Physiology Flashcards
Mesangial cells role
can contract and alter blood flow
not part of the filtration barrier. It forms an anchor for the glomerulus
Juxtaglomerular cells role
produce renin
Macula densa cell role
Chemoreceptors, detect reduction in Cl content in distal convoluted tubule –> renin release if decreases
Tubuloglonerular reflex
Podocyte cell role
Found in glomerulus and important in filtration
Foot like projections
Layers of the filtration membrane and what substances can get through
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
What forces affect filtration in the glomerulus
glomerulus hydrostatic pressure
-> afferent arteriole pressure
Opposed by Bowmans capsule pressure and glomerular osmotic pressure
What is GFR and what affects it
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
How do changes in afferent/efferent tone affect GFR
Afferent dilation –> increased GFR
Decreased afferent pressure (constriction) –> decreased GFR
Efferent constriction –> increased GFR
dilation -> decreased GFR
Substance characteristics important for GFR measure
completely excreted by the kidneys (not metabolised elsewhere) and not reabsorbed or secreted in the tubules
Example of good measure is inulin
Source of renin and mechanisms that cause its release
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
Steps in RAAS pathway and outcome
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.
How is renal blood flow regulated
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)
Steps of Urine production
Glomerular filtration
Tubular reabsorption
Tubular secretion
–> Excretion
Reabsorption in proximal convoluted tubule
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
Outline of urea handling by the kidney
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.
Role of the vasa recta and loop of henle
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
Role of distal convoluted tubule
Site of aldosterone action and manipulation of Na retention.
Also secretes K+ under the influence of aldosterone
K+also affected by tubular flow rate
Role of collecting ducts
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
What is tissue RAAS and what is its relevance (JSAP RAAS review)
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
Pathological effects of long term AngII and aldosterone excess (review)
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
How does hypokalaemia cause PUPD
ADH resistance
How does hypoadrenocorticism cause PUPD
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
How does pyelonephritis cause PUPD
inflammation of renal pelvis can destroy counter-current concentration mechanism of renal medulla. And bacterial endotoxin competition for ADH Rs causing ADH resistance
Mechanisms of PUPD (6)
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.
How is protein normally reabsorbed from the glomerular filtrate
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
