Urinary Flashcards

Question

What is the major calyx?

Answer 1

Minor calyces merge to form a major calyx

Answer 2

Urine passes through major calyx to the renal pelvis | Flattened and funnel shaped structure

Answer 3

Deep fissure that marks the medial margin of each kidney | Gateway: by which renal vessels and ureter enter and exit

Answer 4

Nephron (1.5 million in each kidney)

Answer 5

``` Glomerulus PCT Loop of Henle DCT Collecting duct ```

Answer 6

Highly specialised filter Water, electrolytes and small molecules secreted from blood Only plasma cells and proteins remain in the blood Afferent arterioles and efferent arterioles 20% of blood filtered at one time, 80% is removed via efferent arterioles almost immediately

Answer 7

``` Proximal convoluted tubule Major site of reabsorption 60/70% Na+ and H2O 80/90% K+ ~90% bicarbonate 100% aa's and glucose Water follows osmotic gradients ``` Reabsorbed materials leave by peritubular arterioles

Answer 8

Further site of reabsorption which is more regulated than in the PCT Creates a gradient of increasing osmolarity in the medulla by countercurrent multiplication Allows formation of concentrated urine if water has to be conserved Thin descending limb, thin ascending limb, thick ascending limb

Answer 9

Distal convoluted tubule Major site of variable reabsorption of electrolytes and water Fluid leaving loop of henle is hypotonic Removes more Na+ and Cl- Actively secretes H+ ions (acid base balance) Water may or may not follow reabsorption of electrolytes If it doesn't a large volume of dilute urine is formed - diuresis

Answer 10

Passed through high osmolarity environment of medulla (created by LoH) If water can cross the epithelium it will lead the urine down the osmotic gradient - produce low volume of concentrate urine If it cannot- urine remains dilute

Answer 11

Na+ recovery- renin angiotensin system, control ECF volume Water recovery- ADH dependent, control permeability of DCT and collecting duct to water; controls ECF osmolarity

Answer 12

Renal artery - segmental - interlobar- arcuate - interlobular - afferent arterioles - glomerulus - efferent arterioles - - - renal vein Kidneys receive about 20% of cardiac output Renal artery arises from abdominal aorta at level of L1/L2 immediately below superior mesenteric artery Due to position of aorta and IVC the right renal artery is longer than the left

Answer 13

2 or more arteries to a single kidney Most common vascular anomaly 25-40%

Answer 14

The ureters arise from the renal pelvis on the medial aspect of each kidney at transverse processes , before descending towards the bladder on the front of the psoas major muscle (moving laterally to medially). The ureters cross the pelvis brim near the bifurcation of the iliac arteries (cross anteriorly over the common iliac), under the uterine artery/ductus deferens and down the pelvic sidewall to insert in the posterior surface of the bladder in an oblique manner

Answer 15

Creates a one way valve where high intramural pressure collapses the ureters preventing back flow of urine

Answer 16

Females - Ureters close to ovaries as they cross the pelvic brim - Be careful not to damage ureters in an ovariectomy esp. in ligation of ovarian arteries - 2cm superior to ischial spine- ureters run underneath the uterine artery: in a hysterectomy where the uterus and uterine artery are removed ureter is in danger of being accidentally damaged - water under the bridge Males - in men, instead of uterine arteries the vas deferens cross the ureters anteriorly

Answer 17

Bony Landmarks for Course of Ureters 1. Arise at ~level of L2 2. Descend in front of tips of Lumbar spine transverse processes 3. Cross into pelvic brim roughly in front of the sacroiliac joint 4. Enter the bladder (Vesico-ureteric junction) at the level of the Ischial spines Important for x rays too- as ureters are soft tissue and so are difficult to see

Answer 18

Abdominal: Renal artery and testicular/ ovarian artery Pelvic: Superior and inferior vesicle arteries

Answer 19

Renal, testicular/ ovarian and hypo gastric plexuses Sensory fibres from ureter enter spinal cord at T11-L2 Ureteric pain in dermatomal areas

Answer 20

1) the junction of the renal pelvis and ureter 2) point at which the ureters cross the pelvic brim (Iliac bifurcation) 3) where the ureters pass into the wall of the urinary bladder

Answer 21

Sits right behind the pubic bone in an adult (above it in a child) Distended upwards when it fills with urine

Answer 22

Collection, temporary storage and expulsion of urine (bladder muscle contraction and sphincter relaxation)

Answer 23

Empty - flattened by overlying intestines | Filling - oval shaped

Answer 24

Hollow organ, distensible, folded, internal rugae Apex- located superiorly, pointing towards pubic symphysis, connected to umbilicus by medial umbilical ligament (remnant of Urachus) Body- main part of bladder between apex and fundus Fundus/ Base- located posteriorly, triangular, apex facing backwards Neck- formed by convergence of fundus and 2 inferolateral surfaces, joins bladder and urethra

Answer 25

2 entrances of the ureters and the 1 exit of the urethra in the bladder Triangular area within the fundus -smooth walls unlike rest of the bladder

Answer 26

External spinchters

Answer 27

Internal (prevent ejaculate entering the bladder- circular smooth muscle fibres under autonomic control) and external spinchters (skeletal muscle, voluntary, relaxes in urination to allow urine flow)

Answer 28

Smooth muscle- detrusor muscle Fibres orientated in 3 directions - maintains structural integrity when stretched SNS & PNS innervation Contracts during micturition (urination)

Answer 29

Internal iliac vessels - superior vesicle branch Obturator and inferior gluteal arteries (small branches) Males- + inferior vesical artery too Females- + vaginal arteries too

Answer 30

Vesical venous plexus- internal iliac vein(hypogastric vein)

Answer 31

Autonomic and somatic - SNS--> hypo gastric nerve (T12-L2) - somatic --> pudendal nerve (S2-S4) Sensory afferent nerves found in bladder wall- need to urinate with a full bladder Relaxing of detrusor muscle promotes urine retention, and external spinchter constricts/ relaxes

Answer 32

Primitive spinal reflex- urination stimulated in response to stretch Toilet training in infants - spinal reflex overridden by higher centres of brain- gives voluntary control over micturition Reflex arc 1. Bladder fills with urine and bladder walls stretch, sensory nerves detect stretch and transmit information to spinal cord 2. Interneurons in spinal cord relay signal to PS efferents (pelvic nerve) 3. Pelvic nerve acts to contract the detrusor muscle and stimulate micturition Non functional post childhood but needs to be considered in spinal injuries and neurodegenerative diseases

Answer 33

Vessel that transports urine from the bladder to external opening in perineum

Answer 34

15-20cm long Exit for semen and urine Pre-prostatic - internal urethral orifice, neck of bladder, passes through wall of bladder, ends at prostate Prostatic- passes through prostate gland, ejaculatory and prostatic ducts drain into urethra here Membranous- passes through pelvic floor and deep perineal pouch; surrounded by external urethral spinchter - volume control of urination Spongy- passes through bulb and corpus spongiosum of pelvis, ends at external urethral orifice, glans penis, urethra dilates- navicular fossa, bulbourethral glands empty into proximal urethra

Answer 35

Short ~ 4cm Predisposes women to UTIs Begins at neck of bladder passes inferiorly through perineal membrane and muscular pelvic floor Opens directly into perineum in an area between labia minora (vestibule) Within the vestibule the urethral orifice is located anteriorly to the vaginal opening and 2-3 cm posterior to clitoris -distal end of urethral marked by 2 mucous glands on either side

Answer 36

The embryonic kidney and gonad both originate from the urogenital ridge, a region of intermediate mesoderm.

Answer 37

The first kidney system, never functions in humans. However, it produces the pronephric duct, which extends from the cervical region to the cloaca and drives the development of the next stage (becoming the Mesonephric duct)

Answer 38

The mesonephros sprouts tubules that develop caudal to the pronephric region. These tubules plus the Mesonephric duct makes up the embryonic kidney. The Mesonephric duct also sprouts the ureteric bud, which induces development of the definitive kidney. The Mesonephric duct also has an important role in the development of the reproductive system in the male.

Answer 39

The Ureteric bud sprouts from the Mesonephric duct. It induces the development of the definitive kidney within the intermediate mesoderm of the caudal region of the embryo that lies closet to it. The ureteric bud then expands and branches into this differentiated intermediate mesoderm, the metanephric blastema, forming the definitive kidney’s structure. The ureteric bud drives the development of the definitive kidney. The collective system is derived from the ureteric bud itself. The excretory component is derived from the intermediate mesoderm under the influence of the ureteric bud.

Answer 40

The metanephric kidney first appears in the pelvic region. It then undergoes an apparent caudal to cranial shift, crossing the arterial fork formed by vessels returning blood from the foetus to the placenta. However the kidneys don’t actually move. Development is cranial to caudal, and the trunk just extends downwards, making it appear as though the kidneys

Answer 41

The ureteric bud fails to interact with the intermediate mesoderm. Can affect one (unilateral) or both (bilateral) kidneys.

Answer 42

If a kidney fails to cross the arterial fork (as the kidneys don’t actually move its more the fork snags the kidney as it develops, pulling it down), it ends up much lower than it should be (A). During their ‘ascent’ the kidneys lie extremely close to one another. If they both get caught on the arterial fork they can fuse and form a horseshoe kidney (B).

Answer 43

Splitting of the ureteric bud, either partial or complete can lead to abnormalities. The systemic consequence is an ectopic opening, for example into the vagina or urethra, bypassing the bladder and causing incontinence.

Answer 44

Multicystic Kidney Disease – Atresia of ureter | Polycystic Kidney Disease – Recessive, presents early, poor prognosis.

Answer 45

As the kidneys ascend they require new arterial supply, and the previous supply disappears. If it remains, they are accessory, or supernumerary arteries. These arterials are end arteries, as the main renal artery will not branch to supply that area of the kidney if an accessory artery is present. This means there is no collateral supply.

Answer 46

The bladder is a hindgut derivate, meaning it is derived from the caudal portion of the primitive gut tube formed during embryonic folding in the fourth week of development. The caudal portion is a dilated, blind pouch called the cloaca. The cloaca is separated from the outside by the cloacal membrane, one of the two mesoderm-less regions left present after gastrulation. The cloaca is divided by the urorectal septum into the urogenital sinus (future bladder and urethra) and anorectal canal (future rectum and anal canal). Also involved in the development of the bladder is the allantois, which is a superoventral diverticulum of the hindgut and extends into the umbilical cord. The lumen on the allantois becomes obliterated to become the urachus, which is the median umbilical ligament in adults.

Answer 47

o Mesonephric ducts (MD) reach the urogenital sinus (UGS) • Drains Embryonic urine into the cloaca o Ureteric Bud (UB) Sprouts from MD • Ureteric bud will become ureter opening into the bladder o Smooth musculature begins to appear • Will become the trigone of the bladder o UGS begins to expand o UBs and MDs make independent openings in UGS

Answer 48

The female bladder develops in much the same way, but without male hormones the Mesonephric duct regresses. Therefore females do not form prostates or the tubes of the male reproductive system.

Answer 49

The female urethra is formed by the pelvic part of the urogenital sinus. ``` The male urethra is divided into four parts: o Pre-Prostatic o Prostatic o Membranous o Spongy ``` The first three parts are analogous to the female urethra. The spongy urethra is the phallic part.

Answer 50

A congenital anomaly in which part of the urinary bladder is present outside the body. It occurs due to maldevelopment of the lower abdominal wall, leading to a rupture that causes the bladder to communicate with the amniotic fluid. Exstrophy of the bladder may be due to a urachal fistula. This is a patent urachus, which normally becomes the median umbilical ligament. If it remains as a duct, it will connect the bladder to the umbilicus.

Answer 51

A defect in fusion of urethral folds. The urethra opens onto the ventral surface, rather than at the end of the glans. The incidence of this is increasing.

Answer 52

Parietal layer- simple squamous epithelium Filtration barrier layer- fenestrations capillary endothelium Visceral layer- podocytes- invest in endothelium making filtration slits -produces ultra filtrate of plasma

Answer 53

Simple cuboidal epithelia with pronounced brush border | -reabsoprtion begins

Answer 54

Thin descending and thin ascending limb- simple squamous epithelium no brush border (like a small capillary without RBCs) - no active transport- reabsorption Thick ascending limb- simple cuboidal epithelium, no brush border, circular lumen - active transport- reabsorption

Answer 55

Simple cuboidal epithelium with lots of mitochondria and no brush border (larger lumen than pct) Juxtaglomerular cells and extra glomerular mesangial cells- macula densa of DCT - reabsorption- active transport

Answer 56

Simple cuboidal epithelium, no brush border, (larger lumen and more irregular than thick ascending limb of loop of henle) - no reabsorption - transport

Answer 57

Transitional epithelia, 2 smooth muscle layers (3 in lower 1/3) - transport of urine from kidney to bladder

Answer 58

Transitional epithelia, 3 smooth muscle layers, outer Adventitia -storage of urine

Answer 59

The millions of afferent arterioles each deliver blood to a single nephron, and the diameter of each afferent arteriole is slightly greater than the diameter of the associated efferent arteriole. This diameter difference increases the pressure of the blood inside the glomerulus. This increased hydrostatic pressure helps to force the below components out of the blood in the glomerular capillaries. However, only 20% of the delivered blood is actually filtered, 80% exits via the efferent arteriole. o Most of the water o Most/All of the salts o Most/All of the glucose o Most/All of the urea The above are all filtered, as they are relatively small particles. RBCs and plasma proteins are not filtered, as they are too large. The size limit for filtration is molecular weight 5,200 or an effective molecular radius of 1.48nm. Further to this the basement membrane and podocytes glycocalyx have negatively charged glycoproteins, which repel protein movement. The water and solutes that have been forced out of the glomerular capillaries pass into Bowman’s space and are called the glomerular filtrate or the ultrafiltrate.

