosis through the cell membrane occurs - The effect is an increase in extracellular fluid volume

What happens if a hypertonic solution is administered?

- The osmolarity of the extracellular fluid increases - Osmosis pushes water out of the cell and into the extracellular space - The effect is a large increase in extracellular fluid volume and a decrease in intracellular fluid volume

Microscopically, what are the two sections of the kidneys?

- The outer cortex - Inner medulla

What are the two outputs of the kidneys?

- The renal vein - The ureter

What happens in the late distal convoluted tubule and the early collecting tubule?

- There is fine tuning of the filtrate - Sensitive to a variety of stimulants

Diuretics can be used in the treatment of hypertension, even though they are not used as the first line of treatment. What diuretics are used?

- Thiazide diuretics - Loop diuretics in chronic kidney disease - Spironolactone in primary hyperaldosteronism (Conn's syndrome)

What do the main therapeutically usefule diuretics act on?

- Thick ascending loop of Henle - Early distal convoluted tubule - Collecting tubules and ducts

What are the four sections of the loop of Henle?

- Thick descending limb - Thin descending limb - Thin ascending limb - Thick ascending limb

What are the two types of nephropathies?

- Thin glomerular basement membrane nephropathy - Alport syndrome

What is respiratory alkalaemia (alkalosis)?

- This is hyperventilation that leads to hypocapnia - Falls in the partial pressure of carbon dioxide cause pH to rise This is respiratory alkalaemia (alkalosis)

What are the two classifications of the permeability of epithelia?

- Tight - Leaky

What can cause IgA and acute kidney injury?

- Tubular occlusion by red blood cells - Glomerular where there is necrotising glomerulonephritis and cellular crescent formation

How do struvite stones arise?

- UTIs - Antibiotics - Urine pH

Where else is urothelium found in the body?

- Ureter - Bladder - Urethra

Describe the histological appearance of the ureter

- Ureter has two layers of muscle - Third appearing in the lower third - Lined by transitional (urinary) epithelium or urothelium

What organs work together to pass urine into the urinary bladder and store it for many hours?

- Ureters - Urinary bladder - Internal and external urethral sphincters

What are the typical symptoms of a lower UTI?

- Urinary frequency, urgency and / or strangury (tiny drops of pee which hurts to pass) - Dyruria - Urine that is offensive smelling, cloudy or contains blood - Constant lower abdominal ache (prostatitis) - Non-specific malaise, such as aching all over, nausea, tiredness and cold sweats - Urge incontinence

How does ANP decrease blood pressure?

- Vasodilation of the afferent arteriole - Increased blood flow increases GFR - Inhibits sodium ion reabsorption along the nephron - Acts in the opposite direction to the other nuero-humoral regulators

Describe the usual clinical presentation of prostate cancer

- Vast majority are asymptomatic Urinary symptoms: - Benign enlargement of the prostate - Bladder overactivity Bone pain - In advanced metastatic prostate cancer

What factors predispose a person to persistent infection, recurrent infection, or treatment failure?

- Virulent organism (e.g. Staphylococcus aureus) - Impaired host defences (diabetes, immunosuppression) - Impaired renal function - Abnormal urinary tract (stone, vesicoureteric reflux, neurogenic bladder, catheter, urinary obstruction, instrumentation)

What is the fenestrated capillary permeable to?

- Water, salts, glucose - Filtrate moves between the cells

In microscopy, what is looked for?

- White blood cells - Red blood cells - Squamous epithelial cells

Describe the pronephros

-First kidney system Never functions in humans = Provides useful data on kidney development So why bother ? Pronephric duct extends from the cervical region to the cloaca and drives the development of the next development

What transporters does the apical membrane of the S2-S3 region of the PCT have?

-Na+ / H+ exchanger - Trans cellular chloride - Aquaporin

Label the following diagram

1) Anterior fibro - muscular septum 2) Transition zone 3) Peripheral zone 4) Ischiorectal fossa 5) Body of the pubic bone 6) Capsule - prostate 7) Obturator internus

Label the following histological slide

1) Bowman's capsule and glomerulus 2) Proximal convoluted tubule cross section

What are the five factors that influences blood pressure?

1) Cardiac factors - volume of blood from left ventricle contraction 2) Peripheral resistance - diameter, which is variable 3) Blood volume - constant volume of blood cells and plasma within the system. If blood volume is low blood pressure is reduced 4) Viscosity - increased blood viscosity due to greater osmolarity causes greater resistance to flow and there is higher arterial pressure 5) Elasticity - when elasticity of larger arteries decreases, systolic pressure rises

How does congestive heart failure lead to extracellular fluid expansion and oedema?

1) Congestive Heart Failure: - Increases systemic venous pressure that leads to oedema - Drop in cardiac output which leads to the activation of RAAS - Leads to sodium ion and water retention - Causes the expansion of the extracellular fluid and oedema

What are the two phases of the functional activity of the lower urinary tract?

1) Contiencence phase (filling and storage) 2) Voiding phase (micturition)

Label the following histological slide of the kidneys

1) Convoluted tubules 2) Fibrous capsule 3) Cortex 4) Bowman's capsule 5) Glomerulis 6) Renal corpuscle 7) Medullary rays 8) Medulla 9) Loops of Henle and Collecting tubules

Label the following diagram of the scrotum

1) Corpus cavernosum (base of muscle of the penis) 2) Penile urethra 3) Corpus spongiosum 4) Epidymis 5) Testis

Label the following image to show the relation of organs to the left kidney

1) Cystic pancreatic tumour 2) Spleen 3) Stomach 4) Pancreas 5) Psoas

What are the three muscle components of the bladder?

1) Detrusor urinae muscle (involuntary and smooth) 2) Internal urethral sphincter (involuntary and smooth) 3) External urethral sphincter formed by the pelvic floor muscles (somatic and voluntary)

Describe the three pathways in which we can diagnose prostate cancer

1) Digital rectal examination (DRE), this feels for lumps, bumps and asymmetry 2) Serum prostate specific antigen level (see if they are raised) Both of these look for abnormalities, and if abnormalities are found a biopsy is then carried out via TRUS (TransRectal UltraSound), which is a guided biopsy of the prostate

Hence, what are the direct action of angiotensin II on the kidney?

1) Enhances sodium ion reabsorption at the proximal convoluted tubule 2) Vasoconstriction of the afferent and efferent arteriole (which is corrected by autoregulation)`

Label the following diagram

1) Extraglomerular mesangial cells 2) Distal convoluted tubule 3) Macula densa 4) Proximal convoluted tubule

What are the three layers of the filtration apparatus?

1) Fenestrated capillary 2) Basal lamina 3) Podocyte slit pores

In the nephron, what is the path the ultrafiltrate has to go through from the plasma to the tubules?

1) Fenestrated capillary endothelium 2) Capillary basement membrane 3) Podocytes In the Bowman's capsule

Label the following histological section

1) Glomerulus 2) Bowman's space 3) Bowman's capsule

State the causes of hypercalcaemia

1) Hormonal - Primary hyperparathyroidism - Hypervitaminosis 2) Non-hormonal - Renal failure - Milk alkali syndrome (taking high doses of calcium) 3) Drugs e.g. - Thiazides - Lithium

Label the following sections of the kidneys

1) Kidney Medulla 2) Kidney Cortex

Label the axial plan T1 weighted MRI (check answers on moodle)

1) Liver 2) Right kidney medulla 3) Spinous process of vertebrae 4) Aorta 5) Left suprarenal gland

Label the following organs

1) Liver 2) Spleen

Label the following diagram of the coronal plane T1 - weighted MRI (check answers on moodle)

1) Liver 2) Spleen 3) Diaphragm 4) Left kidney

What is the compartmentalisaton of calcium?

1) Located in the bone - around 1kg 2) In extra - cellular fluid has 2.1mM.1-1 of calcium in three forms: - Free ionised calcium (the only form which is physiologically active) - Rest bound to anionic sites on serum proteins e.g. albumin - Complexed with low-molecular weight organic anions (e.g. citrate an oxalate) 3) Intra - cellular (cytoplasmic) concentration very low 10-5mM.1-1

What are the six types of diuretics?

1) Loop diuretics 2) Thiazide diuretics 3) K+ sparing diuretics 4) Aldosterone antagonists 5) Inhibitors of carbonic anhydrase 6) Osmotic diuretics

Label the rest of the bladder

1) Middle umbilical ligament 2) Detrusor muscle 3) The body of the bladder 4) Centre of trigone 5) Neck of the bladder 6) Prostate gland 7) Prostatic urethra 8) Membranous urethra 9) External urethral sphincter 10) Internal urethral sphincter 11) Ureteral openings 12) Lateral umbilical ligament 13) Ureter

Label the example of a normal intravenous urogram IVU (check answers on moodle)

1) Minor calyx 2) Sacro-iliac joint 3) Bladder 4) Right kidney 5) Ureter 6) Renal pelvis 7) Ureter

What are the four mechanisms in which the resistance of the afferent and efferent arterioles are regulated in order to ensure that the GFR is maintained despite changes in blood pressure? Describe if these are fast or slow

1) Myogenic response - reflex so it is fast 2) Sympathetic nervous system - relatively fast 3) Hormones: Angiotensin II, ANP, Aldosterone - slow 4) Tubulo-glomerular feedback (JGA and macula densa) - slow

Please mark on the X-ray where the most common sites for stones becoming lodged in the urinary tract are located.

1) Pelvoureteric junction 2) where the ureter lies on the pelvic brim 3) where ureter passes obliquely into the bladder so is squashed when the bladder contracts

What are the three ways in which renin is released?

1) Reduced Na+ and Cl- delivery to the distal tubule - more is reabsorbed. There is low sodium in the distal convoluted tubule which is detected by the macula densa. The lower the rate of transport of these ions, the higher the rate of rening secretion 2) Reduced perfusion pressure in the kidney causes the release of renin, where this is detected by the inter-renal baroreceptors found in the afferent arteriole. 3) Sympathetic stimulation of the juxtaglomerular apparatus (JGA). If there is a lower blood pressure, the sympathetic stimulation increase to cause greater renin production

What are the four neuro-humeral, medium and longer term control pathways, that control blood pressure?

1) Renin-angiotensin-aldosterone system RAAS 2) Sympathetic nervous system 3) Antidiuretic hormone (ADH) 4) Atrial natriuretic peptide (ANP)

Label the coronal plane of the following female pelvis

1) S1 nerve root 2) Right ovary 3) Bladder 4) Vagina 5) Cervix 6) Parametrium 7) Puborectalis

What are the four functions of the nervous system in relation to the lower urinary tract?

1) Sensations of bladder filling and pain 2) Allow the bladder to relax and accommodate increasing volumes of urine 3) To initiate an integrated regulation of smooth muscle and skeletal muscle sphincters of the urethra

What does the permeability of a substance through the filtration barrier depend on?

1) Size: Smaller molecular weight and radius means a greater permeability 2) Shape e.g. haemoglobin is better filtered than albumin 3) Charge: Negative charges are repelled by the basement membrane so their permeability is reduced

What are the three classifications of LUTs (Lower Urinary Tract Symptoms)?

1) Storage 2) Voiding 3) Post-micturition

What are the four sites of glomerular injury?

1) Subepithelial - Anything that affects podocytes / podocyte side of the glomerular basement membrane 2) Within the glomerular basement membrane 3) Subendothelial - Inside the basement membrane 4) Mesangial / paramesangial - Supporting capillary loop

In the tubular, epithelial cell, how is hydrogen carbonate recovered?

1) The 3Na+-2K+ATPase pump on the basolateral membrane uses energy to move K+ in and Na+ out, against their concentration gradients. This sets their concentration gradients, that are used as a store of energy for ions to move down 2) The Na+-H+ exchanger allows sodium ions to move down their concentration gradient from the apical, into the epithelial cell, . Sodium ions gives off an energy, that is used to transport the hydrogen ions out against its concentration gradient 3) The H+ in the lumen then reacts with HC03-, which forms carbon dioxide and water 4) The carbon dioxide then enters the cell and reacts with water to re-create H+. 5) H+ is then exported out again in a loop in the Na+-H+ exchanger 6) Hydrogen carbonate then leaves the baso-lateral membrane to the ECF

Label the three blue arrows

1) The body of the bladder 2) Trigone 3) Neck of bladder

What are the three layers of the filtration barrier to filter blood from the afferent arteriole into the glomerulus?

1) The fenestrated capillary 2) The basement membrane 3) Podocyte layer

What are the two mechanisms of autoregulation?

1) The myogenic mechanism which is pressure sensitive 2) NaCl concentration dependent mechanism

Label the layers of the wall of the bladder

1) Transitional epithelium 2) Lamina propria These two make up the mucosa 3) Submucosa 4) Detrusor muscle 5) Adventitia

Label the following diagram of the female pelvis

1) Uterine fundus 2) Endometrium 3) Right ovary 4) Vaginal fornix 5) External iliac vein 6) Parametria 7) Cervix

In the following histological structure of the renal corpuscle, label the parietal and visceral layer

1) Visceral layer 2) Parietal layer

Label this diagram

1. Arcuate arteries and veins 2. Interlobular arteries and veins 3. Interlobar arteries and veins 4. Segmental arteries and veins 5. Renal artery 6. Renal vein 7. Ureter 8. Lobar arteries and veins 9. Renal pyramids

List the 7 main functions of the kidneys

1. Excrete waste 2. Keep in whats important 3. Control Volume 4. Control Osmolarity 5. Control PH 6. Produce hormones (vit D - calcium heomostasis, erythropoietin - RBC production) 7. Homeostasis maintained

What things can go wrong ?

1. Fistula from median umbilical ligament 2. Urachal cysts 3. Exstrophy of the baldder - bladder opens onto abdominal wall 4. Ectopic urethral orifices

What is a nephratome ?

1. Glomerulus 2. Bowmans capsule 3. Proximal and Distal convolute tubule 4. Collecting duct

Label the following Diagram

1. Human urinary system 2. Capsule (kidney) 3. Renal Pelvis 4. Ureter 5. Urinary bladder 6. Urethra 7. Adrenals 8. Renal artery/Vein 9. IVC 10. Abdominal Aorta 11. Internal illiac (common iliac artery/vein) 12. Liver 13. Large intestine 14. Pelvis

Give some reasons for why you would catheterise someone ?

1. Inability to void bladder (urinary retention) 2. Incapacitated → post surgery

Give some reasons why male catheterisation difficulties and dangers ?

1. Navicular fossa (mucosal fold superiorly) 2. Angle at penile bulb & membranous urethra 3. Prostate (crest/ enlarged lobes) 4. Sphincters

The male urethra consists of different regions, a pre-prostatic region that lies between the bladder and the prostate and three others. One as it passes through the prostate, one as it passes through the deep peritoneal pouch, and one as it passes through the corpus spongiosum. Label the diagram of the male urethra.

1. Pre-prostatic urethra 2. Prostatic urethra 3. Bublos region of the penis 4. Spongy urethra 5. Glandular region of the penis

Label this diagram

1. Renal vein 2. Interlobar vein 3. Arcuate vein 4. Interlobular vein 5.Interlobular arteries 6. Arcuate artery 7. Interlobar artery 8. Renal Artery

Label the following diagram

1. Right kidney 2. Left kidney 3.IVC 4. Aorta 5. Left gonadal vein (testicular/ovarian) 6. Ureter 7. Renal Artery 8. SMA 9. Renal vein

Label this image

1. Rugae 2. Prostate 3. Membranous urethra 4. Erectile tissue of the penis 5. Ureteric orifces 6. Prostatic urethra 7. Spongy urethra 8. External urethral orifice

Label the following diagram

1. Spongy urethra 2. Prostate 3. Urethra 4. Bladder 5. Detrusor muscle

What is the role of the mesonephros

1. Sprouts the ureteric bud - which induces development of the definitive kidney 2. Role in the development of the reproductive system in males

List what can go wrong in the development of the urogenital system:

1. Ureteric bud fails to interact with intermediate mesoderm − renal agenesis ** The ureteric bud that grows out of the end of the mesonephric duct, fails to meet/ interact with the mesoderm in the mesonephric blastema --> if no contact is made there will be no kidney (aka RENAL AGENESIS) Patients may be not be aware of it: they may have an x-ray and find out: doesn't affect them because you only need 1 kidney, but if you have kidney disease its nice to have another one 2. Migration goes awry The ascent of the kidney can go wrong and you will end up with kidneys in the wrong place 3. Renal dysgenesis: renal agenesis or renal hypoplasia Tissue differentiation problems: Doesn't differentiate properly; its too small or hasn't developed fully so its unable to preform its activities. 4. Wilm's tumour Most in children : malignant tutor of the kidney that arise from the stem cells that form the kidney tubules that we saw in the embryological development : Since they are malignant they will grow but they can be cured surgically if they are caught early --> child will be fine 5. Duplication defects Sometimes you can get double up kidneys so you get 2 ureteric buds coming out of the end of the mesonephric duct sticking into intermediate mesoderm. May get double ureteres 6. Ectopic ureter When the ureter is in the wrong place 7. Cystic disease You have these S shaped tubes that drain into a duct if that connection to the duct fails you have a tube which has got blood vessels at one end draining the filtrate into the the tube If there is no where for it to go you get a Cysts ( a bag of fluid)

What are the 3 points of constriction of the ureters ?

1. Uretropelvic junction (where ureter leaves the pelvis of the kidney ) 2. Pelvic inlet ( where ureter passing over pelvic brim) 3. Entrance into bladder why are these constrictions important ?→ Kidney stones. Calcium within filtrate comes out of solution and forms discrete stones that may pass down the ureter into the bladder. [ very painful] Will get stuck at these sites of construction these are sites where when you x-ray you may expect to find the stones.

Describe how the urine travels ?

1. Urine passes into bladder from ureters 2. Urine passes obliquely through bladder 3. Reflux of urine is prevented 4. Internal urinary sphincter controls movement of urine from bladder to proximal urethra 5. External urinary sphincter controls voluntary voiding of urine

Label the following diagram

1. Uterus 2. Bladder 3. Rectum 4. Urethra 5. Vagina

What is the typical renal blood flow?

1.1 Litres per minute

If E.coli or Staphylococcus saprophyticus are shown in cultured urine, what value is needed from cultured urine to confirm this

10^3 colony forming units per ml

If there are urinary symptoms, what value is needed from the culture?

10^4 colony forming units per ml of a single microorganism

How many colony forming units should be present in cultured urine to be termed significant bacteriuria defined by Kass?

10^5 colony forming units of a single organism per ml of urine. This is to distinguish between an actual bacterial infection and contamination of the sample

What is the size of a normal kidney?

11 x 5 x 2.5 cm

What is GFR?

120 - 125ml/min... 180L/day

How much does each kidney weigh?

150g

How much TBW does ECF contain?

15L - 35%

Label the following image

1= Esophagus 2=Left suprarenal gland 3= Left Kidney 4=Cut edges of peritoneum 5= Abdominal aorta 6= Right Kidney 7=Diaphragm 8= Right suprarenal Gland 9= Inferior vena cava

Label the diagram

1= Glomerulus 2= proximal convoluted tubule 3= Descending Loop of Henle 4= Ascending LOH 5= Distal tubule 6= Collecting duct

Label this diagram

1= Inferior phrenic arteries 2= Superior suprarenal arteries 3= Left suprarenal gland 4=Middle suprarenal artery 5= Inferior suprarenal artery 6= Left kidney 7=Abdominal aorta 8= IVC 9= Right suprarenal gland 10= Right Kidney

Label the following diagram

1= Jugular Notch 2= End of ninth costal cartilage 3= Kidney 4= Pubic Symphysis 5=Neck of pancreas 6= Duodenum 7= Transpyloric plane 8= Superior mesenteric artery

Label the following diagram

1= Renal column 2=major calyx 3= Renal artery 4= Hilum of kidney 5= Renal Vein 6= Renal pelvis 7= Ureter 8=Pyramid in renal medulla 9= Renal Cortex 10=Renal Papilla 11=Renal Sinus 12=Minor Calyx

Label the following diagram

1= Rib cage 2= Spleen 3= Stomach 4= Small Intestine 5= Costal Margin 6= Liver 7= Colon

Label the following image

1= Right suprarenal 2= Liver 3= Descending part of the duodenum 4= Right colic flexure 5= Small intestine 6= Left suprarenal gland 7= Stomach 8= Spleen 9= Pancreas 10= Left colic flexure 11= Descending colon 12= Jejunum

Label the following picture.

1= inferior vena cava 2= aorta 3= peripheral fat capsule 4= fibrous capsule of kidney 5=peritoneum 6= renal vein 7= renal artery 8= body of vertebra L2 9= body wall 10= left renal vein 11= left kidney 12= erector spinae muscle in posterior abdominal wall 13= jejunum 14= duodenum 15= liver 16= inferior vena cava 17= aorta 18= right kidney 19= vertebra L1

Label the following diagram

1=Esophagus 2=Diaphragm 3= Left suprarenal gland 4= Left Kidney 5= Abdominal Aorta 6= Gonadal Vessels 7= Quadratus Lumborum 8= Bladder 9= Inferior vena cava 10= Right suprarenal gland 11= Right Kidney 12= Ureter 13= Psoas 14= Iliacus

Label the following diagram of the posterior relationships of the kidneys?

1=Right Kidney 2= Rib 12 3=Diaphragm 4= psoas major muscle 5=quadratus lumborum muscle 6= Transverse abdominis muscle 7=Rib 12 8= Rib 11 9=Left Kidney

Label the following diagram

1=Superior mesenteric artery 2= Left Kidney 3= Left renal artery 4= Left renal vein 5= Abdominal aorta 6= Inferior vena cava 7= Right kidney 8= Right renal artery 9= Right renal vein

What is the prostate and seminal vesicle ?

2 major glands associated with reproduction in the male.

How much plasma from the renal artery is filtered at any one time?

20% (20% of 600ml) 80% therefore exists via efferent arteriole - forming peritubular capillaries

What quantity of the renal blood flow is filtered?

20% = 120 / 125 ml per minute

How much of the renal blood flow is filtered into the glomerulus?

20% of blood from the renal artery is filtered at a time, where 80% exits through the efferent arteriole

How much ECF does the kidneys filter?

22%

How much does cardiac output does the kidney use?

25% at rest. Uses 1.1L/min in 70kg male

How much TBW does ICF contain?

25L - 65%

What channels are present on the S2 - S3 regions of the of the basolateral membrane?

2Na-2k-ATPase

What percentage of sodium ions are reabsorbed in the ascending loop of Henle, and through which channel?

30% of filtered sodium ions are reabsorbed through the NaK2Cl transporter

What is the osmolarity of the extra and intra cellular fluid?

300mOsm

How long is the cervix?

30mm

List the components that make up the ECF TBW?

35% = Intrastitual fluid = 28% Intravascualr (plasma) = 7% Lymph Synovial Intestinal CSF Sweat Urine Pleura Peritoneal Pericardial Intraoccular

In the late distal convoluted tubule and the collecting duct, describe how sodium ions are reabsorbed

3Na+-2K+-ATPase in the basolateral membrane pumps out sodium. The gradient created is used by ENaC which allows sodium ions to enter

Describe the process by which potassium ions are secreted by the principal cells in the distal tubule

3Na+-2K+-ATPase sets the sodium ion gradient, and also pumps potassium ions from the extracellular fluid to the principal cell through the basolateral membrane. This sets up the gradient for this. On the apical membrane ENaC reabsorbs sodium ions by using the Na+ gradient gradient. This in turn, causes potassium ions to exit through the K+ channel into the lumen to be excreted into the lumen. Hence, the more sodium ions reabsorbed, so more potassium ions are excreted into the lumen

What pump is the dirver for the operation of symporters located on the apical membrane?

3Na+-2k+-ATPase located on the basolateral membrane (the part of the plasma membrane that faces the inside of the cell)

What transporter is present on the basolateral membrane of the thick ascending limb?

3Na-2K-ATPase

What is the canal diameter of the cervix?

3mm

How long is the uterus in females ?

4 cm

What would the filtration load of glucose be if the patient was diabetic and had a plasma glucose concentration of 4mg per ml?

4 x 120 = 480mg per ml

What is the minimum pH of urine?

4.5 - so the urine is good at carrying acid out of the body

What percentage of the total body weight is water?

40%

What percentage of upper tract transitional cell carcinomas spread to the bladder?

40%

What is the total body water (TBW)?

40L

What is the mortality rate is pH is above 7.55?

45%

Why is water reabsorbed in the S2-S3 phases of the PCT?

4mOsmol gradient favours water uptake from the lumen because the tubule as reabsorbed ion

What percentage of upper tract transitional cell carcinomas are due to the spread of cancer from the bladder up the ureter?

5%

What pressure change is needed to stimulate baroreceptors?

5-10% pressure change

A normal healthy female presents to the GP with dysuria (painful and difficult urination) with increased frequency. What is the probability that this female has a UTI?

50% positive urine cultures

What is the total acid excretion per day?

50-100 mmol H+ per day

What is the capacity of the bladder?

550 ml Range = 300-700 ml

PCT - major site of reabsorption, describe the breakdown

60-70% of Na+ and Water 80-90% of K+ 100% of HCO3- 100% glucose and amino acids Filtrate remains isotonic as water follows gradients

What is the normal range of pH?

7.38 - 7.42

How much fluid is in the body?

70kg healthy male - 40L water (60% of total body weight)

What is the mortality rate if pH is above 7.65

80%

What values is the renal blood flow and the glomerular filtration rate maintained between?

90 - 100mmHg

What is the percentage change of a patient having similar symptoms with a previous UTI has a UTI this time?

90%

State the intracellular and extracellular concentrations of potassium ions

98% of potassium ions are within cells Intracellular concentration is about 130mmol.l-1 Extracellular concentration range = 3.5 - 5 mmol.l-1

How is acute pyelonephritis managed?

A 7 day course of the antibiotic Ciprofloxacin 500mg Treat the pain and fever with paracetamol Maintain fluid hydration Review culture and sensitivity results and change the antibiotic if indicated

What do the letters indicate?

A = A filtration capillary network covered by podocytes B = Bowman's capsule D = Parietal capsule wall made of simple squamous E = Distal convoluted tubule = small, compact cuboidal cells F = Nephron loop, thin limb with simple squamous cells G = Collecting duct lined with cuboidal cells H = Peritubular capillary filled with red blood cells

What is the change of a person having a UTI if nitrite test is positive with or without a positive leucocyte esterase test?

A UTI is highliy likely - over 90% will have a UTI

What is the chance of a person having a UTI if the leucocyte esterase is positive, but the nitrites are negative?

A UTI is moderately likely - 50% change of having a UTI

If a person has a positive urine culture, what infection does this indicate?

