Kidney 3+4 Flashcards
ECF osmolarity
Body cells need to be bathed in an ECF with a constant electrolyte concentration. This depends on the fluid which enters and leaves the body
The kidneys can excrete urine with osmolarities ranging from 50 – 1400 mOsm/l (plasma ≈ 300)
Similarly, the kidney can excrete small concentrated volumes (0.5 l/day) or large dilute volumes (20 l/day)
So the kidney can regulate water excretion independently of solute secretion. ADH is important to regulate water (but not solute) excretion
After drinking 1 l of water, urine flow rate can increase 600 % after 45 mins, but this is dilute urine (see fig.)
This is achieved by reabsorbing solutes from the distal parts of the nephron, without reabsorbing water. ADH is not being released now
Obligatory urine loss
Obligatory urine loss – an average human must lose 600 mOsm of solute/day and if the maximum urine concentration is 1200 mOsm/l, then:
600 = 0.5 l/day (where else do we lose 1200 water from?)
If one is shipwrecked, can you drink seawater?
No. As seawater is 3 % NaCl (≈ 2400 mOsm/l) and if you drink 1 l:
2400 = 2 l
1200
You need 2 l of urine to get rid of the solutes (and a net loss of 1 l of body fluids per litre of seawater). What about softdrinks, especially caffeinated ones?
2 things are needed for making a hyperosmotic urine:
A high level of ADH
A high osmolarity of the medullary interstitium
The high osmolarity is made by the:
COUNTER CURRENT MULTIPLIER MECHANISM
COUNTER CURRENT MULTIPLIER MECHANISM
This mechanism depends on 25 % of nephrons; the juxtamedullary ones. They have long loops of Henle and vasa recta, some going close to the renal pelvis. The factors responsible to build up the solute in the renal medulla are:
Reabsorption of Na+, K+ and Cl- from the thick ascending loop of Henle.
Active reabsorption of ions from the collecting ducts into the medulla
Passive urea diffusion from the medullary collecting ducts to the medulla
Diffusion of little water from the medullary collecting ducts to the medulla
The most important of all of these to increase medullary osmolarity is the active transport of sodium & co-transport of potassium and chloride (by luminal Na+/H+ ATPase and the Na+/K+/2Cl- co-transporter) in the thick ascending limb.
This can create a 200 mOsm gradient between the lumen and interstitium.
This is also due to the impermeability of water through this segment. The descending limb is permeable to water and water is reabsorbed, but as the tip of the loop is reached the tubular fluid osmolarity goes up.
Hyperosmotic renal medulla
To understand this, we can follow these steps:
- Assume the loop of Henle gets a fluid of 300 mOsm/l, from the PT.
- Na+ is actively pumped into the medulla from the thick ascending limb, causing a 200 mOsm/l gradient. It cannot get more as ions move back paracellularly when this gradient is reached.
- Due to osmosis, the descending limb and interstitium reach an equilibrium, and the thick limb keeps reabsorbing ions, keeping the interstitium at 400 mOsm/l.
- The hyperosmolar fluid from the descending limb goes to the ascending limb.
- At the ascending limb, ions from here are again reabsorbed, until a 200 mOsm/l gradient is made, making the interstitium now 500 mOsm/l.
- Again descending limb and the interstitial fluid equilibrate, and as this hyper-osmotic fluid goes to the ascending part, again more ions are pumped in the medulla.
- Steps 4 – 6 are repeated again and again until the interstitium has a osmolarity of about 1200 mOsm/l and the sodium chloride reabsorption has multiplied in the interstitium.
Why can’t it increase to >1200 mOsm/l?
The following are responsible:
Length of the Loop
Nephron length:kidney mass ratio
Cortical:medullary nephron ratio
As fluid flows into the DT, it is dilute and the early DT makes it more dilute, as it is like the ascending limb.
As fluid flows into the CCT, water reabsorption is dependent on the [ADH]. With no ADH, there is little water reabsorbed, but with high ADH, water is reabsorbed into the cortex.
