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Physiology

The Kidneys

The kidneys are the primary functional organ of the renal system.

They are essential in homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and the regulation of blood pressure (by maintaining salt and water balance).

They serve the body as a natural filter of the blood and remove wastes that are excreted through the urine.

They are also responsible for the reabsorption of water, glucose, and amino acids, and will maintain the balance of these molecules in the body.

In addition, the kidneys produce hormones including calcitriol, erythropoietin, and the enzyme renin, which are involved in renal and hemotological physiological processes.

Anatomical Location

The kidneys are a pair of bean-shaped, brown organs about the size of your fist. They are covered by the renal capsule, which is a tough capsule of fibrous connective tissue.

Right kidney being slightly lower than the left, and left kidney being located slightly more medial than the right.

The right kidneys lie  just below the diaphragm and posterior to the liver, the left below the diaphragm and posterior to the spleen.

Resting on top of each kidney is an adrenal gland (adrenal meaning on top of renal), which are involved in some renal system processes despite being a primarily endocrine organ.

They are considered retroperitoneal, which means that they lie behind the peritoneum, the membrane lining of the abdominal cavity.

The renal artery branches off from the lower part of the aorta and provides the blood supply to the kidneys.

 Renal veins take blood away from the kidneys into the inferior vena cava.

The ureters are structures that come out of the kidneys, bringing urine downward into the bladder.

Internal Anatomy of the Kidneys

There are three major regions of the kidney:

1.         Renal cortex

2.         Renal medulla

3.         Renal pelvis

The renal cortex is a space between the medulla and the outer capsule.

The renal medulla contains the majority of the length of nephrons, the main functional component of the kidney that filters fluid from blood.

The renal pelvis connects the kidney with the circulatory and nervous systems from the rest of the body.

Renal Cortex

The kidneys are surrounded by a renal cortex

The cortex provides a space for arterioles and venules from the renal artery and vein, as well as the glomerular capillaries, to perfuse the nephrons of the kidney. Erythropotein, a hormone necessary for the synthesis of new red blood cells, is also produced in the renal cortex.

Renal Medulla

The medulla is the inner region of the parenchyma of the kidney. The medulla consists of multiple pyramidal tissue masses, called the renal pyramids, which are triangle structures that contain a dense network of nephrons.

At one end of each nephron, in the cortex of the kidney, is a cup-shaped structure called the Bowman's capsule. It surrounds a tuft of capillaries called the glomerulus that carries blood from the renal arteries into the nephron, where plasma is filtered through the capsule.

After entering the capsule, the filtered fluid flows along the proximal convoluted tubule to the loop of Henle and then to the distal convoluted tubule and the collecting ducts, which flow into the ureter. Each of the different components of the nephrons are selectively permeable to different molecules, and enable the complex regulation of water and ion concentrations in the body.

Renal Pelvis

The renal pelvis contains the hilium. The hilum is the concave part of the bean-shape where blood vessels and nerves enter and exit the kidney; it is also the point of exit for the ureters—the urine-bearing tubes that exit the kidney and empty into the urinary bladder. The renal pelvis connects the kidney to the rest of the body.

Supply of Blood and Nerves to the Kidneys

•  The renal arteries branch off of the abdominal aorta and supply the kidneys with blood. The arterial supply of the kidneys varies from person to person, and there may be one or more renal arteries to supply each kidney.

•  The renal veins are the veins that drain the kidneys and connect them to the inferior vena cava.

•  The kidney and the nervous system communicate via the renal plexus. The sympathetic nervous system will trigger vasoconstriction and reduce renal blood flow, while parasympathetic nervous stimulation will trigger vasodilation and increased blood flow.

•  Afferent arterioles branch into the glomerular capillaries, while efferent arterioles take blood away from the glomerular capillaries and into the interlobular capillaries that provide oxygen to the kidney.

•  renal vein

The veins that drain the kidney and connect the kidney to the inferior vena cava.

•  renal artery

These arise off the side of the abdominal aorta, immediately below the superior mesenteric artery, and supply the kidneys with blood.

Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.

Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The  resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :

1. Depolarization phase (Phase 0 ) :

A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.

2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :

a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains  depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3  ( Rapid repolarization) :  opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.


Absolute refractory period:

Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and  relax to be filled by blood ..

Relative refractory period : 

Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.

Factors , affecting excitability of cardiac muscle:

I. Positive bathmotropic effect :

1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2.  Drugs : Catecholamines and  xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia

II. Negative bathmotropic effect :

1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.

Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole  is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)

Membrane Potential

  • Membrane potentials will occur across cell membranes if
    • 1) there is a concentration gradient of an ion
    • 2) there is an open channel in the membrane so the ion can move from one side to the other

The Sodium Pump Sets Up Gradients of Na and K Across Cell Membranes

  • All cells have the Na pump in their membranes
    • Pumps 3 Nas out and 2 Ks in for each cycle
    • Requires energy from ATP
      • Uses about 30% of body's metabolic energy
    • This is a form of active transport- can pump ions "uphill", from a low to a high concentration
    • This produces concentration gradients of Na & K across the membrane
    • Typical concentration gradients:

 

 In mM/L

 Out mM/L

 Gradient orientation

 Na

 10

 150

 High outside

 K

 140

 5

 High inside

  •  
  • The ion gradients represent stored electrical energy (batteries) that can be tapped to do useful work
  • The Na pump is of ancient origin, probably originally designed to protect cell from osmotic swelling

Inhibited by the arrow poisons ouabain and digitalis

As the contents of the stomach become thoroughly liquefied, they pass into the duodenum, the first segment  of the small intestine. The duodenum is the first 10" of the small intestine

Two ducts enter the duodenum:

  • one draining the gall bladder and hence the liver
  • the other draining the exocrine portion of the pancreas.

From the intestinal mucosal cells, and from the liver and gallbladder. Secretions from the pancreas and bile from the gallbladder enter the duodenum through the hepatopancreatic ampulla and the sphincter of Oddi. These lie where the pancreatic duct and common bile duct join before entering the duodenum. The presence of fatty chyme in the duodenum causes release of the hormone CCK into the bloodstream. CCK is one of the enterogastrones and its main function, besides inhibiting the stomach, is to stimulate the release of enzymes by the pancreas, and the contraction of the gallbladder to release bile. It also stimulates the liver to produce bile. Consumption of excess fat results in excessive bile production by the liver, and this can lead to the formation of gallstones from precipitation of the bile salts. 

The acid in the chyme stimulates the release of secretin which causes the pancreas to release bicarbonate which neutralizes the acidity

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

  • Intracellular (inside cells) = ~ 34 liters
  • Interstitial (outside cells) = ~ 13 liters
  • Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

  • Capillary walls (1 cell thick) separate blood from interstitial fluid
  • Cell membranes separate intracellular and interstitial fluids
  • Loss of about 30% of body water is fatal

 

Ions = atoms or molecules with unequal numbers of electrons and protons:

  • found in both intra- & extracellular fluid
  • examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

  • Giving up electron leaves a + charge (cation)
  • Taking on electron produces a - charge (anion)
  • Ions conduct electricity
  • Without ions there can be no nerves or excitability
    • Na+ and K+ cations  
    • Ca2+ and Mg2+ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

  • High K+ in cells, high Na+ outside
  • Ion gradients maintained by Na pump (1/3 of basal metabolism)
  • Think of Na+ gradient as a Na+ battery- stored electrical energy
  • K+ gradient forms a K+ battery
  • Energy stored in Na+ and K+ batteries can be tapped when ions flow
  • Na+ and K+ produce action potential of excitable cells

Typical Concentration Gradients and Membrane Potentials in Excitable Cells

The Na Pump is Particularly Important in the Kidney and Brain

  • All cells have Na pumps in their membranes, but some cells have more than others
  • Over-all Na pump activity may account for a third of your resting energy expenditure!
  • In the kidney the Na pump activity is very high because it is used to regulate body salt and water concentrations
    • Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of the oxygen supply
  • Pump activity is also high in the brain because Na and K gradients are essential for nerves
    • The brain is another high energy organ; it is 2% of body weight, but uses 18% of the oxygen supply

In the Resting State Potassium Controls the Membrane Potential of Most Cells

  • Resting cells have more open K channels than other types
  • More K+ passes through membrane than other ions- therefore K+ controls the potential
  • Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells
    • Raising K will make the membrane potential less negative (depolarization)
  • High blood K+ can cause the heart to stop beating (it goes into permanent contraction)

During an Action Potential Na Channels Open, and Na Controls the Membrane Potential

  • Whichever ion has the most open channels controls the membrane potential
  • Excitable cells have Na channels that open when stimulated
  • When large numbers of these channels open Na controls the membrane potential

Properties of cardiac muscle

Cardiac muscle is a striated muscle like the skeletal muscle , but it is different from the skeletal muscle in being involuntary and syncytial .

Syncytium means that cardiac muscle cells are able to excite and contract together due to the presence of gap junctions between adjacent cardiac cells.

Cardiac muscle has four properties , due to which the heart is able to fulfill its function as a pumping organ. Studying and understanding these properties is essential for students to understand the cardiac physiology as a whole.

1. Rhythmicity ( Chronotropism )
2. Excitability ( Bathmotropism ) 
3. Conductivity
4. Contractility

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