A bacterial cystitis. This is a lower UTI which presents with frequency and dysuria, often with pyuria (presence of pus in the urine) and haematuria

Describe the varying levels of differentiation that neoplasms show under a microscope

A benign neoplasm has cells that closely resemble the parent tissue i.e. they are well differentiated. Malignant neoplasms range from well to poorly differentiated Cells with no resemblance to any tissue are called anaplastic

How is Trousseau's sign elicited?

A blood pressure cuff is placed around the arm and is inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcaemia and subsequence neuromuscular irritability will induce spasm of the muscles of the hand and forearm

Describe how diuretics, especially loop diuretics, cause hypovolaemia

A decrease in the extracellular fluid volume due to excessive loss of sodium ion and water

What is the continence phase controlled by?

A dedicated by a set of neuronal apparatus called the continence neurones

What causes the secretion of renin?

A drop in blood pressure

What is the kidney surrounded by?

A fibrous capsule

Calculate the filtration load for glucose where its normal plasma concentration is 1mg per 1ml

A glucose is freely filtered in the Bowman's capsule the ultra-filtrate has the same concentration as the plasma concentration. The GFR = 120ml per minute so the filtered load would be: 1mg per ml x 120ml per minute = 120mg per minute

How do grades describe differentiation of neoplasms?

A high grade indicates poor differentiation

Describe how a lower motor neurone lesion causes overflow incontinence

A lower motor neurone lesion causes low detrusor pressure. This is because it affects the pelvic nerve, which is part of the sympathetic nervous system, responsible for contraction of the detrusor muscle. This low detrusor pressure means that there is a large residual urine as it can't push it out. This can happen with or without overflow incontinence, where there is retention of the urine causing the bladder to swell.

Hence what happens if a nerve lesion happens below S3?

A lower nerve lesion happens, where there is damage to the pelvic nerve to cause low detrusor pressure, as the detrusor muscles can longer contract. This leads to a large residual volume, and can happen with or without incontinence?

What is the notocord a beginning of ?

A neural tube

In a radical cystectomy, what is done to assume normal function of the urinary tract?

A piece of ileum may be used to make a conduit from the ureters to the abdomen, where urine can be collected in a bag (see photo) May also attempt to reconstruct the bladder from a piece of the small intestine

How would we treat an established, localised prostate cancer if the risk was greater?

A radical prostatectomy can be performed, which removes the prostate gland and some of the tissue around it in order to remove prostate cancer. This can be done by the following three methods: - Open surgery - Laproscopic surgery (surgery that uses a thin, lighted tube put through an incision to look at the abdominal organs) - Robotic durgery Radiaotherapy can be used, where an external beam is used or low dose brachytherapy (this treats the cancer by permanently inserting tiny radioactive seeds into the prostate with the aim of destroying the cancer. Hence it is not an external beam)

Describe the process by which creatinine is used to find the GFR

A single plasma sample is taken and a 24 hour urine collection.

What is a diuretic?

A substance / drug that promotes a diuresis, to cause an increased renal excretion of water and sodium, which causes the reduction of extracellular volume

Define aquaretics

A substances that causes a net excretion of water

The Kidney contains numerous terminal arteries, this type of artery also occurs in the brain and the retina.; What is important about terminal arteries?

A terminal artery has insufficient anastomoses to maintain viability of the tissue supplied if occlusion of the artery occurs

What has formed embryologically after gastrulation?

A trilaminar embryonic disc

If someone has the symptoms of a UTI, what investigations must take place?

A urine dipstick

What is the mandatory investigation for those suspected with urinary incontinence?

A urine dipstick test, to eliminate differential diagnosis - UTI - Haematuria - Proteinuria - Glucosuria

Apart from cleaving angiotensin I into its active form, angiotensin II, what is the other function of the angiotensin converting enzyme?

ACE is also important in breaking down bradykinin into peptide fragments. Bradykinin is a vasodilator and hence preventing this having an effect. So: The vasoconstriction effects of angiotensin II are further increases because ACE is also one of the kinase enzymes which breaks down the vasodilator bradykinin

When is the ADH and thirst efferent pathways stimulated?

ADH is stimulated when there is a 1% change in osmolarity, and so is sensitive to small amounts. Thirst on the other hand is activated when there is large deficits or salt, which can only be partially compensated for in the kidney

How does the antidiuretic hormone act?

ADH stimulates the insertion aquaporin-2 (water channels) in the apical membrane (lumen of DCT) or principal cells of the DCT. This means more water leaves the tubules into the capillaries to increase water reabsorption. This increases the blood volume, and increases the GFR to normal. It also increases blood pressure

What are the two types of angiotensin II receptors?

AT1 and AT2

Which of these is the main receptor of angiotensin II

AT1 receptor which is a G-protein coupled receptor

If someone presents with the symptoms of a lower UTI (dysuria and frequency), but does not have a positive urine culture, what is this condition called?

Abacterial cystitis

Where do the abdominal wall muscles come in contact directly with the kidneys ?

Abdominal wall muscles come in contact with the posterior side of the kidneys

What developmental treatments are used to treat renal cell carcinoma?

Ablation which is the removal of a tumour from the surface of a kidney via an erosive process

Give an example of carbonic anhydrase inhibitors

Acetazolamide

Give an example of inhibitors of carbonic anhydrase

Acetazolamide

Why is acidaemia dangerous?

Acidaemia leads to potassium movement out of the cells, resulting in hyperkalcaemia. This mainly affects the heart. Acidaemia also affects enzyme function which: - Reduces cardiac and skeletal muscle contractility - Reduces glycolysis in many tissues - Reduces hepatic function

Describe the effects of acidosis on potassium ion concentration

Acidosis means that there is a greater concentration of hydrogen ions. This causes more potassium ions to leave cells, in order for hydrogen ions to be absorbed. This also causes less potassium to be excreted by the kidneys, as hydrogen ions are favoured to be excreted. This results in hyperkalaemia

What processes happen in the thick ascending limb and distal convoluted tubule to reabsorb filtrate?

Active and passive transport

Describe sodium ion reabsorption in the early distal convoluted tubule

Active sodium ion reabsorption takes place here to further dilute the filtrate. But this may not happen if enough has been reabsorbed previously

What is the function of the body of the bladder?

Acts as the temporary store of urine

How is hypocalcaemia treated?

Acute management: - IV calcium gluconate infusion and titrate until calcium levels are normal Any hypomagnesaemia needs to be corrected Once stabilised, vitamin D / oral calcium therapy is required If vitamin D deficient, give cholecalciferol (D3)

What is the classic presentation of renal stones?

Acute, colicky flank pain radiating to the groin or scrotum As the stone descends in the ureter, pain may localise to the abdomen overlying the stone. Renal and ureteral colic are often considered among the most severe pain experienced by patients

What is the mediator of the tubular glomerulus feedback?

Adenosine and Renin

Describe what happens when there is a rapid increase of sodium chloride in the tubular glomerulus feedback

Adenosine is released which causes vasoconstriction of the afferent arterioles. This decreases the GFR by decreasing renal blood flow

What is the function of the adrenal medulla?

Adrenaline and noradrenaline

How do we manage hypercalcaemia?

Advised to increase the intake of fluids. This lowers calcium serum levels by expanding the intravascular volume and promoting renal excretion calcium ions. Bisphosphonates can be used to inhibit bone resorption to prevent more calcium being released. The main use for this is for hypercalcaemia of malignancy

What is the vascular pole of the renal corpuscle?

Afferent and efferent arterioles

Describe the risk factors of prostate cancer?

Age: - There is a correlation with increasing age - Uncommon in men younger than 50 Family history: - 4 times increased risk if one 1st degree relative is diagnosed with prostate cancer before age 60 - After the age of 60 any diagnosis is probably age related Race: Incidence in Asians are more then Caucasians, which is more than Afro-Caribbeans

What is autoaugmentation?

Aims to increase functional capacity of the bladder and decrease intravesival pressure created by involuntary detrusor muscles. Not widely used

What happens in the cortical collecting ducts?

Aldosterone controls sodium reabsorption and potassium ion loss. Acid-base control by secreting either protons or HCO3-.

What is the effect of aldosterone on principal cells?

Aldosterone increases the expression of 3Na+2K+-ATPase, ENaC and K+ channels.

What is the action of aldosterone on the kindey?

Aldosterone increases the expression of ENaC and 3Na+-2K+-ATPase in the principal cells of the collecting duct. This increases sodium ion reabsorption and water reabsorption to increase the blood pressure.

What is the mechanism of aldosterone?

Aldosterone increases the reabsorption of sodium ions and water by principal cells of the distal convoluted tubule collecting duct. As water follows sodium ions, this increases the blood volume, which increases the GFR to normal. This in turn increases blood pressure

What stimulates the active reabsorption of Na+ and Cl- in the thick ascending limb and the distal convoluted tubule?

Aldosterone that acts on the cortical collecting ducts

Why is alkalaemia dangerous?

Alkalaemia reduces the solubility of free calcium ions, which means the free calcium ions leaves the extra-cellular matrix and binds to bones and proteins. The resulting hypocalcaemia makes nerves much more excitable, producing paraesthesia and eventually uncontrolled muscle contractions - tetany

Describe the effects of alkalosis on potassium ion concentration

Alkalosis means that there is a lower concentration of hydrogen ions in the cells. This causes potassium ions to enter cells and more potassium to be excreted by the kidney. This results in hypokalaemia

What happens if women are presented with a classic UTI symptoms?

All are treated as though they have a UTI until proven otherwise, because this doesn't mean that they 100% have a UTI

Where do the 3 kidney systems come from embryologically ?

All come from intermediate mesoderm

Describe the sequence from the primary nephric duct to the ureteric bud.

All these kidney tubules along the urogenital ridge upper most ones will die out then mesonephric wil die out too Leaving us with the meta-nephros which will ultimately rise up to reach its adult position.

What cells reabsorb potassium ions in the distal tubule?

Alpha-intercalated cells

What is alport syndrome?

Alport syndroms is a X-linked disease. Type IV collagen is abnormal and this results in dysfunction of the glomerular basement membrane. This results in an abnormal appearing glomerular basement membrane which progresses to renal failure

How does hypercalcaemia affect the CNS?

Altered behaviour, lethargy (lack of energy), depression, decreased alertness, confusion, coma

Why is hypertension important to treat?

Although hypertension may be asymptomatic, it can have unseen damaging effects on the: - Heart and vasculature - Potentially leading to heart failure, MI, stroke, renal failure and retinopathy

Why does this happen?

An decrease in osmolarity means that there is more water in the extracellular fluid, which means water is lost to decrease the blood pressure

What stimulates aldosterone?

An increase in angiotensin II due to decreased blood pressure.

Describe the spinal control of the bladder alone

An increase in volume of fluid in the bladder, causes expansion of the wall which is then sensed (maybe by stretch receptors). The signal is then sent to the spinal cord which carries out the following response: - Decrease in sympathetic activity - Increase in parasympathetic activity - Decrease in somatic motor neurone activity This causes the following actions in the bladder - Relaxation of the internal urethral sphincter - Contraction of the detrusor muscle These two cause the opening of the internal urethral sphincter - Relaxation of the external urethral sphincter Which causes the opening of the external urethral sphincter The result is micturition

What is an overactive bladder?

An overactive bladder is when there is a feeling of needing to frequent feeling. This is due to the contraction of the detrusor muscle, where the bladder can't expand to hold the urine

Describe the hormonal response when there is decreased blood volume and decreased blood pressure

Angiotensin II is released to cause constriction of the afferent arterioles. This decreases the GFR and increases blood pressure

Describe how the sympathetic nervous system contributes to the medium and longer term control of blood pressure

Angiotensin II stimulates the sympathetic nervous system to release noradrenaline High levels of sympathetic stimulation reduces the renal blood flow, where noradrenaline causes vasoconstriction of the blood vessels. This in turn reduces the GFR which reduces the sodium ion excretion by: Activation of the apical Na+-H+ exchanger plus the basolateral Na+-K+ ATPase pump in the proximal convoluted tubule. This also increases water uptake, increasing extracellular volume, to increase blood pressure Stimulates the production of renin release from the juxtaglomerular cells causing: - Increased angiotensin II levels - Increased aldosterone levels All these act to increase blood pressure by increase sodium and thus water reabsorption

How does hypercalcaemia affect GI?

Anorexia, constipation, nausea and vomiting

Label the following image

Answer on next slide

Where are the adrenals located in relation to the diaphragm?

Anterior to the diaphragm

What is meant by glomerulonephritis?

Any condition associated with inflammation in the glomerular tuft

Label the following

Aorta in the centre - too big The other two are the right and left adrenal glands

What procedure is the gold standard method of treating males with stress urinary incontinence?

Artificial urinary sphincter

What is the clinical presentation of nephrotic syndrome?

As a lot of protein is being filtered, oncotic pressure is reduced in the blood, which means more water is retained. This gives generalised oedema. Especially look for oedema in the face, because the other common site of the legs is associated with other diseases, while the face is specific to nephrotic syndrome

When is duloxetine used?

As an alternative to surgery, because it is not recommended by NICE as a first line or routine treatment

Describe the oncotic pressure in the afferent and efferent arterioles

As blood flows through the afferent arterioles ions are removed while proteins remains. This causes the oncotic pressure to increase (water wants to follow the ions). This is the same for the efferent arterioles

Why is this increase in hydrostatic pressure in the glomerulus useful?

As it helps force the components of the blood out of the glomerular capillaries and into the ultra-filtrate

How can metabolic acidosis be compensated?

As it is the fall in hydrogen carbonate that has changed, it can be compensated by changing the ventilation. This is: - Detected by peripheral chemoreceptors [HCO3-] - Where increased ventilation lowers the partial pressure of carbon dioxide - Restores the pH towards normal

Why is low urine magnesium associated with stones?

As magnesium appears to improve the solubility of anions, which free calcium binds to

Why mustn't this figure be applied to all clinical situations?

As the interpretation of culture depends on clinical details (symptoms, previous antibiotics etc), nature, quality of specimen, delay in culture and counts, evidence of contamination, or so-called "sterile pyuria" - white blood cells present in the urine without bacterial growth

Explain why cells move K+ into and out of the cells to regulate the extracellular fluid concentration of potassium ions

As the kidneys provide a slow response in excreting potassium ions to balance out those ingested, the cells uptake potassium ions in the short term to reduce the risk of hyperkalaemia.

What two stages of development happen after the pro-nephros ?

As the pro-nephros disappears Mesonephros forms; it occupies a lot of space (most of the longitudinal axis of the developing embryo) As the meso-nephros regresses Metanephros develops which is considered the adult kidney. It is in the position of the future pelvic region.

Where do the collecting ducts join?

As they reach the renal pelvis

To change the plasma volume, why can't we just add or remove water?

As this would change osmolarity

At what age is IgA nephropathy most common?

At any age

When do we start feeling the need to urinate and why?

At around 400ml of filling, afferent, sensory, nerves in the bladder wall start to signal the need to void the bladder. These are thought to be stretch receptors, not fully recognised yet

How is the activation of vitamin D into calcitriol controlled?

At the 1-alpha hydroxylation step in the liver where it is converted to 25-hydroxyvitamin D3 Stimulated by increased PTH and low phosphate Inhibited by decreased PTH an by high phosphate Calcitriol itself causes negative feedback on its production

How can renal parenchymal disease result in secondary hypertension?

At the earlier stages of this disease, there may be a loss of vasodilator substances. In the later stages this causes sodium ion and water retention due to inadequate GFR. Hence this is volume-dependent hypertention, where sodium ions and water are reabsorbed increasing blood volume, which increases hypertension

At the end of urination, what is the residual volume of urine?

At the end of normal micturition, less than 10ml of urine remains in the bladder

Where in the kidney is the convergence of the renal collecting system, ureter, renal artery and renal vein

At the hilum

What does the world paraxial mean ?

At the side of the axis

What is the overall effect of the proximal convoluted tubule on the reabsorption of water?

Attracts H20 back into the blood, due to the 67% of sodium that is reabsorbed, allowing volume to increase

What is our first line of defence to control blood volume?

Autoregulation - to keep the GFR in normal limits: 1) Myogenic response - quick 2) Glomerular Tubular Feedback - slow

When does autoregulation function?

Autoregulation is able to function to maintain the GFR when the blood pressure is within physiological limits - 80-180mmHg

What mechanism is the control of low-pressure baroreceptors the opposite of?

Bainbridge reflex

What is the short term regulation of blood pressure?

Baroreceptor reflex Adjust sympathetic and parasympathetic inputs to the heart to alter the cardiac out. Parasympathetic dilates the blood vessels which reduces blood pressure, while the sympathetic contracts the blood vessels to increase the blood pressure. Hence it alters the total peripheral resistance

What are the sensors called in the vascular system that detect increases in extracellular fluid volume?

Baroreceptors

What detects this drop in blood pressure?

Baroreceptors - nerve endings that are sensitive to stretch. Increased arterial pressure stretches these receptors

Where does the base of the urinary bladder sit in females?

Base of urinary bladder sits inferior to the uterus and anterior to the vagina

Describe the external genitalia ?

Basic components: 1. Genital tubercle (GT) 2. Genital folds 3. Genital swelling In the male the GT elongates& genital folds fuse to form the spongy urethra

What is the shape of a normal kidney?

Bean shaped with medial hilum

Between which Vertebral levels do the kidneys lie ?

Bean-shaped organ Posterior abdomen T12→L3 vertebra Right kidney is LOWER.. why ? Becuase of the liver on the right hand side The presence of the liver

In respiratory alkalaemia and acidaemia, these are usually referred to as alkalosis and acidosis. Why isn't this correct?

Because -osis means a change in the hydrogen carbonate concentration not the partial pressure of carbon dioxide

Why should this, in theory, be easy to correct?

Because HCO3- is rapidly excreted in the kidneys. A rise in intracellular pH should reduce the H+ excretion and HCO3- recovery

Why does this happens?

Because an increase in osmolarity means that there is less water in the ECF, and so water is conserved for an increase in blood pressure

Why are we diluting the filtrate as it moves along the nephron's tubules?

Because as the filtrate moves along the filtrate more sodium ions are reabsorbed, diluting the filtrate

Why is the excretion of H+ different in the distal convoluted tubule in comparison to the proximal?

Because by the distal tubule most of the hydrogen carbonate has been reabsorbed, so this cannot be used as a buffer

Why is there an over-estimation in the GFR when using creatinine?

Because creatinine is secreted by the tubules and therefore overestimates the GFR by a small amount. Consequently, the rate of excretion of creatinine exceeds its rate of filtration by 5% to 10%

Why is urine culture used for antenatal screening for UTIs in pregnancy instead of dipstick tests?

Because dipstick tests are insufficiently sensitive

However, why in practise is metabolick alkalosis not easy to correct?

Because if there is also volume depletion, due to dehydration because of the persistent vomiting, the capacity to lose HCO3- is less, because of high rates of recovery of sodium ions favouring HCO3- recovery and H+ recovery as well

Why is the diagnosis of UTIs in children difficult?

Because it is often presented with non-specific signs and symptoms

Why is there a transport maximum?

Because many substances are reabsorbed by carrier mediated transport systems, where the carriers can become saturated leading to a transport maximum

Think about the relationship of the left and right kidney to the other abdominal organs, can you explain why the left kidney is usually higher than the right kidney?

Because of the position of the liver, the right kidney is about 1 cm lower than the left kidney

Why can changes in the partial pressure of carbon dioxide be compensated as well as corrected?

Because plasma pH depends on the ratio of the concentration of hydrogen carbonate ions to the partial pressure of carbon dioxide, not their absolute values

Why do infants lack voluntary control over urination?

Because the required cortico-spinal connections have not yet been established

Why is the action carbonic anhydrase inhibitors self-limiting?

Because the urinary loss of bicarbonate depletes the extra-cellular bicarbonate, and hence the diuretic effect of of carbonic anydrase inhibitors is self-limiting. Hence they are not the main therapeutically useful diuretics

Why do we have asymmetrical venous drainage of the kidney ?

Because the venous system develops asymmetrically in the embryo

Why are adherence rates low for those on anticholinergics to treat urinary incontinence?

Because there are many side effects due to affects on M receptors on other sites

Why are disorders of the nerves that supply the bladder result in varied and complex outcomes?

Because there are three main peripheral nerves that supply the bladder, where the spinal cord innervates it bilaterally from the ANS, and the external sphincter is also under control for the supraspinal centres via the spinal cord.

Why are these methods optional and rarely used?

Because they are invasive urodynamics

Why is the thick ascending limb very sensitive to hypoxia?

Because this region uses more energy than any other

Why is it called minimal change glomerulonephritis?

Because when looking at the glomeruli under a light microscope, they appear to be completely normal

At what pH is acidosis life threatening?

Below 7

At what pH is there severe consequences of acidaemia?

Below 7.1

When are beta blockers used?

Beta blockers are not the first line of treatment of hypertension. They are used if there are other indications such as a previous MI

What is the urachus ?

Between the urinary bladder as it leads to the umbilicus you have a urachus this is from an embryological structure called the [allentois ?] → It turns into a ligament (median umbilical ligament) that anchors the umbilicus to the bladder

Describe the pathway by which information is sent from the bladder, and back again to initiate a response

Bladder Spinal Thalamus - PONS Cerebral cortex (sensory) Cerebral cortex (motor) Thalamus - PONS Spinal cord Bladder

Describe how beta blockers treat hypertension

Blocking beta1 receptors in the heart will reduce the effects of the sympathetic output to reduce heart rate and contractility

What investigations would you carry out for someone presenting with haematuria

Blood count: - Full blood count - Urea and electrolytes which assess kidney function Radiology: - Ultrasound - Intravenous urogram (IVU) - allows imaging of the urinary tract Endoscopy - Flexible cytoscopy which is a procedure to check for any problem in your bladder using a flexible telescope Urine - Culture and sensitivity - Cytology (looks for abnormal cells)

Describe the passage of blood to the afferent arterioles to each individual nephron

Blood enters the kidney through the renal arteries. These the divide: Renal artery --> Segmental arteries --> Interlobar arteries --> Arcuate arteries ---> Interlobular arteries --> Millions of afferent arterioles

By what methods is hypertension treated?

Blood pressure = cardiac output x total peripheral resistance Hence cardiac output and TPR can be targeted and reduced in order to decrease blood pressure As cardiac output = stroke volume x heart rate Stroke volume and heart rate can be targeted in order to treat hypertension

What is the main factor that influences the GFR?

Blood pressure as this affects the glomerulus hydrostatic pressure

What supplies the suprarenal glands ?

Blood supply to suprarenal glands: Arterial supply: Inferior Phrenic artery Middle & inferior suprarenal artery Venous Drainage: Right side: Into the IVC Left side: Into Left renal vein Asymmetric pattern of venous draining

Why is phosphorous homeostasis closely linked with calcium homeostasis?

Both are the principle components of hydroxyapatite crystals that make up the bone. They are regulated by the same hormones, PTH and 1,25-dihydroxyvitamin D mainly, and to a lesser extent calcitriol

What are the risks of using K+ sparing diuretics and aldosterone antagonists?

Both can produce life threatening hyperkalaemia, especially id they are used with ACE inhibitors, K+ supplements or in patients with renal impairment

How do we decide between radiotherapy and radical prostatectomy?

Both of these are equally successful, so treatment choice is based on the patient's factors that influence treatment decisions. Patient choice is taken if they are eligible for both, where the doctor advises risks of the both and they decide finally

How do K+ sparing diuretics and aldosterone antagonists act on the late distal convoluted tubule and collecting duct?

Both reduce sodium ion channel activity. Both reduce the loss of potassium and are called potassium sparing diuretics.

What is between the visceral and parietal layers?

Bowman's capsule

What is the urinary pole of the renal corpuscle?

Bowman's capsule

Draw structure of nephron

Bowmans capsule - filtration in cortex PCT - in cortex Loop of henle - dips in and out of medulla DCT - in cortex Collecting duct - Passes through Medulla to pelvis

In which cancers if PTHrP associated?

Breast and prostate cancer Occasionally with myeloma - a malignant tumour of the bone marrow

Explain the bump in the kidney shown

Bulge in lower left kidney is normal cortex in foetal lobulation - "dromedary" hump. This is a harmless developmental abnormality that can be confused with a tumour

How is the thirst efferent pathway stimulated?

By an increase in fluid osmolarity, and stimulated when we are already 10% dehydrated

How do aldosterone antagonists work?

By antagonising the action of aldosterone. Aldosterone acts on the principal cells of the late distal convoluted tubule and the collecting duct to increase the sodium ion reabsorption via ENaC. Aldosterone antagonists act through the competitive inhibition of the aldosterone receptor, to decrease sodium ion reabsorption

How do we change plasma osmolarity?

By changing how we control water retention

How do we classify glomerulopathies?

By clinical presentation - Nephrotic: Lots of protein little blood in urine - Nephritic: Lots of blood with little protein in urine - Rapid progressive glomerlopathies: Progression into acute renal failure happens rapidly By histological appearance Immunulogical features Pathogensis Hereditary glomerulopathy Genetic classification (research happening where genome sequencing is offered to those with rare diseases in order to find out more about them)

How must we complete a urine sample for someone with suspected acute pyelonephritis?

By collecting a midstream specimen of urine

How is the hypokalaemia and alkalosis therefore treated?

By correcting the dehydration

How is concentrated urine created?

By counter - current multiplication Countercurrent multiplication is the process of using energy to generate an osmotic gradient that enables you to reabsorb water from the tubular fluid and produce concentrated urine

How is chloride reabsorption driven?

By coupling it to the 2Na-2k-ATPase pump

How can we calculate the renal plasma flow?

By knowing that the volume of red blood cells, expressed as a percentage, is around 40% of the total renal blood flow. Hence: 0.6 x 1.1 litres per minute = 600ml per minute is the plasma that enters the glomerulus, in which 20% will be filtered (120ml per minute)

How would we screen for prostate cancer?

By looking for prostate specific antigens.

When is the control of hydrogen carbonate concentration disturbed?

By metabolic and renal diseases

How is water reabsorption driven?

By osmolarity differences across epithelium

when is the control of the partial pressure of carbon dioxide disturbed?

By respiratory disease

How is secondary hypertension treated?

By teating the primary cause

How is the concentration gradient between the medulla and tubules created?

By the difference of permeability of the tubule and because of the cycling of urea

How does ADH function?

By the insertion of the water channel aquaporin 2. Apical membranes do not contain water channels in the absence of ADH. When ADH is released the apical membrane has aquaporin 2 channels inserted into the later parts of the DCT and CT to make water more permeable. Water then goes out through the basolateral membrane, where aquaporins are always present

How is respiratory acidaemia (acidosis) compensated?

By the kidney increasing the hydrogen carbonate reabsorption

How is respiratory alkalaemia (alkalosis) compensated?

By the kidneys decreasing the hydrogen carbonate concentration by excreting more

By what other simple observation could a damaged glomerular filtration membrane be detected?

