Wk 26 Flashcards
What are the 5 roles of the kidneys in homeostasis?
Fluid and electrolyte balance
Acid base balance
Endocrine functions
Waste excretion
Blood pressure control
What are the 3 major tasks the kidney performs to produce urine?
Filtration
Reabsorption
Secretion
What are the 3 parts of the kidney? anatomy
Cortex
Medulla
Pelvis
What does the cortex contain? (filtering apparatus- 2 things)
Renal corpuscles and convoluted tubules
What does the medulla contain? 3
Blood vessels
Loops of Henle
Collecting ducts
What does the pelvis of the kidney do?
Receives urine and sends to ureters
What are the kidney artery and vein?
Renal artery and renal vein
What are the functional units of the kidneys?
Nephrons
What are the 2 classes of nephrons?
Which are more common?
Cortical nephrons (more common -85%)
Juxtamedullary nephrons
How do kidneys maintain fluid and electrolyte balance…
What determines electrolyte balance?
What is it largely regulated by?
Balance of filtration, reabsorption, secretion (excretion of water and electrolytes must match intake)
Endocrine signals
How do kidneys maintain acid-base balance?
What affects concentrations and pH in tubules?
Bicarbonate buffer system
Electrolyte concentrations
What hormones (not all hormones) does the kidney produce? 4
Erythropoetin (in response to cellular hypoxia)
Renin
Prostaglandins
Vitamin D
What 6 hormones have affects on the kidney?
Atrial natriuretic peptide (reduce blood vol)
Antidiuretic hormone (increases blood vol)
Aldosterone (increase blood vol)
Cortisol
Parathyroid hormone
Calcitonin
What is the Juxtaglomerular Complex made up of?
Part of the afferent arteriole, just before it enters the Bowmen’s capsule and a set of the DCT of the same nephron
What do juxtaglomerular cells do?
They contain renin so when the systolic blood pressure is low in the afferent arteriole, they release renin which activates the angiotensin system which increases BP
What are macula densa cells?
What do they do?
Modified DCT cells in the juxtaglomerula complex
They are sensitive to Na conc co when there is lower BP, there is lower amounts of Na coming by so it stimulates the release of renin via juxtaglomerula cells
What are Lacis cells/ Polkissen cells?
Extra glomerular mesangial cells
What is the waste excreted by the kidneys?
Nitrogenous wastes (urea, creatinine)
By-products of metabolism (Ammonia, uric acid, urea, creatinine)
Protein deamination occurs in the liver and the product is ammonia (NH3) which is toxic.
What does it turn into?
NH3 goes into the urea cycle and produces urea (which is excreted by the kidneys)
Nucleic acid components (nucleosides) are metabolised into…
Pyrimidines (cytosine, uracil and thymine)=
Purines (adenine, guanine)=
Pyrimidines= NH4 (which enters urea cycle)
Purines= uric acid
What does the urea cycle and where does it take place?
It converts ammonia to urea
Takes place in the mitochondria and cytosol of hepatocytes
What is creatinine the breakdown product of?
Creatine and phosphocreatine
What is Azotaemia?
Increased circulating nitrogenous products (BUN- blood urea nitrogen) due to kidneys not excreting waste properly
What are the effects of Nitrogenous wastes (primarily urea and creatinine) on the CNS?
How do the nitrogenous wastes affect the digestive system?
How does it affect the skin?
Confusion
Seizures
Coma
Loss of appetite
Nausea
Mucosal bleeding
Pruritus and ‘uraemic frost’ on skin as urea crystalises
When the kidney is struggling and it doesn’t clear waste as efficiently, Gout and Nephrolithiasis (kidney stones) occur- why is this?
Because decreased uric acid clearance so higher concentration in blood so it crystalizes in joints (gout) and in the kidneys
How do the kidneys change blood pressure?
Direct effect on blood volume
Indirect effect on vascular tone through release of endocrine signals
Kidneys excrete…
Which solutes?
Which nitrogen compounds?
