Physiology

Question 1

Mesangial cells role

Answer 1

can contract and alter blood flow

not part of the filtration barrier. It forms an anchor for the glomerulus

Question 2

Juxtaglomerular cells role

Answer 2

produce renin

Question 3

Macula densa cell role

Answer 3

Chemoreceptors, detect reduction in Cl content in distal convoluted tubule –> renin release if decreases

Tubuloglonerular reflex

Question 4

Podocyte cell role

Answer 4

Found in glomerulus and important in filtration

Foot like projections

Question 5

Layers of the filtration membrane and what substances can get through

Answer 5

Capillary endothelial cell lumen membrane (excludes negatively charged molecules)

Capillary basement membrane

podocyte foot processes the outermost portion of the filtration membrane and can engulf macromolecules.

Only small and/or positively charged molecules can pass through the filtration membrane

Question 6

What forces affect filtration in the glomerulus

Answer 6

glomerulus hydrostatic pressure

-> afferent arteriole pressure

Opposed by Bowmans capsule pressure and glomerular osmotic pressure

Question 7

What is GFR and what affects it

Answer 7

The volume of fluid that filters into the Bowmans capsule per unit time. It is a good indicator of renal function

Affected by the net filtration pressure - so changes to afferent/efferent arteriole pressure, bowmans capsule pressure or glomerular osmotic pressure can alter GFR

Question 8

How do changes in afferent/efferent tone affect GFR

Answer 8

Afferent dilation –> increased GFR
Decreased afferent pressure (constriction) –> decreased GFR

Efferent constriction –> increased GFR
dilation -> decreased GFR

Question 9

Substance characteristics important for GFR measure

Answer 9

completely excreted by the kidneys (not metabolised elsewhere) and not reabsorbed or secreted in the tubules

Example of good measure is inulin

Question 10

Source of renin and mechanisms that cause its release

Answer 10

Juxtaglomerular cells located near the afferent arteriole and diffuses into the glomerular vessel

1) BaroR mechanism detect reduction in pressure. Stops signal if pressure normalises

2) Sympathetic NS release of noradrenaline –> renin release

3) MAcula densa –> detect changes in distal convoluted tubule NaCl –> increase renin release if this decreases

Question 11

Steps in RAAS pathway and outcome

Answer 11

Renin from juxtaglom cells meet angiotensinogen from liver in circulation —> AngI

Ang I in lungs converted to AngII by ACE

AngII –> stimulates aldosterone release and ADH release

AngII also: increases Na retention, causes EFFERENT >afferent vasoconstriction (increasing GFR) as well as constriction of the mesangium and may promote fibrosis with chronicity

In peripheral vasculature AngII causes endothelial dysfunction (vasoconstriction and remodelling) and increases endothelin which provides negative feedback to renin.

Question 12

How is renal blood flow regulated

Answer 12

Preserved in isolation to the rest of the body (impaired by GA)
MYOGENIC REFLEX
At normal MAP of 70-80 afferent arterioles are dilated
–> stretch of afferent arteriole wall causes constriction (via stretch activated Na channels) of the vessel which then lowers net filtration pressure
This prevents damage to the glomerulus from higher pressures

TUBULOGLOmERULAR REFLEX
Reduced ECV/BP –> reduced GFR –> reduced NaCl in distal collecting –> detected by macula densa cells –> stimulation of renin release from juxtaglomerular cells (via PGE2)

Question 13

Steps of Urine production

Answer 13

Glomerular filtration

Tubular reabsorption

Tubular secretion

–> Excretion

Question 14

Reabsorption in proximal convoluted tubule

Answer 14

NaCl isoosmotic

Most of glucose and amino acids via pinocytosis

HCO3

K, PO4, Ca, Mg urea all passively
PTH acts here to increase PO4 reabsorption

Question 15

Outline of urea handling by the kidney

Answer 15

Proximal tubule reabsorbs passively (increases with reduced flow rate)

As water is reabsorbed along the nephron urea concentration in tubule increases

Once at the collecting duct the high urea concentration would inhibit water reabsorption so ADH also incease urea uniporters here.

