Arthritis

                                            Arthritis

•       inflammation of the joints

•       Over 200 forms of arthritis.

•       About 30% of adults have arthritis.

•       Major symptom - pain in or around joints

•       often a constant and may be localized to the joint affected

Risk Factors for Arthritis

•       Age > 40 years

•       Women > men

•       Obesity

•       Previous joint injury

•       Ethnic background

Common types

•       Ankylosing spondylitis

•       Gout and pseudo-gout

•       Juvenile idiopathic arthritis

•       Osteoarthritis

•       Rheumatoid arthritis

•       Septic arthritis

•       Still's disease

Osteoarthritis

•       most common form of arthritis

•       can affect both larger and smaller joints of the body, including the hands, feet, back, hip or knee

•       acquired from daily wear and tear of the joint

•       begins in the cartilage and eventually causes the two opposing bones to erode into each other

•       starts with minor pain while walking

•       Later pain can be continuous and even occur at night

•       affects weight bearing joints such as back, spine, and pelvis

•       disease of the elderly

•       Risk factors: prior joint trauma, obesity, and a sedentary lifestyle

•       Common sites of osteoarthritis

•       hips

•       knees

•       hands, especially base of thumb

•       base of great toe

•       spine

Rheumatoid arthritis

•       disorder in which the body's own immune system starts to attack body tissues

•       not only directed at the joint but to many other parts of the body

•       most damage occurs to the joint lining and cartilage which eventually results in erosion of two opposing bones

•       often affects joints in the fingers, wrists, knees and elbows

•       disease is symmetrical (appears on both sides of the body) and can lead to severe deformity in a few years if not treated

Gout

• caused by deposition of uric acid crystals in the joint, causing inflammation
• Crystals of uric acid form inside a joint and cause inflammation, which makes the joint red, hot, swollen and painful
• runs in families
• more common in men, women after menopause
• Other risk factors include -
• obesity
• high blood pressure
• drinking too much alcohol
• kidney failure   
• uncommon form of gouty arthritis caused by the formation of rhomboid crystals of calcium pyrophosphate known aspseudogout                                                              

Serious types of arthritis

• Lupus (systemic lupus erythematosus)
• Rheumatoid arthritis
• Scleroderma
• Sjogren’s syndome
• Lyme disease
• Ankylosing spondylitis
• Psoriatic arthritis
• Infectious arthritis

Route of infection

•       dissemination of pathogens via the blood, from distant site…. (most common)

•       dissemination from an acute osteomylitic  focus

•       dissemination from adjacent soft tissue infection,

•       entry via penetrating trauma

•       entry via iatrogenic means

Pathology

•       acute synovitis with a purulent joint effusion

•       Synovial membrane becomes edematous, swollen and hyperemic, and produces increase amount of cloudy exudates contains leukocytes and bacteria

•       As infection spread through the joint, articular cartilage is destroyed by bacterial and cellular enzymes

•       cartilage may be completely destroyed

•       Pus may burst out of the joint to form abscesses and sinuses.

•       The joint may be become pathologically dislocated.

Clinical presentation

•       Typical features are acute pain and swelling in a single large joint ,commonly the hip in children and the knee in adults, however any joint can be affected.

•       The most commonly involved joint is the knee (50% of cases), followed by the hip (20%), shoulder (8%), ankle (7%), and wrists (7%). interphalangeal, sternoclavicular, and sacroiliac joints each make up 1-4% of cases.

Hepatitis B(Clinical aspect)

                Hepatitis B(Clinical aspect)

Clinical features

—  Generally asymptomatic

—  Prodormal illness (<2weeks) includes:

         fever, chills, headache, myalgia, arthalgia, nausea and anorexia.

—  Icteric phase

            dark urine with yellow discoloration of sclera , pale stool.

            accompanied by vomiting, diarrhea and abdominal pain.

—  Recovery phase (3-6 weeks):

            improved apetite, GI symptoms subside, jaundice decreases.

