The Kidney and its function

Question 1

What is the function of the urinary system?

Answer 1

Excretion: the removal of organic waste products from body fluids Elimination: The discharge of waste products into the environment

Question 2

What are the two major layers of the kidney?

Answer 2

• Cortex (outer layer): composed of ~1.25 million nephrons - Medulla (inner layer): pyramids drain into pelvis which drain into the ureters

Question 3

Name the two types of nephrons that exist

Answer 3

• Cortical Nephrons: 70-80%, located in the cortex, part of the short loop of Henle into the medulla - Jextamedullary Nephron: 20-30%, closer to the medulla, loop of Henle extends deep into the renal pyramids

Question 4

Label the blood supply of the kidney: Renal artery to Nephron to the renal Vein

Answer 4

Question 5

Label the blood supply of the nephron,

Answer 5

• diagram

Question 6

Explain the Sympathetic Nerve supply of the Kidney

Answer 6

Sympathetic supply: postganglionic fibres from the sympathetic chain and fibres from the coeliac ganglion

• supplies arteries, afferent and efferent arterioles and granular cells
• reduces blood supply to kidney during stress

Question 7

Explain the Parasympathetic Nerve supply of the Kidney

Answer 7

Parasympathetic supply: efferent supply from the vagus nerve and the ganglion in the hilum

• may control the tone of the efferent arterioles
• may modify glomerular filtration rate (GFR) and renal blood flow (RBF) Maybe??

Question 8

What happens to endogenous substances drugs that cannot be filtered at the glomerulus

Answer 8

• specialised pumps in the proximal tubule transport the compounds from the plasma into the nephron for excretion
• there are two pumps: organic acids or drugs and organic bases and drugs

Question 9

What is Glomerular filtration dependent on?

Answer 9

• blood pressure
• renal blood flow

Question 10

What is the pathway for glomerular filtrate in the Bowmans capsule?

Answer 10

• through the pores in the glomerular capillary epithelium
• the basement membrane of the Bowman’s capsule: including the contractile mesangial cells
• through the epithelial cells of Bowman’s capsule called podocytes via filtration slits into the capsular space

Question 11

What are the following forces in relation to Glomerular Filtration?

- PGC

- π_BS

- P_BS

- π_GC

Answer 11

- PGC: Glomerular capillary Hydrostatic Pressure

- π_BS: Bowman’s space Oncotic Pressure ( plasma protein pressure)

- P_BS: Bowman’s space Hydrostatic Pressure

- π_GC: Glomerular capillary oncotic Pressure

Question 12

What does P_GC and π_BS equal?

Answer 12

• the total pressure out of the glomerulus
• however, the π_BS is almost 0

Question 13

What does P_BS and π_GC equal?

Answer 13

• the pressure going into the glomerulus

Question 14

What is the equation for filtration pressure and how does it work?

Answer 14

P_GC - (PBS- π_GC)

• π_{BS = <span>0 so it isn’t included in the equation</span>}

_{<span>- the net filtration is out of the glomerulus at <strong>10mmHg</strong></span>}

_{<span>- this gradually decreases by the glomerular capillary</span>}

Question 15

What is the GFR?

Answer 15

Glomerular Filtration rate

• 125mL/day
• remains constant even when there is a systematic change in BP
• this is due to autoregulation of renal blood flow

Question 16

What are the two hypotheses for Autoregulation of Renal Blood Flow?

Answer 16

Myogenic response: (Starling’s Law) change in BP causes arterioles to stretch or constrict to maintain the RBF and in turn GFR

Metabolic response: renal metabolites modulate afferent and efferent arteriolar contraction and dilation. i.e Adenosine, Nitric Oxide

Question 17

What are the five major stages of urine formation, and where do they occur in the kidney?

Answer 17

1. Filtration of blood in the Glomerulus
2. Reabsorption of filtrate and Secretion into tubule in the Proximal tubule
3. Concentration of urine in the Loop of Henle
4. Modification of urine in the Distal tubule
5. Final modification of urine in the Collecting Duct

Question 18

Explain what happens when the FR falls.