Solutes: Sulfates Phosphates Na K Small conc of Ca, Mg, HCO3
Nitrogen compounds: Ammonia/ Ammonium Urea Uric acid Creatinine
What are Glomeruli?
What happens at the glomerulus?
Glomeruli= capillaries in the capsule of the nephron
Glomerulus is where filtration occurs
What filters through the glomerulus?
Is this active or passive?
Water and small plasma components
Passive (driven by blood hydrostatic pressure)
Hydrostatic vs osmotic pressure=
Hydrostatic is going from high to low pressure
Osmotic pressure is blood following where the highest concentration is
Where does the most resorption occur?
What are the 2 types of passive resorption?
What is the active type?
Proximal convoluted tubule
Osmosis, facilitated diffusion
Driven by counter current exchange
ATPase pump
What are the main substances that get through the glomerular filtration barrier?
Na K Cl- H2O urea Glucose
(hemoglobin and serum albumin are big so only a tiny bit of these get through)
Proximal convoluted tubule…
What is reabsorbed into the blood?
What is secreted into the tubule?
65% of filtrate volume is reabsorbed
- H2O
- Na, HCO3 and other ions
- Glucose, AA and other nutrients
H+ and NH4 (also some drugs) secreted
Loop of Henle…
What is reabsorbed into the blood?
What is secreted into the tubule?
H2O
-Na, K, Cl-
Urea
Distal convoluted tubule…
What is reabsorbed into the blood?
What is secreted into the tubule?
Aldosterone causes reabsorption of Na, Cl-
K+
Collecting duct….
What is reabsorbed into the blood?
What is secreted into the tubule?
What can be both and why?
H2O and Na and urea
K+
To maintain blood pH, reabsorption or secretion of H+, HCO3- and NH4+
How many layers does the Glomerular filtration barrier have and what are they?
3
Endothelial cells
Glomerular basement membrane
Epithelial cells (podocytes)
What percentage of glomerular filtration rate is excretion of urine?
1%
What controls glomerular plasma flow and glomerular filtration rate?
Afferent and efferent arteriole resistances
What mechanisms keeps renal blood flow and glomerular filtration rate relatively constant?
Renal myogenic response and tubuloglomerular feedback (TGF) mechanism
What is the myogenic response?
Afferent arterioles can detect changes in vessel circumference by contracting or relaxing (decreasing or increasing glomerular filtration rate)
What is Tubuloglomerular feedback….
What mediates it?
How does it work?
The juxtaglomerular apparatus mediates it
The macula densa cells in the distal convoluted tubule sense an increase in GFR so they tell the juxtaglomerular cells to contract the afferent arteriole, which lowers the GFR
What is the juxtaglomerular complex consist of?
What cells are in this complex?
Part of the afferent arteriole, just before it enters the bowman’s capsule and a section of the distal convoluted tubule of the same nephron
Macula densa cells
Extraglomerular mesangial cells (Lacis cells/ Polkissen cells)
Granular cells (juxtaglomerular cells)
What do juxtaglomerular cells do?
They contain renin so when they sense a decrease in BP in the afferent arteriole, they release renin (stimulates the renin-angiotensin-aldosterone mechanism) increasing BP
What are macula densa cells and what do they do?
Modified DCT cells
They sense Na conc (indicates BP) and they stimulate release of renin if BP is low
How does Arginine Vasopressin affect renal blood flow and therefore GFR?
Decreases vascular resistance so increases renal blood flow and GFR
How does Atrial Natriuretic Peptide (ANP) affect renal blood flow and GFR?
Vasodilates so increases renal blood flow and GFR
Do these things decrease or increase GFR?
Adrenalin/ Noreadrenalin?
Endothelin?
Nitric oxide?
Prostaglandins?
Decrease
Decrease
Increase
Increase
*Prostaglandin synthesis occurs throughout the kidney
Which prostaglandins are most important in the kidney?
How do they affect GFR?
PGE2 and prostacyclin (PG12)
They increase GFR
What class of enzymes are important for (phase 1) drug metabolism in the kidney?