Physical signs

—  Liver

          tender  and minimally enlarged

—  Spleen

             splenomegaly

—  Lymph nodes

          cervical lymphadenopathy

Complications

—  Acute liver failure

—  Aplastic anemia

—  Relapsing hepatitis

—  Chronic liver disease

           progression to chronicity

                          i. Vertical transmission- 90%

                          ii. Horizontal transmission- 10%

—  Cirrhosis

—  Hepatocellular carcinoma

—  Renal failure

—  Henoch-Schonlein Purpura

Poor prognostic features

—  Marked increase in AST and ALT

—  Bilirubin >20mg/dl

—  Liver not enlarged

—  PT prolongation by 5 seconds

—  Recurring attacks of hypoglycemia

—  Renal failure

—  Associated conditions

Investigations           

—  Immunological tests

           detection of the viral antigens and the host antibodies against them

    i. HBs Ag

             viral surface antigen

           active infection

           appear late in IP before the prodormal stage at about 3-4 weeks and

           disappear by 5 months

  

    ii. HBc Ag

            viral core antigen, not found in blood

           denotes a recent infection

          iii. HBe Ag

              indicate active viral replication in liver and infectivity

                detected early in course

iv. Anti HBc Ag

               IgM type with IgG Ab

                first antibody to appear, persist life long

 v. HBs Ag and anti HBc(IgG) in blood denote progression to chronicity.

 vi. HBV-DNA

                by polymerase chain reaction

                measures viral load and active viral replication

 Laboratory tests

   i. liver function tests

            - raised bilirubin level (conjugated and unconjugated)

            - raised aminotransferses (ALT and AST)

            - ALP level may be raised but less than twice the normal.

    ii. Low total count with neutropenia, relative lymphocytosis

         and atypical lymphocytes.

   iii. Urine shows bilirubinemia, slight microscopic

         hematuria and mild proteinuria.

   iv. Marked prolongation of prothrombin time signifying

         extensive hepatocellular damage.

Management

          no specific t/t, only supportive with monitoring for ALF.

          full recovery in (90-95)% and (5-10)% chronicity for life.

—  Rest

           complete rest during the symptomatic phase

         gradual ambulation.

—  Diet

           2000-3000Kcal/day, light diet, fruit drinks and glucose

         protein diet

         i.v. fluids in case of severe vomiting.

—  Drugs

          use of any other drugs (sedative and hypnotics) is avoided.

          alcohol avoided for about 6 months.

          OCP is resumed after  clinical and biochemical recovery.

          Antiviral drugs for Hepatitis B Infection

—  Interferon-α

          - augment native immune response

          - c/i  in cirrhosis

—  Lamivudine

         - inhibit DNA polymerase

         - effective in improving liver function in pt with

            decompensated cirrhosis. 

—  Adefovir

          - inhibit DNA polymerase

—  Entecavir and Telbivudine

          - decrease viral load

          - used in chronic hepatitis

Prevention

—  Active immunization

            recombinant vaccines containing HBsAg

            i.m. injection at 0, 1 and 6 months.

            1o µg for <1o yrs and 2o µg for >10 yrs.

            recommended- all children along with high risk groups as health

            workers, hemodialysis pts, injection and drug users, hemophiliacs

            sexual contact of HBsAg carriers.

—  Hyperimmune B immunoglobulin (HBIG)

            prepared from blood containing anti-HBs.

            given within 24 hrs or at most a week of exposure.

            dose - 0.06ml/kg

            indication- accidental needle puncture, gross personal

            contamination with infected blood, oral ingestion or

            contamination of mucosal membranes and exposure to cuts

            or grazes.

—  Active-passive immunization

            given together with Hyperimmune globulin

            recommended for post exposure prophylaxis in unvaccinated.

            Perinatal exposure to infants to HBsAg positive mother– a single

            dose of 0.5 ml of HBIG in thigh immediately after birth is followed   

            by 3 doses of vaccine within 12 hrs of birth.

—  Others

           screening of blood donors for HBV infections.

           voluntary blood donation.

           use of sterilized instruments while handling blood and body

           fluids

         

        

Bone Marrow Aspiration

                          Bone Marrow Aspiration

Structures of bone marrow
Bone marrow consists of :

1) Vessels-Venous sinusoids lined by endothelial cells.

