Physiology - Kidney part 1 Flashcards
Name functions of kidneys
- Regulation of water and salt
- Regulation of acid-base balance
- Excretory function
- Endocrine function
- Blood pressure regulation
- Gluconeogenesis
Explain regulation of water and salt
Balances the salt and water intake and excretion. In case of sudden change in salt consumptions, kidneys adapt within 2-3 days.
Explain regulation of acid-base balance
Kidneys can excrete H+ ions into the tubular fluid where it will then be neutralised by a buffer system and then excreted out of the body.
Acidosis - kidney with stimulate H+ into urine to decrease acidity of blood.
Alkalosis - kidney will decrease H+ excretion which will cause more HCO3- excretion.
Explain excretory function
Kidney excretes waste products such as:
Urea - from amino acid metabolism and will be high in concentration in blood if the kidney is not functioning properly.
Creatinine - comes from muscle creatine and high will be high in concentration in blood if the kidney is not functioning properly.
Uric acid - comes from nucleonic acid metabolism. Accumulation will lead to gout attack and joint pain.
Drugs and food additives - toxic substances in food or drinks are excreted.
Explain endocrine function
Erythropoietin:
- Produced in peritubular cells in case of hypoxia and stimulation of sympathetic nervous system.
Renin:
- Produced in case of low blood pressure, low Na+ and high K+ in blood.
- Produced by juxtaglomerular cells
- Activate renin-angiotensin-aldosterone system which releases angiotensin II and aldosterone and increases blood pressure.
Vitamin D3:
- Activation occurs in tubular epithelial cells.
- Vitamin D3 is necessary for calcium and phosphate equilibrium regulation in blood.
Explain blood pressure regulation
Intermediate blood pressure control:
- renin is released
- activation of angiotensin system
- production of angiotensin II
- vasoconstriction
- increased blood pressure.
Slow blood pressure control:
- Pressure volume diuresis or high blood pressure
- Filtration increases, reabsorption decreases.
- Decreases blood plasma volume and blood pressure.
Explain gluconeogenesis
Fat state = low gluconeogenesis.
Fasting state = intense gluconeogenesis.
Gluconeogenesis gets a-ketoglutarate from glutamine produced in tubular epithelial cells.
How many nephrons are in each kidney
Around 1 million nephrons
How much of the nephron is needed for normal kidney function
1/4
What does nephrons consist of
Tubular part and vascular part
Are dead nephrons substituted
No, the number of nephrons decreases throughout life.
What happens to nephrons in case of glomerulonephritis or infection
The nephrons are destroyed very rapidly leading to kidney failure.
What does the tubular part of nephron consist of
- Renal corpuscle
- Bowmans capsule
- Proximal convoluted tubule
- Nephron loop
- Distal convoluted tubule
- Collecting duct
- Calyces
What are the types of nephrons
Cortical nephrons (85%) and Juxtamedullary nephrons (15%)
What are cortical nephrons
- Control filtration and reabsorption
- Located in superficial layer fo cortex
- Small
- Have short nephron loops which only go to the outer part of the medulla.
What are juxtamedullary nephrons
- Control osmolarity gradient in medullary part
- Bigger corpuscle that are located deeper in the cortex
- Long loops that go into the inner part of the medulla.
What is the juxtaglomerular complex
Consists of the macho dense cells in the distal convoluted tubule and the juxtaglomerular cells in the afferent and efferent arterioles.
What does the juxtaglomerular complex do
- Control general arterial blood pressure
- Control of blood in glomerular capillary network
- Control of renal blood flow
What do macula densa cells do
- Control Na+ and Cl- concentration in urine that transports through distal convoluted tubule.
- Signals juxtaglomerular cells in the arterioles of renin production needs to be stimulated or inhibited.
What are the three events of urine formation
- Filtration
- Reabsorption
- Secretion
Urine formation - explain filtration
Goes down the concentration gradient from the glomerular capillary to the bowman capsule.
The primary urine then flows along the tubular system.