By the presence or red blood cells in the urine Meaning the Fenestrated capillary of the glomerulus are not working properly as well as the basal membrane and podocytes

How is the concentration gradient maintained?

By the vasa recta acting as a counter-cuttent exchanger

In frail elderly men, how may a urine sample be collected?

By using a clean condom catheter, with a sterile collection bag attached. When there is a long-term placement of a urinary catheter, you should drain and discard a few millilitres of urine from the catheter to collect the urine sample. Do not take from the bag as it is likely to be contaminated

How is the GFR calculated?

By using a concept of clearance. If a substance which is filtered is not altered as it travels through the nephron (not secreted or reabsorbed) then it will be the same as the GFR as will be in the urine

How are CT scanners used in relation to renal cancer?

CT scans are used to diagnose and state the staging of renal cancer

Where in the kidney does urine collect before passing through the renal pelvis

Calyx

What are peritubular capillaries?

Capillaries that travel alongside nephrons allowing exchange between blood and inner nephron. Formed by efferent arterioles.

What is the filtration barrier in the kidneys made up of?

Capillary endothelium and the visceral layer of the Bowman's capsule called podocytes

What is the only class of diuretics that act on the proximal convoluted tubule

Carbonic anhydrase inhibitors

How do we calculate the mean arterial blood pressure?

Cardiac Output x Total Peripheral Resistance

What is the predominant cation and anionic in the intracellular space ?

Cation = K+ Anion = A- ( negative charged amino acid)

In what direction does the mesonephric tubule develop ?

Caudal to pronephric region (cervical)

How does this affect the filtrate exiting the distal convoluted tubule?

Causes further dilution to the filtrate, and more hypo-osmotic fluid leaves the distal convoluted tubule

How does hypercalcaemia affect the cardiovascular system?

Causes or exacerbates hypertension

Failure to control ECF osmolarity leads to?

Cell shrinkage or swelling

Describe the prostate lobes in terms of zones

Central zone: surrounds the ejaculatory ducts all the way to the verumontanum Transitional zone: Surrounds the urethra. Labile to nodular benign enlargement (stroma & glandular) from 40 years Peripheral zone: surrounds that other two zones. 70% of cancers start there. It is pushed peripherally by benign enlargement and compressed Overgrowth of the prostate → will put pressure on urethera because its in the central and transitional zones → makes it hard for the man to pee. Cancer forms in the more peripheral zone → at first doesn't have an effect on the urethra so they usually don't know. To test: Digital examinations of the prostate → Finger into anal canal → Immediately anterior to your finger will be the Prostate Cancers → will feel hard nobly like nodules in that region. Unlike an infection of the prostate which makes the prostate very soft

What does intravenous mannitol treat?

Cerebral oedema

How much urine do you produce?

Changes depending on how much u drink but 1.5L average of urine produced a day Urinary flow = 1ml/min = 1.5L/day

Why is osmolarity important?

Changes in ECF have effects on ICF Changes can cause problems in cell function and volume, can induce cytolysis

What is prioritised, changes in blood volume or osmolarity?

Changes in blood volume and pressure have an effect on the response to changes in osmolarity. Volume is more important than osmolarity when volume crashes as we can tolerate changes is osmolarity but not volume

How is plasma pH compensated?

Changes in the partial pressure of carbon dioxide can be compensated through changing the hydrogen carbonate concentration in order to restore the ratio. The kidney controls the hydrogen carbonate concentration

How is the filtrate isosmotic (no change in osmolarity) when the concentration of ions change as we go through the PCT?

Chloride reabsorption lags behind the other reabsorption ions, where the concentration rises. This compensates for the other ions lost, which allows osmolarity to be built and remain constant

Why is low urine citrate a common feature of stone formers?

Citrate appears to improve the solubulity of calcium.

What happens to the chloride accumulated in the S1 region of the proximal convoluted tubule?`

Cl- will move out passively

What do we look for when interpreting a culture report?

Clinical details - Symptoms - Previous antibiotics Quality of the specimen Delays in culture Microscopy (if available) Organisms located

A 70 year old man was catheterised for benign prostatic enlargement. He presents with: - Nausea and vomiting - Confusion - Tachypnoea - Tachycardia - Hypotension What does this indicate?

Clinically unwell with sepsis

What are the commonest pathogens in young women and hospitalised patients?

Coagulase negative staphylococci e.g. Staph saprophyticus. This is due to increased risk factors such as catheterisation

What epithelium is present in the cortex of the adrenal glands?

Coelemic epithelium (simple squamous epithelium?)

Whats the function of the collecting ducts?

Collecting ducts are controlled by hormones that cause dilation or constriction of the ducts based on the body's electrolyte balance. Constriction conserves water while dilation allows more fluid to leave the body through elimination. Aldosterone and antidiuretic hormone are important. Essential in correcting dehydration. These tubes reabsorb a significant amount of water within the body to restore the body's fluid and electrolyte balance.

What is the response of the peripheral chemoreceptors that enable the control of the partial pressure of carbon dioxide within tight limites?

Compensation of respiration, driven by changes in plasma pH

What sits next to the mucosa of the ureters?

Connective tissue, which consists of blood vessels, lymphatics and nerves

What does the pelvic cavity contain ?

Contains connection between urinary and reproductive tracts

Why is the descending limb permeable to water?

Contains lots of aquaporins and has appropriate loose junctions to allow water through

What is the function of the lateral region of the Pontine Contienence Centre (PMC)?

Continence - the storage of urine. Stimulation results in a powerful contraction of the urethral sphincter

How is continence achieved in the urethra?

Continence is achieved in the urethra by the combined effect of smooth muscle contraction of the urethra, the surrounding per-urethral striated muscle, and the elasticity of the connective tissue. The support of the urethra by the muscles and ligaments of the pelvic floor are important for the efficiency of the sphincter mechanisms of the urethra.

What happens in the medullary collecting ducts?

Control the reabsorption of water and urea by ADH (vasopressin) and V2 receptors. ADH causes the insertion of AQP2 containing vesicles in the luminal membrane. This allows osmotic reabsorption of water into the hypertonic medullary interstitium (APQ3 , 4 in basal membrane)

How is the excretion of potassium controlled in the nephron?

Controlled by changing the balance of reabsorption and secretion in the distal tubule

What happens in the collecting duct?

Controlled reabsorption - 3% sodium ions - Permeability affected by ADH in principal cells - Variable amount of calcium ion reabsorption - Absorbs and secretes K+, Na+, H+, ammonia - Secretes drugs, creatinine toxins

Whats the function of the RAS?

Controls ECF volume by Na+ reabsorption

Describe the anatomy of the kidney itself

Cortex Medulla Pyramids Papila Renal columns Major and minor calyces Renal pelvis Ureter

Macroscopic structure of the kidney

Cortex Medulla Renal pelvis connected to the ureter

Describe where the levels of control are for the continence phase

Cortical storage centres - above the brainstem Lower pontine centres Sympathetic neurones from spinal cord levels T11, L1 and L2 (thoracolumbar)

Describe where the levels of control are for the voiding phase

Cortical voiding centres - above the brain ste, Medial pontine centres Spinal cord: - Parasympathetic S2, 3, 4 - Somatic neurones S2, 3, 4

What is the major function of the LOH?

Create a gradient of increasing osmolarity in the medulla Allows formation of concentrated urine

What is used instead to estimate the GFR?

Creatinine

Under the microscope, what does it mean and tell us if we see crescents in the glomerulus?

Crescents are an accumulation of inflammatory cells (mostly mononuclear) withing the Bowman's space, where they often compress the capillary tuft and are associated with more severe disease. Suggests the disease is rapidly progressing and aggressive

What epithelium does the collecting ducts have?

Cuboidal epithelium

What epithelium does the distal convoluted tubule consist of?

Cuboidal epithelium

What is the epithelium that is found in the proximal convoluted tubule?

Cuboidal epithelium due to the active transport of ions, needs lots of pumps

How would we investigate to diagnose this patient?

Culture urine

Where does controlled reabsorption of salts and water happen?

DCT

Fluid leaving LOH hypotonic what happens in the DCT?

DCT removes more Na+ and Cl- actively secretes H+ ions Water may or may not follow reabsorption of electrolytes (more or less dilute urine)

What happens if the neurones that control the voiding phase are damaged?

Damage to neurones that promote micturition will lead to the failure to pass urine voluntarily, resulting in urinary retention.

What do we see under an electron microscope in minimal change glomerulonephritis?

Damage to the podocytes, where there are widening fenestration slits allowing proteins to leak through.

What is Hypospadias ?

Defect in fusion of urethral folds Urethra opens onto the ventral surface rather than the end of the glans Incidence increasing → why ?

What structures define the trigone

Defined by the entrance of the ureteres at the top of both sides Defined by the exist of the urethra in the middle at the bottom.

Where doe we find the ureter?

Descending from the kidney through the retroperitoneum that overlies the tips of the transverse process It crosses the iliac vessels and the common iliac sacro-iliac joint Swings laterally around the pelvic sidewall Passes anteriorly to the bladder at level of the ischial spines

What does the extent to which the reversible reaction proceeds depend on?

Determined by the ratio of the concentration of dissolved carbon dioxide and the partial pressure of carbon dioxide in the plasma, which is controlled by the lungs, to the concentration of hydrogen carbonate, created in the red cells, but whose concentration is controlled by the kidneys

How is autoaugmentation carried out?

Detrusormyectomy - large disc of detrusor removed from dome Detrusormyotomy - incision through detrusor muscle with edges everted

What is the first stage in the development of the kidney

Development of the pro-nephros

What four disease can cause diuresis (polyurea)?

Diabetes mellitius - glucose in the filtrate = osmotic diuresis Diabetes insipidus (cranial) - decrease in ADH release from the posterior pituitary gland leading to diuresis Diabetes insipidous (nephrogenic) - poor resistance of collecting ducts to ADH causing diuresis Psychogenic polydipsia - increased intake of fluid

Describe the ionic compositions between the intercellular and extracellular fluid

Different fluid compartments have different ionic compositions. Inside the cell K+ is in high concentration, while outside Na_ is in high concentration

How does the apical membrane differ in the tubules of the nephron

Different segments of the tubule have different types of Na+ transporters and channels on the apical membrane

How does it move into its adult position in the abdomen?

Differential growth of the foetus results in the kidneys "ascending" into the abdomen

Does angiotensin II and atrial natriuretic peptice act directly or indirectly?

Directly

What is the problem of having disorders of water balance?

Disorders of water balance manifest as changes in body fluid osmolarity, where symptoms reflect changes in plasma osmolarity

How does hypercalcaemia affect renal function?

Diuresis - increased or excessive production of urine. This leads to dehydration and the rises of kidney stones

How can diuretics cause hypokalaemia?

Diuretics reduce the extracellular fluid volume, which cases the activation of RAAS. This leads to increased aldosterone secretion. Aldosterone increases th amount of sodium ions reabsorbed and the potassium ions that are secreted. This is what cause hypokalaemia

Describe urethra resistance during emptying

Drastic decrease in outflow resistance

Why is the left kidney higher than the right?

Due to the liver on the right hand side that pushes down the right kidney

Why can carbonic anhydrase inhibitors cause metabolic acidosis?

Due to the loss of HCO3 in the urine, which is an alkali substance. Plasma HCO30 concentration declines during the chronic use of these drugs because of the increased urinary excretion of HCO3-. Carbonic anhydrase inhibitors increase the excretion of bicarbonate with accompanying Na+ and K+ ions and water, resulting in an increased flow of an alkaline urine and metabolis acidosis

Describe the dangers in potassium ion concentration of the extracellular fluid, that vomiting and diarrhoea can cause

Due to the loss of gut contents, more HCl is made, meaning that the extracellular fluid concentration of hydrogen carbonate increases, so the hydrogen ion concentration falls. This makes K+ move into the cells, causing the extracellular fluid potassium ion concentration to fall Also due to the vomiting and diarrhoea more potassium ions are lost from the gut, making the extracellular fluid concentration of potassium ions fall further Also, alongside this, the kidney excretes less hydrogen ions due to the lower concentration, so more potassium ions are secreted instead. Hence, there are 3 actions that decrease the potassium ion concentration As there is dehydration due to the vomiting and diarrhoea, this limits the loss of hydrogen carbonate in the urine. So alkalosis and hypokalaemia tend to persist

In a normal kidney, why doesn't proteins pass into the ultrafiltrate?

Due to the negative charges found on the basement membrane. Proteins are repelled by this and hence do not pass through

Where is the transpyloric plane present?

Due to the physical presence of the liver

How do we know that the following histological slide is taken from the renal cortex?

Due to the presence of corpuscles that indicates that this is the renal cortex

Explain why the low pressure baroreceptors respond to total venous volume

Due to their location in the venous of high compliance side of the circulatory system where the majority of blood is, making them respond to the total venous volume

Describe the actions of duloxetine

Duloxetine is a combined noradrenaline and serotonin uptake inhibitor. It increases activity of the External Urethral Sphincter during the filling phase

Define homeostasis

Dynamic equilibrium that keeps the body within certain set points

Label the following ultrasound of the testis

E = Head of epididymis T = Testis, speckle appearance normal for solid organs t = Tail of testis

What is meant by a complicated UTI?

E.g. a UTI during pregnancy, treatment failure, suspected pyelonephritis, complications, in males and paediatric

Why is reabsorption needed?

ECF = 15L (1/3 TBW) 180L/day filtrated = 7.5L/hr so in 2 hrs all ECF would be lost

What transporters, responsible for sodium ion reabsorption, are located on the apical membrane of the late distal convoluted tubule and collecting tubule?

ENaC - Epithelial Na+ channel

What sodium transporters are present on the apical membrane of the late distal convoluted tubule and collecting duct?

ENaC - epithelial Na channels

What is the effect of diuretics that block the ENaC on the principal cells?

ENaC blockers block the reabsorption of sodium ions, this prevents the reabsorption of water, reducing the extracellular volume. The blockage of ENaC also reduces K+ secretion, as less Na+ reabsorption means that a less negative lumen potential, which in turn reduces K+ secretion

What is the cloaca

Early in development, the GI; urinary and reproductive tracts end at a single structure = The cloaca The cloaca is a common chamber at first for both GI and the urinary system. We develop a septum that passes between the two.

These vessel originate from the renal glomeruli of cortical nephrons and branch into the cortical peritubular capillary bed A. Efferent arteriole B. Vasa recta C. Afferent arteriole D. Segmental arteries E. Renal artery

Efferent arteriole

What are the main adverse effects of diuretics?

Electrolyte imbalances, importantly potassium disturbances

What surgical treatment is there for children with UTIs?

Endoscopic injection of a bulking agent. Ureteric reimplantation

What is described in this picture ?

Enhanced MRI image of an additional kidney Two kidneys in the right place : One is smaller But the one thats the right size is in the wrong place. What do we have, kidney thats being induced in the urogenital ridge from a ureteric bud Inducing kidney metanephros one gets up to the right position other arrested at the pelvis

What is the tight or leaky epithelial classification based on ?

Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement

What are tubules lined with?

Epithelial cells

How are epithelial cells held together in urinary system?

Epithelial cells are held together by tight junctions on the apical (lumen) side

What adverse effects can thiazides cause?

Erectile dysfunction

What is secreted by the tubules?

Excessive quantities of certain dissolved substances from the body to remove them e.g. protons to maintain the blood's pH and: - Potassium ions - Ammonium ions - Creatinine - Urea - Some hormones - Certain drugs e.g. penecillin

In a female, what else would you do to examine a patient with suspected urinary incontinence?

External genitalia Vaginal examination - the stress test which simulates the accidental release of urine (urinary incontinence) that may occur when you cough, sneeze, laugh, or exercise

What allows the voluntary control of micturation that surrounds the urethra

External sphincter muscles

What is filtration fraction?

FF = 20% Ratio of GFR to RPF Proportion of fluid that reaches kidneys which passes into the renal tubules

How does focal segmental glomerulosclerosis respond to steroids?

FSGS is less responsive to steroids than minimal change glomerulonephritis

State the five bacterial risk factors of developing a UTI

Faecal flow - the anus and urethra are close together. Potential urinary / faecal pathogens can colonise the periurethral area (the tissues surrounded the urethra) Adhesion - Fimbriae (projections) and adhesions allow the attachment to urethral and bladder epithelium Haemolysins - These are lipids or proteins that causes the lysis of red blood cells by destroying their cell membrane. They can damage membranes and cause renal damage K antigens - Allow some E. coli to resist host defences by producing a polysaccharide capsule Urease - Produced by some bacterial e.g. proteus where they break down urea for energy

What happens if there is a failure to control ECF volume?

Failure to control the extracellular fluid means theres a change to the: 1. Changes in BP 2. Tissue fluid 3. Cell function For ex. a high volume means an ↑ BP, ↑ Tissue fluid and ↑ cell function Failure to control the extracellular osmolality causes cells to shrink or swell due to the differences in water potential Hence kidney can only directly affect the extracellular fluid, but have an indirect effect on the intracellular fluid.

Describe the interaction between pH and potassium ion concentration in the extracelullat fluid, when there is a fall

Falls in the extracellular fluid concentration of hydrogen ions leads to the movement of potassium ions into the cells. Hence a high extracellular fluid pH means a falling extracellular concentration of K+ Falls in the extracellular fluid concentration of K+ leads to a movement of H+ into the cells so K+ goes out. Hence a low extracellular fluid concentration of potassium ions means a rising extracellular pH

What is the rate in which the myogenic mechanism acts?

Fast

From what embryologically is the female urethra formed ?

Female urethra is formed by the pelvic part of the urogenital sinus

How can we tell the difference between a female and a male pelvis when looking at imagery?

Females have bigger, more oval pelvises, while males have it heart shaped

What type of capillaries surround the glomerulus?

Fenestrated capillaries

How much cardiac output does the kidneys filter?

Filters about 25% of cardiac output Filters about 20% of body water

What is filtrate?

Filtrate is the same as plasma but without cells and proteins

How is filtration pressure maintained?

Filtration pressure is maintained by specialised circulation Afferent efferent arterioles Determines the Glomerular filtration rate (GFR)

When is the fluid filtered?

Fluid leaving the capillaries is filtered as it passes to Bowman's space

Hence, where does the substance goes when it enters the kidneys?

For any substance that enters the kidney in the renal artery, an equal amount must leave in the urine and the renal venous blood. This can only hold for substances that are not metabolised or synthesised

What are the other ways in which nephrotic syndrome is treated?

For their complications: - Anticoagulants used - Lipid lowering therapy

How long can urine be preserved with boric acid without being refrigerated, and is still suitable for culture and microscopy?

For up to 96 hours

Where are the Pontine centres located?

Found in the brainstem

What basic urodynamic investigations can take place for those suspected with urinary incontinence?

Frequency volume chart Bladder diary (for 3 days or more - records what they eat and drink along with how much they urinate) Post-micturition residual volume - in patients with voiding dysfunction

Describe what happens to the osmolarity in the tubules and the meduallry interstitium with the action of counter current multiplication in the second round

Fresh fluid enters from the glomerulus pushing concentrated fluid (400 mOsm/L) into the ascending limb We are creating the concentration gradient. Each time the filtrate is more concentrated than before

How do we measure how much protein is present in the urine?

From easiest to hardest: - Urine dipstick - Urine protein to creatinine ratio - 24 hour urine collection

Where does tubular secretion occur?

From the epithelial cells that line the renal tubules and collecting ducts into the glomerular filtrate

Where do reabsorbed materials go?

From the peritubular kidneys to the circulating blood

Where does reabsorption happen?

From the tubular component to peritubular capillary (vascular component)

What is the function of the medial refion of the Pontine Micturition Centre (PMC)?

Function - micturition centre Stimulation results in decrease in urethral pressure and silence of the pelvic floor (the somatic innervation) signal, followed by a rise in detrusor pressure

Name two types of loop diuretics

Furosemide Bumetanide

How many Litres do the kidneys filtrate? (GFR)

GFR = 180L per day to keep homeostasis Blood 1L/min

What is the glomerular filtration rate?

GFR is a measure of the filtration process of all the nephrons

What is the conservative management of urinary incontinence?

General lifestyle interventions: - Modify fluid intake - Weight loss - Stop smoking - Decrease caffeine intake if urge urinary incontinence - Avoid constipation - Timed voiding - fixed schedule

Describe urethra resistance during filling

Generates high resistance to prevent urine leakage

What is the second line of autoregulation of plasma volume?

Glomerular tubular balance

What is the structure in the kidney that allows filtration to occur

Glomerular tuft [ Network of capillaries of the glomeruli)

Describe filtration

Glomerulus - highly specialised filter Filter water, electrolytes and small molecules, these are pushed through by filtration pressure in capillaries

Where does filtration take part in the nephron?

Glomerulus/bowmans capsule

What are the commonest pathogens for UTIs?

Gram negative rods, particularly eneterobacteriaceae - Coliforms especially E.coli

What ion is secreted under control?

H+

What is one substance that is actively secreted by the kidney?

H+ ions (so lose more than filtered)

What is the relationship between HSP and IgA nephropathy?

HSP can progress to IgA nephropathy and vice versa

What is Henoch-Schoenlein Purpura (HSP)?

HSP has the same pathology and histopathology in the kidneys as IgA nephropathy, except it is more likely in younger aged individuals. It includes small-vessel vasculities which is the inflammation of blood vessels, that therefore affects the highly vascularised kidneys. It also affects the skin, joints and gut

What happens to the urine in alport syndrome?

Haematuria

What is the appearance of the urine in nephritic syndrome?

Haematuria to show, smoky brown in colour

Describe the unusual clinical presentation of prostate cancer?

Haematuria, which is in advanced prostate cancer

When does glomerular tubular balance come into play?

Happens all the time, but also occurs in pathology where the first line of autoregulation did not work

What doesn't get filtrated into the glomerulus?

Hematocrit = 40% of renal blood flow, as this contains cells and large proteins that are too big to get filtered. This is about 600 ml per minute.

Describe what governs uptake into the capillaries specifically in the peritubular capillaries

High oncotic pressure in the peritubular capillary due to the proteins that remain after reabsorption. High hydrostatic pressure in the interstitium due to the water reabsoprtion from the tubules These two forces push water back into the body

What is the net filtration pressure?

Hydrostatic pressure in plasma = 50mmHg Hydrostatic pressure in Bowman's capsule = 15mmHg Osmotic pressure in glomerulus = 23mmHg 50 - 15 - 23 = 10mmHg

What is a healthy response to hypercalcaemia?

Hypercalcaemia is an increase in plasma calcium This decreases PTH secretion In the kidneys there's a decrease in calcitriol production which means there's less calcium to be taken in from the gut. It also decreases calcium re-absorption so less calcium is excreted in the urine Causes a decease in bone breakdown, where bone building is increased

What reabsorption does take place in the distal convoluted tubule?

Hypo osmotic fluid enters the DCT in which there is: - Active transport of 5% - 8% of sodium ions (variable) - Low water permeability - Na+ / Cl- enters across the apical membrane via the elctro-neutral NCC transporter - Major site for calcium ion reabsorption under control from PTH

In what circumstance is hypo-osmotic urine produced?

Hypo-osmotic means that the urine has a lower osmolarity than the plasma, and this happens when plasma osmolarity decreases

What are the complications of nephrotic syndrome?

Hypoalbuminaemia and other protein loss leads to: - Hyperlipidaemia (see picture, shows xanthelasmas under the eyelids). The main cause is increased hepatic lipogenesis, a non-specific reaction to falling oncotic pressure secondary to hypoalbuminaemia - Hypercoagulability as albumin is part of the anti-clotting system. This gives a greater risk of DVT and renal thrombosis - Loss of immunoglobulines, especially in younger patients. This increases the likelihood of getting infections

What is the body's normal response to hypocalcaemia?

Hypocalcaemia is the decrease in plasma calcium ion concentration This causes an increase in PTH secretion In the kidneys this increases the production of calcitriol which means more calcium is taken in from the gut and an increase in calcium absorption from the kidney Increase of bone breakdown and decrease in bone building

What are the causes of hypocalcaemia?

Hypoparathyroidism - Post surgery most common - Autoimmune - Pseudohypoparathyroidism (PTH resistance) Hypovitaminosis D - Dietary deficiency, lack of sun exposure, defects in vitamin D synthesis or receptor function - Rickets / osteomalacia GI malabsorption Renal loss Endocrine response to non-hypoparathyroid hypocalcaemia - Secondary hyperparathyroidism

What are the causes of hypocalcaemia?

Hypoproteinaemia Critical illness Renal disease Inadequate intake: - Vitamin D / calcium - Malabsorption Hypopararthyroidism - Post surgical - Magnesium deficient - Autoimmune - Infiltrative Acute pancreatitis Rhabdomyolysis Tumour lysis Drugs - Bisphosphonates - Penytoin - Calcium chelators

Describe the difference between Hypospadias & epispadias

Hypospadias is a congenital defect, primarily of males, in which the urethra opens on the underside (ventrum) of the penis. The corresponding defect in females is an opening of the urethra into the vagina and is rare. Epispadias (also called bladder exstrophy) is a congenital defect of males in which the urethra opens on the upper surface (dorsum) of the penis. The corresponding defect in females is a fissure in the upper wall of the urethra and is quite rare.

What is osmotic equilibrium?

ICF and ECF ionic composition are unequal Difference in concentration and permeability result in different chemical composition of ECF and ICF fluids

What happens to renal water excretion if osmolarity decreases?

If osmolarity decreases, renal water excretion increases

What happens to the renal water excretion is osmolarity increases?

If osmolarity increases, the renal water excretion decreases

How does renal control of the concentration of hydrogen carbonate change if someone is alkalotic?

If someone is alkalotic they have an increase in hydrogen carbonate concentration. The kidney: - Recovers all the filtered HCO3- - AND makes new HCO3- This is because the HCO3- made is not enough to preserve the concentration in the blood, as other factors make it fall. Hence, for a constant concentration is needed to be achieved, everything must be recovered and also production must increase

Describe the changes that take place in the urothelium to adapt to the amount of urine in the bladder

If the bladder is empty, the urothelium is folded, highly rounded cells. When the bladder is full, the cells are stretched and flat

If the haematuria is visible, what does this tell us?

If the haematuria is visible, there is a 20% chance of a malignancy being present

What is the problem of this?

If the kidney takes the water out of the collecting tubules, we will then dilute the medulla of the kidney. But we do not want to do it as we need the maintenance of a hyperosmotic medullary interstitium

In what cases of acute pyelonephritis, should an investigation be ordered of an underlying abnormality of the renal tract?

If the patient is male If a woman has ha two or more episodes of acute pyelonephritis All people with a urinary tract infection caused by Proteus species (renal calculi)

How is the juxtaglomerular apparatus important for controlling blood pressure?