2) Nerves

3) Hemopoietic cells

4)Reticuloendothelial cells

5) Fat tissue

6) Stroma

Composition of stroma:

A) Cells:

•      Macrophages

•      Fibroblasts

•      Endothelial cells

•      Fat cells

B) Extracellular matrix:

•      Fibronectin

•      Laminin

•      Collagen

•      Proteoglycan

•      hemonectin

Indications of bone marrow aspiration

A) To diagnose:

1) Red cell disorders:

            megaloblastic anemia and pure red cell aplasia.

2) White cell disorders:

            subleukemic leukemia/ aleukemic leukemia, all leukemias for FAB typing, agranulocytosis

3) Megakaryocytic disorders: ITP and other thrombocytopenia

4) Myeloproliferative disorders: Chronic myeloid, polycythemia vera.

5) Storage disease: Gaucher’s disease

6) Parasitic disease: kala-azar

7) Plasma cell disorders: Multiple myeloma

8) For iron stores

9) Metastatic deposits

10) Fungal disorders: Histoplasma

B) Assessment of response to treatment

Contraindications

•      Major disorders of coagulation- Hemophilia and other coagulation disorders.

Needles:

•      7-8 cm length

•      Well-fitting stilette

•      Adjustable guard

1) Salah

2) Klima

Marrow is obtained by

1)      Bone marrow aspitation (marrow)

2)      Bone marrow trephine biopsy (marrow+bone)

Sites of bone marrow aspirate:

1)      Sternum

2)      Posterior superior iliac spine

3)      Iliac crest

4)      Anterior superior iliac spine

5)      Spinous process of lumbar vertebra

6)      Upper end of tibia-infants

Method:

1)      position-lie in lateral position, legs flexed, thighs against abdomen to make posterior superior iliac spine prominent.

2)      Skin covering the area cleaned with iodine, draped.

3)      5 ml of 1-2% xylocaine injected into skin and then to periosteum.

4)      Guard on the needle adjusted taking into account of subcutaneous tissue.

5)      5) Salah needle along with its stylet and introduced through skin with rotary clockwise and anticlockwise movement. Needle is pushed through the cortex into medullary bone and resistance gives way as needle enters the medullary cavity. Guard prevents further pushing in of needle.

6)      6) Stylet is withdrawn and 10 ml syringe is attched to the needle. Suction is applied into syringe to draw 0.2 to 0.4 ml of marrow into syringe. Suction stopped. Do not aspirate more marrow as it may dilute marrow.

7)      9) Good marrow smears contain marrow particles as well as trails of particles. At least 6 smears are made.

8)      10) 3 smears-fixed in methanol and stained with Giemsa. 1 for iron stain. Rest used for cytochemistry/immunophenotyping as per requirement of the case.

Biopsy Technique

•       Bone marrow biopsy is usually done following this.

•       Bone biospy needle is held with palm and index finger,  stilette is locked in place. Once needle touched  bone, stilette is removed.

•       Using firm pressure, needle is rotated clockwise and counterclockwise till entering bone cavity till an adequate amount of marrow can be aspirated, 1.5-2cm in length.

•       Rotate needle along the axis to help cut specimen.

•       Pull back about 2-3mm and the insert the needle again slightly, at a different angle to obtain specimen.

•       Slowly pull out needle in clockwise-counterclockwise motion.

•       The marrow sample is removed from syringe, using a thin wire.

•       Dry tap: Failure to aspirate marrow.

•       Causes:

•       1) Myelofibrosis

•       2) Inflitration of bone marrow

•       Suggest trephine biopsy.

Evaluation of bone marrow aspirates

1)      Detailed clinical history

2)      PBS

3)      Choose smears having marrow particles and cell trails of particles

4)      Examine under scanner and low power to assess

                a) cellularity b)megakaryocytes c) metastatic carcinoma cells

5) Select the area where cells are very well spread out. Trails made by marrow particles provide enough cells to study their morphology and carry out a differential count on the smears

6) In report, PBS and bone marrow findings should be given.

