Nyrer Flashcards
Main functions of kidneys
Homeostatic role:
– water, salt, acid/base, nutrient balance
Excretion:
– removal of metabolic waste products (e.g. urea, uric acid, ammonia, creatinine)
- removal of foreign chemicals and excretion in the urine
Endocrine function:
– produces hormones involved in erythrogenesis (EPO), calcium metabolism (1,25-dihydroxy Vit. D) and blood pressure/flow regulation (renin)
Gluconeogenesis
Kidney diseases
Various defects
Genetic defects
Regulation defects
Various defects
Chronic kidney disease
Diabetic nephropathy
Toxic chemicals (e.g. ochratoxin)
Obstruction of ureter/urethra
Kidney stones
Infections
Glomerulonephritis
Tumors
Regulation defects
Impaired response to vasopressin (Diabetes Insipidus)
hypoaldosteroidism
Too much renin - renal hypertension
Genetic defects
Defect in Na-K-Cl cotransporter – Barter syndrome
Defect in Na channels – Liddle ́s disease
Defect in AQP2 channels – nephrogenic diabetes insipidus
Polycystic kidney disease – defects in primary cilia
Kidney is also a target for drugs used to treat
High blood pressure
Oedema
Type 2 diabetes
Nyren
binyre
nyrebark
nyremarv
nyrebækken
nefron
Nyren er forbundet til arterie og vene
også forbundet til urinblæren via urinlederen
Nephron
Renal copuscle (nyrelegeme)
- Glomerulus + Bowmans kapsel
–>
Proximal tubulus
–>
Loop of Henle
–>
Distal tubulus
–>
Collecting duct
Main elements of nephron function
The nephron forms an ultrafiltrate of the blood plasma and then selectively reabsorbs the tubule fluid and secretes solutes into it
Main renal processes:
Filtration - bulk transport
Absorption - membrane transport processes
Secretion - membrane transport processes
Excretion - filtration + absorption
Filtration
Renal corpuscle (nyrelegeme)
- Glomerulus, Bowman’s capsule and Juxtaglomerular apparatus
Ultrafiltrate føres ud til proximal tubulus og videre ud til collecting duct
Ultrafiltrate
= glomerular filtrate = pre-urine
What molecules do and do not get into the glomerular filtrate
Molecules < 8nm
Water, ions (0.02-0.05 kDa)
Urea (0.06 kDa)
Glukose (0.18 kDa)
Inulin (5.5 kDa)
Myoglobin (17 kDa)
What does not pass through:
- Albumin
- Hemoglobin
- Blood cells
- Protein-bound hormones and minerals
Kidney vascular bed
Important for filtrate formation
- and secretion and absorption and for concentrating mechanism
Renal artery
–> afferent arteriole
–> glomerular capillary network
–> efferent arteriole
–> capillary network surrounding renal tubules
–> renal vein
Blood pressure in the kidney vascular bed
The blood pressure drops as you move through the kidney vascular bed
Starts around 120 mmHg ved renal artery
Falder til ca. 50 mmHg ved glomerular capillaries
Falder til ca. 15 mmHg ved renal vein
Filtration depends on:
Hydrostatic (P) and osmotic (Π) pressures
Net glomerular filtration pressure
= P(GC) - P(BS) - Π(GC)
Favoring filtration:
- glomerular capillary blood pressure (P(GC)) (60 mmHg)
Opposing filtration:
- Fluid pressure in Bowman’s space (P(BS)) (15mmHg)
- Osmotic force due to protein in plasma (Π(GC)) (29mmHg)
Glomerular filtration rate (GFR)
GFR in healthy person is ca. 125 ml/min (which makes about 1/5th of renal plasma flow)
CALCULATE AND REFLECT: 125 ml/min
How much plasma is filtered each day ?
If plasma volume is 3 L, how many times does kidney filter?
How much is filtered each day ? 180 l/day
If plasma volume is 3 L, how many times does kidney filter? 60x day!
Autoregulation
The kidney maintains constant renal blood flow (RBF) and glomerular filtration rate (GFR)
Why is auto regulation important
Ability of kidney to maintain constant RBF and GFR – innate and occurs in isolated kidney or even a nephron
Aim is to hold RBF and GFR about constant
– or serious consequences to the body water and salt balance – i.e. loss in urine
e.g. increased BP (exercise) > if not regulated increased RPF and GFR> increased urine production
Two mechanism:
a)myogenic control – property of the smooth muscle cells in afferent arteriole, e.g. increase in BP like during exercise will first stretch arteriole, which will reflexly constrict to keep RBF and GFR down
b) tubuloglomerular feedback
Myogenic
Contractile property of smooth muscle cells surrounding arterioles
Example of myogenic control of renal blood flow and GRF
reaction to increased blood pressure Constriction of AA»_space; to maintain stable GFR
Three basic components of renal function
1) Glomerular filtration
2) Tubular secretion
3) Tubular reabsorption
Amount excreted in urine of any substance
Amount filtered + amount reabsorbed - amount secreted = amount excreted in urine
Renal handling of p-aminohippurate (PAH)
Some is absorbed in Bowman’s space
The rest is absorbed by tubule
All is filtered and secreted
Renal handling of sodium
Some is absorbed in Bowman’s space
Most is reabsorbed by peritubular capillary
Only a tiny amount is secreted
Filtered and reabsorbed
Renal handling of glucose
Some is absorbed in Bowman’s space
All is reabsorbed in peritubular capillary
Filtered and reabsorbed
Renal handling of inulin og creatinine
Filtered
Some is absorbed by Bowman’s space
Arterial input
Venous output + urine output
P(S,a) * RPF(a)
P = concentration in plasma
S = substance
a = arterial
RPF = renal plasma flow rate
Venous output
P(S,v) * RPF(v)
P = concentration in plasma
S = substance
v = venous
RPF = renal plasma flow rate
Urine output
U(S) * V
U = concentration in urine
V = urine flow rate
S = substance
Renal Clearance
The Clearance of a solute/substance is the virtual volume of blood that would be cleared of a given solute in a given time and expressed in units ml/min
Each solute/substance has a its own clearance, depending on how the kidney handles it
C(S) = (urine output)/P(S). (ml/min)
Clearance of substances can vary between:
up to 700 ml/min - substances that are totally removed from plasma in a single pass through kidney; can be used to estimate renal plasma flow and therefor renal blood flow (substance X, e.g. PAH)
0 ml/min - substances that do not appear in urine, because they are reabsorbed (substance Z, e.g. glucose)
And in special cases
ca. 125 ml/min – substances that are only filtered; can be used to estimate glomerular filtration rate (substance O, e.g. inulin)
The clearance of a substance becomes the estimate of GFR in which case?
