PHYS: The Kidneys

Created by KrisOsborne 

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Explain filtration.

The movement of fluid from plasma into Bowman's capsule. (Blood to lumen)
Occurs in the renal corpuscle. It's non-specific filtration that creates a filtrate (plasma minus plasma proteins)

Explain reabsorption.

The movement of filtered materials from the tubule of the nephron back into the blood via peritubular capillaries. Most takes place in proximal tubule. Finely regulated reabsorption takes place in the distal tubule. It can be active or passive.

Explain secretion.

The movement of selected molecules from blood to tubule (active process - usually 2ndary active transport). More specific than filtration. Enhances excretion of a substance.

Describe the process of glomerular filtration.

Happens in the renal corpuscle. Substances leaving the plasma must pass through 3 filtration barriers: The capillary endothelium, basal lamina, and the epithelium of the Bowman's Capsule.

Describe the role of the capillary endothelium in more detail.

It's made up of fenestrated capillaries that allow most components in. The pores are small enough, however, to prevent blood cells from leaving the capillaries. Mesangial cells lie btwn & around the glomerular caps. They are able to contract & alter blood flow thru the caps. They also secrete cytokines.

Describe the role of the basal lamina in more detail.

An acellular layer of EC matrix that separates the capillary endothelium from the epithelial lining of Bowman's Capsule. It acts like a coarse sieve excluding most plasma proteins.

Describe the role of the epithelium in the Bowman's Capsule in more detail.

Consists of specialized cells called podocytes. They have long cytoplasmic extensions or foot processes that wrap around the glomerular capillaries creating narrow filtration slits (openings thru which filtration takes place).

1. Explain excretion.
2. What 2 things does the excretion rate depend on?

1. The elimination of materials from the body (at lungs, intestine, skin, or kidneys)
Excretion = filtration - reabsorption + secretion
2. The excretion rate of a solute depends on (1) Its filtered load and (2) whether it is reabsorbed or secreted as it passes through the nephron.

Compare and contrast the roles of podocytes and mesangial cells.

Podocytes: They have long cytoplasmic extensions/foot processes that wrap around the glomerular capillaries creating narrow filtration slits where filtration occurs.
Mesangial cells: lie between & around the glomerular capillaries. Have cytoplasmic bundles of actin-like filaments that enable them to contract and alter blood flow. They also secrete cytokines (re:immune & inflammatory processes).

Describe what is meant by the term "filtration fraction".

The % of total plasma volume that filters into the tubule. Only about 20% of plasma is filtered.

Compare and contrast hydrostatic and osmotic, and fluid pressures, including factors affecting them

Hydro: It's the blood pressure inside glomerular capillaries. It favours fluid mvmt out of capillaries & into BC. It's opposed by:
1.Colloid osmotic pressure which also occurs inside glom. caps.It favours fluid mvmt back into the capillaries. 2.Fluid pressure: hydrostatic pressure that opposes fluid mvmt into the capsule.

What forces affect filtration?

Hydrostatic pressure, colloid osmotic pressure, and fluid pressure.

What is the myogenic response in reference to the autoregulation of the GFR?

The intrinsic ability of the vascular smooth muscle to respond to pressure changes.
Vascular smooth muscle cells contract when stretched, reducing blood flow AND they
relax and dilate when not stretched, increasing blood flow.

What is tubuloglomerular feedback in reference to the autoregulation of the GFR?

It's a paracrine signaling mechanism through which changes in fluid flow through the loop of Henle influences the GFR.
When NaCl delivery past the macula densa cells increases as a result of ↑ GFR, the MD cells send a paracrine signal to the neighbouring afferent arteriole. The arteriole constricts, ↑ resistance and ↓ GFR.

Define clearance in relation to the renal system.

Clearance of a solute is the rate at which that solute disappears from the body by excretion or by metabolism.
For any solute that is cleared ONLY by renal excretion, clearance is expressed as the volume of plasma passing through the kidneys that has been totally cleared of that solute in a given period of time.

What is inulin? Why is it a good indication of GFR?

Inulin is a polysaccharide isolated from plants. It is used to determine ECF volume and GFR. As is passes through the kidney tubule, inulin is neither reabsorbed or secreted. Therefore 100% of inulin that filters into the tubule is excreted.

What is the relationship between inulin and GFR?

1. Filtered load of inulin = excretion rate of inulin
2. GFR = excretion rate of inulin / [inulin]plasma
3. Inulin clearance = excretion rate of inulin / [inulin]plasma
THEREFORE
4. GFR = insulin clearance

Why is inulin not a practical way of measuring GFR?

Inulin is not practical for routine clinical applications because it does not occur naturally in the body and has to be administered by IV infusion. Unfortunately, no substance that occurs naturally in the body is handled by the kidneys exactly the way inulin is handled.

What then do physicians use in clinical settings to estimate GFR?