In the inner medullary collecting duct a urea uniporter facilitates urea reabsorption –> contributes to medullary interstitial concentration gradient

ADH mediates expression of aquaporins and urea uniporters.

Question 16

Role of the vasa recta and loop of henle

Answer 16

runs in close proximity to the loop of henle and maintains the inner medullary concentration gradient through blood running in the opposite direction to tubule flow.

In the descending branch NaCl from the ascending tubule is removed actively.
This means that as the ascending vasa recta travels alongside the descending loop of henle (which has more dilute tubular fluid) it can reabsorb water passively.

This is called counter current exchange. And mostly reabsorbs NaCl and Water.

The continual flow of both blood and urine prevents passive diffusion of water from diluting the medullary interstitium (but increased blood flow can contribute to medullary washout)

Active Mg regulation also occurs here

Question 17

Role of distal convoluted tubule

Answer 17

Site of aldosterone action and manipulation of Na retention.

Also secretes K+ under the influence of aldosterone
K+also affected by tubular flow rate

Question 18

Role of collecting ducts

Answer 18

The duct portion in medulla is another site of urea and water reabsorption (mediated by ADH urea uniporter). Again maintaining medullary tonicity

ADH increases CORTICAL collecting duct permeability to water via aquaporin –> increasing water reabsorption

Also site of aldosterone mediated K+ excretion

Also site of H+ and NH3 secretion

Question 19

What is tissue RAAS and what is its relevance (JSAP RAAS review)

Answer 19

Locally produced RAAS hormones play important roles in normal cardiovascular function and electrolyte-fluid homeostasis, yet also mediate abnormal remodelling in the tissues

Chymase (released from mast cells, cardiac fibroblasts, and vascular endothelial cells during acute and chronic tissue injury and remodeling), a serine protease, catalyzes the formation of AngII from both angiotensin (1,12) and AngI, allowing ACE-independent formation of AngII in the tissue, and this pathway is likely the primary generator of tissue AngII

Question 20

Pathological effects of long term AngII and aldosterone excess (review)

Answer 20

Myocardial remodelling
Vascular remodelling and hypertrophy with endothelial dysfunction (mediated by ET1, ACh, COX2 and inhibition of NOS)
Both often attended by fibrosis through multifactorial mechanisms.

increased ROS
Increased proinflammatory cytokines –> immune cell infiltration
(Macrophages express mineralocorticoid receptors that polarize them to pro-inflammatory M1 subtype when activated)

Glomerular damage, increased intraglomerular pressure
Systemic hypertension
Tubulointerstitial injury
Increased SNS tone
Na and H2O retention
Direct increase in heart rate

Question 21

How does hypokalaemia cause PUPD

Answer 21

ADH resistance

Question 22

How does hypoadrenocorticism cause PUPD

Answer 22

hypoNa due to reduced aldosterone mediated retention → impaired urine concentrating ability through ↓ medullary osmolarity (chronic Na wasting and renal medullary washout

Also loss of glucocorticoid inhibition of ADH

Question 23

How does pyelonephritis cause PUPD

Answer 23

inflammation of renal pelvis can destroy counter-current concentration mechanism of renal medulla. And bacterial endotoxin competition for ADH Rs causing ADH resistance

Question 24

Mechanisms of PUPD (6)

Answer 24

Primary PD - psychogenic, hyperAdr, hepatic encephalopathy, hyperTH, hypothalamic lesion affecting thirst.

Absence/interference of response to ADH: CDI, NDI, hyperAdr, hyperCa, hypoK, pyometra

Increased metabolism and renal blood flow rate: hyperTH

Osmotic diuresis: glucosuria

Reduced medullary hypertonicity: hypoNa (hypoAdr, gut Na loss), decreased urea concentration (ADH deficiency, liver disease)

Structural renal tubule damage.

Question 25

How is protein normally reabsorbed from the glomerular filtrate

Answer 25

Normally the glomerular filtration barrier limits the passage of high MW proteins from blood into glomerular filtrate. Proteins that do undergo filtration are reabsorbed by megalin in health