How much primary urine does kidneys filter per day
180 L of primary urine
Urine formation - explain reabsorption
Substances are transported from the urine —> peritubular capillaries
Substances: Na+, Cl-, K+, HCO3-, H2O
Urine formation - explain secretion
Substances are transported from peritubuar capillaries —> tubular system
Substances: K+ and H+ is excreted into the urine.
What is the product produced when filtration, reabsorption and secretion has occurred
Secondary urine
What formula is used to calculate excretion of secondary urine
E = Filtration - reabsorption + secretion
How much of secondary urine does kidneys filter per day
1.5 L of secondary urine
What is dialysis
Procedure that removes waste products and excess glue from the blood when the kidneys do not work properly.
Explain hemodialysis
Persons blood runs through a machine with big surface area of semipermeable membranes.
Substances that are in too high concentration leave the blood, pass the membrane and then travel to the dialysate.
Blood from the machine then returns back to the circulatory system.
What does dialysate consist of
Na+ = 135 - 145 (normal)
Cl- = 102 - 106 (normal)
Potassium = 0 - 4 (low so that excessive K+ can be removed from blood)
HCO3- = 30 - 39 (high to control acid base regulation)
Acetate = 2 - 4
Calcium = 0.0 - 3.5
Magnesium = 0.5 - 1.0
Dextrose = 11 (higher to keep glucose in blood)
pH = 7.1 - 7.3
Life of patient with kidney failure
Go to dialysis every second or third day, get attached to the machine for 4-6 hours.
Explain peritoneal dialysis
More advanced method. Dialysate is transported into the peritoneal cavity.
The peritoneal membrane acts as a semipermeable membrane = substances in high concentration go into the dialysate.
The bag of waste fluid can then be emptied after several hours.
This method can be used at home, day or night.
Explain general idea of glomerular filtration
Occurs from the glomerular capillary network into the Bowman’s capsule.
Goes down the concentration gradient and depends on filtration pressures.
What are the components of filtration pressure
- Hydrostatic pressure in the glomerulus.
- Colloid osmotic pressure in glomerular capillaries.
- Capsule pressure.
Explain hydrostatic pressure in glomerulus
P(h) = 50 - 70 mmHg
It shows the pressure in the glomerular capillary network.
Regulated by the vasoconstriction or vasodilation of afferent or efferent arterioles.
The higher the hydrostatic pressure the greater the filtration intensity.
Explain colloid osmotic pressure in glomerular capillaries
π = 20 - 30 mmHg
It shows the amount of plasma proteins.
Since plasma protein cannot cross the wall of capillaries it will attract water to the plasma = inhibiting filtration.
What happens to colloid osmotic pressure in case of liver cirrhosis
The filtration membrane is broken = protein leak into Bowman’s capsule = decreased colloid osmotic pressure = increased filtration rate.
Explain capsule pressure
P(c) = 10 - 20 mmHg
Shows the hydrostatic pressure in nephron/Bowman’s capsule.
The less fluid leaves the proximal convoluted tubule the greater the capsule pressure.
Inhibits filtration.
What happens to capsule pressure in case of kidney stones or accumulation of haemoglobin
Renal tubules will be obstructed = capsule pressure rises and inhibits filtration.
What formula determines effective filtration pressure
Pef = P(h) - (π + P(c))
Should be around 10 mmHg to clear blood plasma from unwanted substances and to maintain normal water and salt balance.
How does effective filtration pressure affect filtration rate
The higher the effective filtration pressure the higher the filtration intensity.
How does filtration membrane affect filtration rate
Surface area:
The greater the surface area = greater filtration intensity
Permeability:
Greater permeability = greater filtration intensity
The filter membrane consists of fenestrated endothelial cells that provide great water-soluble substance transport. Basement membrane of Bowman’s capsule consists of pericytes. Damage to these = increased permeability.
What happens in glomerular nephritis
The basement membrane is damaged.
Greater diameter of pores = more proteins are filter into urine.
Protein are NOT supposed to be found in urine.
