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Physiology - NEETMDS- courses
NEET MDS Lessons
Physiology

Regulation of glomerular filtration :

1. Extrinsic regulation : 

- Neural regulation : sympathetic and parasympathetic nervous system which causes vasoconstriction or vasodilation respectively .
- Humoral regulation : Vasoactive substances may affect the GFR , vasoconstrictive substances like endothelin ,Angiotensin II , Norepinephrine , prostaglandine F2 may constrict the afferent arteriole and thus decrease GFR , while the vasodilative agents like dopamine , NO , ANP , Prostaglandines E2 may dilate the afferent arteriole and thus increase the filtration rate .

2. Intrinsic regulation : 

- Myogenic theory ( as in the intrinsic regulation of cardiac output) .
- Tubuloglomerular feedback: occurs by cells of the juxtaglomerular apparatus that is composed of specific cells of the distal tubules when it passes between afferent and efferent arterioles ( macula densa cells ) , these cells sense changes in flow inside the tubules and inform specific cells in the afferent arteriole (granular cells ) , the later secrete vasoactive substances that affect the diameter of the afferent arteriole.

Carbon Dioxide Transport

Carbon dioxide (CO2) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H+) and a bicarbonate ions:

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3

95% of the CO2 generated in the tissues is carried in the red blood cells:

  • It probably enters (and leaves) the cell by diffusing through transmembrane channels in the plasma membrane. (One of the proteins that forms the channel is the D antigen that is the most important factor in the Rh system of blood groups.)
  • Once inside, about one-half of the CO2 is directly bound to hemoglobin (at a site different from the one that binds oxygen).
  • The rest is converted — following the equation above — by the enzyme carbonic anhydrase into
    • bicarbonate ions that diffuse back out into the plasma and
    • hydrogen ions (H+) that bind to the protein portion of the hemoglobin (thus having no effect on pH).

Only about 5% of the CO2 generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO2 we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!)

When the red cells reach the lungs, these reactions are reversed and CO2 is released to the air of the alveoli.

Cell, or Plasma, membrane

  • Structure - 2 primary building blocks include

protein (about 60% of the membrane) and lipid, or

fat (about 40% of the membrane).

The primary lipid is called phospholipids, and molecules of phospholipid form a 'phospholipid bilayer' (two layers of phospholipid molecules). This bilayer forms because the two 'ends' of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic):

  • Functions include:
    • supporting and retaining the cytoplasm
    • being a selective barrier .
    • transport
    • communication (via receptors)

Membrane Structure & Function

Cell Membranes

  • Cell membranes are phospholipid bilayers (2 layers)
  • Bilayer forms a barrier to passage of molecules in an out of cell
  • Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
  • Cholesterol (another lipid) stabilizes cell membranes
  • the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water

Membranes Also Contain Proteins

  • Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
  • Hydrophobic = doesn't like water = likes lipids
  • Membrane proteins have many functions:
    • receptors for hormones
    • pumps for transporting materials across the membrane
    • ion channels
    • adhesion molecules for holding cells to extracellular matrix

cell recognition antigens

Blood Groups

Blood groups are created by molecules present on the surface of red blood cells (and often on other cells as well).

The ABO Blood Groups

The ABO blood groups are the most important in assuring safe blood transfusions.

Blood Group

Antigens on RBCs

Antibodies in Serum

Genotypes

A

A

Anti-B

AA or AO

B

B

Anti-A

BB or BO

AB

A and B

Neither

AB

O

Neither

Anti-A and anti-B

OO

When red blood cells carrying one or both antigens are exposed to the corresponding antibodies, they agglutinate; that is, clump together. People usually have antibodies against those red cell antigens that they lack.

The critical principle to be followed is that transfused blood must not contain red cells that the recipient's antibodies can clump. Although theoretically it is possible to transfuse group O blood into any recipient, the antibodies in the donated plasma can damage the recipient's red cells. Thus all transfusions should be done with exactly-matched blood.

The Rh System

Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. They are named for the rhesus monkey in which they were first discovered.

There are a number of Rh antigens. Red cells that are "Rh positive" express the one designated D. About 15% of the population have no RhD antigens and thus are "Rh negative".

The major importance of the Rh system for human health is to avoid the danger of RhD incompatibility between mother and fetus.

During birth, there is often a leakage of the baby's red blood cells into the mother's circulation. If the baby is Rh positive (having inherited the trait from its father) and the mother Rh-negative, these red cells will cause her to develop antibodies against the RhD antigen. The antibodies, usually of the IgG class, do not cause any problems for that child, but can cross the placenta and attack the red cells of a subsequent Rh+ fetus. This destroys the red cells producing anemia and jaundice. The disease, called erythroblastosis fetalis or hemolytic disease of the newborn, may be so severe as to kill the fetus or even the newborn infant. It is an example of an antibody-mediated cytotoxicity disorder.

Although certain other red cell antigens (in addition to Rh) sometimes cause problems for a fetus, an ABO incompatibility does not. Rh incompatibility so dangerous when ABO incompatibility is not

It turns out that most anti-A or anti-B antibodies are of the IgM class and these do not cross the placenta. In fact, an Rh/type O mother carrying an Rh+/type A, B, or AB fetus is resistant to sensitization to the Rh antigen. Presumably her anti-A and anti-B antibodies destroy any fetal cells that enter her blood before they can elicit anti-Rh antibodies in her.

This phenomenon has led to an extremely effective preventive measure to avoid Rh sensitization. Shortly after each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies. The preparation is called Rh immune globulin (RhIG) or Rhogam. These passively acquired antibodies destroy any fetal cells that got into her circulation before they can elicit an active immune response in her.

Rh immune globulin came into common use in the United States in 1968, and within a decade the incidence of Rh hemolytic disease became very low.

A rise in blood pressure stretches the atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by:

  • relaxing arterioles
  • inhibiting the secretion of renin and aldosterone
  • inhibiting the reabsorption of sodium ions in the collecting ducts of the kidneys.

The effects on the kidney reduce the reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.

The Heartbeat

During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.

The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.

The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.

When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles.

The contraction of the heart in response to this electrical activity creates systole.

A period of recovery follows called diastole.

  • The heart muscle and S-A node become recharged.
  • The heart muscle relaxes.
  • The atria refill. 

The Electrocardiogram

The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG

Control of the Heart

Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.

  • One sends nerve impulses down accelerator nerves.
  • The other sends nerve impulses down a pair of vagus nerves

Accelerator Nerves

The accelerator nerves are part of the sympathetic branch of the autonomic nervous system, and  like all post-ganglionic sympathetic neurons  release noradrenaline at their endings on the heart.

They increase the rate and strength of the heartbeat and thus increase the flow of blood. Their activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25-30 liters/minute.


Vigorous exercise accelerates heartbeat in two ways;

  • As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay  by the accelerator nerves  to the heart.
  • As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.

Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure

The Vagus Nerves

The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat.

Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these  by way of the vagus nerves  to the heart. Heartbeat and blood pressure diminish.

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.

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