If there is a fall of sodium in the filtrate, this means there is a decreased blood pressure due to the decreased glomerular filtration rate. This then releases renin which cause: - Increased sodium uptake from the DCT to leads to increased water uptake = increased blood pressure - Constriction of the peripheral blood vessels hich causes blood pressure to rise

How is osmolarity affected when water intake is less than water excretion?

If water intake is less than water excretion the plasma osmolarity increases

Why is it important that the kidneys match what we injest with what we excrete?

If we accumulate more Na+ than we excrete we would have to keep more water in order to keep the osmolarity and if we excrete more sodium ions than we ingest, we would have to excrete more water to not change our osmolarity. This also keeps the blood pressure at a constant level

What is the commonest glomerular nephropathy?

IgA nephropathy (form of nephritis)

How does IgA nephropathy vary from person to person?

IgA nephropathy has variable histological features and course.

In the female under what surgical circumstances might you be in danger of damaging the ureter?

In a hysterectomy, the ureter may be accidentally divided when clamping the uterine vessels, especially if the pelvis has been distorted by previous surgery.

In what age group is focal segmental glomerulosclerosis most common?

In adults

What causes hypertension?

In around 95% of cases the cause is unknown - this is called essential hypertension. This may be because: - Genetics - high BP tends to run in families - Environmental factors (high salt intake, alcohol, caffeine, OCP etc) - Pathogenesis is unclear Where the cause can be defined it is referred to as secondary hypertension. Examples include: - Renovascular disease - Chronic renal disease - Aldosteronism - Cushing's syndrome

How do we diagnose those with minimal change glomerulonephritis?

In children, no biopsy is required as it is a common condition. So if protein in the blood is noted then it is assumed that it is this, which is confirmed if they have a positive response to the treatment in the trial period. If there isn't a positive response, then it indicates it is due to another cause and then a biopsy is taken. No biopsy is taken straight away as it is an invasive procedure to occur on children

What are the clinical uses of diuretics?

In conditions where sodium ions and water retention cause the expansion of the extracellular volume e.g. in heart failure (i.e. not only used to treat hypertension)

Where is control of storage and contincence of the bladder found above PONS?

In continence centres in the brain, located in the cerebral cortex, which in turn control the continence centres of the spinal cord

What happens to the mesonephric duct in females and males ?

In females= largely disappears ( sometimes remnants are left in female --> cyst) In males= Persists and is the basis for the ductus defferens ( tube for sperm in males) without it ; there would be no reproductive capability.

How is this altered in pathology of the kidneys?

In many disease processes, the negative charge on the basement membrane of the filtration barrier, which usually functions to repel negatively charge molecules, is lost so these negative proteins are filtered more easily and have a higher clearance ratio. This condition is called proteinuria

What are the causes or urinary retention?

In men, this may develop secondary to the enlargement of the prostate gland Kidney stones

What is the anion gap used for?

In metabolic acidosis, the HCO3- reacts with H+ to produce carbon dioxide which is then breathed out. This leaves the anion from the acid produced metabolically, and hence some HCO3- is replaced by this anion. The anion gap indicates whether any hydrogen carbonate has been replaced with something other then Cl-, and hence indicates if someone as metabolic acidosis

Why is the maintenance of osmolarity important?

In order to keep osmotic pressure and blood volume constant

When do these pathways happen in relation to each other?

In parallel to each other (i.e. at the same time)

When may microscopy be done to diagnose and investigate a UTI

In relation to complicated UTIs - when symptoms other than dysuria and frequency show In cases of which UTIs cause kidney disease: - Loin pain - Nephritis - pyelonephritis - Hypertension - Toxaemia - Renal colic - Haematuria - Renal TB - Casts Suspected endocartitis Children under 6 Schistosomiasis - a chronic disease common in Africa and South America, caused by the infestation of blood lukes Supra-pubic aspirates When requested

How do we grade bladder cancer?

In relation to how differentiated the biopsy is under the light microscope

When does extreme hypercalcaemia happen?

In renal failure or extreme dehydration

When is ADH released?

In response to an increase in osmolarity (i.e. a decrease in water) this stimulates the release of ADH from the posterior pituitary glands

In what circumstances doesn't the baroreceptor reflex work well and explain why

In sustained increases in blood pressure because the threshold for baroreceptor firing increases. This is because if blood pressure is chronic, this will change the sensitivity and firing rate, and hence accommodates to that situation. This causes a shift to the right, where for a set response, you need a higher mean arterial pressure in order to carry out the same response. Hence the baroreceptor reflex fails to correct blood pressure if happens over a long period of time

What is the goof thing about IgA nephropathy that is triggered by an upper respiratory infection?

In that it should resolve

Where are high pressure baroreceptors found?

In the arterial side of the circulatory system in the carotid sinus and arch

How does ADH effect the later parts of the nephron?

In the ascending loop of Henle: It increases sodium ion, potassium ions and chloride ion reabsorption In the late DCT controls water reabsorption In the cortical collecting duct increases water re-absorption and potassium ion secretion, alongside urea reabsorption

Where in the kidney does ADH affect?

In the ascending loop of henle and the later parts of the distal convoluted tubule and the collecting tubule

Where are low-pressure baroreceptors located?

In the atria and pulmonary vasculature

Where is atrial natriuretic peptides synthesised and stored?

In the atrial myocytes

Where does the pro-nephros first appear ?

In the cervical region (high up in the neck)

Where are glomeruli found?

In the cortex

What are the differences between the organelles present in the descending and ascending regions?

In the descending there is not much mitochondria as there is not much active transport. In the ascending there is lots of mitochondria due to lots of active transport

Where is the medial region of the PMC located?

In the dorsomedial Pontine tegmentum, also called the M region

Where do thiazide diuretics act?

In the early distal convoluted tubule

Where does the filtration of blood take place in the kidney ?

In the glomeruli, which are specialised leaky capillaries found in the kidney cortex

Where is reabsorption regulated?

In the late distal convoluted tubule and collecting duct

In which region, does the metanephric tissue develop?

In the pelvic region

Where are the kidneys found ?

In the posterior part of the abdomen on each side of the vertebral column

Where is ADH secreted?

In the posterior pituitary glands

Where does the majority of sodium ion reabsorption take place?

In the proximal convoluted tubule

Where is the majority of the volume of the glomerular filtrate solution reabsorbed?

In the proximal convoluted tubule

Describe how hydrogen carbonate is produced in the proximal tubule?

In the proximal tubule the amino acid glutamine is broken brown into ammonium ions and alpha-ketogluturate. Each alpha-ketogluturate produces two molecules of hydrogen carbonate which enters into the extracellular fluid. The ammonium enters into the lumen to be excreted

What is the kidney's celullar response to acidosis?

In the proximal tubule, there is enhanced H+-Na+ exchange. This allows for more H+ to be excreted out and more Na+ to be excreted in. This also means that there is full reabsorption of all the filtered hydrogen carbonate ions. This excess of excretion in the proximal tubule means that there is enhanced ammonium production in the proximal tubule which excretes the H+ In the distal tubule there is increased activity of H+ ATPase in the distal tubule. There is increased capacity to export HCO3- from the tubular cells to the ECF. Hence there are two ways in which hydrogen carbonate concentration increases

Reabsorption is an energy demanding process, where is most of the energy consumed?

In the reabsorption of sodium ions. The reabsorption of other things in the filtrate is coupled to the active transport of sodium ions

In which part of the nephron does ADH act?

In the thick ascending limb

Where does passive transport mainly take place in the nephron?

In the thin parts of the loop of Henle

What conditions are carbonic anhydrase inhibitors used?

In the treatment of glaucoma to reduce the formation of aqueous humour in the eye by about 50%, and in some unusual types of infantile epilepsy

What treatment is provided for patients that are unsuitable for surgery and have failed conservative or medical management?

Incontinence is contained instead: Indwelling catheter - urehtral or suprapubic Sheath advice - analogous to an adhesive condom attached to catheter tubing and bag Incontinence pads

How does hypercalcaemia affect skeletal?

Increased bone resorption, fracture risk

Define kaliuresis

Increased potassium excretion

Define natriuresis

Increased sodium ion excretion

How does coffee interfere with diuretic action?

Increases the GFR and decreases the tubular sodium ions reabsorption

In the sympathetic nervous system, what response results in the binding of angiotensin II to AT1 receptors?

Increases the release of noradrenaline

In the hypothalamus, what response results in the binding of angiotensin II to AT1 receptors?

Increases the thirst sensation - stimulated ADH release

Why aren't chloride ions reabsorbed in the S1 section of the proximal convoluted tubule?

Increasing chloride ion concentration in S1 creates a concentration gradient for chloride reabsorption by diffusion in S2 -3

What can NSAIDS exacerbate in patients with heart failure or hypertension?

Increasing sodium chloride and water retention, increasing the blood pressure further

What are the symptoms in children with UTIs?

Infants: - Failure to thrive - Fever - Vomiting - Diarrhoea - Anorexia - Lethargy Older children: - Voiding symptoms - Abdominal pain

Define an uncomplicated UTI

Infection of the urinary tract by a usual a common pathogen in a person with a normal urinary tract and with normal kidney function

What is the most likely consequence of an enlargement of the prostate ? why ?

Inferior relationship of the baldder Urethra passes through the centre of the prostate 2 things happen when you get older 1. Hypertrophy 2. Cancer (prostate cancer) → Quite common

How much to people usually ingest and urinate?

Ingest 600 - 1000 mOsm/day Urinate 1 - 1.5 litres / day

List two factors that can continuously disturb composition of ECF?

Ingestion Loss of salts and water

What are the medium to long term factors that affect the extracellular concentration of potassium ions?

Ingestion of potassium - Many foods are rich in K+ e.g. bananas, beans etc - 90% of ingested potassium is absorbed - This is about 100 mmol per day Loss of potassium from the body - This is to equal the amount ingested - Controlled to maintain balance - Controlled mainly be the kidneys - Some via the gut e.g. large increase can cause vomiting and diarrhoea

How does alcohol interfere with diuretic action?

Inhibits ADH release

What is the role of insulin in the regulation of potassium ion extracellular fluid concentration?

Insulin stimulates the Na+-K+ ATPase to stimulate cellular uptake of K+. This is so ingested potassium ions can move rapidly into cells in order to prevent hyperkalaemia until the kidneys can excrete more.

When treating people with ketoacidosis, why do we have to be careful in giving them insulin?

Insulin would cause potassium ions to move back into cells, depleting the ECF [k+] further. The lower acidic conditions as ketone production would be reduced, would also favour cell uptake of K+. Hence presenting a serious risk of hypokalaemia Hence when providing insulin, potassium may be needed to be given as well

These arteries are given off at right angles from the side of the arcuate arteries and pass directly outward between the medullary rays, where they end in a capillary network A. Interlobar artery B. Afferent arteriole C. Segmental arteries D. Interlobular arteries E. Renal artery

Interlobular arteries

What mesoderm layer is crucial for the formation of the kidneys ?

Intermediate mesoderm

What is plasma osmolarity a guide to?

Intracellular osmolarity

What surgical procedure is performed in women with temporary intention of treating stress urinary incontinence?

Intramural bulking agents

Describe bladder pressure during emptying

Intravesical pressure rises to overcome outflow resistance.

Why does catheterisation increase the risk of UTIs?

Introduces organisms into the bladder. It promotes colonisation by providing a surface for bacterial adhesion and causes mucosal irritation.

What is the disadvanage of polysaccharide inulin?

Inulin does not occur naturally in the body and requires several hours of infusion to reach a steady state concentration.

What is the classical presentation of those with IgA nephropathy?

Invisible / visible blood in their urine

What is stress urinary incontinence (SUI)?

Involuntary leakage or effort on exertion, effort, sneezing or coughing

What is urge urinary incontinence (UUI)?

Involuntary leakage, accompanied by or immediately proceeded by urgency

What usually causes stress urinary incontinence in males?

Iratogenic causes (caused by medical exams or treatment): - Radical prostatectomy - Colorectal surgery - Radical pelvic rafiotherapy

What is a nephron?

Is a filter unit Connected to a long tube for reabsorption 2 parts: Corpuscle and tubule 2 components: Tubular and vascular

What is the main role of the antidiuretic hormone ADH?

Is the formation of concentrated urine by retaining water and to control plasma osmolarity

What is the driving force for peritubular capillary reabsorption from the proximal convoluted tubule?

Is the osmotic gradient established by solute reabsorption and the increase in oncotic force in the peritubular capillary due to the loss of 20% filtrate at the glomerulus, while the cells and proteins are left in the blood

What is metabolic acidosis?

Is tissues produce acid e.g. lactate, it enters the blood and dissociates into an anion and cation. The cation is H+ (because the substances produced are acids), this reacts with the hydrogen carbonate in the plasma to produce carbon dioxide in the venous blood. This is then breathed out through the lungs, leaving a directly proportional deficit of the concentration of hydrogen carbonate in the arterial blood. It is the reduction of the concentration of hydrogen carbonate that causes metabolic acidosis.

What is the main function of the thick ascending limb?

Is to form concentrated urine by a net Na+ pumping into the interstitium, and not allowing water to follow as it is impermeable to water. This creates the hyperosmolar environment in the intersistium. This generates an osmotic force, as it drags the water out from the collecting ducts made permeable by vasopressin

How does calcitonin affect phosphate homeostasis?

Isn't involved

At time zero, what is the osmolarity of the medulla intersitium and the loop of Henle?

Isosmotic - both 300mOsm/l

Why is ROMK needed on the apical membrane of the thick ascending limb?

It allows potassium ions to diffuse back into the lumen through ROMK, where due to 3Na+2K+-ATPase and NaKCl2 it ensures that potassium isn't accumulated within the tubular cell. If concentration of potassium ions was to accumulate in the tubular cell, then NaKCl2 wouldn't be able to function. Hence the concentration gradient maintained ensures the continued activity of NaKCl2 transporter

What are the disadvantages of male artificial urinary sphincter (SUI)?

It can cause infection, erosion and device failure

How is metabolic alkalosis compensated?

It can only be partially compensated by decreasing ventilation, as this can't be decreased too much because an adequate oxygen supply is needed

How does non-visible hamaturia present itself?

It can symtpmatic or asymptomatic

What is the function of the ureter ?

It carries urine from the kidneys to the bladder

What is the function of the neck of the bladder?

It connects the bladder to the urethra

How does the difference in ionic composition of the compartments affect the osmolarity?

It doesn't - this to is ensure that cells do not shrink or swell

Where does the mesonephric duct end up in the embryo ?

It ends up at the caudal position feeding into the future cloaca (waste product for urinary and GI system)

What is the histological appearance of the collecting duct?

It has a similar appearance to the thick limbs in the loop of Henle. But the lumen is larger and tends to be more irregular rather than circular. It consists of cuboidal cells

Why is the early distal convoluted tubule fairly impermeable to water?

It has tight junctions and no aquaporins

Why is the positive potential of the lumen in the loop of Henle important?

It helps to drive the re-absorption of the positively charged calcium ions and magnesium ions back into the loop Henle epithelium

What is the second function of ADH, apart from increasing the permeability of tubules to water?

It increases the permeability to urea, where it recycles urea to help create a concentrated interstitium. When we have an increase of osmolarity in our plasma, we release ADH and recycle urea. 45$ of the urea is reabsobed in the PCT Under the influence of ADH, excretion of urea decreases and urea recycling increases in the medullary collecting duct

How is the GFR relevant clincally??

It is a measure of kidney function. A fall in GFR means kidney disease is progressing whilst a recovery in the GFR indicates kidney function recovery. Knowing the GFR of a patient is clinically very importance and helps determine and course of kidney disease

Describe how mainly sodium is able to be reabsorbed

It is a transcellular process, which is mainly active, and driven by 3Na-2K-ATPase pump on the basolateral membrane

What is the basement membrane made of?

It is an acellular gelatinous layer of collagen / glycoproteins

What is the male sling procedure?

It is an experimental. emerging treatment, using bone-anchored tape. The long term results are unknown

What is the advantage of oxybutanin?

It is cheap

How is the concentration of hydrogen carbonate determined?

It is controlled by the kidney

How is the tubule fluid different from the filtrate that entered?

It is hypo-osmotic - it is more dilute than the plasma, where at the top of the ascending loop the filtrate is very diluted

What happens in the descending thick segment?

It is lined by simple cuboidal epithelium

When is atrial natriuretic peptides released?

It is released from atrial cells in response to stretch where there are pressure volume sensors in the atria

Where is calcitonin released from?

It is secreted from the parafollicular cells of C cells of the thyroid gland

Describe the histological appearance of the collecting duct

It is similar in appearance to the thick limbs of Henle's loop, but the lumen is larger and tends to be more irregular rather than circular

What is the nerve supply of the detrusor muscle?

It is supplied by the autonomic nervous system, and hence is not under voluntary control. It is from the spinal levels of T11 - L2. The spinal nerve supply is bilateral where: - Hypogastric nerve - Parasympathetic, pelvic nerve (S1 - S3)

Describe how the hypogastric nerve (T10 - L2) acts on the internal urethral sphincter?

It is sympathetic and therefore contracts the internal urethra sphincter in order to increase its tone in order to prevent urine from escaping. It uses the neurotransmitter noradrenaline which acts on the alpha-1 receptors to cause contraction

What is the function of the renal corpuscle?

It is the filtering component of the blood

What is the importance of the solute Na+?

It is the major osmotically effective solute in the extra cellular fluid so therefore water in the exctra cellular compartment depends on the Na+ content. Changing the Na+ concentration will affect the Effective Circulating Volume (ECV) and alter blood presssure

How common is membranous glomerulopathy?

It is the most common cause of nephrotic syndrome in adults

What is the prognosis of those with vasculitis?

It is treatable if it is spotted early

How do we treat goodpasture syndrome?

It is treated by immunosuppression and plasmaphoresis if caught early. Plasmaphoresis is a process by which the liquid part of the blood, or plasma, is separated from the blood cells. If there are antibodies that attack the immune system, this machine is used to remove the affected plasma and replace it with good plasma or a plasma substitute.

What is the function of 3Na+-2K+-ATPase in cells?

It maintains the intra-cellular environment by setting up concentration gradients and the membrane potential

What is the function of atrial natriuretic peptide?

It promotes the sodium ion excretion to decrease blood pressure

Why is urothelium used to line the ureters?

It protects against damage of urine, and the folds can contract and expand

Why is carbon dioxide is acidic

It reacts with water to produce hydrogen carbonate and hydrogen ions

How does the primitive kidney go from being in the cervical region to the future pelvic region ?

It starts by differentiating from intermediate mesoderm to form: 1. Pronephros (cervical) 2. Mesonephros (most of the middle) 3. Metanephros (future pelvic region) As each previous layer regresses the next one develops.

Describe the effects of a upper motor neurone lesion on bladder function

It will cause detrusor sphincter dyssynergia. This is the dis coordination of the detrusor muscles of the bladder and the external urethral sphincter muscles. This causes them both to contract, which means that voiding cannot take place where bladder pressure rises. The features are: - Dilated ureters - Thickened detrusor - High pressure detrusor contractions - Poor coordination with sphincters This is because there's lesions above S3 which means there's damage to the: Hypogastric, sympathetic nerve (T10-L2), which usually contracts the internal urethral sphincter and relaxes the detrusor muscles. Hence these do not happen to cause: - High pressure detrusor contracts - Poot coordination with sphincters

In what circumstances are thiazide diuretics used to treat congestive heart failure?

Just as a complimentary drug to the loop diuretics

What is the JGA?

Juxtaglomerula apparatus DCT touches the bowman capsule, found where blood enters renal corpuscle and DCT of same nephron

How are potassium ions moved into cells?

K+ is pumped into the cell, of which it is exchanged for Na+ out of the cell through the 3Na+-2K+-ATPase

How active is the kidney?

Kidney is second most metabolically active organ after the brain therefore second organ to suffer if metabolism poor uses about 25% of food we eat

Where does the lower pole of the kidneys lie in ration to the vertebral column ?

L3

What is meant by a neurogenic bladder?

Lack of bladder control due to brain, spinal cord or nerve problems

What causes vitamin D deficiency?

Lack of exposure to UVB radiation Inadequate dietary intake Malabsorption Renal failure Hepatic rickets

Describe the renal control of hydrogen carbonate

Large quanitites of HCO3- are filtered each day at the glomerulus, about 4500 mmol per day. This is then all reabsorbed to maintain the acid base status

What 3 parts does the urogenital sinus divide into ?

Largest upper part (future bladder) Pelvic & phallic (parts of future urethra)

What is the result if there are bilateral lesions in the lateral Pontine storage Centre?

Lateral side i.e. in charge of storing - An inability to store urine - Reduction in bladder capacity - Excessive detrusor muscle activity - Relaxation of the urethra - Premature voiding - Leaky bladder (incontinence)

Describe what leaky epithelia do ? and give

Leaky epithelia do not have these tight junctions, or have less complex tight junctions. For instance, the tight junction in the kidney proximal tubule, a very leaky epithelium, has only two to three junctional strands, and these strands exhibit infrequent large slit breaks.

Lecture 3.2

Lecture 3.2

What is nutcracker syndrome ?

Left renal vein passes under the SMA. The SMA can sometimes put pressure on the left renal vein and this is called the nutcracker syndrome. When pressure is put on the left renal vein →impaired venous drainage from the left kidney → Eventually renal failure Causes: - Changing dynamics in the abdominal aorta - Atheroma -Tumors

In relationship to the aorta and the IVC, where do the left renal vein and right renal arteries pass?

Left renal vein: Left renal vein passes anterior to the aorta and under Superior Mesenteric Artery (SMA) Right renal artery: Right renal artery passes posterior to the IVC

What does the urine dipstick test look for in regards to a UTI?

Leukocyte esterase - indicates the presence of white blood cells Nitrite - Indicates the presence of nitrate reducing bacteria

What vertebral level do the kidneys lie at

Lie each side of vertebral column between T12 & L3

What are the disadvantages of using non-pharmacological approaches to treating hypertension?

Lifestyle changes can have a limited effect. Failure to implement lifestyle changes could limit the effectiveness of antihypertensive therapy

Who is the urethra longer in ?

Longer in males 18-20 cm

What is meant by a metabolic screen?

Looking at the blood and urine for any abnormalities

Describe the mechanism by which loop and thiazide diuretics exert their main adverse effect

Loop and thiazide diuretics increase the loss of potassium ions in the urine to cause hypokalaemia.

What diuretics act on the loop of Henle?

Loop diuretics

What diuretics are used to treat congestive heart failure?

Loop diuretics - furosemide or bumetanide

What diuretics are used to treat nephrotic syndrome?

Loop diuretics like Furosemide or Bumetanide are used, where thiazide diuretics like Metalazone are used as an adjunct

Describe water reabsorption in the early distal convoluted tubule?

Low as water permeability is low

What is rickets / osteomalacia?

Low vitamin D, low calcium and low phosphate. Increases alkaline phosphatase

What are the three main locations of metastases from renal cell carcinoma?

Lymph nodes Perinephric spread - into the subscapular fat Into the vena cava into the right atrium

What is described in this picture

MRI pancake How does this happen ? Those Metanephric blastema (Intermediate mesoderm with their ureteric buds) have crossed the midline and fused You can see the 2 ureters emerging on the anterior side feeding down into urinary bladder Here no quite over the midline exactly- but still 1 single kidney Can or cannot be sufficient for the functional needs of the person May put pressure on the underlying vessels especially the veins (because they are under low pressure) so you start to see oedema especially of the lower limbs

What does the juxtaglomerular apparatus consist of?

Macula Densa - Dense staining region of the DCT Juxtaglomerular cells - Cells of the afferent arteriole of the glomerulus - Blood vessels bringing blood to Bowman's communicate with dDCT Extraglomerular Mesangial Cells - Aka lacis cells

What are the functions of calcitriol?`

Main action is on the gut to promote absorption of calcium on the diet Acts on bone stimulate re-modelling, which allows the calcium from the diet to be incorporated into the bone as calcium stores In the parathyroid gland calcitriol feedback inhibits PTH secretion

What types of urinary incontinence is autoaugmentation usually used for?

Mainly neurogenic cases of overactive bladder with urge urinary incontinence

How is the concentration gradient maintained?

Maintained because of the different flow direction of the vasa recta (the blood supply to the tubules) that run in the opposite direction to the flow of fluid through the tubules

DCT what happens?

Major site of variable reabsorption of: Electrolytes and Water.

Whats the difference in the urinary bladder between females and males

Male: Ductus deferens crosses over ureter posterior to bladder on the back wall of the urinary bladder there are the accessory reproductive glands (seminal vesicles) one on each side feeding into the urethra along with the prostate Female Uterine artery crosses over the ureter lateral to cervix of uterus.

Describe what encloses around the urethra in males and females

Males: - Prostate - Pelvic floor Females - Pelvic floor only

What does management of urinary incontinence depend on?

Management of urinary incontinence depends on: - What symptoms the patient has - The degree of bother they cause - Previous or current treatments - Effects of treatment on any other symptoms they may have The management should be individualised with a systematic approach

Give an example of an osmotic diuretic

Mannitol

Give an example of osmotic diuretic

Mannitol

What do we need in order for the water balance to function?

Mechanisms to detect plasma osmolarity

Fill in the blank about the male urethra: passes through the deep peritoneal pouch

Membranous urethra

What is the urinary flow rate in both men and women?

Men: 20-23 ml/s (lasting around 24s) Women: 25-30 ml/s (lasting around 22s)

What can be the outcomes of IgA nephrotic syndrome to the structure of the glomerulus?

Mesangial proliferation and scarring may occur

What is the embryonic kidney made up of ?

Mesonephric tubules + mesonephric duct = embryonic kidney (aka mesonephros)

Name two examples of thiazide diuretics

Metalozone Indapamide

Give an example of a thiazide diuretic used in the extracellular fluid expansion and oedema?

Metolazone

What is the most common type of nephrotic syndrome in children?

Minimal change glomerulonephritis

What are the normal urinary tract defence mechanisms to prevent someone from having a UTI?

Most important is the regular flushing during voiding, which removes organisms from the distal urethra. Flow rinses away non-attached or weakly adherent microbes Therefore UTIs are more common in females because the urethra is short. There are also antibacterial secretions into the urine and urethra. There is secretion of glucosamines transitional cells that prevent bacterial adherence by forming a mucin layer Low pH of the bladder and the presence of urea in urine reduce bacterial survival. Tamm-Horsfall glycoprotein binds to UPEC type 1 fimbrae that usually allows the adhesion of bacterial Inflammation of the urinary tract leads to exfoliation. This eradicates both attached and internalised bacteria from the bladder epithelium

What are the two types of Cystic kidney disease ?

