Phases of cardiac cycle :

1. Early diastole ( also called the atrial diastole , or complete heart diastole) : During this phase :

- Atria are  relaxed
- Ventricles are relaxed
- Semilunar valves are closed
- Atrioventricular valves are open
During this phase the blood moves passively from the venous system into the ventricles ( about 80 % of blood fills the ventricles during this phase.

2. Atrial systole : During this phase :

- Atria are contracting
- Ventricles are relaxed
- AV valves are open
- Semilunar valves are closed
- Atrial pressure increases.the a wave of atrial pressure appears here.
- P wave of ECG starts here
- intraventricular pressure increases due to the rush of blood then decrease due to continuous relaxation of ventricles.

The remaining 20% of blood is moved to fill the ventricles during this phase , due to atrial contraction.

3. Isovolumetric contraction : During this phase :

- Atria are relaxed
- Ventricles are contracting
- AV valves are closed
- Semilunar valves are closed
- First heart sound
- QRS complex.
The ventricular fibers start to contract during this phase , and the intraventricular pressure increases. This result in closing the AV valves , but the pressure is not yet enough to open the semilunar valves , so the blood volume remain unchanged , and the muscle fibers length also remain unchanged , so we call this phase as isovolumetric contraction ( iso : the same , volu= volume , metric= length).

4. Ejection phase : Blood is ejected from the ventricles into the aorta and pulmonary artery .

During this phase :

- Ventricles are contracting
- Atria are relaxed
- AV valves are closed
- Semilunar valves are open
- First heart sound
- Intraventricular pressure is increased , due to continuous contraction
- increased aortic pressure .
- T wave starts.

5. Isovolumetric relaxation:  This phase due to backflow of blood in aorta and pulmonary system after the ventricular contraction is up and the ventricles relax . This backflow closes the semilunar valves .

During this phase :

- Ventricles are relaxed
- Atrial are relaxed
- Semilunar valves are closed .
- AV valves are closed.
- Ventricular pressure fails rapidly
- Atrial pressure increases due to to continuous venous return. the v wave appears here. 
- Aortic pressure : initial sharp decrease due to sudden closure of the semilunar valve ( diacrotic notch) , followed by secondary rise in pressure , due to elastic recoil of the aorta ( diacrotic wave)  .
- T wave ends in this phase

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.

The Sliding Filament mechanism of muscle contraction.

When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens

The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands.

It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together

Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. 

The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

GENERAL VISCERAL AFFERENT (GVA) PATHWAYS

Pain and Pressure Sensation via the Spinal Cord

Visceral pain receptors are located in peritoneal surfaces, pleural membranes, the dura mater, walls of arteries, and the walls of the GI tube.

Nociceptors in the walls of the GI tube are particularly sensitive to stretch and overdistension.

General visceral nociceptors conduct signals into the spinal cord over the monopolar neurons of the posterior root ganglia. They terminate in laminae III and IV of the posterior horn as do the pain and temperature pathways of the GSA system , their peripheral processes reach the visceral receptors via the gray rami communicantes and ganglia of the sympathetic chain

Second-order neurons from the posterior horn cross in the anterior white commissure and ascend to the thalamus in the anterior and lateral spinothalamic tracts,

Projections from the VPL of the thalamus relay signals to the sensory cortex.

The localization of visceral pain is relatively poor, making it difficult to tell the exact source of the stimuli.

Blood Pressure, Blood Chemistry, and Alveolar Stretch Detection

The walls of the aorta and the carotid sinuses contain special baroreceptors (pressure receptors) which respond to changes in blood pressure. These mechanoreceptors are the peripheral endings of GVA fibers of the glossopharyngeal (IX) and vagus (X) nerves

The GVA fibers from the carotid sinus baroreceptors enter the solitary tract of the brainstem and terminate in the vasomotor center of the medulla (Fig-14). This is the CNS control center for cardiovascular activity.

Stretch receptors in the alveoli of the lungs conduct information concerning rhythmic alveolar inflation and deflation over GVA X fibers to the solitary tract and then to the respiratory center of the brainstem. This route is an important link in the Hering-Breuer reflex, which helps to regulate respiration.

Carotid body chemoreceptors, sensitive to changes in blood PO2 and, to a lesser extent, PCO2 and pH, conduct signals to both the vasomotor and respiratory centers over GVA IX nerve fibers

GVA X fibers conduct similar information from the aortic chemoreceptors to both centers

The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. However, scattered through the pancreas are several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:

• beta cells, which secrete insulin and amylin;
• alpha cells, which secrete glucagon;
• delta cells, which secrete somatostatin, and
• gamma cells, which secrete a polypeptide of unknown function.

Beta Cells

Beta cells secrete insulin in response to a rising level of blood sugar

Insulin affects many organs. It

• stimulates skeletal muscle fibers to
  • take up glucose and convert it into glycogen;
  • take up amino acids from the blood and convert them into protein.
• acts on liver cells
  • stimulating them to take up glucose from the blood and convert it into glycogen while
  • inhibiting production of the enzymes involved in breaking glycogen back down (glycogenolysis) and
  • inhibiting gluconeogenesis; that is, the conversion of fats and proteins into glucose.
• acts on fat (adipose) cells to stimulate the uptake of glucose and the synthesis of fat.
• acts on cells in the hypothalamus to reduce appetite.

Diabetes Mellitus

Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are:

• a failure of the kidney to retain glucose .
• a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood).

There are three categories of diabetes mellitus:

• Insulin-Dependent Diabetes Mellitus (IDDM) (Type 1) and
• Non Insulin-Dependent Diabetes Mellitus (NIDDM)(Type 2)
• Inherited Forms of Diabetes Mellitus

Insulin-Dependent Diabetes Mellitus (IDDM)

IDDM ( Type 1 diabetes)

• is characterized by little or no circulating insulin;
• most commonly appears in childhood.
• It results from destruction of the beta cells of the islets.
• The destruction results from a cell-mediated autoimmune attack against the beta cells.
• What triggers this attack is still a mystery, although a prior viral infection may be the culprit.

Non Insulin-Dependent Diabetes Mellitus (NIDDM)

Many people develop diabetes mellitus without an accompanying drop in insulin levels In many cases, the problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles. Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter. This transporter forms a channel that permits the facilitated diffusion of glucose into the cell. Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen is reduced. This is called insulin resistance. NIDDM (also called Type 2 diabetes mellitus) usually occurs in adults and, particularly often, in overweight people.

Alpha Cells

The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids. Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose (glycogenolysis) which is deposited in the blood.

Glucagon secretion is

• stimulated by low levels of glucose in the blood;
• inhibited by high levels, and
• inhibited by amylin.

The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.

Delta Cells

The delta cells secrete somatostatin. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine.

Gamma Cells

The gamma cells of the islets secrete pancreatic polypeptide. No function has yet been found for this peptide of 36 amino acids.

Abnormalities of Salt, Water or pH

• Examples:
  • Hyperkalemia: caused by kidney disease & medical malpractice
    • High K+ in blood- can stop the heart in contraction (systole)
  • Dehydration: walking in desert- can lose 1-2 liters/hour through sweat
    • Blood becomes too viscous to circulate well -> loss of temperature regulation -> hyperthermia, death
  • Acidosis: many causes including diabetes mellitus and respiratory problems; can cause coma, death