Answer 60

There are three layers to pass through: 1. Capillary endothelium o Water, salts, glucose o Filtrate moves between cells 2. Basement Membrane o Acellular gelatinous layer of collagen/glycoproteins o Permeable to small proteins o Glycoproteins (-‘ve charge) repel protein movement 3. Podocyte Layer o Pseudopodia interdigitate to form filtration slits

Answer 61

Plasma filtration is only due to three physical forces. 1. Hydrostatic pressure in the capillary (can be regulated) (PGC) 2. Hydrostatic pressure in Bowman’s capsule (PBC) 3. Osmotic pressure difference between the capillary and tubular lumen (pGC)

Answer 62

Neutral Molecule – The bigger it is, the less likely to get through Anions – Negative charge also repels, more difficult to get through Cations – Positive charge allows slightly bigger molecules through In many disease processes, the negative charge on the filtration barrier is lost so that proteins are more readily filtered. This condition is called proteinuria (protein in the urine).

Answer 63

Only about 1% of glomerular filtrate actually leaves the body, the rest is reabsorbed into the blood as it passes through the renal tubules. This process is called tubular reabsorption and occurs via three mechanisms, osmosis, diffusion and active transport. It is called reabsorption and not absorption as these substances have already been absorbed once (particularly in the intestines). Reabsorption in the PCT is isosmotic, and driven by sodium uptake. Other ions accompany sodium to maintain electro-neutrality, e.g. Chloride and Bicarbonate. Solutes move from Tubular lumen to Intersticium to Capillaries, and reabsorption can either be transcellular or paracellular (around cells through tight junctions).

Answer 64

1. Na+ is pumped out of tubular cells across the basolateral membrane by 3Na-2K-ATPase. 2. Na+ moves across the apical (luminal) membrane down its concentration gradient o This movement of Na+ utilises a membrane transported or channel on the apical membrane. 3. Water moves down the osmotic gradient created by the reabsorption of Na+

Answer 65

Glucose is reabsorbed in the PCT using the Na-Glucose Symporter SGLUT. This moves glucose against its concentration gradient into the tubule cells. Glucose then moves out of the tubule cell on the basolateral side by facilitated diffusion. 100% of glucose is normally reabsorbed, but the system has a maximum capacity, or Transport Maximum (Tm). If the plasma concentration exceeds Tm, the rest spills over into the urine. If this happens, water follows into the urine, causing frequent urination (polyuria).

Answer 66

``` Secretion provides a second route, other than glomerular filtration, for solutes to enter the tubular fluid. This is useful as only 20% of plasma is filtered each time the blood passes through the kidney. It also helps to maintain blood pH (7.38 – 7.42). The substances secreted into the tubular fluid are: o Protons (H+) o Potassium (K+) o Ammonium ions (NH4+) o Creatinine o Urea o Some hormones o Some drugs (e.g. penicillin) ```

Answer 67

1. Entry by passive carrier a. Mediated diffusion across the basolateral membrane down favourable concentration and electrical gradients, created by the 3Na-2K-ATPase pump. 2. Secretion into the lumen a. H+-OC+ exchanger that is driven by the H+ gradient created by the Na+-H+ Antiporter.

Answer 68

``` Different segments of the tubule have different types of Na+ transporters and channels in the apical membrane. This allows Na+ to be the driving force for reabsorption, using the concentration gradient set up by 3Na-2K-ATPase (active transport). o Proximal Tubule • Na-H Antiporter • Na-Glucose Symporter (SGLUT) o Loop of Henle • Na-K 2Cl Symporter o Early Distal Tubule • Na-Cl Symporter o Late Distal Tubule and Collecting Duct • ENaC (Epithelial Na-Cl) ```

Answer 69

The volume of plasma from which a substance (X) can be completely cleared to the urine per unit time The renal artery is the input to the kidney and the kidney has two possible outputs, the renal vein and the ureter. Therefore, if a substance is not metabolised or synthesised, an equal amount must leave in the urine and the renal venous blood. Clearance can be calculated with the equation: Clearance = (amount in urine x urine flow rate) / arterial plasma conc E.g. Substance X is present in the urine at a concentration of 100mg/ml. The urine flow rate is 1ml/min. The excretion rate of substance X is therefore: Excretion rate = 100mg/ml x 1ml/min = 100mg/min If Substance X was present in the plasma at a concentration of 1mg/ml then its clearance would be: Clearance = 100/1= 100ml per min 100ml of plasma would be completely cleared of substance X per minute.

Answer 70

The volume of plasma from which any substance (X) is completely removed by the kidney in a given amount of time (usually 1 minute) GFR is a measure of the kidney’s ability to filter a substance, thus overall function. It is an indication of how well the kidney works and is therefore useful in clinical practise, as a fall in GFR generally means kidney disease is progressing and vice versa. To measure GFR, a substance (X) must be freely filtered across the glomerulus. This substance must not be reabsorbed, secreted or metabolised by the cells of the nephron. It must pass directly into the urine. Examples of substances that can be used to calculate GFR are Creatinine and Inulin. GFR= (amount in urine x urine flow rate) / arterial plasma concentration Normal GFR for Males = 115 – 125 ml/min Normal GFR for Women = 90 – 100 ml/min

Answer 71

The kidney receives ~1.1 litres of blood a minute. About 45% of this is RBCs and 55% is plasma. We can therefore calculate renal plasma flow. 55% of 1.1L = 605ml/min of plasma.

Answer 72

Filtration fraction is the proportion of a substance that is actually filtered. If renal plasma flow is 605ml/min, and 20% of all plasma is filtered, 125ml/min is filtered through into Bowman’s space (normal GFR), and 480ml passes through into peritubular capillaries. Filtration fraction = glomerular filtration rate / renal plasma flow Filtration Fraction is about 20%. (125/605 = 20.8)

Answer 73

Autoregulation: Auto-regulatory mechanisms keep the GFR within normal limits when arterial BP is within physiological limit (80-80 mmHg). Myogenic Response: Arterial BP rises --> Afferent Arteriole Constriction Arterial BP falls --> Afferent Arteriole Dilation Tubular Glomerular Feedback (TGF): Changes in tubular flow rate as a result of changes in GFR change the amount of NaCl that reaches the distal tubule. Macula densa cells respond to these changes. If NaCl increases: - Response is GFR needs to decrease - Adenosine released, causes vasoconstriction of afferent arteriole If NaCl decreases: - Response is GFR needs to increase - Prostaglandins released causing vasodilation of afferent arteriole

Answer 74

General overflow aminoaciduria | Specific overflow aminoaciduria

Answer 75

All AA’s present in the urine. This is normally due to inadequate deamination in the liver, or an increased GFR. It is often seen in early pregnancy.

Answer 76

Only a specific AA is present in the urine. This is usually due to a genetic inability to break down one AA, e.g. phenylalanine in PKU (lack of phenylalanine hydroxylase).

Answer 77

Renal aminoaciduria is mainly confined to the dibasic acids, and it due to a genetically determined lack of the specific transport protein(s). For some reason cysteine is an abnormally insoluble amino acid, especially in acidic urine, and cystinuria may be associated with stone formation.

Answer 78

Na+ balance - (and thus any water that follows)

Answer 79

Water balance

Answer 80

2 simple compartments- ECF and ICF separated by a cell membrane

Answer 81

ECF volume (which includes the vascular system) is determined largely by the concentration of NaCl in the ECF

Answer 82

If sodium in ECF changes then volume if ECF changes and affects the ECV and thus affects blood pressure too

Answer 83

As this would change plasma osmolarity | So instead we move osmoles (NaCl) and water follows

Answer 84

Increases plasma volume - greater reabsorption of NaCl in kidney - more water drawn out of nephron - increases blood pressure

Answer 85

Decreases plasma volume - less reabsorption of NaCl in kidney - less water drawn out of nephron - decreases blood pressure

Answer 86

5% (during water loading) | >24% (during dehydration)

Answer 87

67% is always absorbed regardless of actual amount that is filtered/ GFR Autoregulation prevents GFR from changing too much but if any changes occur despite this, glomerular tubular balance blunts the Na+ excretion response

Answer 88

Balance between GFR and rate of absorption of solutes | Must be kept as constant as possible, so if GFR increases, rate of reabsorption must also increase

Answer 89

3Na+-2K+-ATPase on basolateral membrane

Answer 90

Section 1 - Na+ reabsorption Cotransporter with glucose Na-H exchange Cotransporter with amino acid/ carboxylic acids Cotransporter with phosphate (increase in PTH) Aquaporin [urea/Cl-] creates a conc gradient for Cl- reabsorption in section 2 and 3

Answer 91

``` Section 2 &3- Na+ and water reabsorption Na-H exchanger Paracellular Cl- reabsorption Transcellular Cl- reabsorption Aquaporin- sets up osmole gradient favouring water uptake from lumen ```

Answer 92

PCT is highly permeable to water Allows reabsorption of Na+ to be isosmotic with water The tight coupling between Na+ and water reabsorption is called isosmotic reabsorption. This bulk reabsorption of Na+ and water (the major constituents of ECF) is critically important for maintaining ECF volume

Answer 93

Osmotic gradient established by solute reabsorption Hydrostatic force in intersticium Osmotic force in peri tubular capillary due to loss of 20% filtrate at glomerulus, but cells and proteins remained in blood

Answer 94

No, water and sodium reabsorption is separated

Answer 95

Reabsorbs water but not NaCl

Answer 96

Reabsorbs NaCl but not water- known as the DILUTING SEGMENT (dilutes NaCl in the filtrate and so therefore tubule fluid leaving the loop is therefore hypoosmotic (more dilute) compared to the plasma)

Answer 97

Increase in IC [Na+] set up by PCT allows for para cellular reuptake of water from the descending limb (no tight junctions) Concentrates Na+ and Cl- in the lumen of the descending limb ready for active transport in the ascending limb

Answer 98

Impermeable to water Na+ reabsorption is passive- water reabsorption in descending limb creates a gradient for passive Na+ ion reabsorption in thin ascending limb Epithelia have loose junctions - permits para cellular reabsorption of Na+ NaCl transported from lumen into cells by NaKCC2 channel (apical) Na+ then moves into intersticium due to action of 3Na-2K+-ATPase (basolateral) K+ ions diffuse back into lumen via ROMK Cl- ions move into intersticium

Answer 99

NaKCC2 is target for loop diuretics - increased loss of K + in urine - hypokalaemia

Answer 100

Water permeability of early DCT is fairly low and active reabsorption of Na+ results in dilution of filtrate Hypoosmotic (more dilute) fluid enters from the loop and 5-8% Na+ is actively transported by NaCC2 transporter driven by 3Na+-2K+-ATPase Major site of Ca2+ reabsorption via PTH Further dilution means that fluid leaving is more hypoosmotic

Answer 101

NaCC2 transporter

Answer 102

Region responsible for fine tuning filtrate Able to respond to a variety of stimulants and has 2 distinct cell types Principal cells (70%) - reabsorb Na+ by Epithelial Na+ Cell (ENaC) driven by 3Na+-2K+-ATPase - Produces lumen charge - electrical gradient for para cellular Cl- reabsorption and K+ secretion into lumen - Variable water uptake through Aquaporin 2 - dependent on ADH - Have a more distinct membrane than intercalated cells Intercalated cells - Active reabsorption of chloride - secrete H+ ions or HCO3-

Answer 103

Thick ascending limb of LoH This region uses more energy than any other region of the nephron, and is particularly sensitive to hypoxia Needs energy for active transport

Answer 104

Baroreceptors (aortic arch and carotid body)

Answer 105

RAAS ADH ANP SYMPATHETIC NERVOUS SYSTEM

Answer 106

Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole, causes the release of renin from the granular cells of the juxtaglomerular apparatus. Decreased NaCl Concentration at the Macula Densa cells (Due to low perfusion and therefore low GFR) causes Sympathetic stimulation to the JGA. This also increases the release of renin. (Also causes Macula Densa cells to release Prostaglandins --> Afferent Vasodilation) Renin cleaves Angiotensinogen à Angiotensin I, which is in turn cleaved by Angiotensin Converting Enzyme (ACE) to form the active hormone Angiotensin II. Angiotensin II There are two types of Angiotensin II receptors, AT1 and AT2. They are both G-protein coupled receptors. Angiotensin II’s main actions are via the AT1 receptor Actions of Angiotensin II o Vasoconstriction • Works on vascular smooth muscle cells, increases TPR thus BP • Vasoconstriction of afferent and efferent arteriole o Aldosterone • Stimulates the adrenal cortex to synthesise and release Aldosterone • Aldosterone stimulates Na+ and therefore water reabsorption • Acts on principal cells of CD • Activates ENaC and apical K+ channels • Increases basolateral Na+ extrusion via 3Na-2K-ATPase o Sympathetic Activity o Increase Na+ reabsorption • Stimulates Na-H exchanger in the apical membrane of PCT o Thirst • Stimulates ADH release at hypothalamus o Breaks down Bradykinin • Bradykinin is a vasodilator

Answer 107

o Vasoconstriction • Works on vascular smooth muscle cells, increases TPR thus BP • Vasoconstriction of afferent and efferent arteriole o Aldosterone • Stimulates the adrenal cortex to synthesise and release Aldosterone • Aldosterone stimulates Na+ and therefore water reabsorption • Acts on principal cells of CD • Activates ENaC and apical K+ channels • Increases basolateral Na+ extrusion via 3Na-2K-ATPase o Sympathetic Activity o Increase Na+ reabsorption • Stimulates Na-H exchanger in the apical membrane of PCT o Thirst • Stimulates ADH release at hypothalamus o Breaks down Bradykinin • Bradykinin is a vasodilator

Answer 108

• Vasoconstriction by α1-adrenoceptors • Inc. force/rate of heart contraction β1-adrenoceptors o Decreased Renal Blood flow • Decreased GFR and Na+ excretion • Activates Na/H exchanger in PCT o Stimulates renin release from juxtaglomerular cells • Increased Angiotensin II/Aldosterone levels

Answer 109

The baroreceptor reflex works well to control acute changed in BP. It produces a rapid response, but does not control sustained increases as the threshold for baroreceptor firing resets. A 5-10% drop in blood pressure causes low-pressure baroreceptors in the atria and pulmonary vasculature to send signals to the brainstem via the vagus nerve. This activity modulates both sympathetic nerve outflow, secretion of the hormone ADH and reduction of ANP release. A 5-150% change in blood pressure causes high-pressure baroreceptors (carotid sinus/aortic arch) to send impulses via the vagus and glossopharyngeal nerves. A decrease in blood pressure will increase sympathetic nerve activity and the secretion of ADH. Actions of ADH o Addition of Aquaporin to Collecting Duct • Reabsorption of water • Forms concentrated urine • Release stimulated by increases in plasma osmolarity or severe hypovolemia o Thick Ascending Limb • Stimulates apical Na/K/Cl co-transporter • Less Na+ moves out into the medulla, reduced osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin descending limb

Answer 110

o Addition of Aquaporin to Collecting Duct • Reabsorption of water • Forms concentrated urine • Release stimulated by increases in plasma osmolarity or severe hypovolemia o Thick Ascending Limb • Stimulates apical Na/K/Cl co-transporter • Less Na+ moves out into the medulla, reduced osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin descending limb

Answer 111

Acts in the opposite direction to the others o Synthesised and stored in atrial myocytes o Promotes Na+ excretion • Vasodilation of afferent arteriole o High BP à Stretch Atrial Cells • Increased release • Increased Na+ excretion, volume decreases, BP decreases o Low BP à Atrial Cells less stretched • Reduced release • Reduced Na+ excretion, volume increases, BP increases o Inhibits Na+ reabsorption along the nephron

Answer 112

Sustained increase in blood pressure

Answer 113

>140/90 on more than 3 occasions

Answer 114

In around 95% of cases, the cause is unknown. This is known as Essential Hypertension. Genetic and environmental factors may both be involved and the pathogenesis is unclear.

Answer 115