Multicystic kidney disease -Atresia of ureter Usually in infants lots of cysts in kidney tissues and usually lack of ureter = no function really (if both affected = severe) Polycystic kidney disease - Recessive Presents early Poor prognosis - Developed in adulthood Gradually get taken over by cysts →Renal failure Dialysis or Kidney transplant would help

Describe the ureters

Muscular tubes→ transport urine from kidneys to bladder - Continuous superiorly with renal pelvis →renal pelvis is formed by a condemnation of several minor calices →Renal pelvis becomes the ureter at the ureteropelvic junction Descends on medial aspect of posts major At pelvic prim → cross common/external iliac arteries into pelvis to bladder

Explain why the administration of NSAIDS in people whose renal perfusion is compromised, can further decrease the GFR to result in acute renal failure

NSAIDS inhibit cyclo-oxygenase (COX) pathway which is involved in the formation of prostaglandins. Although the inhibition of prostaglandin production with NSAIDS does not have a clinically significant effect on renal haemodynamics in normal kidneys, in patients with diseased kidneys vasodilator prostaglandind are essential to maintain normal renal function by opposing the action of vasoconstrictors: - Angiotensin II - Vasopressin - Noradrenaline from sympathetic nervous activation In these patients, NSAIDS may cause a massive decline in GFR, which can be life threatening

What happens in the thick ascending limb and distal convoluted tubule?

Na+ and Cl- are actively pumped out and reabsorbed.

What happens in the ascending thin segment?

Na+ and Cl- leave passive but it is impermeable to water

What are the two types of diuretics that act on the collecting ducts and name one example of each

Na+ channel blockers - Amiloride Aldosterone antagonists - Spironolactone

What is the role of sodium pumps?

Na+ extruded across BSL membrane (setting up conc gradient) so Na+ enters across the luminal membrane - down the concentration gradient Energy used from movement drives reabsorption of other substances against its concentration gradient (secondary AT)

What sodium transporters are present on the apical membrane of the early distal convoluted tubule?

Na+-Cl- symporter

What transporters are present on the BSL membrane?

Na+\K+ ATPase Low PNa+? High ROMK Ca2+ ATPase Cl-/OH- exchanger Hormone receptors

What transporters, responsible for sodium ion reabsorption, are located on the apical membrane of the loop of Henle?

Na-Glucose symporter

What transporters, responsible for sodium ion reabsorption, are located on the apical membrane of the early distal convoluted tubule?

NaCl symporter

What transporter in the apical membrane of the macula densa cells (faces inward to the lumen) detects the concentration of sodium chloride in the tubular glomerulus feedback?

NaK2Cl co-transporter

What sodium transporters are present on the apical membrane on the loop of Henle?

NaK2Cl symporter

What is the effect of charge on the clearance ratio?

Negative charged molecules have a lower clearance ratio than neutral, or positively charged molecules with a set molecular radius.

What is the standard treatment of upper tract transitional cell carcinomas?

Nephro-ureterectomy - removal of the: - Kidney - Fat - Ureter - Cuff of bladder

What are the functional units called in the kidneys ?

Nephrons

What is the Collecting duct?

Network of ducts facilitates the transportation of urine by channeling the waste into the renal pelvis for drainage into the ureters. The muscular ureter tubes lead to the urinary bladder from where urine is eliminated.

Through which mechanism do medium and longer term control of blood pressure act?

Neuro-humeral responses that act by controlling sodium ion balance and therefore the extracellular fluid volume. Plasma is part of the extracellular fluid compartment, so to control the ECF volume you control the plasma plasma volume and consequently the blood volume. Water follows sodium ions, therefore controlling the total sodium ion levels controls the plasma volume. Plasma volume affects stroke volume

Is there any hydrogen carbonate present in the urine?

No - all is reabsorbed

Are waste products reabsorbed?

No - lost in urine

What happens in the female in regards to the urethra

No fusion (in genital folds fuse to form the spongy urethra) occurs in the female & urethra opens into the vestibule.

What controls the amount of H+ excreted?

No hormones are involved, the kidneys are just sensitive to the pH of the intracellular fluid of the tubular cells, due to the changes in rate of hydrogen carbonate export to the extracellular fluid, which is produced by changes in the hydrogen carbonate concentration in the ECF

Can kidneys directly affect ICF?

No, only indirectly Can only directly effect ECF

What represents the midline on a trilaminar embryonic disc ?

Notocord (tiny blue circle)

What are the clinical signs and symptoms of hypocalcaemia?

Nueromuscular: Involuntary muscle contraction (tetany), clawed hands, cranial nerve excitability, numbness and tingling in face, hands and feet (Trousseu's sign) - Full blown convulsion, respiratory arrest and death CNS: Irritability, seizures, personality changes, impaired cognition Cardiovascular: Long QT syndrome - causes problems with the electrical activity of the hear

Where is the position of the kidneys?

Obliquely in the retroperitoneum The hila (where vessels come out of the kidney) is on the transpyloric plane The right kidney is slightly lower than the left

Describe the risk factors associated with urinary incontinence

Obstretrics and Gynaecology - Pregnancy and childbirth - Pelvic surgery - Pelvic prolapse (Pelvic organ prolapse occurs when a pelvic organ-such as your bladder-drops (prolapses) from its normal place in your lower belly and pushes against the walls of your vagina. This can happen when the muscles that hold your pelvic organs in place get weak or stretched from childbirth or surgery) Predisposing - Race - Family predisposition - Anatomical abnormalities - Neurological abnormalities Promoting - Increase in intra-abdominal pressure due to: - Cognitive impairment - Menopause (lack of oestrogen, which supports the pelvic floor) - Drugs - UTI - Age - Obesity - Co-morbidities Risk factors include anything that can weaken the pelvic floor muscles e.g. childbirth. The support of the urethra by the muscles and ligaments of the pelvic floor are important for the efficiency of the sphincter mechanisms of the urethra that enable continence

Why is there an increased risk for UTIs in women as they age?

Oestrogen stimulates vaginal colonisation by lactobacilli. This produces lactic acid from glycogen, which proves a low vaginal pH. This inhibits the growth of most uropathogens. In menopause there is oestrogen deficiency. This causes the disappearance of lactobacilli. This increases the vaginal pH and colonisation of the vagina by faecal E.coli Generally, the elderly on more antibiotics. This alters the normal periurethral flora (lactobacilli, coagulase-negatice streptoccoi etc). This increases the risk of colonisation with urinary pathogens Bladder urothelium is coated with mucopolysaccharide with binds to bacterial type I pili, decreasing the adherence capacity of uropathogens. This coat decreases in elderly women

What is meant by a secondary vesicoureteric refluc?

One that is associated or caused by an obstructed or poorly functioning lower urinary tract e.g. posterior urethral valves or a neurogenic bladder

What is meant by a primary vesicoureteric reflux?

One that is involved in an otherwise normally functioning lower urinary tract

How much of the ultra-filtrate actually leaves the body?

Only 1% as the rest is reabsorbed into the blood while it passes through the renal tubules

What percentage of upper urinary tract cancers are upper tract transitional cell carcinomas?

Only 5%, where the other 95% are renal cell carcinomas

In what circumstances is blood pressure regulated in this way?

Only in acute changes of GFR and salt concentration. Long-standing primary disturbance in body fluid volume are not regulated like this

What is the difference between osmolarity an osmolality?

Osmolarity = Estimation of the osmolar concentration of pasma and is proportional to the number of particles per litre of solution - mmol/L Osmolality = Estimation of the osmolar concentration of plasma and is proportional to the number of particles per kilogram of solvent - mOsm/Kg At 37 degrees Celsius these are virtually identical, so any can be used

What do we have that detects plasma osmolarity?

Osmoreceptors situated in the organum vasculoum of the laminae terminalis in the hypothalamus

Which diuretics act through the modification of filtrate content?

Osmotic diuretics - osmotic diuretics are freely filtered into the glomerulue and not reabsorbed, hence increases the osmolarity of the filtrate. This decrease water and sodium reabsorption throughout the tubule, where the osmotic pressure decreases

Describe the counter current exchange

Osmotic gradient created would not last long if osmoles were washed out of the interstitium because flow in vasa recta is in opposite direction to the fluid flos in the tubule so the osmotic gradient is maintained. The vasa recta acts as a counter current exchanger. Vasa recta's function is to maintain the concentration graident and to not allow it to be destroyed. Osmolarity of blood in the vasa recta increases as it reaches the tip of the hairpin loop

State the functions of osteoblasts and osteoclasts

Osteoblasts - Secretes and facilitates mineralisation of the proteoglycan matrix which hydroxyapatite is bound to Osteoclasts - breaks down the matrix and releases calcium and phosphate

Describe the renal fat and fascia

Outside renal capsule, there is an accumulation of extra-peritoneal fat → perinephric fat (perirenal fat) which completely surrounds the kidney to protect and insulate it ( lots of blood there, don't want to loose heat so insulate it ) - Renal fascia → Membranous layer that surrounds the kidney and its fat

What is recovered from the ultra filtrate?

Over 99% of filtered water 99% of filtered Na and Cl ions 100% of HCO3- 100% of glucose and amino acids Few waste products are not recovered

Give an example of an anticholinergic used to treat urinary incontinence

Oxybutanin

Where are most substances reabsorbed in the kidneys?

PCT

Describe the amount of sodium reabsorption that takes place along the nephron at each tubutle

PCT = 67% Descending thin limb of Henle's loop = 0% Ascending thin and thick limb of Henle's loop = 25% DCT = 5% Collecting duct system 3% 0.5% remains for excretion

Why is PH important?

PH of ECF is crucial Failure to control hydrogen carbonate - serious consequences Kidney is important in regulating the concentration of Bicarbonate and carbonic acid in plasma.

What can be used to indicate the liklihood of bone metastasis?

PSA levels - highly unlikely if it is less than 20ng / ml

What abdominal wall muscles are in contact with the kidneys ?

PSOAS major muscle Quadratus lumborum muscle Transverse abdominis muscle

What hormone in the distal convoluted tubule allows for the reabsorption of calcium ions?

PTH

State the three functions of PTH

PTH stimulates the release of calcium from bone, by stimulating bone resorption PTH decreases urinary loos of calcium by increasing calcium re-absorption in the kidneys PTH indirectly stimulates calcium absorption in the small intestine by stimulating the synthesis of calcitriol in the kidneys

What optional tests can take place to investigate those suspected with urinary incontinence?

Pad tests - Used to measure leakage. A sanitory napkin is weighed and then worn for 20-60 minutes, during which time the individual is aked to perform certain activities. The pad is then weighed at the end Cytoscopy - a procedure to look inside the bladder with a camera

Is the pain sensation in the bladder localised or not?

Pain sensation in the bladder is well localised

What are the different types of transport?

Paracellular - between cell membranes? Transcellular - through cell from apical membrane to basolateral membrane

What are the symptoms of hypocalcaemia?

Paraesthesia Carpopedal spasm - spasms of muscles of the hands and feet, especially of the wrists and ankles Muscle cramps

What innervates the detrusor muscles?

Parasympathetic: - Pelvic nerve (S2, 3, 4) Sympathetic: - Hypogastric nerve (T10 - L2)

Where does the collecting duct pass through?

Passes through the medulla The medulla is a high osmolarity environment created by the LOH

What must happen in order to prevent hypovolaemia?

Patients using diuretics must be monitored for their: - Weight - Signs of dehydration - Blood pressure - look for a postural drop

Fill in the blank about the male urethra: passes through the corpus spongiosum

Penile urethra sometimes called the spongy urethra

Describe the results on potassium ion concentration on someone who has diabetic ketoacidosis

People who are diabetic can't produce insulin. So ketones are made to provide energy, which are acidic. This causes less potassium ions to enter the cells as hydrogen ions enter instead. The extracellular fluid concentration of hydrogen ions rises causing H+ to enter the cells, and K+ to leave. So you would expect hyperkalaemia BUT As diabetics can't produce insulin, this causes glucose to be excreted in the urine. Hence the inability of the PCT to reabsorb the glucose, creates an osmotic gradient in the filtrate for the rest of the nephron. This causes an excess of electrolytes to be lost in the urine, including potassium ions. So the ECF K+ does not rise despite the acidosis as it is excreted Hence this makes the body more likely to be hypokalaemic, instead of hyper

By which process allows the urine to be conveyed to the bladder in the ureter?

Peristalsis of the ureter walls

What is the dome of the bladder covered by?

Peritoneum

What are the anterior relationships of the kidneys ?

Peritoneum overlying the kidneys. Liver; small intestine separated from kidney by peritoneum jejunum and stomach

What is the basement permeable to?

Permeable to small proteins

Describe how metabolic alkalosis can occur after persistent vomiting

Persistent vomiting means that you lose the contents of your stomach. The stomach is acidic, but has to make it from plasma which is 7.4 and hence slightly alkaline. You have to split water in the blood, which forms acid and alkali, where the alkali is put back into the blood. Due to persistent vomiting, to remain the constant acidic conditions of the stomach, more H+ is produced, meaning more alkali is put into the blood, causing metabolic alkalosis

Kidneys control...

Plasma osmolarity (water control) Plasma volume (Salts) Plasma PH (hydrogen carbonate - recovering and H+ - secreting)

What do podocytes surround?

Podocytes surround the glomerular capillaries

What is the pathology behind segmental glomerulosclerosis?

Podocytes undergo damage and subsequent scarring, so protein is present in the urine. A circulating factor is responsible for the damage, evidenced by the fact that transplanted kidneys undergo the same damage

What is the only substance that meets this criteria?

Polysaccharide inulin

What centres above the spinal cord, control the bladder?

Pontine Micturition Centre (PMC)

How does diabetes increase the risk of UTIs?

Poor control of blood glucose, diabetic neuropathy and neurogenic bladder

Describe the disadvantages of using the urine dipstick test as a method of diagnosis

Poor specificity for UTIs - the presence of white blood cells (leuococyte esterase) does not always mean that someone has a UTI. This can also indicate dehydration, advanced age, STIs, appendicities etc Poor sensitivity for UTIs - Bacterai which doesn't convert nitrates to nitrites could be infecting the urinary tract, where the dipstick test would be unable to detect this.

Where does the ureters enter the bladder?

Posterolaterally

Where is the urinary bladder positioned in the body ?

Postitioned anteriorly in pelvis

Describe how alpha-intercalated cells in the DCT reabsorb potassium ions?

Potassium ions are reabsorbed on the apical membrane, against its concentration gradient, using the H+/K+ exchange. To recover potassium ions, you need to expel hydrogen ions. Hence, it is driven by the pH of the extracellular fluid. A low ECF pH, means more hydrogen ions, so more potassium ions are rebasorbed A high ECF pH means less K+ is absorbed, as this means there are fewer hydrogen ions in the ECF.

How do we treat muscle invasive transitional cell carcinoma?

Potentially curative: - Radical cystectomy (removes the urinary bladder) - Or radiotherapy If non-curative - Palliative chemotherapy - Palliative radiotherapy

Fill in the blank about the male urethra: lies between bladder and prostate

Pre-prostatic urethra

What 4 parts is the male urethra divided into ?

Pre-prostatic→ Pelvic part of urogenital sinus Prostatic→ Pelvic part of urogenital sinus Membranous→ Pelvic part of urogenital sinus Spongy → (Phallic part)

What would you do if a pregnant women presented with asymptomatic bacteriuria?

Pregnant ladies are screened for UTIs by sending their urine for culture. If asymptomatic bacteriuria is found, you send a second urine sample for culture. If the second urine confirms asymptomatic bacteriuria, you treat it for seven says with an antibiotic which the organism is sensitive to Send urine for culture at every antenatal visit until delivery

When can we not control urination in the urethra?

Pressure increases when 400 - 500 ml of urine accumulates to give a sharp rise in pressure and the urge to urinate

What is the difference between primary and secondary glomerular disease?

Primary - just affects the glomerulus Secondary - Systemic disease that has in turn damaged the glomerulus

What cells in the distal tubule secrete potassium ions into the filtrate?

Principal cells

Where are sensory nerve impulses sent through?

Principally with parasympathetic nerves, but have some limited routes with sympathetic fibres.

What are the two types of cells in the collecting tubule?

Principle cells - 70% Intercalated cells - 30%

What is micturition ?

Process of passing urine through the bladder

What is the main function of the kidneys ?

Produce urine, which drains to the urinary bladder via the paired ureters

What is the function of the renal corpuscle's vascular pole?

Produces a filtrate of plasma

Which prostaglandins do the kidneys produce?

Produces both prostaglandin E2 (PGE2) and prostacyclin (PG12)

What is the conservative treatment for children with UTIs?

Prophylactic antibiotics

What should you do if a pregnant woman's urine culture shows group B streptococcus?

Prophylactic antibiotics should be offered during labour and delivery

Describe what happens when there is a rapid decrease of sodium chloride in the tubular glomerulus feedback

Prostaglandins are released which causes vasodilation of the afferent arterioles. There is also the release of renin that acts to reabsorb the sodium and chloride ions. This cause an increase in the GFR by increasing the renal blood flow

Describe the epidemiology of prostate cancer

Prostate cancer is the most common cancer in men in the UK. It is also the second most common cause of death from cancer in men. However, most men who are diagnosed with prostate cancer are more likely to die with it than of it

Fill in the blank about the male urethra: passes through the prostate

Prostatic urethra

What happens if the fenestrated capillaries are damaged?

Proteins in urine if barrier damaged no blood cells pass

What organisms are most commonly associated with causing UTIs by growing on catheters?

Proteus and Pseudomonas

Why is it named the juxtaglomerular apparatus?

Proximity to the glomerulus of each nephron

Describe the podocyte layer

Pseudopodia interdigitate forms filtration slits

What is the renal plasma flow?

RPF = 600ml/L

Where do the kidneys receive arterial blood supply ?

Receive arterial supply from a direct branch of the abdominal aorta

How do we diagnose nephritic syndrome haematuria?

Red cells get squeezed through the glomeruli where you see damaged red blood cells. If more than 5% changes, then you diagnose it as this

What is the urogenital ridge ?

Region of intermediate mesoderm giving rise to both the embryonic kidney and gonad (GREEN CIRCLE)

Why is the JGA important?

Regulates renal blood flow and GFR

How fast is the regulation of potassium through the kidneys?

Relatively slow

How is hypo-osmotic urine produced?

Remember this means that the urine is dilute, as there is a lower osmolarity in the urine compared with the plasma. This is the process of water diuresis - No ADH stimulation means no aquaporin in the DCT and collecting ducts - This means there's limited water reuptake in the latter DCT and limited in the collecting duct - Tubular fluid rich in water passes through the hyperosmotic renal pyramid with no change in the water constant - This allows a loss of a large amount of dilute urine

What is minimal change focal segmental glomerulosclerosis? (FSGS)

Remember: Focal = Involving less than 50% of glomeruli on light microscopy Segmental = Involving part of the glomerular tuft Gomerular Sclerosis = scarring Hence it is scarring in part of the glomerular tuft, involving less than 50%, causing protein to be lost in the urine due to podocyte damage

Discuss the Renal blood supply

Renal arteries: Lateral branch off the aorta Arise inferiorly to SMA (superior mesenteric arter) Renal veins: Multiple contributions to R and L renal vein Anterior to arteries → into IVC LEFT renal vein is longer (because of the position of the kidney) and passes UNDER SMA why is this important ? → SMA = second of the ventral arteries that branch off the abdominal aorta and its potentially putting pressure on the left renal vein : Can sometimes end up squeezing the renal vein [ Nutcracker syndrome]

What is the long term regulation of blood pressure?

Renin Angiotensin-Aldosterone System (RAAS) Controls the water volume - If blood pressure increases you need to excrete more water.

How can renovascular disease result in secondary hypertension?

Renovascular disease occurs through the occlusion of the renal artery in renal artery stensosis - this causes a fall in the perfusion pressure in that kidney. A decreased perfusion pressure leads to the increased renin production. Activation of the renin-angiotensin-aldosterone system. Leads to the vasoconstriction and sodium ion retention at the other kidney

What is the response of central chemoreceptors that allow the partial pressure of carbon dioxide to be controlled within tight limits?

Respiratory changes that correct respiratory disturbances of pH

Hence in what circumstances do the kidney and breathing account for compensation of blood pH

Respiratory driven changes in pH are compensated by the kidney Metabolic changes in pH are compensated by breathing

What is overflow incontinence?

Retention of urine causing the bladder to swell. Can be low pressure and pain free.

Describe the ascent of the kidney (metanephros)

Rises from the low pelvic position up the posterior wall of the abdomen to achieve its normal adult position: It does not rise up like an elevator : much more that the rest of the body of the embryo gets bigger and the kidney gets carried with that phase of enlargement and ends up higher up.

Describe the interaction between pH and potassium ion concentration in the extra cellular fluid, when there is a rise

Rises in the extracellular concentration of hydrogen ions leads to the movement of K+ out of the cells. Hence a lower pH means a rising extracellular potassium ion concentration. This is because H+ is harmful in the extracellular environment due to pH changes, so it is safer inside the cell. But the only way to get H+ into the cell is if K+ goes out, causing K+ concentration to go up Rises in the extracellular fluid concentration of potassium ions leads to the export of H+ from cells. Hence a high extracellular fluid concentration potassium ions means a falling extracellular fluid pH

What are the parts of the proximal convoluted tubule and state what type of ion reabsorption happens in each

S1 = Sodium reabsorption only S1 and S2 = Sodium and chloride reabsorption only alongside water

What organs are retroperitoneal?

SAD PUCKER Supra renal glands (adrenal) Aorta Duodenum Pancreas Ureters Colon (ascending and descending) Kidneys Eosophagus Rectum

What would you see in a 3D cross section of the embryo in regards to how the mesonephros and metanephros look like ?

Same pattern: Repeated crescent shaped tube lying at repeated intervals all the way along the ridge.

What is meant by sclerosis?

Scarring

What is the initial management of urge urinary incontinence?

Schedule of voiding - Void every hour during the day - Must not void in between, either wait or leak - Intervals increased by 15-30 minutes a week until an interval of 2-3 hours is reached - At least 6 weeks duration

What is meant by glomerusclerosis?

Segmental or global capillary collapse. It is presumed that there is little or no filtration across the sclerotic area

What would you do if someone who was pregnant was suspected of having a UTI?

Send the urine for culture and sensitivity. Prescribe an antibiotic in all cases e.g. - Nitrofurantoin 50mg four times daile or 100mg twice daily - for seven days - Trimethoprim 200mg twice daily for seven days - Cefalexin 500mg twice daily, or 250mg 6-hourly for 7 days Repeat microscopy culture and sensitivity seven days after antibiotic treatment as a test of cure

What is the duration of voiding?

Short, periodic and brief in duration.

What is the action of the bilateral outputs from the lateral region of the Pontine Continence Centre?

Silencing of electrical activity of the Detrusor muscle Relaxation of the Detrusor muscle - done through the hypogastric nerve (T10-L2) which uses noradrenaline to act on the B3 RECEPTORS Increases the urethral spincteric pressure - hypogastric nerve (T10-L2) which uses noradrenaline to act on alpha1 adrenoceptors to cause contraction Hence it increases the sympathetic drive to the bladder in order to stimulate the hypogastric nerve

What is PTHrP actions on the body?

Similar to PTH - Increase in calcium release from the bone - Decrease in renal calcium excretion - Decrease in calcium re-absorption in the kidneys However, PTHrP does not increase C-1 hydroxylase activity and therefore does not increase calcitriol concentration so there is no: - Promotion of gut absorption of calcium - Stimulation of bone remodelling (i.e. calcium uptake) - Inhibition of PTH secretion in the parathyroid glands Hence PTHrP causes hyperparathyroidism

What epithelium is present in the thin descending limb of the loop of Henle?

Simple squamous epithelium

Describe a horseshoe kidney

Simular to pancake Kidney, same kind of development. Patient may not know. May present with recurrent UTI or haematuria Sometimes may be separated

What happens in the loop of henle?

Site of further reabsorption of salts (about 25%) Descending loop of henle - H20 OUT passivley Ascending LOH - Na+ OUT actively

Describe what kind of things in the urinary bladder vary between people

Size, Shape and wall thickness

Describe the changes in the sodium balance needing to ktale place for there to be a decrease, contraction, of the extra-cellular fluid and what follows

Sodium ion excretion becomes greater than ingestion then a patient is in negative balance. Excess sodium ions are lost from the body, so the sodium ion content of ECF decreases and: - Water remains in the nephron - The ECF volume decreases - Blood volume decreases - Arterial pressure decreases

How does the early distal convoluted tubule differ from the loop of Henle

Sodium ion reabsorption reduces calcium ion reabsorption, while in the loop of Henle it promotes calcium ion reabsorption

What is the major cation in the extra cellular fluid?

Sodium ions

Describe how tubular reabsorption of water functions

Sodium ions are first reabsorbed: Sodium ions are pumped out across the baso lateral membrane by 3Na+-2K+-ATPase. Na+ moves across the apical membrane down the concentration gradient. This movement of sodium ions utilises a membrane transporter or channel on the apical membrane. Water then moves down its osmotic gradient created by sodium ion reabsorption

Describe what happens to the osmolarity in the tubules and the meduallry interstitium with the action of counter current multiplication in the first round

Sodium ions are pumped out of the ascending loop, raising the osmotic pressure outside and lowering it inside The maximum gradient (inside to out) is 200 mOsm/L Water flows out of the descending tubule by osmosis, raising the osmotic pressure in the descending tubule to 400mOsm/L

Describe what happens to the osmolarity in the tubules and the meduallry interstitium with the action of counter current multiplication in the third round

Sodium ions pump produces another 200 mOsm/Litre gradient across the membrane, but it is starting from a more concentrated solution so the external osmolarity rises to 500 mOsm/L

How is H+ excreted in the urine?

Soem H+ is buffered by phosphate. The rest is attached to ammonia as ammonium.

What two mesoderm make up the lateral plate mesoderm ?

Somatic mesoderm Splanchnic mesoderm

What branches of the nervous system are responsible for the release of urine?

Somatic nervous system Parasympathetic nervous system

Describe the innervation of the external urethral sphincter

Somatic: - Pudendal nerve (S2, 3, 4, keeps the 3 Ps off the floor)

How do potassium ions move out of the cell?

Some potassium ions leak out of the cells or moves out of excitable cells during action potentials But the majority: Potassium ions leaves the cells by K+ / H+ exchange (this can happen in any direction). This may not be direct - it is due to a complex set of ion movements to result in this.

How does the couse of IgA vary from person to person?

Some, but not all patients have proteinuria, and a significant proportion of patients, but not all, progress to renal failure. The cause of the variation is unknown

In what way is the anion gap not reliable?

Sometimes renal problems can reduce the hydrogen carbonate concentrate without increasing the anion gap, as the hydrogen carbonate is replaced with Cl-

Does nephritic syndrome cause hypertension?

Sometimes yes, sometimes no

What is used for initial management of stress urinary incontinence?