So this shows that proteins are unable to be transported back into the bloodstream.
How does properties of substance affect filtration rate
Molecular weight:
- Substances greater than 70,000 Daltons are not passed through the filter membrane.
- Proteins are not filtrated.
Charge:
- Basement membrane is negatively charged.
- Negative substances are inhibited.
- Positive substances are facilitated.
Radius:
- the greater the radius the lower the filtration rate.
- Maximum radius of 45 angstroms are filtered.
What is ultra filtrate
It is primary urine
What is the ultrafiltrate level in males vs females
M: 125 ml/min or 180 L/day
F: lower
What does ultrafiltrate consist of
- Blood plasma
- Molecules less than 70,000 Daltons
- Blood should not be present in the urine = if fresh blood is present most likely from lower urinary tract. If blood appears in cylinders = damage of the glomerular capillaries.
What drugs are exclusively excreted through the kidneys
Cardiac glycosides and antibiotics
Explain cardiac glycosides
Regulate heart contractility, and if it accumulates in blood then it will have toxic effects on the heart.
Explain antibiotics
Drugs used in chemotherapy, important to know the filtration rate to know the correct dosage.
How do we determine filtration intensity
Renal clearance rate
What does renal clearance test show
Shows the volume of blood plasma that is cleared of substances by the kidneys per unit time.
What conditions are needed to be able to determine renal clearance test
- The substance should be freely filtered = it needs to be filtered through the kidney.
- The substance should not be reabsorbed or secreted.
- The substance should not be metabolised in the organism.
- The substance should not be toxic.
What substances are used for renal clearance test
Inulin and Creatinine
Explain inulin in renal clearance test
- It is a polysaccharide not produce by the human body.
- Infused artificially.
- Golden standard.
- Should be continuously infused to determine clearance test so therefore not commonly used.
Explain creatinine in renal clearance test
- Present in the bloodstream.
- Produced from creatine in the skeletal muscles.
- No infusion required.
- A little about of creatinine is excreted and we use this to calculate the creatinine clearance.
How is renal clearance test conducted
- Person visits bathroom and discards urine.
- In the next 24 hours, urine is collected.
- Blood sample is taken to determine inulin or creatinine concentration.
- To calculate clearance:
(substance concentration in urine*urine flow rate)/substance concentration in plasma
What is the concentration of creatinine in case of normal glomerular filtration rate
Concentration should be stable
What is creatinine concentration in decreased glomerular filtration rate
Concentration should be increasing
What equation can be used to determine filtration rate from the creatinine concentration
2021 CDK-EP1 equation
What variables are used in the 2021 CDP-EP1 equation
Serum creatinine level (Scr) in mg/dl, age and two constants A and B.
What is normal glomerular filtration rate
> or equal to 90 ml/min/1.73 m2
Explain renal blood flow
- Kidneys receive blood from the abdominal aorta through renal arteries
- Renal arteries branches into the interlobar artery which gives rise to the arcuate arteries and interlobular arteries
- From the interlobular arteries the afferent arteriole branches off and forms the primary (glomerular) capillary network
- Gas exchange does not take place
- Glomerular capillaries are specialized for intense filtration of
blood plasma into the Bowman ́s capsule - Glomerular capillaries join together to make efferent arteriole
which branches into the secondary (peritubular) capillary network
- Gas and nutrient exchange take place
- Reabsorption and secretion take place - Peritubular capillaries join into venules and through the interlobular veins flow into the arcuate vein
Blood flow in juxtamedullary nephron
- The efferent arteriole branches into vasa recta.
- Gas + nutrient exchange.
- Reabsorption and secretion occurs. - Vasa recta pours blood into the arcuate veins.
- Blood flows into the interlobular vein.
- Blood leaves kidney through renal veins toward the vena cava inferior.
Explain glomerular capillaries (primary)
- Branch from afferent arteriole.
- Gas exchange does not take place.
- Specific for intense filtration.
- Together can form efferent arteriole which can branch into peritubular capillaries.