``` Where a cause can be defined, hypertension is referred to as secondary hypertension. Here it is important to treat the primary cause. Examples include: o Renovascular disease o Chronic Renal Disease o Aldosteronism o Cushing’s syndrome ```

Answer 116

o ACE Inhibitors • Prevent the production of Angiotensin II from Angiotensin I • Angiotensin II receptor antagonists o Thiazide Diuretics • Inhibit NaCC co-transporter on apical membrane of DCT • May cause hypokalaemia (more K+ lost in urine) o Vasodilators • Ca2+ channel blockers, reduce Ca2+ entry into smooth muscle cells • α1 receptor blockers, reduce sympathetic tone o Beta Blockers • Block β1-receptors in the heart • Reduces heart rate and contractility Non-pharmacological approaches to the treatment of hypertension include diet, exercise, reduced Na+ intake, reduced alcohol intake.

Answer 117

By water balance

Answer 118

Hypothalamic osmoreceptors

Answer 119

Located in hypothalamus in organum vasculoum of laminae terminal is (OVLT) anterior and ventral to 3rd ventricle

Answer 120

ADH and thirst pathways

Answer 121

Made in hypothalamus | Stored and secreted from posterior pituitary

Answer 122

ADH acts in kidney and affects renal water excretions | ADH controls water loss

Answer 123

Increase in osmolarity Increase in ADH Decrease in urine Increase in water reabsorption

Answer 124

Decrease in osmolarity Decrease in ADH Increase in urine Decrease in water reabsorption

Answer 125

Vasoconstriction

Answer 126

Increases Na+, K+, Cl- reabsorption

Answer 127

Increase water reabsorption Aquaporin 2 insertion Apical membrane does not contain water channels in the absence of ADH- held below the surface and can be rapidly inserted when required ADH binds to receptor--> PKA signalling --> AQP2 inserted into apical membrane

Answer 128

Increases water reabsorption (AQP2) | Increases K+ reabsorption

Answer 129

Increase water reabsorption (AQP2) | Urea reabsorption acts as an effective osmole

Answer 130

ADH also increases the permeability of the medullary part of the collecting duct to urea, causing its reabsorption. This in turn causes water to follow. The rise in urea concentration in the tissues causes it to passively move down its concentration gradient into the ascending limb, which is permeable to Urea but impermeable to H2O. Urea then passes back into the collecting duct, where it is reabsorbed in the medullary portion and more water follows. Urea is therefore recycled.

Answer 131

SIADH – Syndrome of Inappropriate Anti-Diuretic Hormone secretion In SIADH the secretion of ADH is not inhibited by the lowering of blood osmolarity (negative feedback is removed). This means that excessive amounts of water is retained, causing blood osmolarity to drop and cause hyponatremia (Low blood Na+ concentration). Symptoms of hyponatremia include nausea and vomiting, headache, confusion, lethargy, fatigue, appetite loss, restlessness and irritability, muscle weakness, spasms, cramps, seizures and decreased consciousness or coma. If hypernatremia comes about because of SIADH the condition may be treated with ADH Receptor Antagonists.

Answer 132

At the cortico-medullary border, there is no osmotic gradient. However the medullary Intersticium is hyperosmotic up to 100 mOsmol/Kg at the papilla. There is a gradient of increasing osmolarity as you descend. The active transport of NaCl out of the TAL and the recycling of urea sets up the osmotic gradient. The action of the TAL is crucial, removing solute without water, diluting the filtrate and increasing Intersticium osmolarity. If you block the NaK2Cl transporters in the TAL with a loop diuretic (E.g. Furosemide) the medullary Intersticium becomes isosmotic and large amounts of dilute urine is produced.

Answer 133

The Loop of Henle acts as a counter current multiplier, to set up the osmotic gradient: Tubule filled initially with isotonic fluid. Na+ ions are pumped out of the ascending loop (Na/K/2Cl co-transporter), raising the osmotic pressure outside the tubule and lowering it inside. (Max concentration difference inside to out is 200 mOsmol/L). Fresh fluid enters from the glomerulus, and enters the descending limb. As the descending limb is permeable to water, it leaves via osmosis to raise the osmotic pressure inside the descending tubule to 400mOsmol/L. More fluid enters from the glomerulus, pushing the concentrated (400mOsmol/L) fluid into the ascending limb. The Na+ pump then produces another 200 mOsmol/L gradient across the membrane. But it started with a more concentrated solution (400mOsmol/L). So external osmolarity rises to 500mOsmol/L. Fresh fluid again enters; water leaves via osmosis until the osmotic pressure in the descending tubule is 500mOsmol/L. This is then pushed into the ascending limb, where the Na+ pump produces yet another 200 mOsmol/L gradient, raising the interstitial osmolarity to 700mOsmol/L. The final gradient will be limited by the diffusional process.

Answer 134

The concentration gradient that the loop of Henle sets up would not last long though without the Vasa Recta. These are blood vessels that run alongside the loops, but with opposite flow direction. This counter-current flow allows for the maintenance of the concentration gradient. Isosmotic blood in the descending limb of the vasa recta enters the hyperosmotic milieu of the medulla, where there is a high concentration of ions (Na+, Cl-, Urea). These ions therefore diffuse into the vasa recta and water diffuses out. The osmolarity of the blood in the vasa recta increases as it reaches the tip of the hairpin loop, where it is isosmotic with the medullary Intersticium. Blood ascending towards the cortex will have a higher solute content than the surrounding Intersticium, so solutes move back out. Water will also move back in from the descending limb of the loop of Henle. Therefore, although there is a large amount of fluid and solute exchange across the vasa recta, there is little net dilution of the concentration of the interstitial fluid because of the U shape of the vasa recta allowing it to act as a counter current exchanger. The vasa recta therefore do not create the medullary hyperosmolarity, but do prevent it from being dissipated.

Answer 135

``` Calcium plays a critical role in many cellular processes: o Hormone secretion o Nerve conduction o Inactivation/activation of enzymes o Muscle contraction o Exocytosis ```

Answer 136

the body very carefully regulates the plasma concentration of free ionised calcium ([Ca2+]), the physiologically active form of the metal, and maintains free plasma [Ca2+] within a narrow range (1.0 - 1.3mmol/L).

Answer 137

In plasma, calcium exists as: o Free ionised species – 45% (Active Form) o Protein Bound – 45%(80% to Albumin) o Complexed– 10% (Citrates, phosphate etc)

Answer 138

The absorption of Calcium is under the control of Vitamin D. About 20-40% of dietary calcium (25mmol) is absorbed and some is excreted back into the gut (2-5mmol). Absorption increases in growing children, pregnancy, lactation and decreases with advanced age. Complexing calcium (e.g. with oxalates) reduces its absorption

Answer 139

``` The kidneys filter 250mmol of Calcium per day, 95-98% of which is reabsorbed, giving a urinary calcium excretion of < 10mmol/day. o 65% Reabsorbed in PCT • Associated with Na+ and water uptake o 20-25% Reabsorbed in loop of Henle o 10% Reabsorbed in DCT • Under the control of PTH ```

Answer 140

Parathyroid Hormone (PTH) regulates the conversion of Calciferol in the kidney to its active form, Calcitriol. Calcitriol is the active form of Vitamin D and works by binding to Calcium in the gut to increase its absorption. - Vitamin D2 Absorbed by Gut Nil - (Prohormone) Vitamin D3 Skin (UV light)Nil - (Prohormone) Calciferol Liver (1st Hydroxylation of Vit D) Nil - (Prohormone) Calcitriol Kidney (2nd Hydroxylation of Vit D), Ca2+ absorption (Binds to Ca2+ in the Gut) - Parathyroid Hormone Parathyroid Gland Conversion of Calciferol to Calcitriol Ca2+ release from bone Ca2+ reabsorption in kidney PTH also affects calcium levels directly; by increasing it’s release from bone and its reabsorption in the PCT of the kidney. It also decreases the reabsorption of phosphate and bicarbonate, as if they are present in the blood with Calcium stones will form. Calcium levels regulate PTH via negative feedback.

Answer 141

o Primary hyperparathyroidism • ~ 1/1,000 of the general population o Haematological malignancies o Non-Haematological malignancies Hypercalcaemia of malignancy comes about due to the production of Parathyroidhormone-Related Peptide (PTHrP). This peptide has AA homology with the active portion of PTH and works to increase plasma Ca2+ concentration via the mechanisms shown above.

Answer 142

``` o Gastrointestinal • Anorexia • Nausea/Vomiting • Constipation • Acute pancreatitis (rarely) o Cardiovascular • Hypertension • Shortened QT interval on ECG • Enhanced sensitivity to digoxin • Renal • Polyuria and polydipsia • Occasional nephrocalcinosis o Central Nervous System • Cognitive difficulties and apathy • Depression • Drowsiness, coma ```

Answer 143

o General measures • Hydration – Increase Ca2+ excretion • Loop diuretics – Increase Ca2+ excretion o Specific Measures • Bisphosphonates – Inhibit the breakdown of bone • Calcitonin – Opposes the action of PTH o Treat underlying condition

Answer 144

Approximately 20% of men and 5-10% of women will develop renal stones in their lifetime, and 70-80% of all renal tract stones are made of Calcium. Factors involved in their formation include low urine volume, hypercalcuria and low urine pH (< 5.47). The mechanism of stone formation is complex, and involves the super-saturation of urine with calcium oxalate. Conservative management of renal stones includes increasing fluid intake, restricting dietary oxalate and sodium, and considering the dietary restriction of calcium and animal protein.

Answer 145

5% (during water loading) | >24% (during dehydration)

Answer 146

67% is always absorbed regardless of actual amount that is filtered/ GFR Autoregulation prevents GFR from changing too much but if any changes occur despite this, glomerular tubular balance blunts the Na+ excretion response

Answer 147

Balance between GFR and rate of absorption of solutes | Must be kept as constant as possible, so if GFR increases, rate of reabsorption must also increase

Answer 148

3Na+-2K+-ATPase on basolateral membrane

Answer 149

Section 1 - Na+ reabsorption Cotransporter with glucose Na-H exchange Cotransporter with amino acid/ carboxylic acids Cotransporter with phosphate (increase in PTH) Aquaporin [urea/Cl-] creates a conc gradient for Cl- reabsorption in section 2 and 3

Answer 150

``` Section 2 &3- Na+ and water reabsorption Na-H exchanger Paracellular Cl- reabsorption Transcellular Cl- reabsorption Aquaporin- sets up osmole gradient favouring water uptake from lumen ```

Answer 151

PCT is highly permeable to water Allows reabsorption of Na+ to be isosmotic with water The tight coupling between Na+ and water reabsorption is called isosmotic reabsorption. This bulk reabsorption of Na+ and water (the major constituents of ECF) is critically important for maintaining ECF volume