Answer 18

• less Na+ enters the proximal tubule
• the macula densa in the distal tubule senses a change in tubular Na+ levels
• this stimulates juxtaglomerular cells to release renin into the blood
• renin release leads to the generation of angiotensin II
• Ang II is a vasoconstrictor, causing BP to increase
• increased BP causes filtration pressure to increase and GFR returns to normal

Question 19

What is reabsorbed in the Proximal tubule and what drives the process

Answer 19

• 60-70% of filtered water, Na+, HCO3-, Cl-, K+ and urea are reabsorbed
• almost complete reabsorption of glucose, amino acids, a small number of filtered proteins
• reabsorption is driven by Na+K+ATPase

Question 20

Describe the action of the Na+K+ATPase pump in the Proximal tubule

Answer 20

• pump is in a 3:2/ Na:K ratio
• PT cells have alow intracellular Na+ conc.
• Cl- follows Na+ by facilitated diffusion,
• phosphate and sulphate are also co-transported with Na+
• PT has an overall negative charge due to the intracellular proteins
• water moves out of PT via osmosis following Na+ out into the interstitial space then the Peritubular capillary

Question 21

What facilitates water reabsorption in the PT?

Answer 21

• PT is very permeable to water
• Transcellular movement of water occurs via aquaporins

the four main ones

• AQP-1: abundant in the PT and the descending limb of the LOH
• AQP-2: abundant in the collecting duct, expression controlled by ADH
• AQP-3/4: present on the basolateral surface of tubular cells involved with water reabsorption

Question 22

Explained how glucose is reabsorbed from the PT?

Answer 22

• co-transported from the PT using Sodium-Glucose transporters (SGLT) found on the apical membrane
• then they are transported into the blood through GLUt channels on the basolateral membrane

in S1: Proximal convoluted tubule

• SGLT2 channels and Glut 2 channels (90% of glucose absorbed)

in S3: Proximal straight tubule

• SGLT1 channels and Glut1 channels (10% of glucose absorbed)

Question 23

How can changing the reabsorption mechanism in the PT treat type II diabetes

Answer 23

• patients excrete more glucose to cause a hypoglycaemic effect

SGLT2 inhibitors

• Dapagliflozin
• Canagliflozin
• Empagliflozin
• Ipragliflozin
• Topogliflozin

Question 24

What is Dapagliflozin?

Answer 24

• A Sodium-Glucose Transport 2 (SGLT2) inhibitor

Question 25

How are protein reabsorbed in the PT (proximal tubule)?

Answer 25

- reabsorbed by pinocytosis - these are vesicles transported into the cell degraded by lysosomes and amino acids returned to the blood - there's only a limited transport capacity - therefore proteinuria is a sign of glomerular damage and impending renal failure as there should only a low amount of protein in the filtrate

Question 26

What do the specialised pumps OAT and MRP do?

Answer 26

- transport compounds that may not be able to be filtered from the plasma into the nephron OAT: Organic Anion Transporter MRP: Multi-drug Resistance Protein alpha-Ketoglutarate is one of the substances OAT3 channels pump into the blood from the PT

Question 27

What is PAH and what is it's use in the PT?

Answer 27

**Para-amino hippurate** - secreted into the PT from the blood - not an endogenous compound so it can be used to measure tubular secretion - transported into PT cells from blood with alpha-ketoglutarate or other ci/tri carboxylates - It is transported out of the PT cells one exchange for the anion present in the PT lumen

Question 28

What occurs in the Loop of Henle?

Answer 28

- recovery of fluid and solutes from the glomerular filtrate - extraction of water in the descending limb - extraction Na+ and Cl- in the ascending limb - in the juxtamedullary nephron this is more important as the nephron is longer hence a longer LOH

Question 29

How is the descending limb of the LOH fit for its purpose?

Answer 29

- cells are flat no active transport channel proteins ( no Na+ or Cl-) - Has AQP-1 channels, freely permeable to water - passive movement of water via tight junctions

Question 30

How is the ascending limb of the LOH fir for purpose?

Answer 30

- tubular wall is permeable to water - has specialised Na+/K+2Cl- (NKCC2) co-transporters: this is electroneutral as the ratio is 1:1:2 - Na+, K+ and Cl- is reabsorbed but no water

Question 31

What is countercurrent multiplication?

Answer 31

- this occurs in the LOH - it creates a large osmotic gradient in the medulla allowing the filtrate to vary from isotonic entering the LOH, to hypertonic in the descending limb, then hypotonic in the ascending limb - this is facilitated by the NKCC2 cotransporter in the ascending limb - it allows passive reabsorption of water from tubular fluid in the descending limb - in the ascending limb, ions are being pumped out into the medulla, - the medulla becomes hypertonic so water in the descending limb moves into the medulla low - this can also be facilitated by the movement of urea into the medulla from the collecting duct

Question 32

What percentage of filtrate is reabsorbed into the blood from the LOH?