Specific management: Pelvic floor muscle training to build it up - 8 contractions three times a day - At least three months in duration - You void the bladder and the stop the stream, as this will use the muscles in the pelvic floor

How does the pudendal nerve (S2, 3, 4) act on the external urethral sphincter?

Spinal motor outflow from Onof's nucleus of the ventral horn of the spinal cord, which forms acetylcholine, where the acetylcholine acts on the nicotinic receptor to cause contraction. Hence somatic (voluntary) input can allow an increase in urine retention

Give an example of an aldosterone antagonist?

Spironolactone

What diuretic is used to treat portal hypertension?

Spironolactone

What diuretics are used to treat cirrhosis of the liver

Spironolactone - a potassium ion sparing diuretic

Why does the bladder appear square in imaging, while in pictures it appears round?

Square = bladder has some urine Round = bladder is empty

What is the clinical significance of the renal fat and fascia ?

Staging of cancer and its survival rates are very closely linked to weather the tumor has penetrated through. Stage 1: 5year survival = 96% Tumor less than 7cm and limited to kidney Stage 2: 5 year survival =82% Tumor more than 7cm and limited to kidney Stage 3: 5 year survival = 64% Tumor in major veins, adrenal gland, or perinephric tissue (not beyond Gerotas fascia) and or 1 regional lymph node involved Stage 4: 5 year survival = 23% Tumor beyond Gerotas fascia, more than 1 regional lymph node involved and or 1 or more distant metastasis = Very good survival rate when it has not gone beyond the Gerotas (renal) fascia

What is the function of the cortex of the adrenal glands?

Steroid production

In the kidney, what response results in the binding of angiotensin II to AT1 receptors?

Stimulates sodium ion reabsorption in the kidney

In the adrenal cortex, what response results in the binding of angiotensin II to AT1 receptors?

Stimulates the release of aldosterone

When do stones occur?

Stones are solutes that occur in amounts that are too high to stay dissolved - supersaturation. As a result of supersaturation the solutes precipitate and aggregate to form concretions of stones.

What is the rhyme that reminds of the symptoms of hypercalcaemia?

Stones, moans and groans Stones = excess calcium causes stones Moans = Depression Groans = Abdominal pain due to stones

What are the four types of incontinence?

Stress urinary incontinence (SUI) Urge urinary incontinence (UUI) Mixed urinary incontinence (MUI) Overflow incontinence

What is incidence of the different types of incontinence

Stress urinary incontinence is the most common with 47% of urinary incontinence is this Mixed urinary incontinence 28% Urge urinary incontinence 21% Other 4%

How do we calculate the cardiac output?

Stroke Volume x Heart Rate

What are the effects of the voiding circuits - Medial pons?

Strong contraction of the Detrusor muscle, which increases the intravesical pressure of the bladder. This is done by the parasympathetic pelvic nerve (S2, 3, 4) which uses ACh on the M3 receptors to bring about contraction Relaxation of the internal urethral sphincter, which is done by the hypogastric nerve in the sympathetic branch (T10-L2). This uses noradrenaline which acts on the B3 receptors to relax them Voluntary relaxation of the external urethral sphincter which is done by the Pudendal nerve (S2-S4), which acts through spinal outflow from Onof's Nucleus of the ventral horn of the cord. Uses acetylcholine which acts on the nicotinic receptor for contraction. This causes the expulsion of urine

Why are the kidneys described as being retroperitoneal organs?

Structures that lie behind the peritoneum are termed "retroperitoneal". A useful mnemonic to aid recollection of the abdominal retroperitoneal viscera is SAD PUCKER: S = Suprarenal glands (aka the adrenal glands) A = Aorta/IVC, D = Duodenum (second and third segments), P = Pancreas, U = Ureters, C = Colon (only the ascending and descending branches), K= Kidney E= Oesophagus R= Rectum

What is the transpyloric plane ?

Surface anatomy plane that passes directly through the pylorus of the stomach and the tip of the 9th costal cartilage Duodenum passes through this plane as well as the pancreas ( that lies in the concavity of the duodenum)

How would we treat an established, localised prostate cancer if it is low risk?

Surveillance: If the cancer is low risk, i.e. the Gleason score is low sometimes it is appropriate just to watch the cancer, as treatment may do more damage than good.

What innervates the internal urethral sphincter?

Sympathetic: The hypogastric nerve - T10-L2

What does stage one cancer mean in terms of TNM?

T = 1-2, there is little local advance of the tumour N = 0, there is no regional lymph node advance M = 0 there is no distant metastasis

What does stage two cancer mean in terms of TNM?

T = 3,4, there is a larger local advance of the tumour N = 0, there is no lymph node advance M = 0, there is no distant metastasis

What does stage four cancer mean in terms of TNM?

T = Any N = Any M = 1, there is distant metastasis Automatically stage four if there's distant metastases

What does stage three cancer mean in terms on TNM?

T = Can be any score N = There is 1 or more than one, lymph node advance M = 0, there is no distant metastasis A tumour becomes stage 3 automatically if there is regional spread into the lymph nodes, no matter what the local advance is

At approximately what vertebral level would you find the upper pole of the left kidney?

T11

Where in the vertebral column does the upper pole of the left kidney lie in relation to ?

T11

Where do the kidneys start?

T11/T12

At approximately what vertebral level would you find the upper pole of the right kidney?

T12

Where in the vertebral column does the lower pole of the right kidney lie in relation to ?

T12

What is the initial, definitive treatment of bladder cancer?

TURBT - Transurethral resection of bladder tumour This is often used to determine if someone has bladder cancer, and if so, whether the cancer has invaded the muscle layer of the bladder wall.Single intravesicle instillation of mitomycin C can be installed, which is a single dose of chemotherapy to reduce the risk of reoccurence

What is the DMSA scan?

Technetium radiopharmaceutical used in renal imaging to evaluate the renal structure. It is used for paediatric imaging for detection of renal scarring and pyelonephritis

When we describe there to be exudate present in histopathology, what does this mean?

That we can see an infiltration of leucocytes

What is the control of voiding above the PONS?

The "Voiding Circuits" - independent neural apparatus of the "Continence Centres". "Micturition Centres" of the brain control the "Micturition Centres" of the spinal cord.

What doesn't change in the different segments of the tubule?

The 2Na+-2K+-ATPase pump which is always on the basolateral membrane

What does the kidney have direct effect on?

The ECF → where it either reabsorbs or secretes ions and small molecules

What is the reponse of the tubulo-glomerular feedback if the Na+ and Cl- decreases

The GFR needs to increase. Prostaglandins are released to cause vasodilatation of the afferent arterioles

What would be the case of a renal disease?

The GFR would be substansially reduced, which is detected by a diminished creatinine clearance, or by elevated pcreatinine

What makes this negative feedback system accurate to the ECF calcium ion concentration?

The GPCR receptor on the parathyroid glands that detect calcium levels are very sensitive

What in the male forms the spongy urethra ?

The GT (genital tubercle) elongates and genital folds fuse to form the spongy urethra

Which part of the nephron is considered the diluting segment?

The Loop of Henle

What does thiazide diuretic target?

The NCC transporter on the apical membrane of the distal convoluted tubule. It will prevent sodium ions to get reabsorbed into the tubular cell, meaning less water follows. This decreases the volume of blood, lowering the blood pressure

What happens when we block the NaK2Cl transporter with a loop diuretic?

The NaKCl2 is placed on the ascending loop of the Henle, and hence prevents the pumping of solutes into the medullary interstitium, which makes it isosmotic and copious dilute urine is produced. The action is to reduce volume and therefore reduce blood pressure

Whats the basic structural and functional unit of the kidney?

The Nephron

What happens to the renin-angiotensin-aldosterone system when the blood pressure increases?

The RAAS system is inhibited. The heart atrial cells secrete atrial natriuretic hormone (ANH) which prevents the renin secretion. Hence this prvents the production of angiotensin II and the stimulation of aldosterone. This allows sodium to be excrete in the urine, where water follows, decreasing the extra cellular volume and therefore decreasing blood pressure

Describe the TNM staging system

The T status = This is the extent of the tumour at the primary site (how far the tumour has locally advanced) T1-T4 The N status = Describes the extent of regional lymph node metastasis N0-N2 The M status = Denotes the extent of distant metastatic spread M0-M1

What is the renal artery a branch of?

The abdominal aorta

What is meant by vesicoureteric reflux?

The abnormal flow of urine from your bladder back up the ureters. This occurs in children

What else is reabsorbed in the distal convoluted tube?

The acid and base H+ and NH4+

Describe how the body deals with lactic acidosis after exercise

The acidic conditions causes hydrogen ions to move into the cells to help buffer acidity. Potassium ions then moves out of the cells in exchange of hydrogen ions, which would cause the ECF [K+] to rise BUT Respiration increases to lower the partial pressure of carbon dioxide, which reduces the ECF [H+], in order to allow the pH to return to normal. The kidney then exports the hydrogen ions from the lactic acidosis to reduce the effect on pH further. This then causes the ECF [K+] concentration to rise Overall the [H+] falls, which causes K+ to enter the cells Hence there is no dangeroud hyperkalaemia

What does the thick ascending limb reabsorb?

The active transport of Na+, K+, Cl- through the pump NKCC2

Where is aldosterone secreted from?

The adrenal cortex

What cells of tubular cells of the distal convoluted tubule does the secretion of H+ ions take place?

The alpha-intercalated cell

How do we increase the volume without changing the osmolarity?

The amount of Na+ we excrete must be changed or we add an iso-osmotic solution to increase the volume without changing the osmolarity - we need to change the Na+ balance

How is the anion gap calculated?

The anion gap is calculated as the difference between: ( [Na+] + [K+] ) minus ( [Cl-] + [HCO3-]) Hence it is the cations minus the anions Normally the range should be 10-15 mmol.l-1 But there will be increased anions from metabolic acid if it has been replaced by plasma HCO3-

What happens when ADH is removed?

The aquaporin 2 channel is retrieved from the apical membrane by endocytosis.

Why is the ascending limb known as the diluting segment?

The ascending limb reabsorbs sodium and chloride ions but not water, allowing the filtrate to be less concentrated (diluted). This allows a gradient for water reabsorption and hence is called the diluting segment

What divisions of the spinal cord innervate the bladder for the two phases of functional activity of the lower urinary tract?

The autonomic (involuntary) and somatic (voluntary) nervous systems

What happens after the fenestrated capillaries act as a barrier to macromolecules?

The basal lamina filters the blood leaving the capillaries. Larger molecules and negatively charged molecules impeded (repeal amnio acids and proteins)

Where does the base of the urinary bladder lie in males?

The base of the urinary bladder lies between the rectum and pubic symphysis

What is the basement membrane impermeable to?

The basement membrane repels negatively charged proteins such as glycoproteins

Why is the basolateral membrane always permeable to water, independent of the apical membrane?

The basolateral membrane always contains aquaporin 3 and 4, so it is always permeable to water. Hence any water which enters across the apical membrane is therefore able to pass into the peritubular blood

Describe bladder pressure in the filling phase

The bladder is relaxed with low intravesical pressure

If the bladder wants to urinare, but the external sphincter does not relax due to the conscious, executive decision of the cerebral cortex, what happens?

The bladder progressively relaxes. An additional increase in bladder volume re-initiates the cycle

Describe how the counter current of the vasa recta to the flow of fluid through the nephrons allow the maintenance of the concentration gradient in the kidneys

The blood flow is parallel to the loop of henle, but in the opposite direction. In the thick ascending limb of the loop of Henle, the blood supply has a low amount of solutes, by which the ascending pumps solutes into, and hence dilutes the filtrate with the removal of solutes without water, to increase the osmolarity of the interstitium This allows the reabsorption of water in the descending tubule due to the difference in osmolarity

How is the concentration gradient created?

The concentration gradient is produced by the loop of Henle acting as a counter current multiplier

Describe glomerular tubular feedback as a mechanism to control the blood volume within normal changes

The concentration of sodium in the nephron is sensed by the NaK2Cl co-transporter in the apical membrane of the macula densa cells. This then affects the regulation of arteriolar tone and filtration rate - If there's a high sodium ions (high BP and volume), this causes vasoconstriction through the secretion of adenosine, decreasing GFR, decreasing sodium reabsoprtion, decreasing the water that follows, reducing volume and pressure - If there's low sodium ions (low BP and volume), this causes vasodilation through the secretion of prostaglandins, increasing GFR, increasing sodium reabsorption, increasing the water that follows, increasing volume and pressure

Describe the reabsorption of sodium ions

The concentration of sodium ions in the glomerular filtrate solution is high, where sodium ions move from the glomerular filtrate, in the tubule, into the cells of the PCT. This is done with symporters on the apical membrane. It facilitates the passage through the PCT apical membrane of both sodium ions and other substances / solutes.

What is osmolarity (mOsm/L)?

The concentration of solute per KG of solvent

What section is this image taken?

The coronal plane

Which region forms the outermost layer of the kidney parenchyma A. Medulla B. Facia C. Perinephric fat D. Capsule E. Cortex

The cortex forms the outermost layer of the kidney parenchyma E

Why do we use creatinine to estimate the GFR?

The creatinine is formed from muscle and is released at a constant rate. Blood creatinine concentration changes are little in 24 hours

Describe the epithelium present in each of the sections in the loop of Henle

The descending thick segment is lined by simple cuboidal epithelium The descending thin segment is lined by simple squamous epithelium The ascending thin segment is also lined by simple squamous epithelium The ascending thick segment is lined with simple cuboidal epithelium

What muscle fibres form the detrusor muscle?

The detrusor muscle is formed by a plexiform meshwork of smooth muscle fibres

How are the detrusor muscle fibres arranged?

The detrusor muscles are arranged in three layers 1) Inner longitudinal 2) Middle circular 3) Outer longitudinal

Describe how the hydrostatic pressure is increased in the blood inside the glomerulus

The diameter of the afferent arterioles is slightly greater than the diameter of the efferent arteriole - due to this difference of the incoming and outgoing arterioles it inreases the hydrostatic pressure of the blood inside the glomerulus.

What is the collecting duct a continuation of?

The distal convoluted tubule

Which part of the nephron has control dependent reabsorption of sodium ions?

The distal convoluted tubule and the collecting tubule

Which of the following organs is not entirely retroperitoneal? A. Aorta B. Duodenum C. Rectum D. Suprarenal glands E. Ureters

The duodenum is not entirely retroperitoneal because the first part of the duodenum lies within the peritoneum but the rest is retroperitoneal B

What are the two mechanisms by which pathologies of the glomerulus arises?

The filter can block e.g. renal failure: - Hypertensive - Haematuria The filter can leak: - Proteinuria - Haematuria - Separately or together, depending on damage

What happens when the sodium and chloride ions move out passively of the thin ascending limb?

The filtrate gets more diluted, and there to be a high concentration of Na+ and Cl- in the tissue of the medulla

Where is renin released from?

The granular cells of the juxtaglomerular apparatus (JGA), which are found in the cells of the afferent arteriole

Describe the correlation between the solute concentration of urine and the volume of urine produced

The greater the osmolarity the greater the concentration of urine, the less the more dilute urine is - this is a balancing act between the two

Why does PTH have a short term effect on the controlling calcium ion concentration?

The half life of PTH is only four minutes

What lies on both sides of the transpyloric plane in regards to the kidneys ?

The hila of the kidneys lies at the transpyloric level Hila (Where the ureters enter/ leave)

How does the the hypogastric nerve, T10 - L2, act on the detrusor muscle?

The hypogastric nerve is part of the sympathetic nervous system, and hence promotes urine storage. They use the neurotransmitter noradrenaline to act on the alpha-1 receptors to stimulate detrusor muscle relaxation

Hence, what is the sympathetic supply of the bladder?

The hypogastric nerve, from nerve roots L1, L2 and L3 This relaxes the detrusor muscles and contracts the internal urethral sphincter

When does incidence of minimal change glomerulnephritis change?

The incidence reduces with increasing age

Describe the response of the myogenic mechanism if there is an increase in systematic blood pressure in order to regulate the GFR

The increase in blood pressure would increase the renal blood flow. This stretches the afferent arterioles, which causes their smooth muscles to contract and vasoconstrict the afferent arterioles. This decreases the renal blood flow and therefore decreases the GFR back to its normal level

Describe the hormonal response when there is an increase in blood volume and pressure

The increase in blood volume stretches the afferent arterioles which stimulates the release of atrial natriuretic peptide from the heart. This causes the relaxation of the mesangial cells that increases the filtration surface. This increases the GFR, decreases the blood pressure and blood volume

Where does the urethra leave the bladder?

The inferior corner - the neck of the bladder

What is meant by the water balancing act?

The ingestion of solutes must equal excretion. Where if we ingest 1000 mOsm / day then solute output must be 1000mOsm / day. The amount we intake water must also be excreted along with the urine, to produce either concentrated or dilute urine

Even with the conscious executive decision of the cerebral cortex, what happens if the bladder reaches above 500ml?

The internal sphincter may be forced open, leading to a reflexive relaxation of the external sphincter

Pick one of the following: The kidney capsule is A. a covering of the kidney which attaches to the peritoneum B. an important cushion that helps to prevent kidney damage C. a site where filtration occurs D. a dense fibrous covering which surrounds each kidney E. The innermost layer of the kidney

The kidney capsule is a dense fibrous covering which surrounds each kidney

Where do the kidneys lie in regards to the peritoneum

The kidneys are paired retro-peritoneal organs

Why are the kidneys described as being retroperitoneal ?

The kidneys are situated behind the peritoneum which is the serous membrane lining the cavity of the abdominal organs

In a healthy individual, describe the amount of Na+ excreted

The kidneys balance the amount of Na+ that is excreted with the amount ingested

When does renal compensation take place?

The kidneys compensate respiratory disturbances of pH by the variable excretion and creation of hydrogen carbonate ions

When does renal correction take place?

The kidneys correct metabolic disturbances of the pH, as they affect the variable that has caused the change in pH in the first place. This is done by the variable excretion and creation of hydrogen carbonate ions

Where do the kidneys lie ?

The kidneys lie on the posterior abdominal wall Retroperitoneal

For hyper-osmotic urine to be produced, what needs to happen?

The kidneys must reabsorb as much water as possible from the kidney tubule, and for this to happen the kidneys need a hypertonic interstitium, in order for water to move from high water potential to a lower water potential in the nephron We have to preserve an isosmotic at the cortico-medullary border (300mOsm / kg) and a hyperosmotic medullary interstitium of up to 1200mOsm / Kg`

Describe the storage of urine in the bladder

The lateral region of the pontine continence centre communicates with the spinal continence centre, which then communicates with the sympathetic neurones. This increases the sympathetic stimulation to the bladder via the hypogastric nerve which causes the detrusor to relax and the internal urethral sphincter to contract. The cerebral cortex then makes a conscious, executive decision not to urinate, increasing somatic stimulation to the external urethral sphincter to contract. This causes it to constrict the urethra The relaxation of the detrusor, couples with the contraction of the internal and external urethral sphincters reduces intravesicular pressure and constricts the urethra, preventing micturition

What pathology can we see in the following image?

The lateral wall is thicker, and shows the presence of a carcinoma

What group of bacteria are UTIs a common source of?

The life threatening Gram negative bacteraemia

What is lateral plate mesoderm going to form ?

The linings and coverings of cavities

What does the Loop of Henle reabsorb?

The loop of Henle is said to have a "split personality" where there is a division of the water and sodium ion reabsorption. The descending: - High permeability to water - Not permeable to solutes The thick ascending: - High permeability to solutes - Not permeable to water

What happens when there is a decrease in filling in the pulmonary vasculature and cardiac atria?

The lower pressure is sensed by the baroreceptors increases sympathetic nerve activity and causes ADH secretion, and thus increases water uptake

Describe the tubular glomerulus feedback system

The macula densa of the distal convoluted tubule in the juxtaglomerular apparatus is sensitive to the concentration of sodium chloride present in the filtrate. This then sends signals to the afferent arterioles. If there is a high concentration of sodium chloride sensed by the JGA the arteriole constricts to reduce the GFR. This is because an increase in sodium chloride concentration due to an increased glomerular filtration rate, hence this needs to be decreased again.

What is the role of the macula densa?

The macula densa of the distal tube is sensitive to the ionic content and water volume of fluid in the distal convoluted tubule - it's role is to detect sodium, potassium, chloride ion concentration It then activates the extraglomerular cells The extraglomerular cells then relays the information to the juxtaglomerular cells The juxtaglomerular cells of the afferent glomerular arteriole have smooth muscle cells. These may contract the afferent arteriole to increase blood flow due to the increased pressure, or decrease blood flow through relaxation The juxtaglomerular cells also produces renin when the macula densa detects a fall of sodium, potassium, or chloride ions in the distal convoluted tubule.

What happens if there's a bilateral lesion of the dorsomedial Pontine tegmentum?

The medial side is in charge of voiding. Bilateral lesions of this region result in severe urinary retention

How do the kidneys produce hydrogen carbonate?

The metabolic activity produces large amounts of carbon dioxide. The carbon dioxide then reacts with water to make: - HCO3- - H+ to enter the urine by binding to ammonia to form ammonium The kidneys can also make HCO3- from amino acids, producing NH4- to enter the urine

When does a horsehsoe kidney arise?

The metanephric elements may fuse in the midline resulting in a horseshoe kidney

How does the kidney get from the low pelvic position to the normal adult position ?

The metanephric kidney first appears in the pelvic region. Undergoes an apparent caudal to cranial shift crossing the arterial fork formed by vessels returning blood from the foetus to the placenta

What are the short term factors that affect the extracellular fluid potassium ion concentration?

The movement of K+ into and out of the cells There is a balance between processes that take potassium ions into the cells and those allow it to leave.

Why does the mucosa of the urinary bladder have folds on the inside ?

The mucosa is thrown into folds by the detrusor muscle in the wall of the urinary bladder being contracted

What is the epithelium that lines the ureters?

The mucosa. This is urothelium which is stratified transitional epithelium.

What is on the outside of the uereters?

The muscular coat, which is smooth muscle outside the mucosa

Describe the myogenic response to control blood volume

The myogenic response allows the maintenance of the GFR despite the normal variations of blood pressure e.g. when sitting and standing An increase in blood pressure (therefore increase in volume) causes afferent arteriole constriction to reduce the GFR, reduce sodium reabsorption, reduce the water the follows, reducing volume When blood pressure decreases, due to a drop in volume, the afferent arterioles dilate to increase the GFR, increase sodium reabsorption, increase the water that follows, increasing the volume

How are urine cultures used?

The number of bacterial colonies cultured from urine specimens are estimated to give a bacterial count

Hence what happens to the osmolarity of the filtrate when leaving the proximal convoluted tubule?

The osmolarity is higher

Describe the osmolarity of the ECF to ICF?

The osmolarity of ICF and ECF are roughly equal

What is the osmolarity of the ultra-filtrate?

The osmolarity of the ultra-filtrate is the same as the plasma = 300mOsm/L

Describe the changes in osmolarity if water is added

The osmolarity will decrease - causing cell swelling

Describe the changes in osmolarity if water is removed

The osmolarity will increase - causing cell shrinkage

The hydrostatic pressure favours filtration. Which forces opposes filtration?

The osmotic pressure in the glomerulus, due to the decreased water potential in the blood as proteins remain in the blood but with less plasma and ions The hydrostatic pressure of the Bowman's capsule, which pushes fluid back into the capillaries (osmotic pressure is low in the Bowman's capsule so this is not referred to)

State the interaction between the parathyroid hormone and calcitriol

The parathyroid hormone stimulates the kidneys to convert more vitamin D to calcitriol to allow the calcitriol levels to rise This increases the action of calcitriol in the gut where more is calcium is absorbed from the diet. This in turn replaces the calcium released from bone

What is the pathogensis of minimal change glomerulonephritis?

The pathogenesis is unknown

How does the pelvic nerve, S2, 3, 4, function on the detrusor muscle??

The pelvic nerve is part of the parasympathetic nervous system, and hence stimulates mituriation. They use the neurotransmitter acetylcholine which acts on the M3 receptors to cause contraction of the detrusor muscle

Hence, what is the parasympathetic supply to the bladder?

The pelvic nerve, from nerve roots S2, S3 and S4 This contracts the detrusor muscle

Pick one of the following: Anatomically how do you describe the Pelviureteric junction A. is the junction between the ureter and the urethral orifice B. is found at the level of the bifurcation of the iliac arteries C. is the junction between the ureter and the renal pelvis D. is found at the level of the pelvic brim

The pelviureteric junction is the junction between the ureter and the renal pelvis

Pick one of the following: What and where exactly is the Perinephric fat found A. is the adipose tissue found in the renal hilum B. is the adipose tissue that surrounds the kidney and is found between the renal fascia and renal capsule C. Is a layer of connective tissue encapsulating the kidneys and the suprarenal glands D. is the adipose tissue found superficial to the renal fascia that accumulates posteriorly and posteriolatterly to each kidney E. Is the adipose tissue that accumulates posteriorly to each kidney

The perinephric fat is the adipose tissue that surrounds the kidneys and is found between the renal fascia and renal capsule

What vessels follow the efferent arterioles?

The peritubular capillaries that go around the tubules of the nephron to secrete and reabsorb substances from the ultra filtrate

State the sections of a podocyte

The podocyte has a main primary process, with secondary processes called pedicles that interdigitate. These form filtration slits

How is a positive potential created in the lumen of the loop of Henle?

The potassium ions carried across the apical membrane in the NAK2Cl transporter drifts back into the lumen via potassium ion channels

What is meant by proteinuria?

The presence of excess serum proteins in the urine. It is less sever nephrotic syndrome where is counts as less than 3.5g filtered in the urine per day, while nephrotic syndrome occurs when there is more than 3.5g of urine per day

Describe the prevalence with age of urinary incontinence

The prevalence of urinary incontinence steadily increases with age

Hence, what is the somatic nerve supply to the bladder?

The pudendal nerve, S2, S3, S4 Contracts the external urethral sphincter

What is autoregulation?

The purpose of autoregulation of renal blood flow is to maintain the GFR. This is where the kidney responds to changes in plasma volume (pressure) to continuously regulate the renal blood flow and ensure that the GFR is maintained

What reflex accompanies the filling of the bladder?

The relaxation of detrusor muscle

Which vessels supply the kidneys?

The renal arteries

What is the input to the kidneys?

The renal artery which supplies the renal blood flow

What is meant by the renal blood flow, and state the typical value

The renal blood flow is where all blood flows through the glomeruli in the cortex. It is about 1.1 litres per minute

What structure begins the nephron?

The renal corpuscle

What happens if the transport maximum of a substance is reached and exceeded?

