Organ Biochemistry: Liver, Kidney and Brain

Let us make an in-depth study of the organ biochemistry.

Liver:

The liver is the largest internal organ in the human body. It lies below the diaphragm in the thoracic region of the abdomen. The liver is the largest gland in the body. It plays a major role in metabolism and has a number of functions in the body. Medical terms related to the liver often start with hepato or hepatic from the Greek word for liver, hepar.

Functions of Liver:

The various functions of the liver are carried out by the liver cells or hepatocytes.

1. The liver performs several roles in carbohydrate metabolism:

(a) Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol).

(b) Glycogenolysis (the breakdown of glycogen into glucose).

(c) Glycogenesis (the formation of glycogen from glucose).

(d) The breakdown of insulin and other hormones.

2. The liver is responsible for the mainstay of protein metabolism, ex. lactic acid is converted to alanine.

3. The liver also performs several roles in lipid metabolism:

(a) Cholesterol synthesis.

(b) The production of triglycerides (fats).

4. The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, protein S and anti-thrombin.

5. The liver breaks down haemoglobin, creating metabolites that are added to bile as pigment (bi­lirubin and biliverdin).

6. The liver produces and excretes bile (a greenish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.

7. The liver breaks down toxic substances and most medicinal products into less toxic and excretable forms.

8. Ammonia is converted to urea by the liver.

9. The liver stores a multitude of substances, including glucose (in the form of glycogen), vitamin B₁₂, iron, and copper.

10. In the first trimester of pregnancy, the fetal liver is the main site of RBC production. By the 32^nd week of gestation, the bone marrow completely takes over this task.

11. The liver is responsible for immunological effects — the reticuloendothelial system of the liver contains many immunologically active cells, acting as a ‘sieve’ for antigens carried to it via the portal system.

12. The liver produces albumin, the major osmolar component of blood serum.

13. Currently, there is no artificial organ or device capable of emulating all the functions of the liver. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.

Diseases of the Liver:

Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakdown of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.

1. Hepatitis:

Inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.

2. Cirrhosis:

Is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.

3. Haemochromatosis:

Hereditary disease causing accumulation of iron in the body, eventually leading to liver damage.

4. Cancer of the liver:

Primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract.

5. Wilson’s disease:

Hereditary disease which causes the body to retain copper.

6. Primary sclerosing cholangitis:

Inflammatory disease of bile duct, likely autoimmune in nature.

7. Primary biliary cirrhosis:

Autoimmune disease of small bile ducts.

8. Budd-Chiari syndrome:

Obstruction of the hepatic vein.

9. Gilbert’s syndrome:

A genetic disorder of bilirubin metabolism, found in about 5% of the population.

10. Glycogen storage disease type-II:

The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skel­etal muscles, liver and nervous system. There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome and progressive familial intrahepatic cholestasis.

Kidney:

The medical field that studies the kidneys and diseases of the kidney is called nephrology. The kidneys are located in the posterior part of the abdomen. There is one on each side of the spine; the right kidney sits just below the liver, the left below the diaphragm and adjacent to the spleen.

Above each kidney an adrenal gland (also called the ‘suprarenal gland’) is present. The asymmetry within the abdominal cavity caused by the liver results in the right kidney being slightly lower in position than the left one while the left kidney is located slightly more medially.

The kidneys are retroperitoneal and range from 9 to 13 cm in diameter; the left being slightly larger than the right. They are approximately at the vertebral level T12 to L3. The upper parts of the kidneys are partially protected by the eleventh and twelfth ribs and each kidney and adrenal gland are surrounded by two layers of fat (the perirenal and pararenal fat) and the renal fascia which help to cushion it. Congenital absence of one or both kidneys, known as unilateral or bilateral renal agenesis, can occur.

Functions of Kidney:

The kidneys are complex organs that have numerous biological roles. Their primary role is to maintain the homeostatic balance of bodily fluids by filtering and secreting metabolites (such as urea) and minerals from the blood and excreting them, along with water, as urine.

Because the kidneys are poised to sense plasma concentrations of ions such as sodium, potassium, hydrogen, oxygen and compounds such as amino acids, creatine, bicarbonate and glucose, they are important regulators of blood pressure, glucose metabolism and erythropoiesis (the process by which red blood cells i.e. eryth­rocytes are produced).

Excretion of waste products:

The kidneys excrete a variety of waste products produced by metab­olism, including the nitrogenous wastes — urea (from protein catabolism) and uric acid (from nucleic acid metabolism) and water.

Homeostasis:

The kidney is one of the major organs involved in whole-body homeostasis. Among its homeostatic functions are acid-base balance, regulation of electrolyte concentrations, control of blood volume and regulation of blood pressure. The kidneys accomplish these homeostatic functions indepen­dently and through coordination with other organs, particularly those of the endocrine system. The kidney communicates with these organs through hormones secreted into the blood stream.

Acid-base balance:

The kidneys regulate the pH of blood by adjusting H⁺ ion levels, referred as augmentation of mineral ion concentration and water composition of the blood.

Blood pressure:

Sodium ions are controlled in a homeostatic process involving aldosterone which increases sodium ion reabsorption in the distal convoluted tubules.