Answer 32

- Water: 15% - Na+: 20-30% - K+: 20-30% - Cl-: 50% - HCO3-: 10-20% - Ca2+ and Mg2+ : variable

Question 33

What is the function of the Distal Tubule?

Answer 33

- Na+ and Cl- exchanged for K+ throughout the DT - Na+ exchanged for K+ in the late DT and early collecting duct - K+ secretion occurs through Principal Cells: these are sensitive to aldosterone - this is part of the RAAS - Na+ exchanged for H+ in the DT and early collecting duct - involves intercalated cell type alpha or beta: these are involved in acid-base regulation

Question 34

How does the RAAS work in the DT?

Answer 34

- low sodium in the Distal tubule leads to low BP - sensed by the macula densa - stimulates juxtaglomerular cells which release Renin - concerts angiotensinogen to angiotensin I - angiotensin converted to angiotensin II using ACE from the lungs - increased secretion of aldosterone from the adrenal glands - increases NA+ reabsorption from the DT into the peritubular capillary - increased H2O reabsorption into peritubular capillary following Na+

Question 35

What is the action of alpha-intercalated cells

Answer 35

- Secretes acid via H+/Na+ or H+/K+ exchange, involving ATPase or H+ATPase - resulting in the reabsorption of HCO3-

Question 36

What is the action of beta-intercalated cells in the DT?

Answer 36

- secrete HCO3- via Pendrin - results in Reabsorption of H+

Question 37

What is Vasopressin, where is it released from what is its action?

Answer 37

- it is human antidiuretic hormone (ADH) - it is released from the posterior pituitary gland, following hypothalamic stimulation - has a plasma half-life of 10-15 mins - acts on vasopressin V₂ receptors on the basal membranes of principal cells in the DT and collecting duct - activates AQP2 water channels

Question 38

What is Diabetes Insipidus?

Answer 38

- lack of ADH causing a water-impermeable collecting duct - this leads to large volumes of water being excreted each day - treated with synthetic ADH - two major presenting forms can be Nephrogenic or Neurogenic other forms Diposeogenic or Gestational

Question 39

What is Nephrogenic Diabetes Insipidus and what is its treatment?

Answer 39

- the inability of the kidney to respond to ADH normally Treatment - chlorthalidone (diuretic) - Indometacin (anti-inflammatory)

Question 40

What is Neurogenic Diabetes Insipidus and what is its treatment?

Answer 40

- Due to lack of ADH production by the brain Treatment - Desmopressin (ADH analogue) - Vasopressin - Carbamazepine (anti-convulsive)

Question 41

What is SIADH?

Answer 41

- Syndrome of Inappropriate ADH - excessive release ADH : head injury, unwanted effect of drugs (ecstasy) - can cause hyponatraemia (low blood Na+ conc.) and possibly fluid overload

Question 42

What is the treatment for SIADH?

Answer 42

- Syndrome of Inappropriate ADH - V₂ receptor blockers (ADH inhibitors) e. g: demeclocycline, Tolvaptan

Question 43

What substances can increase or inhibit ADH?

Answer 43

Increase - Nicotine - Ether - Morphine - Barbiturates Inhibit - Alcohol

Question 44

What are the 7 groups of patients at risk of developing renal failure?

Answer 44

- Extremes of **Age:** GFR matures at 4 yrs, decreases after 40 yrs - **Polypharmacy** **-** Specific **Disease States:** diabetes, hypertension, CHF, rheumatoid arthritis, renal disease, recurrent UTI - Patients receiving **long-term Analgesia:** NSAIDs = nephrotoxic - **Transplant** patients - **Drug therapy:** antibiotics, anti-HIV etc - Patients undergoing **Imaging procedures:** radiocontrast used

Question 45

What are the 3 main ways to Monitor Renal Function

Answer 45

* Patients clinical condition: * clinical assessment * Use of bedside clinical tests * Modern imaging techniques * macroscopic views of the renal blood flow, filtration and excretory function * Biochemical data * measurement of renal clearance of various substances i.e creatinine * allows evaluation of the ability of the kidney yo handle water and solutes

Question 46

What basic functions should be monitored in the clinical assessment?

Answer 46

- Fluid balance - Electrolyte regulation: K⁺, Na⁺, Ca²⁺, PO₄^2- - EPO production - Vitamin D3 - Excretion of substances - Acid-base balance

Question 47

What are the clinical signs and presenting symptoms of power fluid balance?