Answer 152

Osmotic gradient established by solute reabsorption Hydrostatic force in intersticium Osmotic force in peri tubular capillary due to loss of 20% filtrate at glomerulus, but cells and proteins remained in blood

Answer 153

No, water and sodium reabsorption is separated

Answer 154

Reabsorbs water but not NaCl

Answer 155

Reabsorbs NaCl but not water- known as the DILUTING SEGMENT (dilutes NaCl in the filtrate and so therefore tubule fluid leaving the loop is therefore hypoosmotic (more dilute) compared to the plasma)

Answer 156

Increase in IC [Na+] set up by PCT allows for para cellular reuptake of water from the descending limb (no tight junctions) Concentrates Na+ and Cl- in the lumen of the descending limb ready for active transport in the ascending limb

Answer 157

Impermeable to water Na+ reabsorption is passive- water reabsorption in descending limb creates a gradient for passive Na+ ion reabsorption in thin ascending limb Epithelia have loose junctions - permits para cellular reabsorption of Na+ NaCl transported from lumen into cells by NaKCC2 channel (apical) Na+ then moves into intersticium due to action of 3Na-2K+-ATPase (basolateral) K+ ions diffuse back into lumen via ROMK Cl- ions move into intersticium

Answer 158

NaKCC2 is target for loop diuretics - increased loss of K + in urine - hypokalaemia

Answer 159

Water permeability of early DCT is fairly low and active reabsorption of Na+ results in dilution of filtrate Hypoosmotic (more dilute) fluid enters from the loop and 5-8% Na+ is actively transported by NaCC2 transporter driven by 3Na+-2K+-ATPase Major site of Ca2+ reabsorption via PTH Further dilution means that fluid leaving is more hypoosmotic

Answer 160

NaCC2 transporter

Answer 161

Region responsible for fine tuning filtrate Able to respond to a variety of stimulants and has 2 distinct cell types Principal cells (70%) - reabsorb Na+ by Epithelial Na+ Cell (ENaC) driven by 3Na+-2K+-ATPase - Produces lumen charge - electrical gradient for para cellular Cl- reabsorption and K+ secretion into lumen - Variable water uptake through Aquaporin 2 - dependent on ADH - Have a more distinct membrane than intercalated cells Intercalated cells - Active reabsorption of chloride - secrete H+ ions or HCO3-

Answer 162

Thick ascending limb of LoH This region uses more energy than any other region of the nephron, and is particularly sensitive to hypoxia Needs energy for active transport

Answer 163

Baroreceptors (aortic arch and carotid body)

Answer 164

RAAS ADH ANP SYMPATHETIC NERVOUS SYSTEM

Answer 165

Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole, causes the release of renin from the granular cells of the juxtaglomerular apparatus. Decreased NaCl Concentration at the Macula Densa cells (Due to low perfusion and therefore low GFR) causes Sympathetic stimulation to the JGA. This also increases the release of renin. (Also causes Macula Densa cells to release Prostaglandins --> Afferent Vasodilation) Renin cleaves Angiotensinogen à Angiotensin I, which is in turn cleaved by Angiotensin Converting Enzyme (ACE) to form the active hormone Angiotensin II. Angiotensin II There are two types of Angiotensin II receptors, AT1 and AT2. They are both G-protein coupled receptors. Angiotensin II’s main actions are via the AT1 receptor Actions of Angiotensin II o Vasoconstriction • Works on vascular smooth muscle cells, increases TPR thus BP • Vasoconstriction of afferent and efferent arteriole o Aldosterone • Stimulates the adrenal cortex to synthesise and release Aldosterone • Aldosterone stimulates Na+ and therefore water reabsorption • Acts on principal cells of CD • Activates ENaC and apical K+ channels • Increases basolateral Na+ extrusion via 3Na-2K-ATPase o Sympathetic Activity o Increase Na+ reabsorption • Stimulates Na-H exchanger in the apical membrane of PCT o Thirst • Stimulates ADH release at hypothalamus o Breaks down Bradykinin • Bradykinin is a vasodilator

Answer 166

o Vasoconstriction • Works on vascular smooth muscle cells, increases TPR thus BP • Vasoconstriction of afferent and efferent arteriole o Aldosterone • Stimulates the adrenal cortex to synthesise and release Aldosterone • Aldosterone stimulates Na+ and therefore water reabsorption • Acts on principal cells of CD • Activates ENaC and apical K+ channels • Increases basolateral Na+ extrusion via 3Na-2K-ATPase o Sympathetic Activity o Increase Na+ reabsorption • Stimulates Na-H exchanger in the apical membrane of PCT o Thirst • Stimulates ADH release at hypothalamus o Breaks down Bradykinin • Bradykinin is a vasodilator

Answer 167

• Vasoconstriction by α1-adrenoceptors • Inc. force/rate of heart contraction β1-adrenoceptors o Decreased Renal Blood flow • Decreased GFR and Na+ excretion • Activates Na/H exchanger in PCT o Stimulates renin release from juxtaglomerular cells • Increased Angiotensin II/Aldosterone levels

Answer 168

The baroreceptor reflex works well to control acute changed in BP. It produces a rapid response, but does not control sustained increases as the threshold for baroreceptor firing resets. A 5-10% drop in blood pressure causes low-pressure baroreceptors in the atria and pulmonary vasculature to send signals to the brainstem via the vagus nerve. This activity modulates both sympathetic nerve outflow, secretion of the hormone ADH and reduction of ANP release. A 5-150% change in blood pressure causes high-pressure baroreceptors (carotid sinus/aortic arch) to send impulses via the vagus and glossopharyngeal nerves. A decrease in blood pressure will increase sympathetic nerve activity and the secretion of ADH. Actions of ADH o Addition of Aquaporin to Collecting Duct • Reabsorption of water • Forms concentrated urine • Release stimulated by increases in plasma osmolarity or severe hypovolemia o Thick Ascending Limb • Stimulates apical Na/K/Cl co-transporter • Less Na+ moves out into the medulla, reduced osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin descending limb

Answer 169

o Addition of Aquaporin to Collecting Duct • Reabsorption of water • Forms concentrated urine • Release stimulated by increases in plasma osmolarity or severe hypovolemia o Thick Ascending Limb • Stimulates apical Na/K/Cl co-transporter • Less Na+ moves out into the medulla, reduced osmotic gradient for water to exit the lumen into the peritubular capillaries from the thin descending limb

Answer 170

Acts in the opposite direction to the others o Synthesised and stored in atrial myocytes o Promotes Na+ excretion • Vasodilation of afferent arteriole o High BP à Stretch Atrial Cells • Increased release • Increased Na+ excretion, volume decreases, BP decreases o Low BP à Atrial Cells less stretched • Reduced release • Reduced Na+ excretion, volume increases, BP increases o Inhibits Na+ reabsorption along the nephron

Answer 171

Sustained increase in blood pressure

Answer 172

>140/90 on more than 3 occasions

Answer 173

In around 95% of cases, the cause is unknown. This is known as Essential Hypertension. Genetic and environmental factors may both be involved and the pathogenesis is unclear.

Answer 174

``` Where a cause can be defined, hypertension is referred to as secondary hypertension. Here it is important to treat the primary cause. Examples include: o Renovascular disease o Chronic Renal Disease o Aldosteronism o Cushing’s syndrome ```

Answer 175

o ACE Inhibitors • Prevent the production of Angiotensin II from Angiotensin I • Angiotensin II receptor antagonists o Thiazide Diuretics • Inhibit NaCC co-transporter on apical membrane of DCT • May cause hypokalaemia (more K+ lost in urine) o Vasodilators • Ca2+ channel blockers, reduce Ca2+ entry into smooth muscle cells • α1 receptor blockers, reduce sympathetic tone o Beta Blockers • Block β1-receptors in the heart • Reduces heart rate and contractility Non-pharmacological approaches to the treatment of hypertension include diet, exercise, reduced Na+ intake, reduced alcohol intake.

Answer 176

By water balance

Answer 177

Hypothalamic osmoreceptors

Answer 178

Located in hypothalamus in organum vasculoum of laminae terminal is (OVLT) anterior and ventral to 3rd ventricle

Answer 179

ADH and thirst pathways

Answer 180

Made in hypothalamus | Stored and secreted from posterior pituitary

Answer 181

ADH acts in kidney and affects renal water excretions | ADH controls water loss

Answer 182

Increase in osmolarity Increase in ADH Decrease in urine Increase in water reabsorption

Answer 183

Decrease in osmolarity Decrease in ADH Increase in urine Decrease in water reabsorption

Answer 184

Vasoconstriction

Answer 185

Increases Na+, K+, Cl- reabsorption

Answer 186

Increase water reabsorption Aquaporin 2 insertion Apical membrane does not contain water channels in the absence of ADH- held below the surface and can be rapidly inserted when required ADH binds to receptor--> PKA signalling --> AQP2 inserted into apical membrane

Answer 187

Increases water reabsorption (AQP2) | Increases K+ reabsorption

Answer 188

Increase water reabsorption (AQP2) | Urea reabsorption acts as an effective osmole

Answer 189

ADH also increases the permeability of the medullary part of the collecting duct to urea, causing its reabsorption. This in turn causes water to follow. The rise in urea concentration in the tissues causes it to passively move down its concentration gradient into the ascending limb, which is permeable to Urea but impermeable to H2O. Urea then passes back into the collecting duct, where it is reabsorbed in the medullary portion and more water follows. Urea is therefore recycled.

Answer 190

SIADH – Syndrome of Inappropriate Anti-Diuretic Hormone secretion In SIADH the secretion of ADH is not inhibited by the lowering of blood osmolarity (negative feedback is removed). This means that excessive amounts of water is retained, causing blood osmolarity to drop and cause hyponatremia (Low blood Na+ concentration). Symptoms of hyponatremia include nausea and vomiting, headache, confusion, lethargy, fatigue, appetite loss, restlessness and irritability, muscle weakness, spasms, cramps, seizures and decreased consciousness or coma. If hypernatremia comes about because of SIADH the condition may be treated with ADH Receptor Antagonists.

Answer 191

``` Calcium plays a critical role in many cellular processes: o Hormone secretion o Nerve conduction o Inactivation/activation of enzymes o Muscle contraction o Exocytosis ```

Answer 192

the body very carefully regulates the plasma concentration of free ionised calcium ([Ca2+]), the physiologically active form of the metal, and maintains free plasma [Ca2+] within a narrow range (1.0 - 1.3mmol/L).

Answer 193

In plasma, calcium exists as: o Free ionised species – 45% (Active Form) o Protein Bound – 45%(80% to Albumin) o Complexed– 10% (Citrates, phosphate etc)

Answer 194

The absorption of Calcium is under the control of Vitamin D. About 20-40% of dietary calcium (25mmol) is absorbed and some is excreted back into the gut (2-5mmol). Absorption increases in growing children, pregnancy, lactation and decreases with advanced age. Complexing calcium (e.g. with oxalates) reduces its absorption

Answer 195

``` The kidneys filter 250mmol of Calcium per day, 95-98% of which is reabsorbed, giving a urinary calcium excretion of < 10mmol/day. o 65% Reabsorbed in PCT • Associated with Na+ and water uptake o 20-25% Reabsorbed in loop of Henle o 10% Reabsorbed in DCT • Under the control of PTH ```

Answer 196

Parathyroid Hormone (PTH) regulates the conversion of Calciferol in the kidney to its active form, Calcitriol. Calcitriol is the active form of Vitamin D and works by binding to Calcium in the gut to increase its absorption. - Vitamin D2 Absorbed by Gut Nil - (Prohormone) Vitamin D3 Skin (UV light)Nil - (Prohormone) Calciferol Liver (1st Hydroxylation of Vit D) Nil - (Prohormone) Calcitriol Kidney (2nd Hydroxylation of Vit D), Ca2+ absorption (Binds to Ca2+ in the Gut) - Parathyroid Hormone Parathyroid Gland Conversion of Calciferol to Calcitriol Ca2+ release from bone Ca2+ reabsorption in kidney PTH also affects calcium levels directly; by increasing it’s release from bone and its reabsorption in the PCT of the kidney. It also decreases the reabsorption of phosphate and bicarbonate, as if they are present in the blood with Calcium stones will form. Calcium levels regulate PTH via negative feedback.

Answer 197

o Primary hyperparathyroidism • ~ 1/1,000 of the general population o Haematological malignancies o Non-Haematological malignancies Hypercalcaemia of malignancy comes about due to the production of Parathyroidhormone-Related Peptide (PTHrP). This peptide has AA homology with the active portion of PTH and works to increase plasma Ca2+ concentration via the mechanisms shown above.

Answer 198

``` o Gastrointestinal • Anorexia • Nausea/Vomiting • Constipation • Acute pancreatitis (rarely) o Cardiovascular • Hypertension • Shortened QT interval on ECG • Enhanced sensitivity to digoxin • Renal • Polyuria and polydipsia • Occasional nephrocalcinosis o Central Nervous System • Cognitive difficulties and apathy • Depression • Drowsiness, coma ```

Answer 199

o General measures • Hydration – Increase Ca2+ excretion • Loop diuretics – Increase Ca2+ excretion o Specific Measures • Bisphosphonates – Inhibit the breakdown of bone • Calcitonin – Opposes the action of PTH o Treat underlying condition

Answer 200

Approximately 20% of men and 5-10% of women will develop renal stones in their lifetime, and 70-80% of all renal tract stones are made of Calcium. Factors involved in their formation include low urine volume, hypercalcuria and low urine pH (< 5.47). The mechanism of stone formation is complex, and involves the super-saturation of urine with calcium oxalate. Conservative management of renal stones includes increasing fluid intake, restricting dietary oxalate and sodium, and considering the dietary restriction of calcium and animal protein.