1)      Differential count of marrow: At least 200-500 marrow cells are counted.

2)      Cellularity:  assessed by visual evaluation of fat and cells. Child-highly cellular with less than 25% fat, adult-40-50% fat. Reported as hypercellular, normocellular, hypocellular. Assessed in scanner and low power.

3)      M:E ratio=3:1 to 15:1

4)      Erythropoiesis: type of reaction-normoblastic/megaloblastic/micronormoblastic and dyserythropoiesis.

5)      5) Myelopoiesis: Evaluation of maturation arrest, granulation, number of blasts, degenerative changes.

6)      6) Megakaryopoiesis: number and maturation is evaluated.

7)      7) Lymphocytes and plasma cells

8)      8) Parasites

9)      9)Other abnormal cells

Possible risks:

•       Persistent bleeding and infection.

•       Pain after the procedure.

•       A reaction to the local anesthetic or sedative.

Malaria

                               MALARIA

Course Objectives

•         Basic understanding of malaria                                   

–       Causative agents; life cycle

–       Epidemiology

–       Symptoms

–       Diagnosis

–       Treatment

–       Prevention

   

Introduction

§  Malaria is a life-threatening parasitic disease caused by Plasmodium (protozoan parasite)

§  Name means “bad air”

§  Vector borne disease

§  40% of the world’s population is at risk

§  90% of the deaths due to Malaria occur in Sub-Sahara Africa, mostly among young children.

§  Around 400-900 million people are affected  with at least 2.7 million deaths annually.

q Cases in Nepal

—  1963- 159 cases detected

—  2002- 12,750 cases detected

—  2006- 4,969 cases detected

Causative agents

•         Plasmodium  species: 

•         P falciparum

•         P vivax

•         P ovale

•         P malariae

Life cycle

•         In 2 different hosts:

–       Man: as an intermediate host

–       Mosquito: Definitive host

Life cycle in human

1, Human infection begins with the bite of

infected female Anopheles mosquito. Mosquito

during bite, sporozoites with saliva inject into

small blood vessels of man.  These motile

sporozoites are carried within half an hour  to

the liver by the blood stream.

Pre erythrocytic schizogony or stage

In the liver cells sporozoites under go a

stage of asexual reproduction forming

schizont which contains 2000 to 50,000

merozoites. Finally mature schizont

ruptures releasing 1000 of merozoites into

the blood stream.

Erythrocytic schizogony or stage

In the blood stream merozoites attach to the

receptors of (glycophorine) RBC and invade

them and develop into young trophozoite.

These feed on the HB and produces malaria

pigment; compound of haematin and ferric

acid as an end product of Hb break down.

The trophozoites multiply with division of

nucleus followed by division of cytoplasm to

become mature schizonts – ruptures- release

merozoites- infects new RBC.

Gametocytogenesis

After 2-3 erythrocytic cycles , some

merozoites  in RBC instead of developing

into trophozoites and schizonts , develop

into male and female gametocytes.

In the mosquito

-          Mosquito during bite ingest these gametocytes. In the mid gut of mosquito male fertilizes the female by fusion forming zygote-become mature and develop into motile ookinete. It penetrates gut wall of the stomach and-grows into oocyst, large no. of sporozoites are formed in the oocyst-when maturation occurs, it ruptures and liberate sporozoites in the body cavity that spread to all parts of the mosquito , particularly to the salivary gland of the mosquito. Sporozoites are infectious to man and gametocytes are infectious to mosquito

Transmission

•         Man is the only important reservoir

•         Vector is female Anopheles mosquito

- Rainfall:        thrive in tropical areas

–        Altitude:          rarely exist above 2000 meters

–        Terrain:           coastal areas and lowlands with lots of freshwater breeding sites

–        Transmission also possible through:

1. Blood transfusion
2. Contaminated needle
3. Organ transplant
4. Congenital

Susceptibility

•         Universal susceptibility

•         No absolute immunity

–        Partial immunity in areas of high endemicity