Answer 47

- Oedema - presenting as breathlessness

Question 48

What are the clinical signs and presenting symptoms of poor EPO production?

Answer 48

- Pallor (check mucous membranes) - presenting as fatigue

Question 49

What are the clinical signs and presenting symptoms of poor electrolyte regulation?

Answer 49

_Abnormal ECG_ - Absent P waves - Broad QRS complex - Peaked T waves

Question 50

What are the clinical signs and presenting symptoms of low vitamin D3 production?

Answer 50

- Osteomalacia - presenting as bone pain

Question 51

What are the clinical signs and presenting symptoms of poor renal excretion?

Answer 51

- raised blood urea and creatinine conc. _presenting with_ - Pruritis (itching) - Nausea and vomiting

Question 52

What are the clinical signs and presenting symptoms of a poor acid-base balance?

Answer 52

- Low blood pH and BIcarb levels - presenting with deep and rapid respiration

Question 53

What are 4 bedside clinical tests/ data that can be gathered for clinical assessment of renal impairment?

Answer 53

- Weight charts - Fluid balance charts - The degree Oedema - Results of urine dipstick testing: urinalysis for protein, blood and glucose levels

Question 54

Give modern imaging techniques that can/could be used in diagnosing renal impairement

Answer 54

Renography others - Gamma camera planar scintigraphy - Positron emission tomography (PET) - Single protein emission computerised tomography (SPECT)

Question 55

What type of data can you get from biochemical testing to help diagnose renal impairment?

Answer 55

- Plasma or serum creatinine (sCR) - Plasma or serum urea - Blood urea nitrogen

Question 56

What makes up Plasma?

Answer 56

- serum + clotting factors (i.e fibrinogen)

Question 57

What is creatinine and how is it excreted? What is its normal plasma range?

Answer 57

- it's a breakdown product of creatine phosphate in muscle: produced at a constant rate - filtered at eh glomerulus, some excretion into the proximal tubule - normal plasma range: 40-120µmol/L

Question 58

What causes plasma creatinine to increase?

Answer 58

- large muscle mass/ dietary intake - drugs which interfere with analysis: methyldopa, dexamethasone, cephalosporins - drugs wich inhibit tubular secretion: cimetidine, trimethoprim, aspirin - ketoacidosis (affects analysis) - Creatine kinase activity

Question 59

What is the correlation between the severity of the renal failure and the plasma creatinine levels?

Answer 59

- the more severe the renal impairment the higher the plasma creatinine levels

Question 60

What is the normal range of Blood urea nitrogen? - what indicates moderate to sever renal failure?

Answer 60

- 2.5-7.5mmol/L - \>20 mmol/L indicates moderate to sever renal failure

Question 61

What causes BUN- blood urea nitrogen to increase?

Answer 61

- High protein diet - Hypercatabolic conditions: severe infections, burns, hyperthyroidism - Gastrointestinal bleeding; digested blood is a source of urea - Muscle injury - Drugs: Corticosteroids (lowers inflammation), Tetracycline (antibiotic) - Hypovolaemia

Question 62

What causes decreased plasma creatinine levels?

Answer 62

- Reduced muscle mass (the elderly) - Cachexia/ starvation - Immobility - Pregnancy: increased plasma volume in the mother - severe liver disease: liver is also a source of creatinine

Question 63

What causes decreased BUN- blood urea nitrogen levels?

Answer 63

- Malnutrition - Liver disease - Sickle cell anaemia due to increased GFR - SIADH: Syndrome of Inappropriate ADH

Question 64

What is the equation used to measure renal clearance?

Answer 64

**C_x= U_x x V/P_x** ## Footnote C_x= Clearance of X U_x= COnc. of X in urine V= Volume of urine formed in a given time P_x= Conc. of X in systemic blood plasma or serum

Question 65

What are the qualities of an ideal marker of kidney function?

Answer 65

- a naturally occurring molecules - not metabolised - only excreted in the kidney - filtered but not absorbed not secretes or reabsorbed by the kidney (Insulins)

Question 66

Define and explain what renal clearance is?

Answer 66

- the volume of plasma completely clearance of a given substance in unite time - compares the rate at which the *glomeruli filter* a substance against the rate at which the *kidney excretes* that substance via urine

Question 67

What 3 basic functions of the kidney does measurement of Renal clearance give information about?

