Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

Gonadotropin-releasing hormone (GnRH)

GnRH is a peptide of 10 amino acids. Its secretion at the onset of puberty triggers sexual development.

Primary Effects

FSH and LH Relaese

Secondary Effects

Increases estrogen and progesterone (in females)

testosterone Relaese (in males)

Growth hormone-releasing hormone (GHRH)

GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44.  GHRH stimulates cells in the anterior lobe of the pituitary to secrete growth hormone (GH).

Corticotropin-releasing hormone (CRH)

CRH is a peptide of 41 amino acids. Its acts on cells in the anterior lobe of the pituitary to release adrenocorticotropic hormone (ACTH) CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.  It may also play a role in keeping the T cells of the mother from mounting an immune attack against the fetus

Somatostatin

Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to

• inhibit the release of growth hormone (GH)
• inhibit the release of thyroid-stimulating hormone (TSH)

Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.

Antidiuretic hormone (ADH) and Oxytocin

These peptides are released from the posterior lobe of the pituitary

• The Autonomic Nervous System (ANS) Controls the Body's Internal Environment in a Coordinated Manner

• The ANS helps control the heart rate, blood pressure, digestion, respiration, blood pH and other bodily functions through a series of complex reflex actions
• These controls are done automatically, below the conscious level
• To exert this control the activities of many different organs must be coordinated so they work to accomplish the same goal
• In the ANS there are 2 nerves between the central nervous system (CNS) and the organ. The nerve cell bodies for the second nerve are organized into ganglia:
  • CNS -> Preganglionic nerve -> Ganglion -> Postganglionic nerve -> Organ
• At each junction neurotransmitters are released and carry the signal to the next nerve or organ.

• The ANS has 2 Divisions, Sympathetic and Parasympathetic

   

• Comparison of the 2 systems:

• 	Anatomical Location	Preganglionic Fibers	Postganglionic Fibers	Transmitter (Ganglia)	Transmitter (Organs)
  Sympathetic	Thoracic/ Lumbar	Short	Long	ACh	NE
  Parasympathetic	Cranial/ Sacral	Long	Short	ACh	ACh

   

  The Sympathetic is the "Fight or Flight" Branch of the ANS

• Emergency situations, where the body needs a sudden burst of energy, are handled by the sympathetic system
• The sympathetic system increases cardiac output and pulmonary ventilation, routes blood to the muscles, raises blood glucose and slows down digestion, kidney filtration and other functions not needed during emergencies
• Whole sympathetic system tends to "go off" together
• In a controlled environment the sympathetic system is not required for life, but it is essential for any stressful situation

• The Parasympathetic is the Rest and Digest Branch of the ANS

• The parasympathetic system promotes normal maintenance of the body- acquiring building blocks and energy from food and getting rid of the wastes
• It promotes secretions and mobility of different parts of the digestive tract.
• Also involved in urination, defecation.
• Does not "go off" together; activities initiated when appropriate
• The vagus nerve (cranial number 10) is the chief parasympathetic nerve
• Other cranial parasympathetic nerves are: III (oculomotor), VII (facial) and IX (glossopharyngeal)

• The Hypothalamus Has Central Control of the ANS

• The hypothalamus is involved in the coordination of ANS responses,
• One section of the hypothalamus seems to control many of the "fight or flight" responses; another section favors "rest and digest" activities

• The Adrenal Medulla is an Extension of the Sympathetic Nervous System

• The adrenal medulla behaves like a combined autonomic ganglion and postsynaptic sympathetic nerve (see diagram above)
• Releases both norepinephrine and epinephrine in emergency situations
  • Releases a mixture of epinephrine (E = 80%) and norepinephrine (NE = 20%)
  • Epinephrine = adrenaline
• This action is under control of the hypothalamus

• Sympathetic & Parasympathetic Systems

• Usually (but not always) both sympathetic and parasympathetic nerves go to an organ and have opposite effects
• You can predict about 90% of the sympathetic and parasympathetic responses using the 2 phrases: "Fight or Flight" and "Rest and Digest".
• Special cases:
  • Occasionally the 2 systems work together: in sexual intercourse the parasympathetic promotes erection and the sympathetic produces ejaculation
  • Eye: the sympathetic response is dilation and relaxation of the ciliary muscle for far vision (parasympathetic does the opposite)
  • Urination: the parasympathetic system relaxes the sphincter muscle and promotes contraction of muscles of the bladder wall -> urination (sympathetic blocks urination)
  • Defecation: the parasympathetic system causes relaxation of the anal sphincter and stimulates colon and rectum to contract -> defecation (sympathetic blocks defecation)

• Organ	Parasympathetic Response "Rest and Digest"	Sympathetic Response "Fight or Flight"
  Heart (baroreceptor reflex)	Decreased heart rate Cardiac output decreases	Increased rate and strength of contraction Cardiac output increases
  Lung Bronchioles	Constriction	Dilation
  Liver Glycogen	No effect	Glycogen breakdown Blood glucose increases
  Fat Tissue	No effect	Breakdown of fat Blood fatty acids increase
  Basal Metabolism	No effect	Increases ~ 2X
  Stomach	Increased secretion of HCl & digestive enzymes Increased motility	Decreased secretion Decreased motility
  Intestine	Increased secretion of HCl & digestive enzymes Increased motility	Decreased secretion Decreased motility
  Urinary bladder	Relaxes sphincter Detrusor muscle contracts Urination promoted	Constricts sphincter Relaxes detrusor Urination inhibited
  Rectum	Relaxes sphincter Contracts wall muscles Defecation promoted	Constricts sphincter Relaxes wall muscles Defecation inhibited
  Eye	Iris constricts Adjusts for near vision	Iris dilates Adjusts for far vision
  Male Sex Organs	Promotes erection	Promotes ejaculation

   

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.

Blood Pressure

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood pressure in the arteries.

The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.

Blood pressure is expressed as two numbers, e.g., 120/80.

Blood pressure in the capillaries

The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.

Blood pressure in the veins

When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins

Exchanges Between Blood and Cells

With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.

When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.

Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)

Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.

Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.

Control of the Capillary Beds

An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m². The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.

The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by

• the autonomic nervous system.
• local controls in the capillary beds

1. Automatic control (sensory) of respiration is in - brainstem (midbrain) 

2. Behavioral/voluntary control is in - the cortex

3. Alveolar ventilation -the amount of atmospheric air that actually reaches the alveolar per breath and that can participate in the exchange of gasses between alveoli and blood

4. Only way to increase gas exchange in alveolar capillaries - perfusion-limited gas exchange 

5. Pulmonary ventiliation not effected by - concentration of bicarbonate ions

6. Central chemoreceptors - medulla -  CO2, O2 and H+ concentrations

7. Peripheral chemoreceptors - carotid and aortic bodies- PO2, PCO2 and pH 

8. Major stimulus for respiratory centers - arterial PCO2 

9. Rhythmic breathing depends on 
1. continuous (tonic) inspiratory drive from DRG (dorsal respiratory group)
2. intermittent (phasic) expiratory input from cerebrum, thalamus, cranial nerves and ascending spinal cord sensory tracts

10. Primary site for gas exchange - type I epithelial cells for alveoli