The rest of the substance will be excreted in the urine

Describe the difference between the two kidneys

The right renal artery is normal. The left renal artery occluded, and hence you see a small, shrivelled kidney

What is the prognosis for those with membranous glomerulus

The rule of thirds: • 1/3rd get better • 1/3rd 'grumble along'. They have proteinuria but are fine • 1/3rd may progress to renal disease

What is the urogenital sinus

The separation of the cloaca is created from hindgut by urorectal septum → a band of connective tissue growing downwards separating the urinary bladder and hindgut → eventually ends up at the level of the skin [The perineum] End up with two separate exit points. One for urine and one for feaces Continous with umbilicus -Urachus Median umbilical ligament

What happens to the osmolarity and plasma ADH when there is a decrease in the extracellular volume?

The set point is shifted higher, where there is higher osmolarity values and the slope decreases. This means there is less ADH in the plasma per osmolarity in order to decrease the volume. We tolerate a much more concentrated plasma in order to decrease the volume

What happens to the osmolarity and plasma ADH when there is a decrease in extracellular volume?

The set point is shifted to a lower osmolarity values and the slope of the relationship is steeper (for a set plasma osmolarity the plasma ADH is greater). Hence the loss of volume means that more plasma ADH is released, in order to bring more water to the body in order to correct the loss. We tolerate a much more diluted plasma in order to increase volume When faced with circulatory collpase the kidneys continue to conserve H2O even though this will reduce osmolarity of the body

Why is knowing the site of damage important?

The site of the glomerular injury determines a patient's clinical presentation

Describe the arrangement of smooth muscle in the bladder

The smooth muscle of the bladder is called detrusor, where they are arranged in 3 layers, allowing it to contract spherically

Describe the changes in the sodium balance needing to take place for there to be an increase in volume of the extra-cellular fluid and what follows

The sodium ion excretion is less than the intake to produce a positive ion balance. The increase of sodium ions retained in the extracellular fluid causes: - Increase in ECF volume as water follows from the nephron - Increase in blood volume - Arterial pressure increase - Oedema may follow

How is H+ secreted in the distal convoluted tubule?

The sodium ion gradient created by the 3Na+-2K+-ATPase is insufficient to drive H+ excretion, so we need H+ to be secreted into the lumen actively. This is because most of the sodium ions have already been removed. H+ is exported into the lumen using the direct energy of ATP H+ then binds to phosphate which acts as a buffer. This is then excreted in the urine, and so allows H+ to be excreted without damaging the urinary tract as it is acidic

What is different?

The sodium transporters present on the apical membrane depending on the where it is in the nephron

Identify the bladder is this transverse section

The square object in centre

What branch of the nervous system is responsible for the storage of urine?

The sympathetic nervous system

What is the thin ascending limb permeable to?

The thin ascending limb is not permeable to water but permeable to ions

Describe what happens to the osmolarity in the tubules and the meduallary interstitium with the action of counter current multiplication in the fourth round

The third round of sodium ion pumping raises the interstitial concentration to 700 mOsm/L and so on. The pumping, osmotic flow and filtration are shown as separate activities, but in reality they occur together as a continuous process. The final gradient will be limited by diffusional processes

Describe the normal voiding reflex

The threshold for feelings suggestive of a full bladder is 400ml. When the bladder is full, an urge to urinate arises. There are three places which act on this reflex - Brain micturition centres - Spinal micturition centres - Parasympathetic neurones The increase in parasympathetic stimulation to the bladder via the pelvic nerve, causes the detrusor muscles to contract and increase intravsicular pressure The cerebral cortex then makes a conscious, executive decisions to urinate, reducing somatic stimulation to the external urethral sphincter The contraction of the detrusor coupled with the relaxation of the external urethral sphincter results in the bladder emptying through the urethra

What is the area of smoothness on the inside of the urinary bladder called ?

The trigone

What mechanism in autoregulation runs by sensing the sodium chloride concentration?

The tubular glomerulus feedback

Is there any relationship between alport syndrome and thin GMN nephropathy?

The two are not completely distinct however, with a grey area between them

What other problems is alport syndrome associated with?

The type IV collagen abnormality also affects the chochlea of the ear, and hence it is associated with deafness

What is the median unbilical ligament a a derivative of?

The urachus, which extends to the umbilicus

What is the function of the ureters?

The ureter is a muscular tube that delivers urine from the collecting tubules to the urinary bladder

What induces the development of the metanephric blastema ?

The ureteric bud induces the development of the metanephric blastema

Describe the 4 components of the urinary system

The urinary system is composed of the: 1. Kidneys 2. Ureters 3. Bladder 4. Urethra

Describe the advantages and disadvantages of each method

The urine dipstick test only can measure the albumin content, doesn't take into account other proteins that may be lost Instead, a longer method can be used in the urine protein to creatinine ratio, as usually the same amount of creatinine is excreted each day But the most accurate is the 24 hour urine collection, but it is the most cumbersome

What makes up the visceral layer of the bowman's capsule?

The visceral layer envelopes capillaries and they are made up of highly specialised cells called podocytes

Which is more critical, the volume of the osmolarity?

The volume, where the extra-cellular fluid can change osmolarity within limits to keep the volume constant due to changes in pressure. While we cannot support variation of volume, but we can support variation in osmolarity

Describe why the bladder has a high compliance (can store a lot of urine)

The walls of the bladder have many folds, which distend when filled with urine. Because of this the volume in the bladder and increase from 10ml to 400ml while the intravesicular pressure hardly changes

What are the triggers of IgA nephropathy?

There is a relationship between this and mucusal infections, as IgA protects the mucosal surface - 50% of patients with IgA nephropahy have been triggered by an upper respiratory tract infection - Serum IgA levels increased in 1/3rd of patients

How does urination happen?

There is a sharp rise in pressure that gives the urge for us to urinate. This then contracts the bladder to squeeze the urine out

What happens in the descending thick segment?

There is active Na+ reabsorption

In the tubules of a nephron, what is always the same?

There is always the 3Na+-2K+-ATPase present on the basolateral membrane

What are the advantages of using urine culture alongside a urine dipstick test?

There is increased sensitivity - actually identifies UTIs from other causes. And it can differentiate between properly collected and contaminated samples as poorly collected samples may contain epithelial cells that can show up in microscopy

Does the ascending thick segment have a brush border?

There is no active transport or brush border

How can we treat IgA nephropathy?

There is no effective treatment

What microbiological investigation are needed to diagnose an uncomplicated UTI?

There is no need to culture urine. Infection is indicated by nitrite / leukocyte esterase dipstick testing

What is the likelihood of those with minimal change glomerulonephritis progressing to renal failure?

There is usually no progression to renal failure and is normally purely protein loss from the kidney

Describe how anticholinergics treat urinary incontinence

These act on muscarinic receptors, including the M3 receptors that cause the Detrusor to contract. Remember it is the pelvic nerve that releases acetycholine, which acts on the M3 receptor to cause Detrusor muscle contraction

What are podocytes?

These are cells found in the Bowman's capsule that wrap around the kidneys of the glomerulus. They have foot projections that wrap around the capillaries and leave slits between them. Blood is filtered through these slits, each known as a filtration slit

What are osmotic diuretics?

These are small, inert molecules that increase the plasma osmolarity, thus drawing out fluid from tissues and cells. They act by altering the osmotic force for renal water reabsorption, so less water goes back into the blood. They are not inhibitors of enzymes or transport proteins. It causes the loss of water, Na+ and K+ in the urine

What is the macula densa

These are the cells of the distal convoluted tubule that joins to the glomerulus

What is the function of loop diuretics?

These block the NaK2Cl transporter. Reduced sodium ion transport, leads to reduced water reabsorption, which leads to a lower extracellular volume

What is the function of umbrella cells of the bladder?

These line the uroethlium on the surface layer making it impermeable

What happens when nephrin and CD2AP are deficient?

These proteins are needed for the foot projections to wrap around the capillaries and function. This means the sits cannot be formed, so the kidneys cannot function

What is the function of the fenestrated capillaries?

They act as a barrier to larger molecules.

How do prostaglandins decrease blood pressure?

They act as vasodilators, which enhance GFR and reduce sodium ion reabsorption. They act as a buffer to excessive vasoconstriction produced by the sympathetic nervous system and the RAA system. Hence they are important when the angiotensin II levels are high

How do thiazide diuretics work?

They act on the early distal tubule to block the NaCl cotransporter

How do K+ sparing diuretics work?

They act on the late distal convoluted tubule and collecting duct by blocking epithelial sodium ion channels

How do loop diuretics work?

They act on the loop of Henle to block NaKCl2 co-transporter

Why do all these increase the risk for UTIs in children?

They all cause urine to remain in the urinary system after micturition

What are low-tension vaginal tapes?

They are a polypropylene mesh that supports the mid-urethra

What is the function of squamous epithelial cells?

They are good for filtration and diffusion, where the thin diffusion pathway allows for an easy transmembrane movement

What is the potency of K+ sparing diuretics and aldosterone antagonists that act on the late distal convoluted tubule and the collecting ducts?

They are mild diuretics affecting only 2% of sodium ion reabsorption

Whats special about the epithelial cells?

They are polarised Different membrane properties on the Apical (luminal) and Basolateral membrane (BLM) This allows transport across the epithelium

Describe the action of thiazide diuretics in the early convoluted tubule

They block the NaCl transporter on the apical membrane of the early convoluted tubule. This increase sodium ion and water loss in the urine, and reduces the calcium ion loss in the urine.

How can hormones change transport in the tubules

They can Insert ion channels - changing transport

What is the action of prostaglandins?

They decrease blood pressure

How do the 3 kidney systems develop ? (time wise)

They develop sequentially ( Starts high up and theres a wave of differentiation downwards towards the future pelvis --> upper most parts disappear. - Disappearing of one system marks the onset of development of the next developmental stage

What are the actions of PTH that allow the calcium ion concentration in the ECF to decrease

They have an immediate action on bone: 1) Binds to osteoblasts to inhibit bone formation 2) Stimulates a chemical messenger that stimulates osteoclasts to: - Increase bone breakdown which - Releases calcium and phosphate 3) Stimulates more re-absorption of filtered calcium in the kidneys 4) Increases loss of phosophate in urine

What is another characteristic of the epithelium in the proximal convoluted tubule?

They have lots of mitochondria in order to supply the energy for the active transport needed. They also have a brush border to maximise the reabsorption needed

How can diuretics cause goat?

They increase the uric acid reabsorption so more is present in the blood

How does lithium and demeclocyline affect diuretic action?

They inhibit ADH action on the collecting ducts

What is the main adverse effect of potassium ion sparing diuretics and aldosterone antagonists?

They reduce the excretion of potassium in the urine to may cause hyperkalaemia

What is the function of high pressure baroreceptors?

They respond to pressure and send impulses via the afferent fibres of the vagus nerve and glosopharyngeal nerves. Here, a decrease in blood pressure increases sympathetic activity and secretion of ADH and vice versa

What is the function of low-pressure baroreceptors?

They send signlas to the brainstem via the vagus nerve. This activity modulates both the sympathetic nerve outflow and the secretion of the ADH hormone

How are uncomplicated UTIs (cystitis) treated?

They should be treated with simple analgesics e.g. paracetamol / NSAIDs for symptomatic relief With a course of an oral antibacterial agent such as trimethoprim or nitrofurantonin. This should be done over a 3 day period

What are rickets and osteomalacia?

They're both diseases of defective bone mineralisation - Rickets is a disease that occurs in childhood - Osteomalacia is a disease of adulthood Can be autosomal recessive or required Causes - Disorders of vitamin D - Phosphate deficiency - Chronic renal failure - Primary disorders of bone metabolism

What type of diuretics act on the distal convoluted tubule?

Thiazide diuretics

Which is less potent, loop diuretics or thiazide diuretics?

Thiazide diuretics, where only 5% of sodium reabsorption is inhibited

What does the ureter look like?

Thin, muscular tube 25cm

What is augmentation cytoplasty?

This aims to increase the functional capacity of the urine, where the bladder is bivalved and detubularised bowek segment is anastomosed

What is the advantage of having transitional epithelium lining the bladder wall?

This allows expansion of the bladder and provides protection and deals with toxins

Why is the hypothalamus surrounded by a fenestrated capillary?

This allows the endothelium to be leaky, so the osmorecptors can be directly exposed to the systemic circulation to sense change in plasma osmolarity

What is the function of principle cells?

This allows the reabsorption of sodium ions via EnaC (epithelial sodium ion channel, which is driven by the 3Na-2K+-ATPase

Why are the detrusor muscle fibres arranged in this way?

This arrangement of the muscle fibres gives the bladder strength, irrespective of which direction it is being stretched in.

Hence what happens if a nerve lesion happens above S3?

This causes an upper motor lesion, damage to the hypogastric nerve, which causes retention of urine and high pressure detrusor contractions

Describe the effects of low ECF potassium ion concentration

This causes hydrogen ions to move into the cells, and hence causes alkalosis again

Describe the effects of high potassium ion concentration in the extracellular fluid

This causes hydrogen ions to move out of the cells, in order to move potassium inside. Hence resulting in acidosis again

What is the result of the permeability to water on the concentration of filtrate in the descending limb

This concentrates the sodium and chloride ions in the lumen of the descending limb ready for active transport in the ascending limb.

What is the function of the urethra?

This conveys urine from the bladder to the outside

What is the function of a male sling?

This corrects stress urinary incontinence

Describe the surgical procedure of open retropubic suspension as a method for treating women with stress urinary incontinence

This corrects the anatomical position of the proximal urethra and improves urethral support.

Why does Na+ reabsorption favour K+ secretion in the principal cells?

This creates a negative potential in the lumen, which repels the positive K+ ions and hence favours K+ secretion from the lumen

What is the problem of changes in sodium ion concentration?

This creates a problem for water balance, but not sodium ion balance as ingestion of sodium ions equal excretion

What happens when the low-pressure baroreceptors are distended?

This decreases the sympathetic nerve activity, decreases ADH secretion, and decreases water uptake

What is meant by rapid progressive GN (crescentic)

This descirbes fast progression into end stage renal disease of an aggresive inflammatory nephritis for example in: - Goodpasture syndrome - Small vessel vasculitis - Immune complex disease - IgA / HSP

Why are K+ channels on the apical membrane that secrete potassium ions back into the filtrate important?

This ensures that the potassium ion gradient in the principal cells (located in the collecting duct) doesn't accumulate, in order for the 3Na+-2K+-ATPase to work, and therefore for ENaC to work

Explain the action of anti-diuresis

This happens when the plasma levels are high of ADH, to produce a small volume of concentrated urine

Describe the procedure of intramural bulking agents as a method for treating women with stress urinary incontinence

This improves the ability of the urethra to resist abdominal pressure by improving urethral coaptation. This is achieved by injections of autologous fat, solicone, collagen or hyaluron-dextran polymers

What is the bainbridge reflex?

This increases right atrial pressure to increase the heart rate

What is the function of ADH?

This increases the permeability of the collecting duct to water in order to bring more water to the body, and also increases the permeability to urea

Why does the proximal convoluted tubule have a bursh border?

This increases the surface area and facilitates transport

What is the difficulty faced by sterile pyuria?

This indicates a UTI is present but the urine is unable to be cultured.

How do carbonic anydrase inhibitors act on the proximal convoluted tubule?

This inhibits the action of carbonic anhydrase in brush border and the proximal convoluted tubule cell They inhibit NaHCO3- reabsorption rather than NaCl reabsorption and so are not as potent as other diuretics as there is less HCO3 in the filtrate, hence there is a reduced effect on sodium ion reabsorption

What is pyelonephritis?

This is a UTI where the bacteria has ascended to the kidney. It is an upper UTI

What is thin glomerular basement membrane nephropathy?

This is a benign familial nephropathy, which is autosomal dominant. It has a benign course, meaning that the long term prognosis for most people are good and people with the disease generally live normal lives. It results in a thing glomerulus basement membrane. which causes isolated haematuria. Hence, no other symptoms are associated

What can we notice here?

This is a catheter angiogram. There is stenosis present in the right renal artery. This can cause hypertension which can be treated by inserting a stent

What is minimal change glomerulonephritis?

This is a condition which causes heavy proteinuria or nephrotic syndrome

What is the collecting duct?

This is a continuation of the DCT via the collecting tubule

Define hypokalaemia

This is a decrease in potassium ion concentration below 3.5 mmol.l-1

What is the action of spironolactone?

This is a diuretic that inhibits the action of aldosterone. It used for the treatment of heart failure and hypertension

What is a supra-pubic aspiration?

This is a method used to collect urine when there's a complicated UTI. A needle is inserted through the abdominal wall

What is parathyroid related peptide (PTHrP) and state how it is used clinically?

This is a peptide hormone produced in tumours which may lead to hypercalcaemia. The measurement of PTHrP can be used to determine the cause of an otherwise unexplained hypercalcaemia as PTHrP secreted by some cancer cells leading to hymeral hypercalcaemia of malignancy - HHM

Describe how Botulinim toxin treats urinary incontinence?

This is a potent biological neurotoxin that inhibits acetylcholine release. Prevents detrusor muscle contraction, as the pelvic nerve cannot release acetylcholine to act on the M3 receptors

What is goodpasture syndrome?

This is a relatively uncommon disease, but is clinically important as it is a very rapidly progressing glomerular nephritis. This disease is brought about by an autoantibody to collagen IV in the basement membrane, but only seems to affect the kidney for an unknown reason. It has an acute onset

What is tertiary hyperparathyroidism?

This is a state of excessive secretion of PTH after a long period of secondary hyperparathyroidism and resulting in a high blood calcium level. It reflects development of unregulated parathyroid function following period of persistent parathyroid stimulation. In this, the kidney shrinks. It causes hypercalcaemia

What is meant by the Gleason grade?

This is a system used to help evaluate the prognosis of men with prostate cancer using samples from a biopsy based on its microscopic appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 through 10

How does a phaeochromocytoma lead to secondary hypertension?

This is a tumour of the adrenal medulla which secretes catacholamines noradrenaline and adrenaline - this causes vasoconstriction causing an increase in blood pressure

What is ileal conduit?

This is a urinary conversion where a segment of the ileum is excied on its pedicle. the yreters are then transected and anastamosed to the proximal end of the ileal segment. The distal end of the ileal segment is brought out as abdominal wall stoma. This can be with or without a cystectomy

How does Conn's syndrome cause hypertension?

This is an aldosterone secreting adenoma that causes hypertension and hypokalaemia

What is systemic lupus?

This is an autoimmune disease in which the body's immune system attacks the healthy tissue. Symptoms vary from person to person leading to: - Skin changes: malar rash, discoid rash, photosensitivity - Oral ulcers - Nonerosive arthritis - Pleuropericarditis - Neurologica disorder (seizures or psychosis in the absence of precipitating circumstances) - Haematologic disorder - Also affects the glomerulus

Define hyperkalaemia

This is an increase in potassium ion concentration about 5 mmol.l-1

What is covert bacteriuria?

This is an upper UTI which is detected only by culture. This is important in children and in pregnancty

What is chronic interstitial nephritis?

This is an upper UTI which results in renal impairment following chronic inflammation. Infection is one of the many causes

Describe how the regulation of the glomerular filtration rate can be neural

This is because regulation can happen by the sympathetic branch of the autonomic nervous system.

What controls the voiding phase?

This is controlled by an entirely separate set of neurones than the continence neurones

What is the partial carbon dioxide in the blood determined by?

This is determined by respiration Hyperventilation decreases the partial pressure of carbon dioxide Hypoventilation increases the partial pressure of carbon dioxide

What is the short term hormonal regulation of serum calcium?

This is done the parathyroid hormone PTH Falls in the calcium ion concentration stimulates PTH release which acts on bone to stimulate the breakdown to release calcium ions, and the kidneys to increase calcium reabsorption. When there are high levels of calcium ions, the calcium ions bind to cells and activates the second messenger system to inhibit secretion This regulation works by negative feedback control

What is the cause of a disorder of plasma osmolarity?

This is due to an inability to control water, not an inability to control the sodium ion concentration

How are the filtration slits formed?

This is due to the capillary endothelium being fenestrated (to make it very leaky). The podocytes invest in it here forming filtration slits

What is the renal threshold of inorganic ions of phosphate and calcium?

This is equal to their normal plasma concentrations, which means that the maximal reabsorption of these ions via transporter carriers in the renal tubule is equivalent to their normal plasma concentrations. PTH can adjust the renal threshold

Trousseau's sign is a sign of hypocalcaemia. What is this?

This is flexion of the wrist and MCPS Extension of PIPs and DIPs Fingers adduct

What is the function of intercalated cells?

This is for the active reabsoprtion of chloride ions Secretion of hyodrogen ions or HCO3- = important for acid base regulation

How is creatinine formed?

This is formed from muscle

What is mixed urinary incontinence?

This is involuntary leakage, associated with urgency and exertion, effort, sneezing or coughing

What is IgA nephropathy?

This is mesangial proliferative glomerulonephritis. The mesangial cells are a ball of tine blood vessels, or capillaries, found in the glomerulus that are involved in the production of urine. This proliferation causes the diffuse (more than 50% of the glomerulus) deposition of IgA

What is the function of NaKCl2 transporter?

This is on the apical membrane of the thick ascending limb which allows the diffusion of chloride, sodium and potassium ions into the tubular cells

What is in the urinary pole of a nephron?

This is part of the glomerulus - Bowman's capsule - Bowman's space

What is nephritic syndrome?

This is renal failure due to the blocking of the filter, which causes urine to be mostly bloody. This is because there is destruction of the basement membrane, causing red blood cells to accumulate in the distal convoluted tubule

What is meant by the filtration load?

This is the amount of a substance filtered by a kidney

What is the trigone?

This is the area between the ureteral openings and the urethra. It funnels the urine into the urethra and forms a fixed base for the bladder

What is glomerular tubular balance GTB?

This is the balancing between the glomerulus and the proximal convoluted tubule. GTB changes sodium excretion in response to any GFR changes which do occur despite autoregulation. This means there is always a set percentage, 67% of sodium ions, that are reabsorbed. So even if the amount of sodium ions in the plasma increase (e.g. due to more ingestion), the amount reabsorbed will always be the same If the PCT reabsorbs a fixed amount of Na+, and in a situation where GFR would go higher, more Na+ would be arriving in the PCT, more than 6 mmol.l would be leaving the PCT. This would end up making us to loose more Na+ in our urine than we should and decrease our volume, but because the PCT absorbs a fixed percentage and not a fixed amount, the problems is sorted out

How do we calculate the filtration load?

This is the concentration of the substance in the plasma multiplied by the GFR

What is meant by hydronephrosis?

This is the distension of renal calyces and the renal pelvis with urine as a result of obstruction of the outflow of urine distal to the renal pelvis

How can Cushing's syndrome cause secondary hypertension?

This is the excess secretion of the glucocorticoid cortisol, where at high concentrations this acts on aldosterone receptors to cause an increase in the sodium ion and water retention

What is hypervitaminosis D?

This is the excessive intake of vitamin D, leading to an increased excessive prodution of 1,25 (OH)2 D. This causes the suppresion of PTH which can lead to hypocalcaemia

What is secondary hyperparathyroidism?

This is the excessive secretion of the PTH by the parathyroid glands in response to low blood calcium levels hypocalcaemia and associated hyperplasia of the glands. This disorder is seen especially in those with chronic kidney failure

Define blood pressure

This is the force exerted by blood against vessel walls. Blood pressure = cardiac output x resistance to blood flow

How do we calculate the filtration fraction?

This is the glomerular filtration rate that is divided by the filtration fraction 120 divided by 600 x 100 = 20%

Define diuresis

This is the increased formation of urine by the kidney

What are eicosanoids?

This is the larger family of closely related vasoactive unsaturated fatty acids that prostaglandins are part of

What is the transport maximum?

This is the maximal amount of a substance in mg than can be transported (reabsorbed or secreted) by the tubular cells per minute

What is meant by the renal threshold?

This is the plasma concentration of a substance at which the transport maximum (Tm) is reached and the substance first starts to appear in the urine.

What is the function of amiloride?

This is the potassium ion sparing diuretics that act as epithelial sodium ion channel blockers in principle cells

What is meant by the filtration fraction (FF)?

This is the ratio of the glomerular filtration rate to the renal plasma flow. It therefore presents the proportion of fluid reaching the kidneys which passes into the renal tubules

What is sacral nerve neuromodulation?

This is the stimulation of S3 / S4 (pelvic nerve) to modulate the reflexes responsible for involuntary bladder contraction. The precise mechanism of action is unknown Initial precutaneous nerve evaluation is needed, where an electrode is implanted with a battery powered generator with a 7 year life span

What is hypertension?

This is the sustained increase in blood pressure, which the diastolic being more than 90mmHg and the systolic being more than 140mmHg

What is renal clearance?

This is the volume of blood or plasma that could be freed of a specified substance in a specified time (usually one minute) by the excretion of the constituent into the urine through the kidneys

What is the renal plasma flow?

This is the volume of blood plasma delivered to the kidneys per unit of time

What is the clearance ratio?

This is the volume of plasma from which a substance can completely cleared to the urine per unit time - i.e. how much of a substance is eliminated from a quantity of blood per unit of time. A high clearance ratio means the substance gets out the blood easier, a low clearance means the substance takes longer.

What is the function of the 2Na+ - 1 glucose symporter? (SGLUT)

This is to transport a glucose molecule per every 2 sodium ions across the basolateral membrane by facilitated diffusion into the peritubular capillaries.

Chvostek's sign is a sign of hypocalcaemia. What is this?

This is twitching of the facial muscles. Refers to an abnormal reaction to the stimulation of the facial nerve

What is hyperparathyroidism?

This is when PTH is above the normal ranges which causes hypercalciuria

What is meant by focal?

This is when less than 50% of the glomeruli is involved in pathology seen under a light microscope

What is meant by diffuse?

This is when more than 50% of the glomeruli is involved in the pathology seen under a light microscope

What is nephrotic syndrome?

This is when over 3.5g of protein is filtered in the urine per day

Describe the process of water diuresis

This is when plasma osmolarity decreases to cause low levels of ADH, so little water is reabsorbed in the late distal tubule or collecting duct. This creases dilute urine = water diuresis

What is tubular secretion?

This is when substances are added to the glomerular filtrate in the nephron tubule. This is useful since only 20% of the plasma is filtered each time blood passes through the kidneys

What is metabolic alkalosis?

This is when the concentration of hydrogen carbonate rises, which causes the pH to rise. This can be the case after vomiting

What is meant by segmental?

This is when the pathology involves part of the glomerular tuft

What is meant by turbidity?

This is when the urine is looked at to see if it is cloudy

What is familial hypocalciuric hypercalcaemia?

This is when there is low calcium concentration in the urine, but a high amount in the blood. Autosomal dominant disorder associated with loss of function mutations in the calcium-sensing receptor This causes lifelong asymptomatic hypercalcaemia, because the receptor's sensitivity to calcium is decreased, resulting in a reduced receptor stimulation at normal serum calcium levels. As a result, inhibition of PTH release does not occur until higher serum calcium levels are attained, creating a new equilibrium. As normal calcium homeostasis is maintained, even at a higher set point, these individuals are not at an increased risk of the complications of hyperparathyrodisim

What is sterile pyuria?