Answer 67

- Glomerular filtrate (F) - Tubular reabsorption (R) - Tubular secretion (S)

Question 68

What are some drawbacks of the renal clearance equation?

Answer 68

- have to measure overall nephron function - this gives the sum of all transport process occurring along nephrons - no information about precise tubular sites or mechanisms of transport

Question 69

Which organic product is best for measuring GFR?

Answer 69

Insulin - it is filtered in the glomerulus but not secreted in the tubules

Question 70

What are some drawback of using Insulin Clearance to measure GFR?

Answer 70

- Insulin must be administered by IV to get relatively constant plasma or serum levels - chemical analysis is technically demanding - radiolabeled compounds could be used instead of i.e Vit B or EDTA (these may bind to proteins and distort results) - an endogenous substance with insulin-like properties i.e creatinine

Question 71

Why can creatinine clearance be used to give the GFR?

Answer 71

- the Jaffe calorimetry method underestimates creatine conc. - this balances out the overestimate from using the C_x equation - this makes creatinine clearance ~ insulin clearance - it can also be adjusted to body surface area measured CrCl x 1.73/ BSA

Question 72

How can GFR be estimated without collecting urine samples?

Answer 72

- using the Cockcroft-Gault Formula est. GFR (eGFR) = [(140 – Age) x mass (in kilograms)/ plasma creatinine (µmol/L)] x multiplier - multiplier = 1.23 men, 1.04 women

Question 73

What is most commonly used in the UK to estimate GFR?

Answer 73

- MDRD (Modification of Diet in Renal Disease) Formula: - eGFR = 32788 X plasma creatinine-1.154 X age-0.203 X multiplier - mulitplier: 1.21 for black people, 0.742 for non-black women

Question 74

What is PAH para-amino hippuric acid and how can it be used for measuring renal function?

Answer 74

- not usually present in the blood flow - when given almost all is cleared from the kidney in one passage, some is filtered in the glomerulus and remainder is secreted by the PT - ~10% by-passes tubule, travels from efferent arterioles into peritubular capillaries and then into venous renal blood and is not secreted - the uncorrected value of PAH clearance is used and is known as Effective Renal Plasma FLow (ERPF)

Question 75

What is the limit for plasma pH levels before Acidosis results?

Answer 75

- below 7.35

Question 76

What is the limit for plasma pH levels before Alkalosis results?

Answer 76

above 7.45

Question 77

What is the consequences of blood pH outside of their homeostatic boundaries?

Answer 77

can result in - coma - cardiac failure - circulatory collapse at pH \<6.8 or \>8.0 death occurs

Question 78

Give the 3 main types of buffer systems?

Answer 78

- Carbonic/bicarbonate - Protein - Phosphate

Question 79

How do the lungs and kidneys work in tandem to achieve an acid-base balance?

Answer 79

- lungs excrete a large amount of CO_2, which could potentially lead to H+ being produced - the kidneys secrete and excrete non-volatile acids produced from metabolism i.e. lactic acid, which the lungs can't excrete - however, kidneys also reabsorbed large amounts of HCO₃^-, which acts as a buffer

Question 80

How is acidemia controlled in the Proximal Tubules of the kidney?

Answer 80

- increased H+ secretion, through Na+ anti-tranporter - Increased HCO₃^- reabsorption through Na+ cotransporter

Question 81

How is acidemia controlled in the Distal Tubule and the Collecting Duct (Intercalated cells) of the kidney?

Answer 81

- Increased H+ secretion into the tubular fluid - Increased HCO₃^- reabsorption from the tubular fluid - HCO₃^- generation from amino acids, destination occurs - HCO₃^- exchanged with Cl- from the peritubular capillary, forms Sodium Bicarb in peritubular capillary

Question 82

What is the cause and treatment of respiratory acidosis?

Answer 82

_Cause_ - inadequate ventilation; chronic or acute _Treatment_ - restore ventilation - treat underlying dysfunction or disease - IV lactate solution (converted to HCO₃^- buffer in the liver)

Question 83

What is the cause and treatment for metabolic acidosis?

Answer 83

_Cause_ - all conditions other than respiratory that decreases pH; always chronic _Treatment_ - IV isotonic HCO₃^- - IV lactate solution (converted toHCO₃^- buffer in the liver); Ringer's or Hartmann's solution

Question 84

How can you suffer a loss of H+ ions (may contribute to alkalosis)?

Answer 84

- use of H+ in the metabolism of organic anions - loss in vomit - loss in urine - Hyperventilation

Question 85

What is the cause and treatment of respiratory alkalosis?