If substance S is inert (such as Inulin), i.e. only filtered and not absorbed or secreted by kidney, Cs becomes an estimate of Glomerular Filtration Rate = GFR
GFR(In) = (U(In) · V) / (P(In)) (ml/min)
Metabolic source of acids/base
carbonic anhydrase
CO2+H2O <–> H2CO3 <–> HCO3- + H+
Volatile acids:
- CO2 (potential acid)
Nonvolatile acids:
- H+
- phosphate
- sulphate
- uric acid
- oxalic acid
- lactic acid
- keto-acids,
- acetate
Kidneys contribution to acid/base homeostasis
must reabsorb all HCO3^- and secrete nonvolatile acids therefore, kidney acidifies urine
Other organs contributing to acid/base balance – lungs and digestive system
Nitrogen homeostasis
Excretion of nitrogen compounds
In humans, kidney excretes urea
N is found in proteins (amino acids) and nucleic acid (nitrogenous bases)
Na+ distribution in the body
Na+ has a central role in salt and water homeostasis
Diet: 120 mmol/day
–> Gut
Gut:
–> Feces: 5-10 mmol/day
–> 110 mmol/day absorbed in extracellular fluid
extracellular fluid:
–> Sweat: 10-15 mmol/day
–> Kidneys: Filter 25,500 mmol/day and reabsorb 25,400 mmol/day
–> Interchange with intracellular fluid
Kidneys:
–> Urine: 100 mmol/day
Recovery of Na+ (and Cl-) along the nephron
Most Na+ and other substances are reabsorbed in the proximal tubule
Fine tuning and regulation of salt and water transport in collecting duct
100% Na+ in renal copuscle (nyrelegeme)
30% Na+ towards end of proximal tubulus
10% Na+ after Loop of Henle
3% Na+ around distal tubulus and beginning of collecting duct
1% Na+ at the end of collecting duct
How is the recovery of Na+ examined?
Using micropipette at different places in nephron
Na+, Cl-, solutes and water in nephron
Different nephron segments use different transporters and channels for Na+ absorption
Cl- absorption follows via transcellular or paracellular route
Solute transport can be coupled to Na+ transport
Water reabsorption is passive and secondary to solute transport (if epithelium is water permeable)
Coupling of Na+ and water transport in the proximal tubulus
Major absorption site
H2O uses aquaporin and diffuses
Sekundær aktiv transport af Na+ and solute into cell. Then Na+/K+ ATPase to get Na+ out of cell.
Absorption of nutrients and small organic molecules in proximal tubulus, e.g. glucose
Na+/glucose symporter into cell. Then glucose uniporter and Na+/K+ ATPase out of cell
Na+/glucose symporter inhibitors used to treat type 2 diabetes?
Cortical collecting tubule (CCT) - fine tuning
Na+ and water transport can be regulated. fine tuning
Water permeability along the nephron
Variable
100% H2O permeability in proximal tubulus, following solute transport e.g. Na+. Aquaporins
Descending limp of loop of hence water permeable
ascending limb og Loop of Henle not H2O permeable
H2O permeability regulated in collecting duct by vasopressin. Aquaporins 2.
Vasopressin
Antidiuretic hormone = ADH
H2O reabsorption
Hormonal regulation of Na+
and water permeability in distal tubules and collecting ducts
Medullary collecting duct:
Aldosterone - Na+ transport
Vasopressin - water transport
Urine concentration: countercurrent multiplier system
Using selective NaCl and water permeability to concentrate urine in the loop of Henle
Regulatory mechanisms: key hormones
- Renin
- Angiotensin
- Aldosterone System (RAAS)
- Vasopressin (Antidiuretic Hormone)
Kidney and cardiovascular system: use of Diuretics and other drugs targeting RAS system
What are they/what do they do?
Why are they so commonly used?
What are they/what do they do?
- Increase volume of urine
Why are they so commonly used?
- To treat high blood pressure, fluid retention in body e.g. congestive heart failure