Answer 201

The effects of Acidaemia are severe below pH 7.1, and life threatening below pH 7.0. They include: o Reduced enzyme function o Reduced cardiac and skeletal muscle contractility o Reduced glycolysis o Reduced hepatic function o Increased plasma potassium

Answer 202

``` Alkalaemia reduces the solubility of calcium salts, which means that free Ca2+ leaves the ECF, binding to bone and proteins, resulting in hypocalcaemia. This increases the excitability of nerves. o pH > 7.45 • Paraesthesia • Tetany (uncontrolled muscle contractions) o pH > 7.55 • 45% Mortality o pH > 7.65 • 80% Mortality ```

Answer 203

Using the CO2 and HCO3- system

Answer 204

The normal ratio, which gives a normal pH is 20 : 1, [HCO3-] : pCO2. Anything that alters this ratio will also alter pH.

Answer 205

As hyperventilation leads to hypocapnia (fall in pCO2), the ratio is altered and pH will rise. There is more than 20x the amount of HCO3- than CO2, so relatively more H+ ions are buffered, causing the pH increase. This is known as Respiratory Alkalaemia (or Alkalosis) (pH > 7.45).

Answer 206

Hypoventilation leads to hypercapnia (rise in pCO2). The ratio is altered and pH will fall. There is less than 20x the amount of HCO3- than CO2, so relatively less H+ ions are buffered, causing the pH decrease. This is known as Respiratory Acidaemia (or Acidosis) (pH < 7.35).

Answer 207

Because the pH is controlled by the ratio between CO2 and HCO3- and not absolute values, respiratory acidaemia or alkalaemia can be compensated for by changes in [HCO3-] controlled by the kidney. The kidney controls [HCO3-] via variable renal excretion/production. o If pCO2 rises, [HCO3-] rises proportionately to restore pH • (Compensates for Respiratory Acidaemia) o If pCO2 falls, [HCO3-] falls proportionately to restore pH • (Compensates for Respiratory Alkalaemia)

Answer 208

Metabolically produced H+ ions (e.g. from the metabolism of amino acids or the production of ketones) react with HCO3- to produce CO2 in venous blood. This CO2 is then breathed out through the lungs, giving a directly proportional (1 mmol acid: 1 mmol HCO3-) reduction in arterial HCO3-. This alters the [HCO3-] : pCO2 ratio, meaning that there is less than 20x the amount of HCO3- than CO2. Relatively less H+ ions are buffered, causing a pH decrease. This is known as Metabolic Acidosis (pH < 7.35).

Answer 209

If plasma [HCO3-] rises, for example after persistent vomiting, the [HCO3-] : pCO2 ratio will be altered. More than 20x the amount of HCO3- than CO2 will be present, so relatively more H+ ions are buffered, causing a pH increase. This is known as Metabolic Alkalosis (pH > 7.45).

Answer 210

Again, as pH depends on the ratio of [HCO3-] : pCO2, these changes may be compensated for by altering pCO2. pCO2 is normally kept within tight limits by the Central Chemoreceptors. Changes in plasma pH drive changes in pCO2 via the Peripheral Chemoreceptors. o If [HCO3-] falls, pCO2 is lowered proportionately by increasing ventilation • Compensates for Metabolic Acidosis o If [HCO3-] rises, pCO2 may be slightly raised by reducing ventilation • Can only partially compensate for Metabolic Alkalosis

Answer 211

Like most ions, a large fraction of HCO3- is reabsorbed in the PCT. o 3Na-2K-ATPase sets up a Na+ concentration gradient in PCT cells. o H+ ions are pumped out of the apical membrane up their concentration gradient in exchange for the inward movement of Na+ down its concentration gradient. o The H+ reacts with filtered HCO3-, producing CO2, which enters the cell and reacts with water to produce H+ ions. o The H+ is quickly exported, recreating HCO3-, which crosses the basolateral membrane to enter the plasma. 80-90% of filtered HCO3- is reabsorbed in the PCT, and up to 15% is also reabsorbed in the TAL of the loop of Henle by a similar method.

Answer 212

By the DCT most/all of the filtered HCO3- has been recovered. The Na+ gradient is also insufficient to drive H+ secretion, so H+ is pumped across the apical membrane by a H+-ATPase. These proton pumps are similar to those found in the stomach. When cells export H+, K+ is absorbed into the blood. So if you export a lot of H+, you will also absorb a lot (perhaps too much) K+. This relationship means that blood pH is linked to [K+].

Answer 213

The minimum pH of urine is 4.5 ([H+] of 0.04mmol/L). There is no HCO3- however, so H+ is buffered by phosphate. Phosphate is a Titratable acid, meaning that it can freely gain H+ ions in an acid/base reaction. The rest of the H+ in the urine is attached to ammonia as ammonium.

Answer 214

Metabolic acidosis is associated with hyperkalaemia. As [K+] rises, the kidney’s ability to reabsorb and create HCO3- is reduced. Hyperkalaemia makes intracellular pH alkaline, favouring HCO3- excretion.

Answer 215

Metabolic alkalosis is associated with hypokalaemia. Hypokalaemia makes intracellular pH acidic, favouring H+ excretion and HCO3- recovery.

Answer 216

[HCO3-] increases after persistent vomiting, alongside dehydration. When this occurs the kidneys cannot excrete HCO3- as they are trying to compensate for the dehydration. HCO3- and Na+ recovery is favoured to increase the osmolarity of the plasma and cause the osmotic movement of water. In this case you cannot rely on the kidneys to correct the [HCO3-], however if you correct the dehydration by giving fluids, HCO3- will be excreted very rapidly.

Answer 217

[HCO3-] increases after persistent vomiting (metabolic alkalosis), so the body stops actively secreting H+, as it would make metabolic alkalosis worse. As H+ secretion has stopped, so has K+ reabsorption (Antiporter, Intercalated cells). This means that a dangerous side effect of persistent vomiting is hypokalaemia, which causes paraesthesia, tetany and CVS problems.

Answer 218

Metabolic acidosis will occur if there is excess metabolic production of acids, (lactic acidosis, ketoacidosis) acids are ingested, HCO3- is lost or there is a problem with the renal excretion of acid. If excess acid is produced, the associated anion (e.g. lactate in lactic acid) will replace HCO3- in the plasma. This will influence the anion gap.

Answer 219

The anion gap is the difference between the sum of the measured concentrations of Na+ and K+ and the sum of the measured concentrations of Cl- and HCO3-. If HCO3- is replaced in the plasma by another anion, which is not included in the calculation, the gap will increase. If the problem causing metabolic acidosis lies with the renal excretion of H+, this will change the [HCO3-] directly without replacement by an unmeasured ion, so the anion gap is less likely to change.

Answer 220

Metabolic acidosis

Answer 221

Respiratory acidosis

Answer 222

K+ ions are the most abundant intra-cellular Cation. o 98% of total body K+ content is intracellular o 2% is in the ECF o The body tightly maintains plasma [K+] to a range of 3.5-5.3 mmol/L

Answer 223

``` High [K+] inside cells and inside mitochondria is essential for: o Maintaining cell volume o Regulating intra-cellular pH o Controlling cell-enzyme function o DNA / Protein synthesis o Cell Growth ```

Answer 224

Low [K+] outside cells is necessary for maintaining the steep K+ ion gradient across cell membranes that is largely responsible for the membrane potential of excitable and non-excitable cells. o high ECF [K+] depolarises the cell membrane o low ECF [K+] hyperpolarises the cell membrane

Answer 225

Therefore, changes in extracellular [K+] can cause severe disturbances in excitation and contraction. The potentially life threatening disturbances of cardiac rhythm that are a result of hyperkalaemia are particularly important. Extremely low extracellular [K+] leads to several metabolic disturbances: o Inability of the kidney to form concentrated urine o A tendency to develop metabolic alkalosis (see above) o Large enhancement of renal ammonium excretion

Answer 226

Freely filtered

Answer 227

Passive process By paracellular diffusion Normal or high K+ diet - 67% Low K+ diet or depletion - 67%

Answer 228

``` Active process Driven by Na+K+ATPase pumps in basolateral membrane and Na-K-2Cl transporter in apical membrane Normal or high K+ diet - 20% Low K+ diet or depletion - 20% ```

Answer 229

Normal or high K+ diet - substantial secretion 15-120% | Low K+ diet or depletion - little secretion

Answer 230

Normal or high K+ diet - 10-12% | Low K+ diet or depletion - 10-12%

Answer 231

K+ secretion in the DCT and Cortical CD o Principal cells o Passive processes • Driven by electro-chemical gradient for K+ between the principal cell & lumen o Na+ is reabsorbed via ENaC o This favours K+ secretion through the SEPARATE K+ channel, by creating a negative charge in the lumen. o This process is driven by Na-K-ATPase in the basolateral membrane • Creates the gradient for Na+ absorption

Answer 232

Tubular Factors – Aldosterone, ECF [K+], Acid base status Luminal Factors – increase in Distal tubular flow rate = increase in K+ loss – increase in Na+ delivery to distal tubule = increase in K+ loss

Answer 233

Aldosterone is a steroid hormone, that increases the transcription of Na-K-ATPase in the basolateral membrane and ENaC / K+ channels in the apical membrane. This increased amount of these channels gives increase K+ excretion.

Answer 234

Hyperkalaemia – Stimulates aldosterone secretion (Inc. K+ secretion)

Answer 235

Changes in the ECF pH cause reciprocal shifts in H+ and K+ between ECF and ICF (See below). Acidaemia decreases [K+] in principal cells, thus decreasing secretion Alkalaemia increases [K+] in principal cells, thus increasing secretion

Answer 236

o Intercalated cells o Active process o Mediated by H+-K+-ATPase in the apical membrane

Answer 237

Two homeostatic mechanisms keep the ECF [K+] tightly controlled, External and Internal balance.

Answer 238

o Regulates the total body K+ content, which depends on dietary intake, and excretion (renal/GI). o Responsible for the long-term control of K+ o Controlled by renal excretion

Answer 239

Internal Balance o Regulates K+ movement between ECF and ICF o Responsible for moment to moment control • Quick, within minutes, acts as a K+ buffer o If ECF/Plasma [K+] increases, K+ moves into cells • ECF to ICF • Na-K-ATPase o If ECF/Plasma [K+] decreases, K+ moves out of cells • ICF to ECF • K+ channels

Answer 240

If ECF/Plasma [K+] high Insulin K+ in splanchnic blood stimulates insulin secretion from the pancreas. Insulin increases the amount of Na-K-ATPase, as it provides the drive for the Na-Glucose transporter. The increase in Na-K-ATPase results in uptake of K+. Catecholamines (b2 Agonists) b2 adrenoceptors stimulate Na-K-ATPase. Exercise and trauma increases K+ exit from cells, but also increases catecholamines to help offset the ECF [K+] rise. Aldosterone Aldosterone is a steroid hormone, that increases the transcription of Na-K-ATPase in the basolateral membrane and ENaC / K+ channels in the apical membrane. This increased amount of these channels gives increase K+ excretion. Alkalosis (low ECF/Plasma [H+])

Answer 241

If ECF/Plasma [K+] low Exercise Skeletal muscle contraction gives a net release of K+ (during recovery phase of action potential K+ exits the cell). Increase in plasma [K+] is directly proportional to the intensity of the exercise. Uptake of this K+ from the blood by non-contracting tissues is important in preventing hyperkalaemia (release of Catecholamines). ``` Cell lysis (Trauma) With cell lysis K+ is released from the ICF into the ECF. Possible causes include trauma to skeletal muscle, intravascular haemolysis and cancer chemotherapy. ``` Plasma Hyperosmolarity Increase in plasma osmolarity causes water to move from the ICF à ECF via osmosis. This increases the [K+] of the ICF, and K+ leaves down its concentration gradient. Acidosis (high ECF/Plasma [H+])

Answer 242

Hypokalaemia hyperpolarises cardiac cells • More fast Na+ channels available in active form • Heart more excitable

Answer 243

Hyperkalaemia depolarises cardiac cells • More fast Na+ channels remain in inactive form • Heart less excitable

Answer 244

Hypokalaemia ([K+] < 3.5 nmol/L)

Answer 245

``` External Balance Problems o Inadequate intake o Excessive loss • GI – Diarrhoea / Vomiting • Renal – Diuretic drugs / osmotic diuresis (Diabetes) • High aldosterone levels Internal Balance Problems o Shift of potassium ECF à ICF • Alkalosis ```

Answer 246

o Heart o GI • Neuromuscular dysfunction leading to paralytic ileus o Skeletal Muscle • Neuromuscular dysfunction leading to muscle weakness o Renal • Dysfunction of CD cells --> Unresponsive to ADH --> Nephrogenic diabetes

Answer 247

o Treat cause o K+ replacement – IV/Oral o If due to high aldosterone • K+ sparing diuretics that block action of aldosterone on principal cells • K+ sparing – Amiloride • Aldosterone Antagonist - Spironolactone

Answer 248

Hyperkalaemia ([K+] > 5 nmol/L)

Answer 249

``` External Balance Problems o Inadequate renal excretion • (Increased intake only causes hyperkalaemia in the presence of renal dysfunction) o Acute kidney injury o Chronic kidney injury o Reduced mineralocorticoid effect • Drugs which reduce/block aldosterone action -K sparing diuretics -ACE Inhibitors • Adrenal insufficiency Internal Balance Problems o Shifts of K+ from ICF à ECF • Acidaemia (Ketoacidosis / Metabolic Acidosis) • Cell Lysis ```

Answer 250

o Heart o GI • Neuromuscular Dysfunction --> Paralytic ileus o Acidosis

Answer 251

