Q.1a. What is reticuloendothelial system? What are its important sites in the body?

Enumerate the functions of reticuloendothelial system? b. Define Inflammation. What are its characteristic features? (2.5+2.5 marks) Key:1a. It is a generalized phagocytic system located in all tissues, especially in those tissue areas where large quantities of particles, toxins, and other unwanted substances must be destroyed. Monocytes, mobile macrophages, fixed tissue macrophages and a few specialized cells in the bone marrow, spleen and lymph nodes constitute the reticuloendothelial system. (1) Location of the reticuloendothelial system:

Tissue Macrophages in the Skin and Subcutaneous Tissues (Histiocytes)

Macrophages in the Lymph Nodes. Alveolar Macrophages in the Lungs Macrophages (Kupffer Cells) in the Liver Sinusoids Macrophages of the Spleen and Bone Marrow. (0.5)

(1)

Functions of reticuloendothelial system Key:1b. (Reference: p 434, 435 Guyton, 11th Ed.)

DEFINITION: When tissue injury occurs, whether caused by bacteria, trauma, chemicals, heat etc, multiple substances are released by injured tissues & cause dramatic secondary changes in the surrounding uninjured tissues. This complex of tissue changes is called inflammation. (0.5 mark) CHARACTERISTIC FEATURES: (1) vasodilation of the local blood vessels, with excess local blood flow; (0.5mark) (2) increased permeability of the capillaries, leakage of large quantities of fluid into the interstitial spaces; (0.5mark)

(3) Clotting of the fluid in the interstitial spaces b/c of excessive amounts of fibrinogen & other proteins leaking from the capillaries; (0.5mark) (4) Migration of large numbers of granulocytes & monocytes into the tissue. (5) Swelling of the tissue cells. (0.5mark) (0.5mark)

Q.2 A healthy 6-years-old girl is brought to the emergency department because of a severe, uncontrolled nose bleed. She has numerous small pin point hemorrhages (blotches) on her arms & legs. Her blood values are as follows: Hb = 13 g/dl, Leukocytes count = 7000/cubic mm, Platelet count = < 10,000/cubic mm a) Give her provisional diagnosis. b) Give the pathophysiology of her disease. c) Mention her treatment. key: (Reference: p 465, Guyton, 11th Ed.) a) DIAGNOSIS: Thrombocytopenic Purpura b) PATHOPHYSIOLOGY: She has a very low number of platelets in the circulating blood, so has a tendency to bleed more from many small venules or capillaries leading to small punctate hemorrhages throughout all the body tissues. (1 mark) Her skin displays many small, purplish blotches, giving the disease the name thrombocytopenic Purpura (0.5mark) Platelets are important for repair of minute breaks in capillaries and other small vessels, but she is deficient in them leading to nose & cutaneous bleed. (0.5mark) Bleeding will not occur until the number of platelets in the blood falls below 50,000/ml, rather than the normal 150,000 to 300,000. Levels as low as10,000/ml are frequently lethal. (1 mark) c) TREATMENT: Giving fresh whole blood transfusions (can control bleeding for 1-4 days) that contain large numbers of platelets (0.5mark) Splenectomy is often helpful, because the spleen normally removes large numbers of platelets from the blood. (0.5mark) (1mark) (1+3+1 marks)

Q3a.: Rashid was started on blood transfusion pre operatively to improve the hemoglobin prior to surgery. He began to feel irritability, chills and palpitation just within 5 minutes after the start of transfusion. But the transfusion was continued and the patient developed fever, shock-like state with fall of blood pressure and scanty urine output. i) What was the possible reason for Rashids symptoms? ii) Give the mechanisms in detail for development of these symptoms? iii) What steps you will take to prevent such situation? iv)Enumerate other hazards of blood transfusion reaction. 3b. What happens when a specific allergen is injected directly into circulation? Give the sequence of events that may follow? (2.5 marks) (0.5+1+1 Marks)