Cytochrome P450 enzymes
What does metabolism do to drugs to make them more easily excreted?
Makes them more hydrophilic and more polar
Drugs excreted from the liver into the bile have 2 possible fates, what are they?
1) into poo
2) Get reabsorbed in SI and go into portal vein, back to liver and into systemic circulation
What are the 2 transporters in Active tubular secretion?
Organic cation transporter (OCT) [positive molecules]
and
Organic anion transporter (OAT) [negative molecules]
How can drugs enter the proximal convoluted tubule (other than OCT and OAT)?
Passive diffusion if molecule is uncharged
Facilitated diffusion (if charged or uncharged too)
What types of molecules undergo net passive reabsorption back into the blood?
What is pH trapping?
Uncharged, weakly acidic or weakly basic
In distal tubule, ionized molecules aren’t able to passively travel back into blood so they are trapped and end up in urine
What 3 things affect renal clearance?
Protein binding
Blood flow
Functional state of nephrons
What 3 things happen in Chronic Kidney Disease (CKD)?
What does this lead to?
Interstitial fibrosis
Tubular atrophy
Nonfunctional glomeruli
- Drop in GFR
- Increased permeability of arterioles and glomerulus
What are the 4 distinct phases of renal drug excretion?
1) Glomerular filtration
2) Active tubular secretion
3) Passive tubular reabsorption
4) Active tubular reabsorption
What happens to the rate of drug elimination as the plasma drug concentration increases?
It also increases until the elimination mechanisms are saturated (Vmax) and then it plateaus
What is a drug’s half life?
The time taken for the plasma conc of a drug to drop by half its original conc
What 2 things can prolong half life of a drug?
Drop in the clearance or an increase in the distribution of the drug (because it is bound to protein and can’t be excreted)
Where are aminoglycosides almost entirely excreted in the nephron?
What does this mean for someone with kidney impairment?
Excreted by glomerular filtration so really short half life
When kidney function impaired, half life is prolonged massively so you have to know the kidney function before administering these drugs or you can overdose
What are the 3 main causes of Chronic Kidney Disease?
Diabetic nephropathy
Hypertension
Glomerulonephritis
What are the 4 systemic effects of CKD?
Hypertension
Oedema (because of protein loss)
Dyspnea (because of metabolic acidosis so lungs try and breathe off acid)
Anaemia (because kidneys not making erythropoetin so bone marrow doesn’t make RBCs)
Diabetic nephropathy is related to chronic hyperglycaemia and ischaemia and it also damages the glomerular basement membrane causing:
Symptoms and signs of this are known as:
The key feature of this is:
This leads to __ma and ______emia
Glomerulosclerosis
Nephrotic syndrome
Proteinuria
Odema and hyperlipidaemia
What does angiotensin II do to the efferent arteriole?
Constricts it so GFR increases
How does hypertension affect the small blood vessels in the kidney?
What does that lead to?
This signals _____ to be secreted, which ____ blood pressure
It damages them
Reduction in GFR
Renin
Raises (now even more hypertension)
Acute Renal Failure types…
Pre-renal=
Intrinsic=
Post-renal=
Pre-renal= marked decrease in renal blood flow
Intrinsic= damage to structures within the kidney
Post-renal= obstruction of urine outflow from kidney
Pyelonephritis vs glomerulonephritis
Pyelonephritis= usually ascend from UTI becomes from ureter into PELVIS (pyelo and pelvis)
Glomerulonephritis is pathogen coming down from blood into kidney
(can get post strep pyogenes GN)
What are the symptoms of nephritic syndrome?
Hypertension Haematuria Proteinuria Odema Oliguria (not producing much urine) (Flank pain, nausea, vomiting, anorexia)
Kidney stones
What are the 2 names?
What is the name for the insoluble stones and where do they get stuck?
What are the major components of kidney stones?
Nephrolithiasis or urolithiasis
Urinary calculi
They get stuck in the renal pelvis
Main components:
Calcium
Phosphate
Urate