``` o Reduce K+ effect on heart • IV Calcium Gluconate o Shift K+ into ICF via glucose and insulin IV • Remove excess K+ o Dialysis ```

Answer 252

``` o Remove excess K+ • Dialysis • Oral K+ binding resins to bind K+ in the gut o Reduce Intake o Treat cause ```

Answer 253

The urinary tract is protected form infection by a variety of defence mechanisms. Most important is the regular flushing during voiding, which removes organisms from the distal urethra. Between voiding such organisms may ascend the urethra, therefore infection in commoner in females because the urethra is comparatively short. Other defence factors include antibacterial secretions into the urine and urethra.

Answer 254

Shorter urethra- More infections in female Obstruction- Enlarged prostate, pregnancy, stones, tumours Neurological- Incomplete emptying, residual urine Ureteric reflux- Ascending infection from bladder, especially in children

Answer 255

Faecal flora- Potential urinary pathogens colonise periurethral area Adhesion- Fimbriae and adhesins allow attachment to urethral and bladder epithelium K Antigens- Allow some E. coli to resist host defences by producing polysaccharide capsule Haemolysins- Damage membranes and cause renal damage Urease- Produced by some bacteria e.g. proteus. Breaks down Urea for energy.

Answer 256

Many UTI’s are mild, but renal infections may lead to long term renal damage, and the urinary tract is a common source of life threatening Gram –‘ve bacteraemia. The commonest UTI is one of the lower tract, cystitis. Upper UTI (pyelonephritis) may result from haematogenous or ascending routes of infection.

Answer 257

Bacterial cystitis- Frequency and dysuria, often with pyuria and haematuria Abacterial cystitis- As above but without ‘significant bacteriuria’ Prostatitis- Fever, dysuria, frequency with perineal and low back pain

Answer 258

Acute pyelonephritis- Symptoms of cystitis plus fever and loin pain Chronic interstitial nephritis- Renal impairment following chronic inflammation – infection one of many causes

Answer 259

Covert bacteriuria- detected only be culture. Important in children and pregnancy

Answer 260

The commonest pathogens in the community (80%) are Gram –‘ve rods, particularly Enterobacteriaceae (‘Coliforms’, especially E. coli). Young women and hospitalised patients may also develop a UTI due to coagulase-negative staphylococci, e.g. Staph. Saprophyticus. This is due to increased risk factors, such as catheterisation (biofilms).

Answer 261

``` Pelvic ureteric junction- calculi Ureter: calculi, Ca2+, retroperitoneal fibrosis Vesicoureteric junction - calculi Bladder neck : hypertrophy Prostate : BPH /Ca2+ Urethra. : stricture ```

Answer 262

Uncomplicated UTI – Healthy women There is no need to culture urine in Uncomplicated UTIs, infection is indicated by Nitrite/Leukocyte esterase dipstick testing.

Answer 263

Complicated UTI – e.g. pregnancy, treatment failure, suspected pyelonephritis, complications, males, paediatric ``` Sterile Pyuria (Pus in urine) A UTI is present, but unable to be cultured. Reasons for this include the patient having already been treated with antibiotics, or infected with bacteria that are difficult to isolate or culture (e.g. chlamydia). Can also be due to tuberculosis, or appendicitis (appendix stuck on the bladder) ```

Answer 264

o A mid-stream specimen is collected, as we do not want to culture the urethra’s normal flora, so allow for a small amount of urine to be passed to ‘clear’ it before collecting the sample. o It can be difficult to collect samples from small children, so an adhesive bag can be placed over their genitals. This gives a false positive rate of 20%. o Catheter samples can be taken, not from the bag but by using a needle up a special tube in the catheter. o Supra-Pubic aspiration can be used to get a sample of bladder urine, by using a needle through the abdominal wall, but this is rare. Collected samples are transported at 40C, with a small amount of boric acid in the collection tube. This stops bacterial division to keep the sample representative of the collection time.

Answer 265

o Turbidity • Look to see if the sample is cloudy. Cloudy urine is indicative of UTI. o Dipstick Testing • Leukocyte esterase – Indicates presence of WBCs • Nitrite – Indicates presence of Nitrate reducing bacteria • Haematuria – Many reasons, can’t diagnose UTI • Proteinuria – Many reasons, can’t diagnose UTI

Answer 266

``` Microscopy o Kidney disease o Loin pain, nephritis, hypertension, toxaemia, renal colic, haematuria, renal TB, casts o Suspected endocarditis o Children under 6 o Schistosomiasis o Suprapubic aspirates o When requested ```

Answer 267

Urine Culture A number of colony forming units > 100,000 per ml (105 cfu/ml) distinguishes bacteriuria/contamination. o A single urine specimen is 80% predictive. o Used to investigate complicated UTI’s o Increased sensitivity (down to 102 cfu/ml) o Epidemiology of isolates o Sensitivity testing o Control of specimen quality o Can differentiate between properly collected and contaminated samples (poorly collected samples may contain epithelial cells).

Answer 268

``` Interpretation of Culture Report o Clinical details • Symptoms • Previous antibiotics o Quality of specimen o Delays in culture o Microscopy (if available) o Organism(s) located ```

Answer 269

Type of complicated UTI Pus in urine A UTI is present, but unable to be cultured. Reasons for this include the patient having already been treated with antibiotics, or infected with bacteria that are difficult to isolate or culture (e.g. chlamydia). Can also be due to tuberculosis, or appendicitis (appendix stuck on the bladder)

Answer 270

Not 100% of adult women who present with classic UTI symptoms have a UTI. All are treated as though they have one though until proved otherwise. o 50% Significant bacteriuria o 50% Urethral syndrome • Low-count bacteriuria • Fastidious organisms • Vaginal infection/inflammation • Sexually transmitted pathogens – urethritis • Mechanical, physical and chemical causes

Answer 271

General – Increase fluid intake, address underlying disorders. Bacteria may be present asymptomatically - only treat once symptoms appear.

Answer 272

o 3 Day course of antibiotics | o 3 day course reduces the selection pressure for resistance

Answer 273

o 7 Day course of antibiotics. | o Amoxicillin not appropriate as 50% of isolates are resistant

Answer 274

o 14 day course of antibiotics | o Use more potent agent with systemic activity

Answer 275

o Three or more episodes in one year o No treatable underlying condition o Single, low, nightly dose of antibiotics to prevent bacteria build up in static urine o All breakthrough infections documented

Answer 276

Diuretics block the reabsorption of Na+ and therefore water by the kidney.

Answer 277

Loop diuretics are the most powerful, capable of causing the excretion of 10-25% of filtered Na+ ions. They work by blocking the Na-2Cl Symporter in the apical membrane. E.g. Furosemide, Bumetanide

Answer 278

Thiazide Diuretics Thiazide Diuretics act on the early DCT. They are less potent than loop diuretics, inhibiting only 5% of Na+ reabsorption. They are ineffective in the treatment of renal failure. They work by blocking the Na-Cl Symporter. E.g. Bendroflumethiazide

Answer 279

Both types act on the late DCT to reduce Na+ channel activity. They are both mild diuretics, inhibiting only 2% on Na+ reabsorption. Both reduce the loss of K+ and are called K+ sparing diuretics, and can both produce life threatening hyperkalaemia, e.g. in renal failure. K+ Sparing Example - Amiloride Aldosterone Antagonist Example – Spironolactone

Answer 280

Work by inhibiting action of carbonic anhydrase in the proximal tubule E.g. Acetazolamide Not currently used as a diuretic Diuretics which act in the PCT by inhibiting the enzyme carbonic anhydrase to interfere with Na+ and HCO3- reabsorption. Not used as a diuretic now, as HCO3- loss leads to metabolic acidosis.

Answer 281

By modification of filtrate contents Freely filtered at glomerulus - no reabsorption E.g. Mannitol Not currently used as a diuretic

Answer 282

Loop and Thiazide diuretics increase the loss of Potassium in urine. This may cause Hypokalaemia. K+ sparing diuretics and Aldosterone antagonists reduce the loss of Potassium in urine. This may cause Hyperkalaemia. Both Hypo and Hyperkalaemia can be life threatening (see session 6). As diuretics reduce ECF volume, they will also cause the activation of RAAS. This increase aldosterone secretion, increasing Na+ absorption and K+ secretion, helping to contribute to hypokalaemia. Hypovolaemia o Decreased ECF volume due to excessive loss of Na+ and water o Monitor weight, signs of dehydration and BP (Look for postural hypotension) Hyponatraemia Increase Uric acid levels in blood o Can precipitate attack of Gout Metabolic effects o Glucose intolerance o Increased LDL levels

Answer 283

Hypercalcaemia Heart failure Oedema - kidney problems etc.

Answer 284

Hypertension

Answer 285

Hypokalaemia

Answer 286

Liver failure, cirrhosis Nephrotic syndrome Heart failure Conns syndrome

Answer 287

Cerebral oedema

Answer 288

Hypokalaemia | Hypocalcaemia

Answer 289

Hypokalaemia | Hypercalcaemia

Answer 290

Hyperkalaemia

Answer 291

Hyperkalaemia

Answer 292

Metabolic acidosis

Answer 293

Increases plasma osmolarity thus drawing fluid out from the tissues and cells Alters driving force for renal water absorption No effect on enzymes/ transport proteins Loss of water, Na+, K+ in urine

Answer 294

``` o Conditions with ECF expansion and Oedema • Congestive Heart failure • Nephrotic syndrome • Kidney failure (loop diuretic) • Ascites and oedema due to cirrhosis of the liver (spironolactone) o Acute Pulmonary Oedema • IV Furosemide • Due to left heart failure o Hypertension • Thiazide diuretics • Spironolactone in primary hyperaldosteronism (Conn’s syndrome) o Hypercalcaemia • Loop Diuretics promote calcium excretion by the Loop of Henle o Osmotic diuretics • E.g. Mannitol • Used in cerebral oedema o Carbonic anhydrase inhibitors • Acetazolamide useful in Glaucoma ```

Answer 295

Left sided- heart not pumping properly so blood fills up in heart, pressure backs up, increasing pulmonary pressure, forcing proteins into ECF, water follows, resulting in pulmonary oedema formation Right sided- (can be secondary to left) heart not pumping properly, CVP increases and backs up, so fluid moves out in peripheral vessels- peripheral oedema

Answer 296

Nephrotic syndrome- protein is leaving blood in kidneys via urine Low protein in the blood therefore means there's a reduced oncotic pressure in the blood and thus fluid moves out of blood into ECF and oedema forms. Kidney detects the low blood volume (despite fluid still being in body but just in ECF) and so RAAS is activated causing the body to retain more fluid in the kidney- but the protein is still low and so more oedema consequently forms

Answer 297

Nephrotic syndrome- less protein/ albumin is being produced by the liver Low protein in the blood therefore means there's a reduced oncotic pressure in the blood and thus fluid moves out of blood into ECF and oedema forms. Kidney detects the low blood volume (despite fluid still being in body but just in ECF) and so RAAS is activated causing the body to retain more fluid in the kidney- but the protein is still low and so more oedema consequently forms

Answer 298

``` o Alcohol • Inhibits ADH release o Coffee • increase GFR and decrease Tubular Na+ reabsorption o Other drugs – Lithium, demeclocyline • Inhibit ADH action on Collecting ducts ```

Answer 299

``` o Diabetes Mellitus • Glucose in filtrate à Osmotic Diuresis o Diabetes Insipidus (Cranial) • deceased ADH release from posterior pituitary to Diuresis o Diabetes Insipidus (Nephrogenic) • Poor response of Collecting ducts to ADH to Diuresis o Psychogenic polydipsia • Increase intake of fluid ```

Answer 300

Loop and thiazide diuretics block Na+ and H2O reabsorption in LoH and early DT More Na+, H2O delivered to late DT and CD Fine tuning of Na+ by principal cells - more K+ lost Also faster flow rate of filtrate in tubule lumen means that K+ is secreted and is washed away faster Also diuretics stimulate RAAS causing increase aldosterone release and increased Na+ reabsorption and K+ secretion Causing hypokalaemia

Answer 301

Less Na + in cell --> less Na+ K+ ATPase activity --> so K+ stays I'm ECF Make sure patient is not on K+ supplements ACE inhibitors, has normal renal function etc

Answer 302

Reversible syndrome of impaired brain function Occurs in cirrhosis with advanced liver failure Causes confusion and coma Signs include constructional apraxia and flapping tremors Mechanisms include elevated ammonia levels in blood (liver not detoxifying ammonia) Hypokalaemia can precipitate hepatic encephalopathy Diuretics which do not cause hypokalaemia (e.g. Spironolactone) preferred for treating oedema and ascites in cirrhosis

Answer 303

Sensory : afferent nerves in bladder wall - stretch receptors When 400ml full- signal to void bladder -pain sensation from irritation of bladder, temperature sensation * not referred pain- it's very well localised Signals sent to spinal cord --> thalamus --> cerebral cortex (sensory) --> cerebral cortex (motor)

Answer 304

Thalamus insula Prefrontal cortex Anterior cingulate Supplementary motor area

Answer 305

Continence

Answer 306

Pontine continence centre | L region - dorsal and lateral to M region

Answer 307

Spinal continence centre Thoracolumbar cord Nerves derived from lumbar splanchnics T10-T12 end on inferior mesenteric ganglion L1&L2 end on neurones of hypogastric plexus or presacral nerves

Answer 308

Hypogastric nerve

Answer 309

Hypogastric nerve ends at B3 receptors in fundus and body of bladder Causing detrusor muscle to relax Reducing intravesicular pressure and thus causing continence

Answer 310

Hypogastric nerve ends at Alpha receptors in neck of bladder at internal urethral sphincter Causing it to constrict Reducing intravesicular pressure and thus causing continence

Answer 311

Physiological

Answer 312

Anatomical

Answer 313