Explain peritubular capillaries (secondary)
- Found around tubules or vasa recta.
- Gas and nutrient exchange occurs.
- Reabsorption and secretion occurs.
Explain renal plasma flow
It is determined by using para-aminohippuric acid (PAH).
PAH is both filtered and secreted (glomerular and peritubular).
Clearance formula is used to calculate it.
Explain renal blood flow
It is calculated by:
(renal plasma flow) / (1-hematocrit index)
What three mechanisms that control the renal blood flow
- Autoregulation
- Neural regulation
- Humoral regulation
What is autoregulation
It maintains renal blood flow if there are changes to the arterial blood pressure between 80-180 mmHg
How does renal blood flow change if BP < 80 mmHg
Renal blood flow and glomerular filtration rate will decrease
How does renal blood flow change if BP > 180 mmHg
Renal blood flow and glomerular filtration rate will increase
What are the two mechanisms of autoregulation
Muogenic and tubuloglomerular feedback
What is myogenic regulation
Depends on the stretch of smooth muscle cells in the blood vessel walls.
Myogenic regulation - if blood pressure rises
1.Smooth muscles stretch.
2. Mechanosensitive Ca2+ channels open.
3. Ca2+ influx
4. Vasoconstriction
Myogenic regulation - if blood pressure decreases
- Smooth muscle stretch decreases.
- Mechanosensitive Ca2+ channels close.
- Ca2+ concentration decreases.
- Contraction decreases.
What is tuboglomerular feedback
Tubules send information to the glomerulus to regulate the blood that flows into the glomerulus.
Tuboglomerular feedback - decreased renal blood flow
- Renal blood flow is decreased = low hydrostatic pressure in glomerulus = decreased glomerular filtration rate.
- Less primary urine is made. Na+ and Cl- is reabsorbed in proximal convoluted tubule.
- In distal convoluted tubule low concentration of ions causes macula densa cells to secrete PGE2 and kinins = dilation of afferent arterioles.
- Macula dense cells also trigger renin release = angiotensin II release = constriction of efferent arteriole.
- More inflow (afferent) less outflow (efferent) = hydrostatic pressure in glomerulus increases and filtration is stimulated.
Tuboglomerular feedback - increased renal blood flow
- Renal blood flow is increased = high hydrostatic pressure in glomerulus = increased filtration rate.
- More primary urine is made. Na+ and Cl- is concentrated.
- In distal convoluted tubule, more Na+ is taken up by Na+/K+ pump.
- Macula densa cells release adenosine and ATP = constriction of afferent arteriole. Inhibits renin = dilation of efferent arteriole.
- Less inflow, more outflow = lower hydrostatic pressure in glomerulus and filtration rate decreases.
What are examples of non-steroidal anti-inflammatory drugs (NSAIDS)
Aspirin, ibuprofen, ibumetin.
What do NSAIDS do
Decrease production of prostaglandins = prevent dilation of afferent arteriole = low renal blood flow.
NSAIDS and people with deficient blood flow to kidneys
Since NSAIDS prevent dilation of afferent, prescribing them can cause even lower blood flow = defective kidney functions.
What nerves innervate renal blood vessels and where do they come form
Only sympathetic fibers from the sympathetic nervous system innervate renal blood vessels.
In kidneys, what receptors does norepinephrine/epinephrine bind to
alpha 1 on smooth muscle cells = vasoconstriction of afferent and efferent arteriole.
Beta 1 on juxtaglomerular cells = vasoconstriction of efferent arteriole by release of renin.
What is humoral regulation
Related to released hormones and locally secreted substances.
Vasoconstrictor - explain epinephrine and norepinephrine
- Released from the adrenal medulla.
- Binds to a1 or B1 receptor causes vasoconstriction in both afferent and efferent arteriole (mostly efferent).
- Filtration rate decreases a little.
Vasoconstrictor - explain vasopressin
- Released from hypothalamus in case of low blood pressure or high osmotic pressure of blood.
- Causes constriction of renal arteries = decreased blood flow to kidneys.