Key: 3a.
i) Mismatched blood transfusion. 0.5 mark

ii) Hemolysis of donors red cells after agglutination by corresponding agglutinin in recipients plasma results release of toxins from hemolysed cells causing irritability, chills and palpitation due to circulatory shock. 0.5 mark Immediate hemolysis and phagocytosis of RBCs results in release of excessive Hb in circulation, much of the excess leaks through the glomerular membranes into the kidney tubules, precipitates. Renal vasoconstriction, circulatory shock, and renal tubular blockage together cause acute renal shutdown. Less or no urine. iii) Blood group typing: ABO and Rh Cross matching KEY:3b When a specific allergen is injected directly into the circulation, it reacts with basophils of the blood & mast cells in the tissues located immediately outside the small blood vessels. (0.5 mark) Widespread allergic reaction occurs throughout the vascular system & closely associated tissues. This is called anaphylaxis. (0.5 mark) Histamine is released into the circulation causes: body-wide vasodilation (0.25 mark) Increased permeability of the capillaries with resultant marked loss of plasma from the circulation. (0.25 mark) An occasion person dies of circulatory shock within a few min unless treated with epinephrine to oppose the effects of the histamine. (0.5 mark) Mixture of leukotrienes called slow-reacting substance of anaphylaxis released from the activated basophils & mast cells cause spasm of the smooth muscle of the bronchioles, eliciting an asthma-like attack. (0.5 mark) 0.5 mark 0.5 mark 0.5 mark

Q:4a. What do you understand by Delayed-Reaction Allergy? b. Classify the various blood groups.

(1) (2)

c. A newborn baby develops deep yellow color of skin and eyes within 24 hours after birth. His blood group is O +ve. Blood picture shows many premature RBCs. i) Give your provisional diagnosis. ii) Briefly discuss the pathogenesis. Key: 4a. Delayed reaction allergy: (0.25 mark each = 1 mark) (0.5) (1.5)

Caused by activated T cells, not by antibodies. Example: repeated exposure to poison ivy causes formation of activated Helper and Cytotoxic T cells. On subsequent exposure, activated T cells diffuse from circulating blood into the skin & simultaneously they elicit cell mediated immune reaction Release of many toxic substances causes extensive tissue invasion by macrophages results into tissue damage, especially where the specific antigen is present, e.g., skin in case of poison ivy, lung in case of lung edema, asthma & some air borne antigens. Key: 4b. Ref Guyton pg: 451 OAB Blood types: (1)

Depending on the presence or absence of the two agglutinogens A and B blood groups are classified into following four groups: Blood group A: When only type A agglutinogen is present Blood group B: When only type B agglutinogen is present Blood group AB: When type A and B agglutinogen both are present Blood group O: When neither A nor B agglutinogen is present Rh Blood types: (1)

There are six common types of Rh antigens each of which is called an Rh factor. The type D is widely prevalent and on the presence or absence of this factor blood group is further classified into following types: Rh positive: Presence of factor D Rh negative: Absence of factor D

Key: 4c. Ref Guyton Pg 454 Diagnosis: Erthroblastosis fetalis or Hemolytic disease of the newborn It is a disease of the fetus and newborn child characterized by agglutination and phagocytosis of red blood cells of fetus. (0.5) Pathogenesis: In most instances of erythroblastosis fetalis the mother is Rh negative and the father Rh positive. The baby has inherited the Rh positive antigen from the father, and the mother develops anti-Rh agglutinins from exposure to the fetuss Rh antigen. (1) In turn, the mothers agglutinins diffuse through the placenta into the fetus and cause red blood cell agglutination. (0.5)

Q.5 Give a brief account of the role of preprocessing in the Thymus and Bone Marrow. Enumerate any 5 functions of plasma proteins. Key: Preprocessing in Thymus: (0.25 marks each) (2.5+2.5 marks)

Bone marrow develops T lymphocyte which migrate to Thymus where they divide & develop diversity for different specific antigens. 1 thymic lymphocyte develops specificity against 1 antigen. Pre-processed T lymphocytes leave thymus then enter into blood & body lymphoid tissue. Thymus derived T lymphocytes are so processed that they do not react against self proteins or other self antigens. Otherwise leads to autoimmune disease. If a T lymphocyte reacts with self antigens produced by the body, it is destroyed & not allowed to release from thymus. Cells that are finally released are non-reactive against self. Duration: shortly before birth few months after birth.

Preprocessing in Bone Marrow:

(0.5 marks)

Duration: late fetal life after birth. Whole of B-Lymphocytes does not react unlike T-lymphocytes but secrete antibodies which is reactive agents (large proteins) that combine & destroy the antigenic substances. B-Lymphocytes are more diverse in forming specific antibodies than T-Lymphocytes. After preprocessing, B & T-Lymphocytes, migrate to lymphoid areas.

b. Enumerate any 5 functions of plasma proteins.

(2.5 marks)

KEY: a) Functions of plasma proteins 1-It exert colliodal osmotic pressure. 2-It perform transport functions. 3-It perform haemostatic functions. 4-Proteins perform nutritive functions. 5-Proteins perform immune functions. 6-Proteins perform buffer functions. 7-Plasma Proteins precursors of active substances. 8-Plasma Proteins responsible for viscosity of plasma and blood pressure. 9-Plasma Proteins include proteins of inflammation. 10-Plasma Proteins albumin enters to lymph, Cerebrospinal fluid and other transcellular fluids. 11-Plasma Proteins include proteins of different enzymes: amylase,transaminase,dehydrogenase. 12.Plasma Proteins effect ESR.