Plasma volume:

Any significant rise or drop in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. A rise in osmolality causes the gland to secrete antidiuretic hormone, resulting in water reabsorption by the kidney and an increase in urine concentration and volume. The two factors work together to return the plasma osmolality to its normal levels.

Hormone secretion:

The kidneys secrete a variety of hormones, including erythropoietin, urodilatin, renin and vitamin D.

Diseases and Disorders:

Congenital:

Congenital hydronephrosis, congenital obstruction of urinary tract, duplicated ureter, horse-shoe kidney, polycystic kidney disease, renal dysplasia, unilateral small kidney, multi-cystic dysplastic kidney.

Acquired:

Diabetic nephropathy, glomerulonephritis, hydronephrosis is the enlargement of one or both of the kidneys caused by obstruction of the flow of urine. Interstitial nephritis, kidney stones are relatively common and particularly painful disorders. Kidney tumors (Wilm’s tumor, renal cell carcino­ma), lupus nephritis, minimal change disease.

i. Nephrotic syndrome:

In this syndrome the glomerulus has been damaged so that a large amount of protein in the blood enters the urine. Other frequent features of the nephrotic syndrome include swelling, low serum albumin and high cholesterol.

ii. Pyelonephritis:

It is infection of the kidneys and is frequently caused by complication of an urinary tract infection.

iii. Renal failure

a. Acute renal failure

b. Stage 5 chronic kidney disease

Brain:

The brain controls the central nervous system (CNS), by way of the cranial nerves and spinal cord, the peripheral nervous system (PNS) and regulates virtually all human activity. Involuntary, or ‘lower’, actions, such as heart rate, respiration and digestion, are unconsciously governed by the brain, specifically through the autonomic nervous system. Complex or ‘higher’ mental activity, such as thought, reason and abstraction, is consciously controlled.

Anatomically, the brain can be divided into three parts: the forebrain, midbrain and hindbrain; the forebrain includes the several lobes of the cerebral cortex that control higher functions, while the mid and hindbrain are more involved with unconscious, autonomic functions. During en-cephalization, human brain mass increased beyond that of other species relative to body mass. This process was especially pronounced in the neo-cortex, a section of the brain involved with language and consciousness.

The neo-cortex accounts for about 76% of the mass of the human brain; with a neo-cortex much larger than that of other animals, humans enjoy unique mental capacities despite having a neuro-architecture similar to that of more primitive species.

Basic systems that alert humans to stimuli, sense events in the environment and maintain homeo­stasis are similar to those of basic vertebrates. Human consciousness is founded upon the extended capacity of the modern neo-cortex, as well as the greatly developed structures of the brain stem.

Functions of Brain:

Brain receives signals through nerves arriving from the sensors of the body. These signals are then processed throughout the central nervous system; reactions are formulated based upon reflex and learned experiences. A similarly extensive nerve network delivers signals from a brain to control important muscles throughout the body. Anatomically, the majority of afferent and efferent nerves (with the exception of the cranial nerves) are connected to the spinal cord, which then transfers the signals to and from the brain.

Sensory input is processed by the brain to recognize danger, find food, identify potential mates and perform more sophisticated functions. Visual, touch and auditory sensory pathways are routed to specific nuclei of the thalamus and then to regions of the cerebral cortex that are specific to each sensory system, the visual system, the auditory system and the somatosensory system. Olfactory pathways are routed to the olfactory bulb, then to various parts of the olfactory system. Taste is routed through the brain stem and then to other portions of the gustatory system.

To control movement the brain has several parallel systems of muscle control. The motor system controls voluntary muscle movement, aided by the motor cortex, cerebellum and the basal ganglia. The system eventually projects to the spinal cord and then out to the muscle effectors. Nuclei in the brain stem control many involuntary muscle functions such as heart rate and breathing. In addition, many automatic acts (simple reflexes, locomotion) can be controlled by the spinal cord alone.

Brain also produces a portion of the body’s hormones that can influence organs and glands elsewhere in the body; conversely, brain also reacts to hormones produced elsewhere in the body. The hormones that regulate hormone production throughout the body are produced in the brain by the structure called the pituitary gland.

Hormones, incoming sensory information and cognitive processing performed by the brain determine the brain state. Stimulus from any source can trigger a general arousal process that focuses cortical operations to processing of the new information.

This focusing of cognition is known as attention. Cognitive priorities are constantly shifted by a variety of factors such as hunger, fatigue, belief, unfamiliar information, or threat. The simplest dichotomy related to the processing of threats is the fight-or-flight response mediated by the amygdala and other limbic structures.

The brain is the source of the conscious, cognitive mind. The mind is the set of cognitive processes related to perception, interpretation, imagination, memories and crucially language, of which a person may or may not be aware. Beyond cognitive functions, the brain regulates autonomic processes related to essential body functions such as respiration and heartbeat. The brain controls all movement from lifting a pencil to build­ing a superstructure.

Extended neocortical capacity allows humans some control over emotional behavior, but neural path­ways between emotive centers of the brain stem and cerebral motor control areas are shorter than those connecting complex cognitive areas in the neo-cortex with incoming sensory information from the brain stem. Powerful emotional pathways can modulate spontaneous emotive expression regardless of attempts at cerebral self-control.