Vasoconstrictor - explain local factors
- Thromboxane A2 and enodothelin’s.
- Cause vasoconstriction and decrease of renal blood flow.
Vasodilator - explain dopamine
- Acts on dopamine 1 receptors.
- Causes dilation of renal blood vessels = increasing renal blood flow.
Vasodilator - explain ANP and BNP
- Produced from endocrine cardiomyocytes due to stretch.
- Causes dilation of renal blood vessels = increasing renal blood flow.
Vasodilators - explain local factors
- NO, PGI2, PGE2, EDHF and histamine.
- Causes dilation of renal vessels = decreases renal blood flow.
Define reabsorption
The transport of substances from tubular fluid into peritubular capillaries (urine —> blood)
Define secretion
The transport of substances from blood into the urine through tubular epithelial cells (blood —> urine)
Reabsorption is more intense that secretion, true or false?
True
How much of ultrafiltrate is reabsorbed and how much is excreted to secondary urine
99% is reabsorbed and 1% is excreted.
180 L ultrafiltrate and 1.8 L of secondary urine per day.
What is the reabsorption intensity in the proximal convoluted tubule
65%
Explain reabsorption in proximal convoluted tubule
- Highest reabsorption intensity
- Glucose and proteins are reabsorbed here.
What is the reabsorption intensity in the nephron loop
25%
Explain reabsorption intensity in nephron loop
Na+ and water is reabsorbed here.
What is the reabsorption intensity in the distal convoluted tubule
5%
What is the reabsorption intensity in the collecting ducts
4%, remaining of the primary urine volume is reabsorbed here.
What are the two surfaces of a tubular epithelial cell
Apical and basolateral surface
What is the apical surface
It faces the urine
What is the basolateral surface
It faces the basement membrane and the interstitial space.
Where are tubular epithelial cells located
On the basement membrane
What are the primary active transport mechanisms
Na+/K+ pump
H+/K+ pump
H+ pump
Primary active transport - explain Na+/K+ pump
- Found on basolateral surface.
- Located all over nephron except descending part of loop of Henle.
- Na+ out and K+ into cell.
Primary active transport - explain H+/K+ pump
- Found on apical surface
- Located in distal convoluted tubule and collecting duct.
- H+ out and K+ into cell.
Primary active transport - explain H+ pump
- Found on apical surface
- H+ out of cell.
What are the secondary active transport mechanisms
Apical surface:
Na+/H+ antiport
Na+/glucose, AA, phosphate, Cl- symporters
Na+/K+/Cl- symport found in the ascending part of nephron
Basolateral surface:
Na+/HCO3- symport
HCO3-/Cl- antiport
What are the passive transport mechanisms
- Diffusion through phospholipid bilayer
- Diffusion through ion channels
- Facilitated diffusion
Passive transport mechanism - explain diffusion through phospholipid bilayer
When substances diffuse through the epithelial cells. CO2 is an example.
Passive transport mechanism - explain diffusion through ion channels
Apical surface: Na+ in cell, K+ out to urine.
Basolateral surface: K+ out into interstitium, Cl- out into the interstitium.
Passive transport mechanism - explain facilitated diffusion
Transport protein that help substances transport across the concentration gradient.
Examples: glucose or AA transport protein, urea transport protein.
What are other transport mechanisms
- Paracellular transport
- Water transport
Explain paracellular transport
When ions can be transported through the contact between cells if they are permeable.
Concentration gradient:
If concentration in urine > interstitium then ions will go to interstitium.
Solvent drag:
In case of intense water reabsorption, ions are washed into interstitium.
Transepithelial charge:
Filter membrane is negative = positive substances are filtered better.
Beginning of nephron positive = positive ion reabsorption.
Proximal convoluted tubule and other parts are negative = negative ion reabsorption.
Explain water transport
Water can be transported paracellularly into the interstitium.
Or through aquaporins into the interstitium.
What is reabsorption threshold
The blood plasma concentration of the substance at which the substance starts to appear in the urine.