The cortex allows the water to move via peritubular capillaries and it also does not affect the hyperosmolar medulla. At this stage, urine concentration can reach that of the medulla, i.e. 1200 mOsm/l.
Olfactory receptors (Gpr41; Olfr78) in the kidney are thought to affect blood pressure when acetate and propionate are made by gut bacteria.
Gpr41 lowers BP, but later Oflr78 activates renin to increase BP, when these fatty acids increase.
Kidney disease
These can be classified into:
Acute problems, which stop kidney function, though they can recover
What are some Causes of Prerenal Acute Renal Failure
- Intravascular volume depletion
Hemorrhage (trauma, surgery, postpartum, gastrointestinal)
Diarrhea or vomiting
Burns - Cardiac failure
Myocardial infarction
Valvular damage
Primary renal hemodynamic abnormalities
Renal artery stenosis, embolism, or thrombosis of renal artery or vein
Excessive blockade of prostaglandin synthesis (aspirin)
*Peripheral vasodilation and resultant hypotension
Anaphylactic shock
Anesthesia
Sepsis, severeinfections
What are some Causes of Intrarenal Acute Renal Failure
- Small vessel and/or glomerular injury
Vasculitis (polyarteritis nodosa)
Cholesterol emboli
Malignant hypertension
Acute glomerulonephritis - Tubular epithelial injury (tubular necrosis)
Acute tubular necrosis due to ischemia
Acute tubular necrosis due to toxins (heavy metals, ethylene glycol, insecticides, poison mushrooms, carbon tetrachloride) - Renal interstitial injury
Acute pyelonephritis
Acute allergic interstitialnephritis
Chronic renal failure
where there is a gradual loss of function and irreversible loss of many functioning nephrons. Has a high prevalence.
What are some causes of chronic renal failure
- Metabolic disorders
Diabetes mellitus
Amyloidosis - Renal vascular disorders
Atherosclerosis
Nephrosclerosis-hypertension - Immunologic disorders
Glomerulonephritis
Polyarteritis nodosa
Lupus erythematosus - Infections
Pyelonephritis
Tuberculosis - Primary tubular disorders
Nephrotoxins (analgesics, heavy metals) - Urinary tract obstruction
Renal calculi
Hypertrophy of prostate
Urethral constriction - Congenital disorders
Polycystic disease
Congenital absence of kidney tissue (renalhypoplasia)
What are the most Common Causes of End-Stage Renal Disease (ESRD)
Diabetes mellitus and Hypertension
Describe the vicious circle of primary kidney disease
Loss of nephrons because of disease may increase pressure and flow in the surviving glomerular capillaries, which in turn may eventually injure these “normal” capillaries as well, thus causing progressive sclerosis and eventual loss of theseglomeruli.
Disorders of Renal Physiology
Pathophysiology can also be related to the major processes in urine formation
Filtration
Cardiovascular defects, pathology of Bowman’s capsule or glomerulus
Tubule functions
Damage to the renal epithelial cells, disruption to solute transporters
Neurological or Endocrine Control
Neuronal pathology
Endocrine pathologies, abnormal hormone levels or receptor defects
Detection & treatment of renal defects
Patient; pain, infection, changes in urinary behaviours, urine colour
Urine flow rate/composition
Presence of proteins e.g. albumins/blood or other foreign materials in the urine
Abnormal urine [ion] or creatinine clearance
Treat the primary cause (e.g. cardiovascular disease, blood pressure control). Resistance exercise has been shown to be beneficial (2021)
Drug treatments to control tubular functions or diuresis (urine flow).
Measuring metal exposure in humans
Occupational exposure, exposure of the general public
Routes of exposure:
inhalation
diet and drinking water
skin
medical procedures or devices
Metal concentrations measured in blood, urine, hair or finger nails
Renal pathology
Metals in urine or tissue
Measurements of renal function
Post mortem: histology