``` ENTIRELY VOLUNTARY Cerebral cortex Onuf's nucleus (same root values as supply to renal sphincter) Ventral horn S2-S4 Perineal branch of pudendal nerve External urethral sphincter Constricts Reduces intravesicular pressure causing continence ```

Answer 314

Pontine micturition centre | M region - dorsomedial pontine tegmentum / Barrington nucleus

Answer 315

Spinal micturition centre Sacral subdivision of ANS S2-S4 (from lateral horn of sacral cord)

Answer 316

Pelvic nerve

Answer 317

Pelvic nerve ends at M3 receptors in detrusor muscle Contraction of detrusor muscle Increases intravesicular pressure causing micturition

Answer 318

Internal sphincter relaxes | Increases intravesicular pressure causing micturition

Answer 319

``` Low detrusor pressure Larger residual urine (painless) +/- overflow Incontinence Reduced perianal sensation Lax anal tone ```

Answer 320

``` Dilated ureters Thickened detrusor High pressure detrusor contractions Poor conduction with sphincters Detrusor sphincter dysnergia ```

Answer 321

Complaint of any involuntary leakage of urine

Answer 322

Stress urinary incontinence Urge urinary incontinence- inc. overflow urinary incontinence Mixed urinary incontinence

Answer 323

Stress urinary incontinence

Answer 324

Involuntary leakage on effort or exertion or on sneezing or coughing

Answer 325

Involuntary leakage, accompanied by or immediately preceded by urgency

Answer 326

Retention of bladder causing bladder to swell- can be low pressure and pain free

Answer 327

Involuntary leakage, associated with urgency and exertion, effort, sneezing or coughing

Answer 328

Steadily increases with age

Answer 329

Anything that can weaken the pelvic floor muscles (levator muscles that make up the EUS) E.g. Child birth Obs&Gyn- pregnancy and child birth, pelvic surgery/DXT, pelvic prolapse Predisposing- race, family predisposition, anatomical abnormalities, neurological abnormalities Promoting- comorbidities, age, obesity, increased intra abdominal pressure, cognitive impairment, UTI, drugs, menopause

Answer 330

Ask patient to record amount of fluid they pass for 2/3 days - assess frequency Judge incontinence by number of oads patients has to use per dayto cope with urine leakage Is leakage continuous or intermittent Precipitating factors: coughing, sneezing to categorise type of Urinary incontinence Urgency and frequency of micturition may be made worse by intravesicular inflammatory condition- UTI, bladder stone, tumour Previous surgery of pelvic floor can be important as this mat lead to denier action of parts of bladder - childbirth - development of a SUI in women due to sphincter damage

Answer 331

Height / weight Abdominal exam to exclude palpable bladder Digital rectal exam - prostate (male) and limited neuro exam Females- external genitalia (stress test) and vaginal exam

Answer 332

Mandatory- urine dipstick (UTI, Haematuria, proteinuria, glucosuria) Basic non invasive urodynamics- frequency volume chart, bladder diary (3days), post micturition residual volume (patients with voiding dysfunction) Optional- invasive urodynamics, pad tests, cystoscopy

Answer 333

``` Modify fluid intake Weight loss Stop smoking Decrease caffeine intake (UUI) Avoid constipation ```

Answer 334

Pelvic floor muscle training 8 contractions 3x a day At least 3 months duration Void bladder, stop stream (use those muscles in pelvic floor training)

Answer 335

Bladder training Scheduled voiding (Void every hour during day, must not void in between - wait or leak) Intervals- increased by 15-30 mins a week until interval of 2-3 hours At least 6 weeks of training required

Answer 336

Duloxetine- combined NA and serotonin uptake inhibitor, increased activity of EUS during filling phase, alternative offer to surgery - but not first line (not really used) (SUI) Anticholinergics- act on muscarinic receptors including M3 receptors that cause detrusor to contract, many other side effects as action of M receptor at other sites - e.g. Oxybutynin (UUI) Botulinum toxin- potent biological neurotoxin that inhibits ACh release, prevents detrusor muscle contraction (as pelvic nerve cannot release ACh to act on M3 receptors) (UUI) B3 agonists (2014)- mirabegron increase bladders capacity to store urine

Answer 337

Low-tension vaginal tapes are the commonest surgical intervention. It is a minimally invasive technique with a success rate of > 90%. They work by supporting the mid urethra with a polypropylene mesh. Open retropubic suspension procedures correct the anatomical position of the proximal urethra and improve urethral support. Classic fascial sling procedures support the urethra and increases bladder outflow resistance. It involves autologous transplantation of the fascia lata or rectus fascia.

Answer 338

Intramural bulking agents improve the ability of the urethra to resist abdominal pressure by improving urethral coaptation. This is achieved by injections of autologous fat, silicone, collagen or hyaluron-dextran polymers.

Answer 339

Medical emergency in which there is an abrupt decreases in GFR, an increase in serum creatinine (>=26.5 umol/L w/i 48 hours OR >= 1.5 x baseline w/i 7 days), a decrease in urine volume (<0.5ml/kg/hour for 6 hours) and an accumulation of nitrogenous waste products (such as urea)

Answer 340

Little urine, less than 500ml of urine/day or less than 20ml/hour

Answer 341

No urine, less than 100ml urine / day indicating blockage of urine flow

Answer 342

Caused by a reduction on renal perfusion If not treated will progress to ATN (at which point cause becomes renal) Appropriate physiological response to renal hypo perfusion- so tubule function is normal Reduced effective volume: - hypovolemia- vomiting, diarrhoea, haemorrhage, dehydration, third spacing (fluid gets moved somewhere else- pancreas) - systemic vasodilation- sepsis, cirrhosis, anaphylaxis- normal blood volume but increased permeability of vessels - cardiac failure- LV dysfunction, valve disease, tamponade- normal blood volume, but decreased blood pressure Impaired renal autoregulation: - preglomerular vasoconstriction of AA- sepsis, hypercalcaemia, hepatorenal syndrome, drugs NSAIDs - post glomerular vasodilation of EA- ACE Inhibitors, Angiotensin II antagonists

Answer 343

Correct volume- administering fluids at slow pace Heart failure- diuretics Infection- appropriate antibiotics

Answer 344

To avoid fluid overloading of the system

Answer 345

Respond very well as initially their renal cells are not damaged and so they can avidly reabsorb salt and water (in response to aldosterone and ADH release)

Answer 346

DIRECT INJURY TO KIDNEYS Acute tubular necrosis (ATN) - continuous from untreated pre renal cause - exogenous and endogenous nephrotoxins damage the tubules - no proteinuria or haematuria Glomerular and Arteriolar disease / Acute Glomerulonephritis (immune disease affecting the glomerulus) - with proteinuria and/or haematuria - Primary- Minimal Change Glomerulonephritis*, Focal Segmental Glomerulosclerosis*, Membranous Glomerulonephritis, Goodpastures syndrome, IgA nephropathy - Secondary- Diabetes Mellitus, Amyloidosis, Vasculitis, SLE Hereditary nephropathies - Thin GBM syndrome -Alports Syndrome Acute Tubulo-Interstitial Nephritis * unknown cause- not due to immune complex deposition- unknown circulating factor more realistic

Answer 347

Reduced perfusion | Nephrotoxins

Answer 348

Damage the epithelial cells lining the tubules and cause cell death and shedding into the lumen

Answer 349

Myoglobin, urate or bilirubin

Answer 350

``` Drugs - gentamicin - ACE inhibitors - Angiotensin receptor blockers - NSAIDs- PG's normally cause vasodilation of AA's in autoregulation, NSAIDs inhibit PG production (by inhibiting cox 1 enzyme), unopposed vasoconstriction of AAs --> low GFR --> AKI Pathogens ```

Answer 351

Supportive treatment, maintaining good kidney perfusion and avoiding nephrotoxins Dialysis- initiated only if kidney can no longer adequately excrete salt, water and potassium - but actually increases mortality risk

Answer 352

Rhabdomyolysis Due to muscle necrosis- release of myoglobin --> ATN Crushing injury- AKI in wars, natural disasters, drug users, elderly Myoglobin is filtered at the glomerulus and toxic to tubule cells- can also cause obstruction

Answer 353

Childhood/ adolescence Responds well to steroids Damage to podocytes, widened fenestrations slits (seen on E.M) Unknown circulating factor damages podocytes (no immune complex deposition) Usually no progression to renal failure

Answer 354

Focal (involves < 50% glomerulus on L.M) Segmental (involving part of glomerular tuft) Sclerosis (scarring) Progresses on from MCGN Adulthood Less responsive to steroids than MCGN Damage to podocytes and scarring Circulating factor responsible for damage (evident by fact that transplanted kidneys undergo same damage) Can progress to renal failure

Answer 355

Because a transplanted kidney will undergo the same damage

Answer 356

Commonest cause of nephrotic syndrome in adults Circulating IgG binds to Phospholipase A2 receptors (PLA2R) on podocytes forming immune complexes which are deposited in subepithelial space Could be secondary and associated with other conditions- malignancies (lymphoma), malaria etc. E.M shows: podocytes damaged by complement activation, dark lumps of immune complexes, new basement membrane material laid down between damaged podocytes Rules of 1/3s- 1/3 get better, 1/3 grumble along, proteinuria, but are fine, 1/3 progress to renal failure

Answer 357

Relatively uncommon but clinically important as it can progress rapidly to glomerular nephritis Autoantibody (IgG) to collagen IV in basement membrane at glomerulus (no extracellular matrix deposit) Crescenteric Glomerulonephritis Can be treated by immunosuppression and plasmapheresis

Answer 358

Commonest glomerular nephropathy at any age Deposition of IgA (normally protects mucosal surfaces) antibody in glomerulus- linked to mucosal infections; mesangial proliferation and scarring may occur Some/ not all patients have proteinuria Lots/ not all progress to renal failure - Visible and invisible Haematuria No effective treatment

Answer 359

Microvascular damage to glomerulus directly, mesangial sclerosis forming nodules (scarring), thickening of the basement membrane (4/5x normal) Diabetes causes an imbalance of the normal turnover of Collagen IV- results in too much collagen Progressive proteinuria and renal failure

Answer 360

Inflammation of blood vessels that will therefore affect the highly vascularised kidneys Blood vessels attacked directly in glomerulus by anti neutrophil cytoplasmic antibody (ANCA) - treatable if caught early Inappropriate activation of neutrophils Crescenteric Glomerulonephritis

Answer 361

Thin Glomerular Basement Membrane Nephropathy Hereditary, Benign, Familial Isolated Haematuria Thin basement membrane (decrease in collagen IV)

Answer 362

``` Hereditary, X linked Abnormal collagen IV Abnormal appearing GBM progresses to renal failure Associated with deafness ```

Answer 363

Inflammation of kidney intersticium - infection- acute pyelonephritis (ascending bacterial infection) - toxin induced- drugs (nephrotics)

Answer 364

Haemolytic uraemia syndrome Malignant hypertension Preeclampsia - endothelial damage --> platelet and thrombi --> partial obstruction of small arteries --> destruction of RBCs --> low platelets, haemolysis, anaemia - microangiopathic haemolytic anaemia

Answer 365

Indication of obstruction to urine flow after urine has left tubules Obstruction can occur at bladder, urethra, ureters (bilateral) Obstructions can be: - within lumen- calculi (stones- both renal pelves, ureters, neck of bladder, urethra, >10mm won't always pass- pain and Haematuria), blood clot, papillary necrosis, tumour of renal pelvis, ureter or bladder - within the wall- congenital (pelviureteric neuromuscular dysfunction, megaureter, neurogenic bladder), ureteric stricture, usually cause chronic not acute injury of kidney - outside the lumen, exerting an inward pressure- prostatic hypertrophy, malignancy, aortic aneurysm, diverticulitis, accidental ligation of ureter in surgery

Answer 366

``` Cool peripheries Increased pulse Low blood pressure Postural hypotension Low jvp Increased skin turgor Dry axillary ```

Answer 367

``` Gallop rhythm Raised BP Raised jvp Pulmonary oedema- basal crackles and dyspnoea Peripheral oedema- sacral/ ankle ```

Answer 368

``` Pyrexia and rigors Vasodilation, warm peripheries Bounding pulse Rapid capillary refill Hypotension ```

Answer 369

``` Anuria Single functioning kidney History of renal stones, prostatism, previous pelvic/ abdominal surgery Palpable bladder Pelvic/ abdominal masses Enlarged prostate (DRE) ```

Answer 370

Asymptomatic glomerular disease is detected incidentally by dipstick urinalysis, e.g. at a health check or life insurance medical. It may be detected as microscopy haematuria, proteinuria or both. Sometimes hypertension is detected at the same time. The first investigation carried out is a cystoscopy, with a renal biopsy not being mandatory. o Microscopic Haematuria • Renal Stones / Tumours • Arteriovenous malformations • Glomerular Disease o Microscopic Proteinuria • Non-nephrotic proteinuria < 3.5g/24hrs protein in urine • May be associated with other conditions other than glomerulonephritis

Answer 371

Urological intervention to reestablish blood flow

Answer 372

Episodic macroscopic haematuria associated with glomerular disease is often brown or smoky in colour rather than red. Clots are very unusual. It needs to be distinguished from other causes of red or brown urine, including haemoglobinuria, myoglobinuria and consumption of food dyes (e.g. beetroot). o Macroscopic Haematuria is usually painless. o Commonest glomerular cause is IgA nephropathy. o Requires urological work up.

Answer 373

A non-specific disorder, where the kidneys are damaged, leaking a large amount of protein into the urine

Answer 374

``` Classic Triad of Findings: o Proteinuria (>3.5g/24hrs) o Hypoalbuminaemia o Oedema • (+ Hyperlipidaemia- xanthelasma, corneal arcus, tendon Xanthoma) • (+ Muehrcke’s Bands) ```

Answer 375

Requires renal biopsy for diagnosis, using an ultrasound-guided needle. The biopsy is aimed at the bottom of the kidney, to try to make sure a piece of cortex is biopsied. As there are no glomeruli in the medulla, it would not be useful for diagnosis.