This is when there's pus in the urine

Describe sensitivity testing of antibiotics

This is when urine is cultured, antibiotic discs are used to see how the bacteria responds. This allows for the best treatment to be allocated

What is transcellular transport ?

This is where a substance is transported through a cell instead of the intracellular space, passing through both the apical membrane (side of the plasma membrane that faces inward to lumen) and the basolateral membrane (the side of plasma membrane that faces away from the lumen)

Describe the functions of calcitonin

This lowers ECF calcium levels by stimulating the uptake into bone. Part of the mechanisms is to ensure incorporation of the calcium absorbed from the diet is put onto bone

What is the function of the parietal later of the Bowman's capsule?

This makes a funnel to collect the ultrafiltrateto drain into the proximal convoluted tubuleat the urinary pole

What needs to happen if plasma osmolarity increases?

This means that the body needs to produce a hyperosmotic urine - where there is a greater osmolarity than the plasma in order to get rid of the excess.

What is the response of the tubulo-glomerular feedback if the Na+ and Cl- increases?

This means there is a greater GFR so the GFR needs to decrease. Adenosine is released to cause vasoconstriction of the afferent arterioles

When we describe histopathology as proliferative, what does this mean?

This means there's an increased number of cells in the glomerulus (mostly mononuclear, endothelial or mesangial cells). These cells can be either proliferating glomerular cells or infiltrating circulating inflammatory cells.

Describe the action of alpha1 receptor blockers in the treatment of hypertension

This reduces sympathetic tone (relacation of vascular smooth muscle)

Why is it important to treat asymptomatic bacteriuria in pregnancy?

This reduces the risk of acute pyelonephritis It can result in urinary stasis due to progesterone induced ureteral smooth muscle relaxation. This causes the dilation of the ureters, renal pelvis and calyces. Results in decreased ureteral tone, increased bladder volume and decreased bladder tone which contributes to increased urinary stasis and ureterovesical reflux Pregnant women may develop glycosuria which encourages bacterial growth in the urine BUT there is inconsistent evidence that treatment may also reduce the incidence of low birthweight and prematurity

What is meant by arterial blood pressure?

This represents the pressure o the blood as it moves through the arterial system

What causes primary membranous glomerulonephritis?

This results from immune complex deposits in the sub-epithelial space and most likely has an autoimmune basis (autoantibody to podocytes). This may be due to: - Anti-PLA2R (in 70-80% of cases) - In others idiopathic (20-30%)

Describe renal correction if there is a fall in tubular cell intra-cellular pH

This stimulates the acid secretion HCO3- recovery, so raising the plasma hydrogen carbonate concentration

Describe the procedure of classic fascial sling as a method for treating women with stress urinary incontinence

This supports the urethra and increases bladder outflow resistance. It involves autologous transplantation of the fascia late or rectus fascia, which is the used to put it around the bladder neck

Describe the procedure of male urinary sphincter as a method for treating men with stress urinary incontinence

This treats males with urethral sphincter deficiency. A cuff is a mechanical, hydraulic (moves to confined space under pressure). device that stimulates the action of a normal sphincter to circumferential close the urethra.

What happens if the continence neurones are damaged?

This will lead to the failure to store urine, resulting in reduced bladder capacity and the frequent passing of urine. This is incontinence

Describe how tubulo-glomerular feedback functions

This works via a concentration-dependent salt uptake through the NaK2Cl co-transporter in the apical membrane of the macula densa cells. The macula densa of the distal convoluted tubule in the juxtaglomerular apparatus is sensitive to the concentration of sodium chloride present in the filtrate. This results in regulation of afferent arteriolar tone and therefore the glomerular filtration rate. The TGF response stimulates the juxtaglomerular apparatus to release chemical that have different actions: - For vasoconstriction adenosine is released - For vasodilation prostaglandins are released

How do we discover non-visible haematuria?

Through a microscopy or through a urine dipstick

How is respiration controlled in order to control the partial pressure of carbon dioxide?

Through chemoreceptors

How can we treat metastatic prostate cancer?

Through hormones: - Surgical castration which removes the testicles in order to remove the main source of testosterone which is a driving factor of the cancer - Medical castration with LHRH agonists (luteinising hormone-releasing hormone produced in the hypothalamus that stimulates the produces testosterone. This drug mimics LHRH in that negative feedback is activated, where the hypothalumus stops making LHRH as it thinks there are high levels of it). But at some point the patient will become resistant to these drugs so others are used. Palliation - when too late, but want to make it as comfortable as possible for the patient - Single dose radiotherapy - Bisphosphonates (build up muscle mass) e.g. Zoledronic acid - Chemotherapy

How do loop diuretics act?

Through inhibiting NaK2Cl2 symport

How do K+ sparing diuretics act?

Through inhibiting renal Na+ channels

How do thiazide diuretics act?

Through inhibiting the Na/Cl symport

How do calcium oxalate stones arise?

Through oxalate containing foods such as spinach, tea and chocolate. This includes calcium

In general, how is micturition controlled?

Through spinal cord reflex activity which is seen in infants. When receptors on the bladder sense that it is full, a signal is sent to the spinal cord and back to cause urination. And then this is then voluntarily inhibited or facilitated by higher centres of control in the brainstem, which is then controlled by the cerebral cortex. The ability of voluntary control develops at the age of 2-3 years

How is this problem resolved?

Through the tubulo-glomerular feedback which is part of autoregulation.

How is vesicoureteric reflux identified

Through ultrasound which identifies hydronephrosis

Describe what tight epithelia prevent ? and give 2 exmaples

Tight epitterm-183helia have tight junctions that prevent most movement between cells. Examples of tight epithelia include: the distal convoluted tubule the collecting duct of the nephron in the kidney

Are the junction loose or tight on the apical membrane of the S1 proximal convoluted tubule? Explain the significance of this

Tight junctions - The water and salt cannot move between cells so ion transport is driven by channels only

Hence, why do we want the medulla to be concentrated?

To be able to collect water from the collecting tubule

What is the aim of a history?

To categorise the type of urinary incontinence

Why do other ions accompany the reabsorption of sodium in the proximal convoluted tubule?

To maintain electro-neutrality e.g. chloride and bicarbonate

What are the objectives when treating a vesicoureteral reflux?

To prevent episodes of acute pyelonephritis and it's morbidity and mortality. Prevent scarring of the kidney (reflux nephropathy increases the risk of hypertension and renal failure)

What is the function of cuboidal epithelium?

To provide the space necessary for pumps for active transport and can be more protective

What is the function of the proximal convoluted tubule?

To reabsorb about 70% - 80% of water. When the filtrate reaches the proximal convoluted tubule 70% Na+, Cl- and K+ actively moves out of the blood, and water follows by osmosis. 100% of glucose and amino acids follow by co-transport

What are the goals of pharmaceutical therapy when treating those with an overactive bladder?

To reduce bladder over activity without interfering with normal micturition and without affecting other systems

What is the function of the bladder?

To store urine

What is the primary clinical situation in which diuretics are used?

To treat conditions with extracellular fluid expansion and oedema

How can insulin be used clinically, besides treating diabetes?

To treat hyperkalaemia, and indirectly pH

Give an example of an aquaretic

Tolvaptan

Rectal examination in the female

Top end of vagine cervix ovary

What transporters are present on the apical membrane?

Trans epithelia Na+ channels Na+/Glucose symporter Na+/Amino acid supporter NKCC2 (NA+, 2Cl-, K+) Symporter NHE (Na+, H+) Antiporter Aquaporins 1 and 2

Describe the surface anatomy from the posterior aspect

Transpyloric plane from the posterior aspect: @ T12

What is the role of the pronephric duct ?

Triggers off the next developmental stage, drives its establishment.

What happens if a stone is sitting in the trigone area ?

Trigone is most sensitive in terms of innervation in the bladder → stones sitting there will be the most painful More than if it where to touch anywhere else in the interior bladder.

Where do the solutes move from and to in the proximal convoluted tubule?

Tubular lumen --> Interstitium --> Capillaries

When the plasma osmolarity changes, what does the hypothalamic osmoreceptors stimulate?

Two different efferent pathways: 1) ADH is released to concentrate the urine by acting on the kidneys to reduce renal water excretion 2) Thrist / drinking to put more liquid into the system, by affecting the brain to affect the drinking behaviour to affect water intake

How many layers if the Bowman's capsule?

Two layers

How does e.coli (and other pathogens) infect the urinary tract?

Type 1 fimbrae allows attachment to the bladder epithelia receptors. P fimbrae attach to renal epithelial cells K antigen polysaccharide capsule stops antibodies and complement binding from killing the virus Heamolysins damage host membranes, and are cytotoxic to red blood cells and white blood cells Flagella allow the bacteria to ascend from the bladder to the kidney

Why is it important that UTIs are treated immediately in pregnant women?

UTI in pregnancies can increase the risk of foetal death, developmental delay and cerebral palsy in the infant

What is the chance of the person having a UTI if no nitrites or leukocyte esterases are found in their urine?

UTI is very unlikely - 5% will have a UTI

What may a shorter urethra predispose females to ?

UTI risk Due to the small distance of the urethra as well as the proximity to the anal aperture In males is more difficult for the bug to get all the way up the length of the penile urethra so they don't get them as common.

Hence, what is the ultra-filtrate?

Ultra filtrate is equal to the plasma minus the cell proteins.

What investigations are used to diagnose upper tract transitional cell carcinomas?

Ultrasound - Hydronephrosis which looks for swelling of the kidneys due to backup of the urine CT Urogram - Filling defect - Ureteric structure Retrograde pyelogram - This injects contrast into the ureter to view ti better Ureteroscopy - Gets a biopsy sample - Washings for cytology (abnormal cells)

What category of UTIs would you class a healthy, non-pregnant female with a normal urinary tract?

Uncomplicated UTI

How can autoregulation be changed?

Under appropriate conditions by several hormones

Does the proximal convulted tubule carry out regulated or unregulated reabsorption?

Unregulated because no hormones or other factors control what is reabsorbed.

Describe the neural control of bladder ?

Up in the pons; which is part of the brainstem there is a micturition centre that control all of this. It sends messages down the spinal cord and the axons synapse with neurones that pass into the external urethral sphincter and stop you from voiding urine Also have some stretch receptors in the bladder wall so you can detect that your bladder wall is getting bit tense because the urine is building up inside that signal is fed up the spinal cord until we end up with a reflex system here where the fibres are passing down back into the bladder wall again and causing the detrusor muscle to contract and urine will pass out.

Name 4 things that are present in urine?

Urea Potassium Chloride Ammonia Water

What solutes become more concentrated in the S1 part of the proximal convoluted tubule?

Urea and chloride ions, due to the increase of absorption of other ions

Why is urea recycled?

Urea reabsoprtion from the medullary collecting duct, acts as an effect osmole. Moving into interstitium and diffusing back in the Loop is helping build up the concentrated gradient medullary interstitium

When urine exits the renal hilum, what structure does it pass down to reach the bladder?

Ureter

Describe the development of the early metaphors

Ureteric bud contacts metanephric blastema The bud then expands and branches Development of the renal pelvis and major+minor calyx

What structure induces the development of the definitive kidney ?

Ureteric bud induces the development of the definitive kidney within the intermediate mesoderm of the caudal region of the embryo

Which upper urinary cancer results in haematuria?

Ureteric cancer. Also called upper tract transitional cell carcinoma. Cancer of the ureters. Cancer heere will not cause pain, and haematuria is only the case in the later stages. Hence prognosis is poor but they are rare.

What defines the boundaries of the trigone of the bladder?

Ureteric orifices and internal urethral orifice are the boundaries of the trigone of the bladder

In males, what accounts for 80% health care acquired infections?

Urethral catheterisation

Describe the male urethra

Urinary bladder with prostate sitting on pelvic floor with elevator ... muscle urethra takes interesting corse changes abruptly from vertical to horizontal to vertical Implication: Cathertization→ when you insert the catheter you need to be aware of the changes in direction → So you don't damage any tissue

What can cause incontinence of the bladder?

Urinary tract infections: chemical stimuli increases bladder activity and hence the urge to void. In women, stress incontinence, due to pelvic floor injury, secondary to childbrith In elderly individuals incontinence can be due to generic loss of muscle tone Detrusor overactivity (leading to an overactive bladder), particularly common in older individuals Damage to the CNS, the spinal cord or the nerve supply to the urinary bladder or external urethral sphincter (e.g. automatic bladder that may accompany Alzheimer's disease or stroke) Damage to pelvic nerves can abolish the micturition reflex

What is micturition?

Urination

What increases the risk in males as they age?

Urine incontinence which needs the catheterisation of the urinary tract. Prostatic obstruction which increases residual urine. More bacteria remains in the bladder after voiding

Therefore, how is urine passed when someone has damage to the neurones that cause the voiding phase?

Urine is only passed by an overflowing bladder i.e. involuntary, overflow incontinence

To minimise contamination, how should urine samples be contained?

Urine should be refrigerated at 4 degrees celsius if microscopy wants to take place. If it can't be refrigerated then culture can still happen, but microscopy cannot. If preserved then this must be done with boric acid to prevent bacterial multiplication in transit (i.e. when it can't be refrigerated as it is stored)

Discuss the differential diagnosis of haematuria

Urological: Cancer - Renal cell carcinoma (kidney cancer) - Upper tract transition cell carcinoma - Bladder cancer - Advanced prostate carcinoma Other: - Stones - Infection - Inflammation - Benign prostate hyperplasia (large) Nephrological (glomerular)

What epithelium lines the bladder?

Urothelium, mucosa - stratified transtional epithelium

When are urine cultures used?

Used to investigate complicated UTIs

What is vasculitis?

Vaculitis is a group of system disorders where there is an inflammation of blood vessels, that will therefore affect the highly vascularised kidney. Blood vessels are attacked directly in the glomerulus by: Anti Neutrophil Cytoplasmic Antibody (ANCA)

What are the symptoms of pylonephritis in young children?

Vague abdominal discomfort rather than flank pain and tenderness which is seen in adults

Describe water reabsorption in the late distal convoluted tubule and collecting tubule

Variable as water permeability is variable depending on ADH hormone

In the arterioles, what response results in the binding of angiotensin II to AT1 receptor?

Vasoconstriction

What are the types of epithelia that surrounds the nephron?

Very leaky at the start, become more selective/tighter

How much protein is present in nephritic syndrome?

Very little, less than 3.5g per day

In the early distal tubule, describe how sodium ions are reabsorbed

Via the Na-Cl transporter on the apical membrane

What is needed for the long-term hormone homeostasis of calcium and where do we get them?

Vitamin D - which is dependent on the vitamin D intake in the diet

How can vitamin D deficiency be treated?

Vitamin D alone Vitamin D with calcium High dose of vitamin D Adequate sunlight exposure

Vitamin D is the collective name for two prohormones. What are they?

Vitamin D3 - Cholecalciferol - made in the skin under the action of sunlight and from dairy foods Vitamin D2 - Ergocalciferol from yeast and fungi

In what other forms is vitamin D present?

Vitamin D3 is bound to the protein transcalciferin, where a small fraction exists in its free form

What happens to these prohormones in the kidneys?

Vitamin D3, cholecalciferol and Vitamin D2, ergocalciferol are both converted to their active form - calcitriol Vitamin D undergoes two hydroxylation reactions to turn cholecalciferol (the inactive form) from the skin or diet into the active calcitriol 1) The liver produces 25-hydroxyvitamin D which is the major circulating hormone 2) The kidney produces active calcitriol (1,23(OH)2)

WORKBOOK

WORKBOOK

What are the mechanical events during urinary continence and storage?

Walls of the bladder are highly folded, making them distensible The folds in the bladder are known as rugae As he bladder fills with urine, the internal urethral sphincter tightens / closes As the bladder fills with urine, the rugae flatten As the rugae flatten, capacity of the bladder increases up to 700ml As the bladder fills up with urine, intravesicla pressure hardly changes, due to the distension of the rugae

What is reabsorbed in the loop of Henle?

Water and salts - much less than the proximal convoluted tubule

What happens in the descending thin segment?

Water goes into the interstitium passively, without Na+ and Cl-. It is permeable to water only

What allows water to be reabsorbed in the ascending?

Water is reabsorbed by osmosis, where the active transport of solutes in the ascending creates the concentration gradient for water, and hence drives what happens in the descending limb

What does ultra filtrate consist of?

Water, ions and all small molecules

Describe the abnormality we can see in the following CT scan

We can see renal cell carcinoma. Here we can see how the tumour has invaded the inferior vena cava

How do we change plasma osmolarity?

We do this by controlling water retention. For example of the osmolarity is high, we need to retain more water

If a catheterised patient with bacteriuria is asymptomatic, how do we treat them?

We don't as because they are asymptomatic they do not require antibiotics

How do we control the plasma volume?

We move salt and the water will then follow to re-establish the volume

How do we control plasma volume?

We need to move salt and the water will then follow to re-establish the volume.

State the homeostasis of calcium

We take in calcium ions through the diet, which is only partially absorbed, where the intestines secrete some of this calcium into the gut for removal. Bone deposition releases calcium which is made to match the amount of calcium that is reabsorbed by the bone. Kidneys filter about 10 times the total amount of calcium ions present in the extracellular fluid each day, where more than 98% of this is reabsorbed. Urinary secretion is made to match net absorption calcium in the intestines

Describe what problems may occur if the urachus does no disappear properly

What can go wrong ? Urarchus → led form outside world to entry of bladder May turn into a cysts → patient presents with irratention in that rrea May become bigger becomes a sinus and stuff may get trapped in there and cause an infection Also may sometimes stay open the whole way → uriney will tickle out of the umbilicus →you would spot that on a newborn infant → can be surgically sealed to prevent urine coming out from there and infections coming in.

What is the problem presented by the regulation of blood pressure through angiotensin II

When blood pressure decreases angiotensin II forms to vasoconstrict the arterioles. This includes the afferent and efferent arterioles of the kidneys, meaning that the GFR is also changed

When is the low pressure baroreceptor reflex more important?

When blood volume is lowered

When is the bainbridge reflex more important?

When blood volume is raised

When does the baroreceptor reflex work best?

When controlling acute changes in blood pressure, where it can produce a rapid response to change blood pressure

When is ADH stimulated?

When plasma osmolarity changes by 1% - very sensitive Or severe hypovolaemia - 5-10% change

When may a pelvic kidney arise instead of the kidney being in the abdomen?

When the ascent fails

When do the rugae disappear?

When the bladder is filled

When does urinary incontinence occur?

When the bladder pressure is greater than the urethral sphincter pressure. This happens either when the detrusor pressure is high or the sphincter pressure is low.

When would there be an increase of sodium chloride in the filtrate?

When the blood pressure is higher causing greater filtration. This is outside the physiological limits, in which the myogenic response cannot control the GFR

Describe the baroreceptor reflex

When the mean arterial pressure increases, this is detected by the baroreceptors, as it stretches the receptors as they are sensitive to stretch. This is then sent in the afferent pathways to the medulla of the brain. which is the coordinating centre. This then sends impulses down the efferent pathways, where vessels are dilated and heart rate is reduced to reduce the overall blood pressure

What are the actions of renin?

When the pressure decreases Renin cleaves the protein angiotensinogen to release angiotensin I Angiotensin I is further cleaved by the angio-converting enzyme (ACE) to form the active hormone angiotensin II Angiotensin II is the active form, and is one of the most potent vasoconstrictors. The vasoconstriction is exerted primarily on the arterioles, leading to a rise in both systolic and diastolic blood pressure. Angiotensin II also acts to increase sodium reabsorption, which increases water reabsorption, which then increases the volume and therefore blood pressure It also acts on the adrenal cortex to stimulate the release of aldosterone. Aldosterone promotes the reabsorption of water from the distal convoluted tubule to increase the extracellular volume

What causes the vesicoureteric reflux?

When the ureterovesical junction fails to function as a one-way valve. The lower urinary tract bacteria access to the normally sterile upper tracts. The ureter passes through the detrusor muscle and a submucosal tunnel before opening into the bladder at the ureteral orifice. If the length of the submucosal tunnel or its muscular backing is inadequate, the valve mechanism is incompetent, resulting in a reflux

Describe the response of the myogenic mechanism of there is a decrease in systematic blood pressure in order to regulate the GFR

When there is a decline in blood pressure there is vasodilation of the afferent arterioles and vasoconstriction of the efferent arterioles. This increases renal blood flow and therefore increases the GFR back to its normal level

Describe the actions of the sympathetic nervous system when there is an acute fall in the systemic blood pressure

When there is an acute fall in blood pressure the sympathetic nervous system is activated and there is a release of noradrenaline. This causes the restriction of all vessels to decrease the total peripheral resistance, including the afferent arterioles. This decreases the renal blood flow and therefore the GFR to maintain blood volume and blood pressure

What is the major stimulus of the antidiuretic hormone, ADH?

When there is increased angiotensin II, which is released in response to low blood pressure, or a decreased volume of extracellular fluid

When does proteinuria happen?

When there is podocyte damage, causing the widening of fenestration slits, causing the protein to be leaked out when it normally would not be filtered.

When is atrial natriuretic peptide inhibited?

When there is reduced effective circulating volume where this results in a reduced filling of the heart (hence less stretch)

When do males get a UTI?

When they have abnormalities of urinary tract function e.g. - Indwelling catheter - Neurogenic bladder - Vesicoureteric reflux in children Abnormalities with urinary tract structure e.g. - Renal tract anatomical abnormalities - Urinary stones Previous urinary tract instrumentation of surgery Men who are immunocompromised (may be more prone to viral and fungal infections)

What happens when water intake is greater than water excretion?

When water intake is greater than water excretion the plasma osmolarity decreases

But why when we ingest potassium, it doesn't result in harmful effects?

When we ingest potassium, K+ is absorbed into the bloodstream alongside glucose. This causes insulin to be released, which causes the uptake of K+ to rapidly move inside the cells. In this process, some hydrogen ions move out due to the exchange process. But for the increased production of HCl into the stomach due to digestion, this means there is extra HCO3- released from the stomach into the blood, and so does not cause acidosis. This means that potassium ions are secured in the cells safely until they can be secreted Hence no hyperkalaemia is caused, and neither is acidosis

In what circumstance would you not choose permanent intention surgical interventions?

When women are planning further pregnancies. In these situation surgery with temporary intention is used

Diuretics can lead to hyponatraemia. What is this?

Where the levels of sodium ions in the blood is low

What is primary hyperparathyroidism

Where there is excessive secretion of PTH in the parathyroid glands due to a problem in the glands causing hypercalcaemia

What will splanchnic mesoderm become

Will cover Abdominal organs especially intestines

What will somatic mesoderm become ?

Will cover the Inside wall of abdomen

How does membranous glomerulopathy present on light microscopy?

With a thickened glomerular capillary wall, alongside the speckly appearance of the basement membrane. - The capillary loop is far too thick - The basement membrane looks speckley

How is metastatic renal cell carcinoma treated?

With palliative intention Molecular therapies targeting angiogenesis of tumours are now first schouse Immunotherapy Remeber that renal cell carcinomas are chemo and radio resistant

What is a major association of goodpasture syndrome?

With pulmonary haemorrhage which happens in smokers

How do we treat minimal change glomerulonephritis?

With steroids where the disease responds well. But it may reoccur once weaned off treatment

How are lower urinary tract symptoms treated?

With treansurethral resection of prostate

Describe how cells change in accordance to worsening differentiation

With worsening differentiation individual cells have increasing nuclear size and nuclear to cytoplasmic ratio There are more mitotic figures and increasing variation in size and shape of cells and nuclei, which is called pleomorphism

What do the adrenals look liked?

Yellowish glands

Can FSGS lead to kidney failure?

Yes, it can progress to kidney failure but the pathogenesis is unknown

Describe how you would conduct a history for someone you would suspect had urinary incontinence

You ask the patient to record the amount of fluid they pass for two or three days to asses frequency of micturition. Incontinence can be judged by the number of pads the patient has to use per day to cope with the urine leakage. It should be possible to determine whether leakage is continuous or intermittent and what precipitating factors there are, such as coughing and sneezing. This will allow you to begin to categorise the type of UI Urgency and frequency of micturition will often be made worse if there is an intravesicular inflammatory condition. Typically this could be a urinary tract infection, but other causes such as a stone in the bladder or even a tumour should be taken into account. Previous surgery of the pelvic floor can be important as this may lead to denervation of parts of the bladder. Childbirth may also be an important factor in the development of stress urinary incontinence in women due to sphincter damage

Why is phosphate excretion increased due to PTH, while for calcium ions it is the reabsorption of the kidneys which increase?

You cannot release calcium from bone without also releasing phosphate and as an increase in phosphate inhibits further release of calcium we want to avoid this, so calcium is excreted through the kidneys. Hence PTH stimulates the kidneys to excrete extra phosphate

Why is it important to refer to the total amount of sodium ions, and not the sodium ion concentration in relation to sodium ion balance?

You could have a low or high concentration of sodium depending on the volume of water without affecting the overall sodium ion amount

What investigations take place to look at vitamin D levels?

You look at the 25-hydroxy vitamin D levels in the blood

In a male, what else would you do to examine a patient with suspected urinary incontinence?

You would do a digital rectal examination (DRE) - Prostate (male), if this is enlarged it can narrow the urethra

How many nephrons are there?

about 1.5 million in each kidney - 85% in cortex 15% in Juxta medullary 2 types: Cortical and Juxtamedullary

where does the urinary bladder sit when its empty ?

behind the pubic symphysis

how is the bladder emptied in infants

in infants theres a reflex that empties the bladder

Glomerular capillaries are surrounded by processes of podocytes. What layer do podocytes make make up?

layer 3: The visceral layer of the Bowman's capsule

How are urine samples collected in order to minimise contamination?

mid-stream urine sample is collected, where the first portion of voided urine is discarded. This is to avoid the presence and culturing of the urine's normal flora, so to allow for a small amount of urine to be passed to clear it before the collecting sample

What does the plasma pH depend on?

pH depends on the ratio of the concentration of hydrogen carbonate to the partial pressure of carbon dioxide

Define acidaemia

pH less then 7.38

Define alkalaemia

pH more than 7.42

Use the Henderson Hasselbalch equation to display the pH of blood

pK = 6.1 There is 20 times as much hydrogen carbonate as dissolved carbon dioxide. The dissolved hydrogen carbonate is normally 25mmol.l-1 Log20 = 1.3 This is the amount dissolved in plasma. The plasma pH is 6.1+1.3 = 7.4

Where does the bladder sit when its full ?

rises up to about the level of the umbilicus