Creatinine - a breakdown product of phosphocreatine ( an energy storage compound found primarily in muscles).
Creatinine is always present in the plasma and easy to measure but not perfect for measuring GFR because a small amount will be secreted into the urine. However the amount is SO small, in most people creatinine clearance is used to estimate GFR.

What is the significance of renal threshold?

Renal threshold is the plasma concentration of a substance at which it exceeds Tm (Tm = transport maximum).
Once carries reach saturation of a specific substrate (ex glucose) we will then start seeing that substrate present in the urine (glucose in urine = glucosuria).

Apply the concepts of saturation, specificity and competition as they apply to renal transport

Because most transport in the nephron uses membrane proteins it will exhibit characteristics saturation, competition and specificity.
Certain membrane proteins will only transport specific molecules (specificity).
There can be proteins which carry more than one type of molecule (competition).
Saturation refers to the max rate of transport that occurs when all available carries are occupied substrate.

What is meant by the term transport maximum?

Substrate concentrations equal or above the saturation point, transport occurs at a maximum rate. The transport rate at saturation is the transport maximum.

What is the difference between filtrate and urine?

Filtrate is formed as soon as the water and its solutes leave the glomerular capillary and enter the Bowman's capsule. Filtrate contains everything that blood plasma does except blood proteins; but by the time filtrate has moved into the collecting ducts, it has lost most of its water, nutrients, and essential ions. When filtrate exits the collecting ducts into the calyces, it is called urine. What remains consists mostly of metabolic waste and unneeded substances.

What is the micturition reflex, including the role of higher CNS input.

Micturition is a simple spinal reflex that is subject to both conscious and unconscious control from higher brain centers. As bladder fills with urine and walls expand, stretch receptors send signals via sensory neurons to SC. Info is integrated and transferred to 2 sets of neurons. Full bladder excites parasymp. neurons of the smooth muscle in the bladder wall. Smooth muscle contracts, increasing the pressure on the bladder contents. Simultaneously, somatic motor neurons leading to the external sphincter are inhibited.

Compare and contrast the internal sphincter with the external sphincter.

Internal sphincter is a continuation of the bladder wall and consists of smooth muscle. Its normal tone keeps it contracted. (involuntary control)
External sphincter is a ring of skeletal muscle controlled by somatic motor neurons. Tonic stimulation from the CNS maintains is contraction except during urination. (voluntary control)

What is net filtration pressure?

Net Filtration Pressure is the pressure that favors the forming of renal filtrate from plasma. Its numerical value is the result of opposing forces - those that would force fluid into the Bowman's capsule against those that would force fluid back into the glomerulus. The glomerular hydrostatic pressure (55 mm Hg) is the chief force pushing water and solutes out of the glomerulus into the capsule. It is opposed by forces that drive fluids back into the glomerulus: (1) glomerular osmotic presssure (30 mm Hg) and (2) capsular hydrostatic pressure (15 mm Hg). Thus the net filtration pressure is 10 mm Hg.

Why is GFR directly proportional to the net filtration pressure?

Because the capillaries are exceptionally permeable and have a huge surface area. So therefore, net filtration pressure is the limiting factor. Normal GFR in both kidneys in adults is approximately 125 ml/min. A change in any of the pressures acting at the filtration membrane changes the NFP and thus the GFR. An increase in arterial blood pressure in the kidneys increases GFR, whereas dehydration inhibits filtrate formation.

Reabsorption of water and solutes from the tubule lumen to the ECF depends on what type of transport? What two specific types are used?

Active transport.
Reabsorption involves:
1. Epithelial (or transcellular) transport - substances cross both the apical and basolateral membranes of the tubule epithelial cell.
2. Paracellular transport- substances pass through junctions between two adjacent cells.
Which route a solute takes depends on the permeability of the epithelial junctions and on the electrochemical gradient for the solute.

How do the electrochemical gradients for solutes determine their transport mechanisms?

Solutes moving down their gradient use open leak channels of facilitated diffusion carries to cross the cell membrane.
Molecules that need to be pushed against their gradient are moved by either primary or secondary active transport. Na is directly/indirectly involved in many instances of both.

What is the primary driving force for most renal absorption?

The active transport of Na.
Active transport of Na from the lumen to ECF creates a transepithelial electrical gradient where the lumen is more - than the ECF. Anions then follow + charged Na out of the lumen. The net mvmt of Na & anions dilutes the luminal fluid and increases the [ ] of the ECF so water leaves the tubule by osmosis.

How is Na transported in the tubules of the nephron?

Na can: a- enter the cells passively by moving down its electrochemical gradient. b- apical mvmt uses a variety of symport and antiport transport proteins (ie: NHE Na - H antiporter). c- Na is transported across the basolateral membrane via the Na-K-ATPase.

How are other substances such as glucose, amoino acids, ions and various organic metabolites transported?

These are all transported through seconary active transport with sodium.
The apical membrane contains a symport protein that harnesses the energy from Na moving down its electrochemical gradient to move the other substance into the tubule. On the basolateral side, there is a facilitated diffusion carrier to bring it to the ECF.

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