Answer 85

_Cause_ - Hyperventilation: acute or chronic _Treatment_ - treat underlying cause - breathe into a paper bag - GIve IV Cl- containing solution- increase HCO₃^- secretion

Question 86

What is the cause and treatment of metabolic alkalosis?

Answer 86

_Cause_ - all conditions other than respiratory that increase pH; always chronic _Treatment_ - give electrolytes to replace those lost - give IV Cl- containing solution (increase HCO₃^- excretion) - treat the underlying condition

Question 87

What physiological factors in the body triggers the release of ADH (vasopressin)?

Answer 87

- Plasma Osmolality - Effective Circulating Volume (ECV):

Question 88

For Plasma Osmalality what is the following? - Sensors - Efferent pathways - Effector - Affect

Answer 88

- Sensors: Osmoreceptors in the hypothalamus - Efferent pathways: ADH, Thirst - Effector: Kidney, Brain: drinking behaviour - Affect: renal excretion of water, water intake

Question 89

For Effective Circulating Volume, what is the following? - Sensors - Efferent pathways - Effector - Affect

Answer 89

- Sensors: Baroreceptors - Efferent pathways: ADH, RAAS, ANP, SNS - Effector: ST: heart, blood vessels, LT: Kidney - Affect: ST: blood pressure, LT: Na+ excretion (decreased in low ECV)

Question 90

Where are the 'Low pressure' blood volume receptors amongst the Central vascular sensors?

Answer 90

- Large systemic veins - Cardiac atria - Pulmonary Vasculature (very important)

Question 91

Where are the 'High pressure' blood volume receptors amongst the Central vascular sensors? give sites of any other receptors as well

Answer 91

- Carotid Sinus - Aortic arch - Renal afferent arteriole (these are less important) - there are also sensors in the CNS and liver which are less important

Question 92

# ECV= Effective circulating volume Explain the effect of a decreased ECV and the RAAS

Answer 92

Decreased ECV stimulates renin release via: - decreased renal perfusion pressure detected in the afferent arteriole (the renal baroreceptor) - decreased Na+ concentration in distal tubule detected by the **macula densa cells** - decreased systemic BP also triggers the effect of the SNS supplying the JGA (where renin is released) - this leads to increased Na+ reabsorption by the distal tubule

Question 93

What are the important actions of Angiotensin II?

Answer 93

All actions of AngII are designed to increase ECV 1. Enhances tubular Na+ transport in the kidney 2. Stimulation of aldosterone release from adrenal cortex: more Na+ and water reabsorbed from DT and CD 3. Acts on the hypothalamus to stimulate thirst and ADH release into circulation 4. Vasoconstriction of renal and other systemic vessels: increased systemic BP 5. Longe term: AngII causes renal cells to hypertrophy: more protein synthesis of Na+ transporters and channels

Question 94

What are the important actions of Aldosterone?

Answer 94

All actions of aldosterone are designed to increase ECV - Stimulates Na+ reabsorption in the DT and CD - exerts indirect negative feedback on the RAAS by increasing ECV and by lowering plasma K+ concentrations - Important in conserving Na+ and water, but also important in preventing large variation in plasma K+ levels (by causing its excretion out of the kidney)

Question 95

What are the 3/4 volume regulation pathways involving the ECV?

Answer 95

_RAAS_ - detected by renal baroreceptors and renal Na+ sensors -\> activation of the RAAS -\> Aldosterone and AngII action _ANS_ - detected by peripheral baroreceptor -\> signals to the hypothalamus in the brain -\> activation of ANS -\> direct effects on renal thermodynamics, activation of the RAAS _ADH_ - detected by peripheral baroreceptor -\> signals to the hypothalamus in the brain -\> release ADH - decreased ECV= increased plasma osmolality -\> detected by osmoreceptors in the hypothalamus -\> release ADH into circulation

Question 96

Describe the action of Atrial Natriuretic Peptide (ANP)

Answer 96

Actions of ANP are all designed to lower ECV * Atrial myocytes synthesize and store ANP * ­ECV causes atrial stretch which leads to ANP released into circulation * ANP promotes natriuresis: (­ Na+ excretion from the kidney) * Also causes renal vasodilatation -\> increased blood flow -\> increase in GFR -\> more Na+ excreted * More Na+ reaches the macula densa so renin release by JGA is reduced – reduces the effects of AngII * **Overall effect: inhibits action of Renin and opposes effects of AngII**