Q . 6A young man received a cut during shaving which started bleeding but after sometime the bleeding stopped spontaneously. a. Give mechanism involved in the spontaneous arrest of bleeding in this man. (4) key:a Hemostasis in this man would involve the following mechanisms:

Vascular constriction: Trauma to vessel wall instantaneously causes it to contract.

Platelet plug:When platelets come in contact with collagen in the vessel wall they undergo certain changes which ultimately lead to formation of platelet plug by the following mechanism 1. Platelets become sticky and adhere to collagen in the tissues 2. They secrete large quantities of ADP and their enzymes form thromboxane A2 which act on nearby platelets to activate them and the stickiness of these additional platelets causes them to adhere to the original activated platelets 3. In this way at the site of damaged vessel wall more and more platelets are activated causing them to adhere to each other and forming platelet plug Extrinsic pathway: Damage to the blood vessel will initiate extrinsic pathway of coagulation. (Fig. 36.3 Guyton 11th Ed)

INTRINSIC PATHWAY OF COAGULATION:

b. What is the process of spontaneous arrest of bleeding called? (1) key.b The process is called hemostasis

Q.7 Illustrate how immune system is regulated & what is the role of helper T cells & MHC. Distribution: 5 marks

Q.8 A 43 years old male pale looking man presents with complaint of difficulty in breathing on exertion. He has history of Inflammatory Bowel Disease followed by surgical removal of terminal portion of Ileum 3 years back. His blood picture reveals: Hemoglobin MCV (Mean Corpuscular Volume) 8.7 gm/dl 106 fl (normal range 80-100 fl) (1) (1) (1)

a) Why he suffered from breathing difficulty? b) What is type of anemia in this case? c) Which nutrient is deficient in this patient?

d) Describe the pathogenesis (mechanism of development of ailment) of his disease. Key: 8 a) Decreased hemoglobin concentration in this patient results in tissue hypoxia. Hypoxia stimulates respiratory centre leading to increased rate of respiration. As a result, the respiratory muscles become over-worked leading to exhaustion resulting into difficulty in breathing. (1) (2)

b) Megaloblastic anemia.

(1)

c) Vitamin B12 is deficient.

(1)

d) Maturation Failure of RBCs, caused by poor absorption of Vitamin B12, (which is required for RBC maturation) from the Gastrointestinal Tract due to surgical removal of ileum (from where B12 is normally absorbed) as a treatment of inflammatory bowel disease. (1) 3 to 4 years of defective B12 absorption are usually required to deplete its stores & cause maturation failure anemia. (1) Q.9 Which cell organelles can increase their number by self replication? Give functions of these organelles. Key:9 Reference: p 16, 17, Organelles with self-replication are: (1+4)

1. PEROXISOMES: Contain oxidizing enzymes including oxidases & catalases. Oxidases combine oxygen with hydrogen ions different intracellular chemicals to form hydrogen peroxide, a highly oxidizing substance, that oxidizes many substances that may otherwise be poisonous. (1.5) 2. MITOCHONDRIA: Almost all oxidative reactions occur inside the mitochondria & the energy that is released is used to form high energy compound ATP, used for cellular transport, synthesis of chemicals & mechanical work. (1.5) 3. NUCLEUS: Their replication takes place in mitosis to produce a copy of parent cell. (Any 2 = 1)

Q.10 What are 3 major categories of cellular function which utilize ATP? Key: 10 (Reference: pp 22, 23 Guyton 11th Ed.) Energy from ATP is used to promote three major cellular functions:

1. Transport of substances through multiple membranes in the cell 2. Synthesis of chemical compounds in the cell 3. Mechanical work. Transport of substances through multiple membranes in the cell: ATP is used to transport sodium, potassium, calcium, magnesium, phosphate, chloride, urate, hydrogen ions and other organic substances. (1) Membrane transport is so important to cell function that some cells use as much as 80% of the ATP formed for this purpose e.g. the renal tubular cells. (1)

Synthesis of chemical compounds in the cell: In addition to the synthesis of proteins cells synthesize phospholipids, cholesterol, purines, pyrimidines and a host of other substances. (1)

Synthesis of almost any chemical compound requires energy. Some cells use as much as 75% of all the ATP synthesized in the cell simply to synthesize new chemical compounds. (1)

Mechanical work: The final major use of ATP is to supply energy for special cells to perform mechanical work. Other cells perform mechanical work in other ways, especially by ciliary and ameboid motion. The source of energy for all these types of mechanical work is ATP. (1)