Answer 376

``` Minimal change Glomerulonephritis Focal segmental Glomerulosclerosis Membranous Glomerulonephritis Diabetes mellitus Amyloidosis ```

Answer 377

A collection of signs (syndrome) associated with disorders affecting the kidneys (specifically glomerular disorders), characterised by having small pores in the podocytes of the glomerulus large enough to permit proteins and red blood cells.

Answer 378

``` o Rapid onset o Oliguria o Hypertension o Generalised oedema o Haematuria with smoky brown urine o Normal serum albumin o Variable renal impairment o Urine contains blood protein and red blood cell casts ```

Answer 379

Goodpastures syndrome | Vasculitis

Answer 380

IgA nephropathy | Hereditary nephropathies - thin GBM and Alports

Answer 381

Rapidly Progressive Glomerulonephritis describes a clinical situation in which glomerular injury is so severe that renal function deteriorates over days. The patient may present as a uraemic emergency with evidence of extrarenal disease. It is associated with crescentic glomerulonephritis. A renal biopsy is required for diagnosis.

Answer 382

The natural course of many forms of glomerulonephritis is slowly progressive renal impairment, including hypertension, dipstick abnormalities and uraemic syndrome. It is often associated with small, smooth, shrunken kidneys. Biopsies are hazardous and unlikely to provide diagnostic material.

Answer 383

``` o Tiredness and lethargy o Breathlessness o Nausea and vomiting o Aches and pains o Sleep reversal o Nocturia o Restless legs o Itching o Chest pains o Seizures and coma ```

Answer 384

Renal failure (also kidney failure or renal insufficiency) is a medical condition in which the kidneys fail to adequately filter waste products from the blood. The two main forms are acute kidney injury, which is often reversible with adequate treatment, and chronic kidney disease, which is often not reversible.

Answer 385

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.

Answer 386

Age o There is a correlation with increasing age. o Uncommon in men younger than 50. Family History o 4x increased risk o If one 1st degree relative is diagnosed with Prostate Cancer before age 60 o After age 60 any diagnosis was probably age related Race o Incidence in Asian < Caucasian < Afro-Caribbean

Answer 387

``` Usual o Vast majority asymptomatic o Urinary symptoms • Benign enlargement of prostate • Bladder over activity • +/- CaP o Bone pain • Advanced metastatic o Urinate more frequently, difficulty in starting to urinate, taking long time while urinating, feeling bladder had not emptied fully Unusual o Haematuria • In advanced prostate cancer ```

Answer 388

A Digital Rectal Examination (DRE) and Serum PSA (Prostate specific antigen) are used to assess whether or not a biopsy of the prostate is necessary. If it is, it is carried out via a TRUS (TransRectal UltraSound) guided biopsy of prostate. Lower urinary tract symptoms (LUTS) are treated with a TransUrethral Resection of Prostate.

Answer 389

Locally established prostate cancer - surveillance, radical prostectomy, radiotherapy Locally developmental prostate cancer- high intensity focussed ultra sound, cryotherapy, brachytherapy Localised advanced prostate cancer- surveillance, hormones, radiotherapy Metastatic - hormones, palliative (chemotherapy, radiotherapy bisphosphonates)

Answer 390

Gleason grading system

Answer 391

Bladder Cancer is the 7th most common cancer in the UK, but its incidence is decreasing. The male to female ratio is 2.5:1, and 90% are Transitional Cell Carcinomas (TCC)/ 10% are Squamous Carcinomas

Answer 392

``` Haematuria UTI / obstructions Prolonged natural history May present with metastases Tumour cells exfoliate into urine ```

Answer 393

o Smoking • 4x Increased Risk o Occupational exposure (20 year latent period) • Rubber or plastics manufacture (Arylamines) • Handling of carbon, crude oil, combustion (Polyaromatic hydrocarbons) • Painters, mechanics, printers, hairdressers o Schistosomiasis (e.g. Egypt)

Answer 394

``` o Ultrasound • Hydronephrosis – Swelling of kidney due to backup of urine o CT Urogram • Filling defect • Ureteric structure o Retrograde pyelogram – Inject contrast into the ureter o Ureteroscopy • Biopsy • Washings for cytology ```

Answer 395

Staging o 75% of Cancers are superficial (Ta/T1) o 5% are Tis (In situ) o 20% are muscle invasive

Answer 396

Renal Cell Carcinoma is the 8th most common cancer in the UK, making up 95% of all upper urinary tract tumours. The incidence and mortality are increasing. There is a Male to Female ratio of 3:2, and 30% of RCC have metastases on presentation.

Answer 397

o Smoking doubles risk o Obesity o Dialysis

Answer 398

``` Usually late Haematuria Abdominal mass +/- loin pain Cannonball metastases in lungs Unknown origin of fever, night sweats Weight loss, malaise Paraneoplastic syndrome ```

Answer 399

``` Treatment High risk non-muscle invasive TCC o Check cystoscopies o Intravesical chemotherapy/immunotherapy Low risk non-muscle invasive TCC o Check cystoscopies Muscle Invasive TCC o Potentially curative • Radical cystectomy or radiotherapy (+/- chemotherapy) o Not curative • Palliative chemotherapy/radiotherapy ``` Radical Cystectomy The removal of the urinary bladder. 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. May also attempt to reconstruct the bladder from a piece of small intestine.

Answer 400

Metastases of RCC can spread: To lymph nodes Up the renal vein and vena cava into the right atrium Into the subcapsular fat (Perinephric spread).

Answer 401

Established o Surveillance o Radical nephrectomy • Removal of kidney, adrenal, surrounding fat, upper ureter o Partial nephrectomy Developmental o Ablation (removal of tumour from the surface of kidney via an erosive process) Palliative o Molecular therapies targeting angiogenesis o Immunotherapy

Answer 402

Only 5% of all malignancies of upper urinary tract (Rest are RCC, see above). o 5% are due to the spread of cancer from the bladder up the ureter. o 40% of cancers of the upper urinary tract spread to the bladder.

Answer 403

Smoking Aniline dyes Analgesic abuse Balkans nephropathy

Answer 404

``` Haematuria UTI / obstructions Prolonged natural history May present with metastases Tumour cells exfoliate into urine ```

Answer 405

Ultra sound | Ct scan

Answer 406

Nephro-ureterectomy – Removal of the kidney, fat, ureter and cuff of bladder.

Answer 407

``` o Ultrasound • Hydronephrosis – Swelling of kidney due to backup of urine o CT Urogram • Filling defect • Ureteric structure o Retrograde pyelogram – Inject contrast into the ureter o Ureteroscopy • Biopsy • Washings for cytology ```

Answer 408

Progressive and irreversible loss of renal function over a period of months to years. Functioning renal tissue is replaced by extra-cellular matrix; histologically this gives rise to glomerulosclerosis and tubular interstitial fibrosis. As a result, there is a progressive loss of both the excretory and hormone functions of the kidney. Most Glomerular disease that lead to Chronic Renal Failure are characterised by the development of proteinuria and systemic hypertension.

Answer 409

``` o Immunologic • Glomerulonephritis o Infection • Pyelonephritis o Genetic • Polycystic Kidney Disease (PCK) • Alport’s Syndrome o Obstruction and reflux nephropathy o Hypertension o Vascular o Systemic Disease • Diabetes • Myeloma o Cause unknown ```

Answer 410

1 >90 GFR Kidney damage with normal or increased GFR Need other evidence of kidney damage (U/A or USS) 3.3% of population

Answer 411

``` 2 60-89 GFR Kidney damage with mild GFR fall Need other evidence of kidney damage (U/A or USS) 3 % of population ```

Answer 412

``` 3 30-59 GFR Moderate fall in GFR Symptoms +/- 6 ```

Answer 413

``` 4 15-29 GFR Severe fall in GFR Symptoms ++ 0.2 ```

Answer 414

5 <10ml/min GFR 0.1

Answer 415

85% of patients with CKD will be identified by looking in registries for diabetes, hypertension and ischaemic heart disease. It is more common in the Elder, Ethnic minorities and the socially disadvantaged.

Answer 416

Cardiovascular o Atherosclerosis o Cardiomyopathy o Pericarditis

Answer 417

o Anaemia | • Decreased or resistance to Erythropoietin

Answer 418

o Renal Bone Disease o Decreased GFR means that less Phosphate is excreted, increasing its serum concentration. It then forms complexes with free Calcium, reducing its effective serum concentration. This stimulates the Parathyroid to produce PTH, causing over activity of Osteoclasts, leading to Osteitis Fibrosa Cystica. o Damage to the kidneys means less Vitamin D undergoes its 2nd Hydroxylation to its active form. This also causes hyperparathyroidism, but additionally causes Osteomalacia. o Non-Bone (e.g. extra articular) Calcification

Answer 419

o Neuropathy o Seizures o Coma

Answer 420

``` o Tiredness o Breathlessness o Restless legs o Sleep reversal o Seizure o Aches and pains o Nausea and vomiting o Itching o Chest Pain ```

Answer 421

Patients with CKD are more likely to die from a CVS event than require dialysis.

Answer 422

Measuring Renal Function A normal GFR range is 80-120ml/min, and renal function can be expressed by a percentage of this. GFR can be measured via Inulin clearance or 24hr Creatinine clearance. If Creatinine is used to measure GFR, it needs to be modified to Estimated GFR (eGFR) by an equation to take into account age, sex, gender and ethnicity. ``` Creatinine is not a perfect marker for renal function, as someone with a GFR of 40% of normal can still have a normal Creatinine level. Further to this it is only accurate in adults and only defines Chronic kidney disease (Not useful in acute renal failure). Assessment of Cause of CKD o Auto-Antibody screen o Complement o Immunoglobulin o ANCA o CRP o SPEP/UPEP o Imagining of kidneys • Ultrasound for size and Hydronephrosis • CT • MRI ```

Answer 423

``` Conservative Management of CKD To prevent of delay progression, there are several potentially modifiable risks: o Lifestyle o Smoking o Obesity o Exercise o Treat Diabetes (If present) o Treat Blood Pressure (If high) o ACE Inhibitors / Angiotensin Receptor Blockers o Lipid Lowers (Diet / Statins) ``` Further to this the patient should be monitored by checking their eGFR and indications for initiation of dialysis

Answer 424

Renal Replacement Therapy (RRT) When native renal function declines to a level when it is no longer adequate to support health, usually when GFR is < 10ml/min. RRT is either dialysis or renal transplantation.

Answer 425

Indications for the Initiation of Dialysis include uraemic symptoms, acidosis, pericarditis, fluid overload and hyperkalaemia.

Answer 426

There are two types of dialysis, Haemodialysis and Peritoneal Dialysis.

Answer 427

Haemodialysis requires the creation of a Ateriovenous (AV) Fistula, a connection between an artery and vein. The difference in pressure means that blood moves from the artery à vein, causing it to dilate and develop a muscular wall. This provides vascular access. Using this vascular access, the patient is connected up to a dialysis machine, which contains highly purified water across a semi-permeable membrane. This allows for ‘filtering’ of the patient’s blood. Anti-coagulation is also needed to prevent the patient’s blood from clotting in the machine.

Answer 428

Effective (Survivors > 25 years) 4/7 days free from treatment Dialysis dose easily prescribed

Answer 429

``` Fluid/Diet restrictions Limits holidays Access problems CVS instability High capital cost ```

Answer 430

Peritoneal dialysis requires the peritoneal membrane, blood flow and peritoneal dialysis fluid. Peritoneal Dialysis Fluid is put into the peritoneal cavity, and the dialysis occurs across the peritoneal membrane (semi-permeable membrane). The fluid is then drained away and disposed of.

Answer 431

``` Low Technology Home technique Easily learned Allows mobility CVS stability Better for elderly and diabetics? ```

Answer 432

``` Frequent exchanges (~4/day) No long term survivors yet Frequent treatment failures Peritonitis Limited dialysis dose range High revenue costs ```

Answer 433

All patients with progressive CKD or end-stage renal failure should be considered from transplantation. ``` Sources of kidneys for transplantation: o Cadaver donors o Non-heart beating donors o Living related donors/friends o Autristic donors ``` When a kidney is transplanted, it is not to the normal anatomical location, but to the iliac fossa. This is because it can easily be connected both to the iliac vessels and the bladder.

Answer 434

``` Restores near normal renal function Allows mobility and “rehabilitation” Improved survival Good long term results Cheaper than dialysis ```

Answer 435

``` Not all are suitable Limited donor supply Operative morbidity and mortality Life long immunosuppression Still left with progressive CKD ```